USD 2337
Pall Solutions for the BioPharmaceutical Industry
Contents and Introduction Global Expertise
Pall Corporation is the leading global provider Time of filtration, purification and separation technologies to the diverse and rapidly Timely process development and the expanding Life Sciences market. Its products procurement of production capacity are are used from the earliest stages of discovery crucial for our customers’ success. We know and development of new drugs, through development of new drug products is a production and delivery of therapies for the demanding and costly exercise. Pall has prevention, diagnosis and treatment of expert teams available at every stage of the disease. Our total sales turnover is more than process for fast and flexible solutions. US$ 1.7 billion. Quality Capabilities Drug products have to be available at a Pall’s unique capability comes from a strong consistently high quality with manufacturing blend of BioPharmaceutical expertise, leading and equipment subject to comprehensive technologies and customer support. We validation and documentation. Pall® products provide reliable and fully integrated solutions already present in more than 1000 for design, manufacture, sales and servicing of applications, fulfill exacting demands in design our products. Comprehensive support is and manufacture, resulting in excellent available in all parts of the world. process reproducibility and reliability.
Experience
Pall Life Sciences handles all purification, filtration, and separation applications from bulk preparation and synthesis to biological and biotech-based production of active ingredients, to downstream processing and formulation and final filling of products. More than 50 years experience in providing proven engineered solutions is a good basis to partner with us.
ii Contents
Introduction Page Direct Flow Liquid Filtration Page Filter Housings Page Introduction ii Mini Kleenpak Sterilizing-grade 77 Junior B series Filter Housings 145 Table of Contents iii Capsule Filters Sealkleen™ Filter Housings 147 Usage Instructions iv Kleenpak Capsules with 79 Pall Advanta™ Junior Filter Housings 149 Supor® EKV Membrane Assemblies Pall Advanta Junior F Liquid 151 Supor EKV Sterilizing-grade 81 Filter Housings Applications Filter Cartridges Pall Advanta ALT Liquid Filter Housings 153 Biotechnology and Cell Culture 2 Supor EBV Sterilizing-grade 83 Flow Diagram Filter Cartridges Pall Advanta In-Line Liquid and Gas 155 Filter Housings Blood Products and Fractionation 4 Kleenpak Capsules with 85 Flow Diagram Fluorodyne® II Membrane Assemblies Pall Advanta Jacketed Housings 157 API - Active Pharmaceutical Ingredients 6 Fluorodyne II Hydrophilic PVDF 87 Pall Advanta AGT Gas Filter Housings 159 Flow Diagram Filter Cartridges Pall Advanta AVL Liquid and Gas 161 Formulation and Filling 8 Kleenpak Capsules with 89 Filter Housings Flow Diagram Ultipor N66 Membrane Assemblies Pall Advanta ALT4 Multi-round Housings 163 Water Purification 10 Sealkleen Membrane Filter Cartridges 91 Veladisc™ Depth Filter Module Housings 165 Flow Diagram Ultipor N66 Sterilizing-grade 93 Pall Advanta Electrical Trace Heater 167 Filter Cartridges MDS Junior Style Industrial Housings 168 Direct Flow Liquid Filtration Kleenpak Capsules with 95 IOL and IDL Single-round 169 Posidyne® Membrane Assemblies Depth Filter Sheets, Modules, and Capsules Industrial Housings Posidyne Filter Cartridges 97 Bio-Series Depth Filter Sheets 15 PCY Polypropylene Filter Housings 171 P-Series Depth Filter Sheets 17 Novasip™ Liquid Sterilizing-grade 99 Megaplast™ Plastic Filter Housings 173 and Modules Capsule Filters K-Series Depth Filter Sheets 19 Kleenpak Nova Sterilizing-grade 101 and Virus Removal Capsule Filters T-Series Depth Filter Sheets 21 Tangential Flow Filtration Novasip DV20 and DV50 103 Z-Series Depth Filter Sheets 23 Tangential Flow Filtration Technology 177 Virus Removal Filter Capsules E-Series Depth Filter Sheets 25 Ultrafiltration and Microfiltration 179 Ultipor VF Grade DV50 105 TFF Cassette Membranes Supradisc® Depth Filter Modules 27 Virus Removal Filter Cartridges – Matching Membrane Cassettes to 180 Supradisc II Modules 29 SBF Junior Style Applications Supracap™ 60 Depth Filter Capsules 31 Ultipor VF Grade DV20 Virus Removal 107 Filter Cartridges Minimate™ Tangential Flow 181 Supracap 200 Encapsulated 33 Filtration Capsules Depth Filter Modules Ultipor VF Grade DV50 Virus Removal 109 Filter Cartridges Minimate TFF System 183 Tangential Flow Filtration 185 Direct Flow Liquid Filtration Membrane Cassettes Air and Gas Filtration Membrane and Depth Filter Cartridges, Tangential Flow Filtration 188 Capsules and Disposable Systems Novasip Capsules with Emflon PFR 113 Membrane Cassette Holders Disposable Systems 37 Membrane Assemblies Pilot and Process 194 Kleenpak™ Connectors 39 Kleenpak Capsules with Emflon II 115 Development Capabilities Membrane Assemblies Kleenpak Nova Particulate and 41 Tangential Flow Filtration Systems 195 Prefilter Capsule Filters Kleenpak Capsules with Emflon PFR 117 TFF Polymeric Hollow Fiber Membranes 197 Membrane Assemblies PreFlow™ Capsule Filters 43 and Ceramic Modules Kleenpak Capsules with HDC II 119 ® Microza* Membranes 198 Mini Profile Capsule Filters 45 Gas Filter Assemblies Kleenpak Membralox® Ceramic 203 Capsules with 47 Emflon PFR Junior-style Filter Cartridges 121 HDC® II Filter Assemblies Membrane Products Emflon PFR Sterilizing-grade Filter 123 HDC II Junior Style Filter Cartridges 49 Pallsep™ Vibrating Membrane 205 Cartridges Filtration Technology Profile II Filter Cartridges 51 Emflon CPFR High-temperature 125 Sheet TFF Membranes 207 Profile II Plus Filter Cartridges 53 Sterilizing-grade Filter Cartridges Profile Star Filter Cartridges 55 Emflon PFA Filter Cartridges 127 Chromatography StarClear™ Filter Cartridges 57 Ultipor GF Plus Air and Gas Filters 129 Mustang® Membrane 211 Profile Filter Cartridges with 59 HDC II Gas Filter Cartridges 131 Chromatography Starter Kits Ultipleat® Construction PallCell® Air and Gas Filter Cartridges 133 Mustang HDC Coin Unit 215 II Filter Cartridges 61 LG Liquid and Gas Coalescing 135 Mustang Chromatography Capsules 217 Ultipor® GF Plus Filter Cartridges 63 Filter Cartridges and Cartridges PreFlow Filter Cartridges 65 Porous Metal Filters for Resolute** Chromatography Columns 221 Marksman™ Elements with 67 Liquid and Gas Service Resolute Slurry Packing Systems 223 Nexus A Series Filters Rigimesh® Sintered Metal Mesh 137 PK Chromatography Skids 225 Marksman Elements with 69 Filter Cartridges ® Poly-Fine XLD Series Filters PSS® Porous Metal Filter Cartridges 139 Marksman Elements with 71 ® PMM Metal Membrane Filter Cartridges 141 Palltronic® Instruments Poly-Fine® II Series Filters Emflon® FM Filter Cartridges 73 Palltronic Flowstar XC 229 Filter Integrity Test Instruments Ultipor N66 Particulate and 75 * Microza is a trademark of Asahi Kasei Corporation. Palltronic Aquawit XC System 231 iii Bioreduction Filter Cartridges ** Resolute is a trademark of Euroflow (UK) Ltd. Palltronic® Instruments Page Pall Technical Services Page Appendices and Index Page Palltronic Flow Check Device 233 Pre-Inspection Reviews 253 Filter Configurations and Dimensions 272 Palltronic Training Program 234 Filter Integrity Test Equipment 255 O-Rings and Gaskets Reference Guide 274 Drivers for Palltronic Filter Integrity 235 Validation Index 275 Test Instruments Troubleshooting and 257 Trademarks 282 Consultancy Services Palltronic Filter Manager 237 International Offices 283
Pall Technical Services Systems Process-Specific Filter Validation 241 Pall Process Engineered Systems 261 Kleenpak Connector Validation 243 DGM Plate and Frame Filter Systems 263 Disposable Filtration System Validation 245 ZHF Centrifugal Discharge 265 Contamination Analysis 247 Filter System Process Development and 249 PEF Multi Purpose Processor 267 Optimization Pure Water Systems 269 Training 251
How to Use this Catalogue
Selecting the Appropriate Pall Solution Symbols
You may refer to the diagrams in the Applications section The following symbols are used throughout the catalog to identify (pp. 8 – 17) for Pall products that have been optimized for specific product categories. Symbols that apply to a specific product appear unit operations. in full color. Symbols that do not apply to the product appear faded. The catalog is organized into the following sections: – Applications Key to Product Symbols – Direct Flow Liquid Filtration Depth Filter Sheets, Modules and Capsules Fluid Clarification, Cartridges Bioburden Reduction and – Direct Flow Liquid Filtration Prefiltration Membrane and Depth Filter Cartridges, Capsules Modules and Disposable Systems – Air and Gas Filtration (including porous Metal Filter Cartridges) Sterile Filtration – Sanitary Housing Sheets – Housings for direct-flow filtration Cartridges Applications – Tangential Flow Filtration (including holders) UpscaleSM Progarm – Chromatography (Mustang and Resolute technologies) Industrial Housing – Palltronic Instruments (for integrity testing and filterability) Tangential Flow Filtration – Pall Technical Services Virus Removal – Palltronic Services Chromatography – Systems. Capsules
iv Applications Biotechnology and Cell Culture Flow Diagram
Upstream Processing Cell Harvest and Product Separation Innoculation
Media Filtration Kleenpak Connector Exhaust
Particulate Virus Sterilizing-grade HDC II J012 Emflon PFR Removal Filter Liquid Filter Air Prefilter Sterilizing-grade Filter Air Filter Aeration
Liquid Gas Coalescer Fermenter
Emflon PFR Depth Filtration Particulate Sterilizing-grade Removal Air Filter Filter
Aeration and Exhaust Media Filtration LG Liquid and Gas Coalescing 135 Particulate Removal Liquid Filters Filter Cartridges PreFlow™ Filters 43, 65 Particulate Removal Air Filters Virus Removal Filters HDC® II Gas and Vent Filters 119, 131 Ultipor VF Virus Removal Filters 103 – 109 Ultipor® GF Plus Air and Gas Filters 129 Sterilizing-grade Liquid Filters ® PallCell Air and Gas Filters 133 Supor® EKV Filters 77 Sterilizing-grade Air Filters 79 Emflon® PFR Sterilizing-grade 113 81 Membrane Filters 117 101 121 Fluorodyne® DFL and DJL Filters 85 123 87 99 101 Innoculation Kleenpak™ Connector 39 Cell Harvest and Cell Separation Depth Filtration Perfusion Culture SupraDisc® Depth Filter Modules 27 Microza* Hollow Fiber Modules 198 SupraCap™ 200 Encapsulated 33 Depth Filter Modules P-Series Depth Filter Sheets 17 * Microza is a trademark of Asahi Kasei Corporation.
2 Biotechnology and Cell Culture Flow Diagram
Downstream Processing and Purification
Supor EKV Supor EKV Buffer Filter Buffer Filter
Capture Sterilizing-grade Concentration Purification Chromatography Liquid Filtration Diafiltration Chromatography
Emflon PFR Sterilizing-grade Air Filter
Virus Tangential Flow Filtration Sterilizing-grade Polishing Removal Liquid Filter Chromatography Filtration
Formulation and Filling
Storage Mustang Membrane Chromatography
Cell Harvest and Cell Separation Tangential Flow Filtration Sterilizing-grade Buffer Filters Supor Cassettes 186 Supor EKV Filters 77 Microza* Hollow Fiber Modules 198 79 81 ® Membralox Ceramic Modules 203 101 PallSep™ VMF System 205 Sterilizing-grade Vent Filters Emflon PFR Sterilizing-grade 113 Downstream Processing and Membrane Filters 117 Purification 121 123 Prefiltration and Clarification Concentration and Diafiltration PreFlow Filters 43, 65 Omega™ and Regen™ Cassettes 186 Sterilizing-grade Liquid Filters for Product Filtration Purification Chromatography Supor EKV Filters 77 Resolute** Chromatography Columns 221 79 and Systems 225, 261 81 Contaminant Removal/Reduction 101 Mustang® Membrane Chromatography 211 Fluorodyne DFL and DJL Filters 85 215 87 217 99 Virus Removal Filters 101 Ultipor VF Virus Removal Filters 103 105 107 109
Note: The products listed are examples only and others may be more suitable for your application. Specific recommendations can be obtained from your * Microza is a trademark of Asahi Kasei Corporation. local Pall or distributor office. 3 ** Resolute is a trademark of Euroflow (UK) Ltd. Blood Products and Fractionation Flow Diagram
Cryo-Precipitation Fractionation Ethanol Filtration
Fractionation Emflon PFR - Albumin Sterilizing-grade - Globulin Vent Filter Particulate Sterilizing- Removal grade Filter Liquid Emflon PFR Filter Sterilizing Vent Filter Anion Centrifugation Exchanger
Plasma Ethanol Filtration Precipitate Harvest
Capsule Bag Systems Kleenpak Connector
Particulate Sterilizing-grade Removal Liquid Filter Storage Membraplan DG/DGM with Cryo-Precipitation Cryo-Poor Plasma Filter - Factor VIII, Fibrinogen - Factor VII, IX, ATIII, C1 Supradur 50P or E-Series Filter Sheets
Supradisc Bio-Depth Filter Modules
Supor EKV Buffer Filter
Immunoaffinity Chromatography Virus Fraction I Inactivation Particulate Supor EKV Removal Filter Sterilizing-grade Liquid Filter Fraction II + III precipitates Immunoglobulin
Supor EKV Emflon PFR Buffer Filter Sterilizing Vent Fraction III Filter
Purification of Supor EKV Fraction IV Storage Contaminant Sterilizing-grade Cryo-Factors Removal Filter
Formulation Fraction V and Filling Albumin
Capsule Bag Systems Mustang Diafiltration Kleenpak Connector Membrane Centrasette Chromatography System with Omega Cassettes
4 Blood Products and Fractionation Flow Diagram
Ethanol Filtration Particulate Removal Filter Emflon® FM 73 Purification of Sterilizing-grade Liquid Filter Immunoglobulin Ethanol Filtration Supor® EKV Filters 77 79 Emflon PFR 81 Sterilizing 101 Vent Filter Fluorodyne® DFL and DJL Filters 85 87 Particulate Sterilizing-grade 99 Removal Liquid Filter Filter 101
Separation Paste III Harvest Paste II Vent Filters Sterilizing-grade Vent Filters Emflon PFR Sterilizing-grade 113 Membrane Filters 117 Suspension Suspension Depth Filtration Depth Filtration 121 and Precipitation and Precipitation 123
Disposable Bag Systems Emflon PFR Supor EKV Supor EKV Kleenpak™ Connector 39 Sterilizing Vent Buffer Filter Buffer Filter Disposable Systems 37 Filter
Chromatography Virus Removal Resolute* Chromatography Columns 221 and Systems 225, 261 Mustang® Membrane Chromatography 211 215 Formulation and Filling 217
Suspension Process Centrasette Chromatography System with Buffer Filtration Omega Cassettes Sterilizing-grade Buffer Filters Supor EKV Filters 77 Depth Filtration 79 81 Clarification Color Removal 101
Supor EKV Sterilizing Product Filtration Liquid Filter Tangential Flow Filtration Omega™ Cassettes 186 Particulate Removal Filters Supradisc EKS P Supradisc AKS5/AKS6 PreFlow™ Filters 65 Depth Filters SupraDisc® Depth Filter Modules 27 Emflon PFR Supor EKV SupraCap™ 200 Encapsulated 33 Sterilizing Vent Buffer Filter Filter Depth Filter Modules Purification of Depth Filter Sheets 15–25 Albumin Sterilizing-grade Filters Supor EKV Filters 77 79 81 101 Formulation Fluorodyne DFL and DJL Filters 85 Pasteurization and Filling 87 Storage Centrasette 99 System with 101 Omega Cassettes Virus Removal Filters Ultipor® VF Virus Removal Filters 103 105 107 109
Note: The products listed are examples only and others may be more suitable for your application. Specific recommendations can be obtained from your local Pall or distributor office. 5 * Resolute is a trademark of Euroflow (UK) Ltd. API - (Active Pharmaceutical Ingredients) Flow Diagram
Upstream Process Activated Carbon or Catalyst Removal
Tank Farm Supracap and Supradisc Depth Filters
Point-of-Use Inert Gas Particulate Removal Filter Gas Reactor Filter
Marksman Filters
Activated Carbon or Catalyst
First Particulate Removal ZHF Automated Systems Filter Point-of-Use Sterilizing-grade Filter
Activated Carbon Modules
AKS Depth Filter Modules
Upstream Process Crystallization Solvent Particulate Removal Filters Solvent Particulate Removal Filters Emflon® FM 73 Emflon FM 73 Prefiltration or 41–76 Solvent Sterilizing-grade Filters Particulate Removal Filters Supor® EKV Filters 77 Gas and Vent Sterilizing-grade Filters121–126 79 81 101 Activated Carbon or Catalyst Removal Fluorodyne® DFL and DJL Filters 85 ® SupraCap 200 Encapsulated 33 87 Depth Filter Modules 99 Depth Filter Sheets 17, 19 101 Depth Filter Modules 29 31 Solvent Recycling Marksman™ Bag Filters 67–72 Liquid – Liquid Coalescer ZHF Automated Systems 265 Note: The products listed are examples only and others may be more suitable for your application. Activated Carbon Filters Specific recommendations can be obtained from your AKS Depth Filters 27, 33 local Pall or distributor office.
6 API - (Active Pharmaceutical Ingredients) Flow Diagram
Crystallization Solvent Recycling
Reactor Clean Distillation Solvent Column Solvent Filter
Solvent Filter Particulate Removal Filter Centrifugal Discharge System
Water Removal Liquid – Liquid Coalescer
Centrifuge
Formulation and Filling
Dryer
7 Formulation and Filling Flow Diagram
Bulk Product Emflon PFR Sterilizing Vent Filter
Emflon PFR Sterilizing Vent Filter Formulation Tank
Particulate Sterilizing-grade Removal Liquid Filter Intermediate Filter Tank
Water
Liquid Filters Particulate Removal Filters Disposable Systems PreFlow™ Filters 43, 65 Kleenpak™ Connector 39 Sterilizing-grade Liquid Filters Disposable Systems 37 Supor® EKV Filters 77 79 Integrity Test Instruments 81 ® 101 Palltronic Flowstar XC instrument 229 Fluorodyne® DFL and DJL Filters 85 Palltronic AquaWIT XC system 231 87 99 Automated Systems 101 Automated Systems 261
Gas and Vent Filters Pharmaceutical Services Sterilizing-grade Filters Pharmaceutical Services 241-257 Emflon® PFR Sterilizing-grade 113 Membrane Filters 117 Note: The products listed are examples only and 121 others may be more suitable for your application. 123 Specific recommendations can be obtained from your local Pall or distributor office. Emflon CPFR High Temperature 125 Membrane Filters
8 Formulation and Filling Flow Diagram
Filling
Particulate Sterilizing-grade Removal Liquid Filter Filter
9 Water Purification Flow Diagram
Pure Water Storage Ultipleat Profile Ultipleat High-flow Particulate Water Tank Particulate Removal Filter Sterilizing-grade Removal Filter Vent Filter
Two Stage Reverse Osmosis High Purity Water/Purified Water
Municipal Water
Ultrafiltration Pure Water Profile Coreless Particulate Softening Removal Filter Activated Ion Carbon Exchange Storage
Point-of-Use Marksman Sterilizing-grade Particulate Carbon Particulate Removal Filter Removal Filter Liquid Filter Removal 0.1 µm and Distillation Bag Filter 0.2 µm Sterilizing-grade Water for Injection Filters
10 Water Purification Flow Diagram
Liquid Filters Metal Filters Rigimesh® Sintered Metal Mesh Filter 137 Particulate Removal Filters High Flow Ultipleat® Profile® Coreless
Gas and Storage Tank/ Sterilizing-grade Marksman™ Bag Filter 67 Compressed Air Fermenter Vent Filter 69 Vent Filter 71 Profile® Star Filters 55 Carbon Removal Filters Autoclave/ Freeze Dryer Steam Sterilizing-grade Liquid Filters Supor® EKV Filters 77 79 81 101 Pharmaceutical Production Formulation Fluorodyne® DFL and DJL Filters 85 Process and Filling 87 99 101
Pure Water Buffers and Gas and Vent Filters Systems Media Sterilizing-grade Filters Emflon PFR Sterilizing-grade 113 Membrane Filters 117 121 123 Emflon CPFR High Temperature 125 Membrane Filters Emflon PFR Steam Filters Sterile Gas ® Filter PSS Porous Metal Filter Cartridges 139 Note: The products listed are examples only and Washing of Primary Packaging others may be more suitable for your application. Compressed Air Specific recommendations can be obtained from your for Blowing local Pall or distributor office. Down Washing Machine
Prewash Final Wash
Water for Injection Profile Star Rigimesh Fluorodyne DLF Particulate Stainless Steel Liquid Filter Removal Particulate Sterilizing-grade Filter Removal Filter Pure Water
11 12 Direct Flow Liquid Filtration Depth Filter Sheets, Modules, and Capsules Depth Filter Sheets, Modules and Capsules
Pall offers a complete line of cellulosic depth In addition to the full line of depth filter sheets, filter sheets, modules and capsules for use in Pall also offers a complete line of Supradisc the pharmaceutical industry. A broad array of and Supradisc II (SD II) depth filter modules. depth filter grades, from coarse filtration The Supradisc modules are designed around through fine prefiltration, is available to ensure a rigid polypropylene core to ensure the maximum efficiency for every process. Pall’s integrity of the filter modules throughout their depth filter sheets are available in a wide use. The SD II modules offer the advantages range of sizes for use in process development of an extremely rigid and durable design with to large-scale manufacturing. patented clip construction and reverse-flow capabilities. The depth filter modules offer Depth filter sheets provide an economical and decreased setup and operation while efficient means of coarse filtration, clarification, increasing the safety of the process. and prefiltration for a wide variety of pharmaceutical and biological fluids. In Supradisc modules are also available in an addition to the mechanical depth filtration encapsulated Supracap format for single-use mechanisms, Pall’s depth filter sheets possess processing minimizing cleaning and cleaning either a slight positive charge or a high validation positive charge that further enhances their filtration capacity. This inherent Positive Zeta The Supracap 60 Depth Filter Capsules offer Potential helps to remove negatively-charged ease of use in a disposable device for scale- contaminants from the fluid stream. up testing and process optimization.
14 Bio-Series Depth Filter Sheets Exceptional Purity and Low Protein Binding
Extractables Release The BIO series of depth filter sheets from 500 0.45 18 Pall (formerly SeitzSchenk) was specially 450 0.4 16 developed for the strict requirements of the 400 0.35 14 350 biotechnological and pharmaceutical 0.3 12 300 industries. Stringent manufacturing and 0.25 250 control methods in line with requirements 10 0.2 Ions in ppm
200 – of the pharmaceutical industry guarantee 8
0.15 Fe Al/Ni – Ions in ppb 150 constant high filtration quality as well as 6 100 0.1 highest purity of the filter medium. Retention rates (µm) 4 50 0.05 BIO depth filter sheets are available with 0 0 2 Bio Depth Filter Non-Pall Non-Pall three different retention rates. Ion Reduced Standard 0 Product Bio 10 Bio 20 Bio 40 Highly purified natural and modified 2 ∆ Extractables in the first rinse fraction (5 L/m ) celluloses are used in manufacture. These p = 1 bar (14.5 psi) with water at 20 °C (68 °F). Aluminum Iron Ions Nickel celluloses are completely free from inorganic materials like kieselguhr, perlite, 1200 1100 or glass fibers. The distinguishing feature of 1000 the BIO depth filters is the low release of 900 extractables. BIO depth filters release 800 essentially less extractable metal ions, such 700 as iron, aluminum, or nickel, than any other 600 /min at 1 bar (14.5 psi) 2 filter sheet. 500 400 When filtering ion-sensitive products like 300 parenteral solutions, therapeutics, and 200
dialysis solutions, as well as protein-based Permeability L/m 100 0 diagnostics, a considerably better filtrate Bio 10 Bio 20 Bio 40 quality is reached with BIO depth filters. ∆p = 1 bar (14.5 psi) with water at 20 °C (68 *F). Due to their electrokinetic adsorption
potential, positively-charged resins increase 40
retention of the smallest particles well 35 above mechanical separation alone. 30
The use of selected cellulose fibers and 25 their arrangement result in a very low 20 protein adsorption in the filter matrix and 15 excellent rinse-out after filtration. loss Rel. protein 10 Pall BIO series depth filters are used 5 worldwide in biotechnological and 0 pharmaceutical applications to provide BIO Depth Filter Conventional reliable and economical filtration. Filter Sheet Tested with bovine serum albumin (20 – 60 µg/mL). Without post rinse With post rinse
15 Bio-Series Depth Filter Sheets Technical Specifications
Characterization The tests are carried out according to the methods of the Technical and Analytical Work Group within the European Depth Filtration Association or in accordance with in-house test methods.
Technical Data
Sheet Weight per Area Thickness Ash Content Extractable Ions Soluble in 0.025 µm H2 SO4 (g/m2) (mm) (%) (mg/m2)
Ca Fe Al
BIO 10 1400 3.0 < 1 350 5 1
BIO 20 1400 3.2 < 1 350 5 1
BIO 40 1200 3.5 < 1 350 5 1
Heavy metals < 50 ppm (according to the recommendation XXXVI/1 BgVV-German Federal Institute for Health Protection of Consumers and Veterinary Medicine). The figures quoted in the diagrams and tables should be regarded as guidelines.
Application Areas Sheet Application
Sterilization and Bacteria Reduction BIO 10 Cell harvest, clarifying filtration of fermenter broths (cell separation), clarifying filtration of TFF permeate, clarifying filtration of cell cultures, filtration of CHO cells, protection for chromatography columns and membrane processes, protection of sterile filter membranes, filtration of pharmaceuticals and BioPharmaceuticals, filtration of therapeutic proteins, vaccines, diagnostics and blood products, therapeutic DNA, filtration of nutrients.
Sterile Prefiltration BIO 20 Cell harvest, clarifying filtration of TFF permeate, clarifying filtration of centrifugation supernatant, filtration of biopharmaceuticals, filtration of therapeutic proteins, of vaccines, diagnostics and blood products, plasma fractionation (fine filtration), filtration of nutrients, protection of chromatography columns and membrane processes, protection of sterile filter membranes.
Fine Clarifying Filtration BIO 40 Fine filtration of pharmaceuticals and biopharmaceuticals, plasma fractionation (fine filtration, protein separation), filtration of antibiotics, filtration of vaccines, separation of adsorbents, filter media, and extraction residues.
BIO Series Depth Filters meet the following Requirements: • Recommendation XXXVI/1 BgVV, 21 CFR 177.260 e-k • Biological Safety: Cytotoxicity, Haemolysis, Plastic Class V • Drug Master File
The following Certificates and Documentation are available: • Certificate of Compliance according to DIN 50049 – 2.1/EN 10204-2.1 • Special Test Report according to DIN 50049 – 2.3/EN 10204-2.3 • Factory Acceptance Test (on demand) • Pharmaceutical Documentation P Depth Filters • Materials Safety Data Sheet
16 P–Series Depth Filter Sheets and Modules Optimized for Low Endotoxins and Low Extractables
Due to their electrokinetic adsorption • K 100 P up to K 250 P are depth filter potential, positively charged resins increase sheets and modules for fine filtration in the retention of smallest particles, such as the pharmaceutical and biotech- P-series depth filter sheets and modules whole and crushed cells, cell lysate nological industries. The application were developed for the strict requirements components, endotoxins, DNA and area is filtration of fermenter broth, TFF in biotechnological and pharmaceutical viruses, which usually are negatively permeate, therapeutical proteins, industries. For many years, manufacturing charged. Pall P-series depth filters are vaccines, diagnostics and blood has been carried out and stringent used worldwide in biotechnological and products, filtration of nutrients, in-process control methods in line with the pharmaceutical applications and provide separation of adsorbents, filter media requirements of the pharmaceutical reliable and economical filtration. and extraction residues. industry. This assures constant high • K 700 P up to K 900 P are depth filter filtration quality as well as a very high purity Product Range and Typical sheets and modules for coarse filtration of the filter medium, both features our Applications in the biotechnological industries. The customers benefit from. • EKS P up to Supra 80 P are application area is filtration of fermenter The P-series depth filter sheets and microorganism-reducing filter sheets broth, cell culture, therapeutical modules are available in 10 different types. and modules for depth filtration in the proteins, vaccines, diagnostics and Due to specific manufacturing methods the biotechnological and pharmaceutical blood product. distinguishing feature of the P-series is high industries. The application area is purity resulting in a very low release of clarification of fermenter broth, TFF Features and Benefits permeate, cell cultures, protection of extractables. The depth filter material has • Low unspecific protein binding been especially optimized to provide a very chromatography columns and low release of endotoxins (< 0.02 EU/mL membrane processes, protection of • High dirt hold capacity after flushing with 50 L/m2 WFI). sterile filter membranes, filtration of • Good membrane protection therapeutical proteins, vaccines, The filter matrix especially developed for • Long life time diagnostics and blood products, the P-series assures retention rates down filtration of nutrients and DNA removal. • Well graded sheets over the entire range to 0.1 µm and thus enables an optimal pre-filtration of biological products like no • P-grade sheets and Supradisc other depth filter for the protection of modules are steam sterilizable at downstream process steps. 125 °C (257 °F) for 30 minutes • All plastic components used in constructions meet the specifications
2500 for the biological test listed in the 2200 current version of the USP class VI
2000 121° C • All P-grade depth filter sheets used in
/min) 1500 2 constructions meet the specifications for the biological test listed in the 980 1000 current version of the USP class V 600 121 °C
Permeability (L/m 500 240 • P-grade sheets in sizes 130 159 29 41 64 93 > 400 x 400 mm (16 x 16 in.) and 0 Supradisc modules as well as all their
EKS-P EKM-P KS 50 P K 100 P K 200 P K 250 P K 700 P K 900 P components are fully traceable SUPRA 80 P SUPRA EK 1 -P
∆p = 1 bar (14.5 psi), T = 20 °C (68 °F), medium H2O
17 P–Series Depth Filter Sheets and Modules Technical Specifications
Typical Values for Ions after Flushing with 50 L/m2 WFI(1) Technical Data
Ca Mg Fe Cu Al Ni Code Retention Ash Content Endotoxin (3) 0.5 ppm < 0.1 ppm < 0.1 ppm < 0.1 ppm < 50 ppb < 10 ppb Rate (µm) (%) Level (1) The tests are carried out according the methods of the Technical and Analytical Work PEKS 0.1 – 0.3 58 < 0.02 EU/mL Group within the European Depth Filter Association or in accordance with in-house tests methods. PEKM 0.2 – 0.4 48 < 0.02 EU/mL PEK1 0.25 – 0.45 47 < 0.02 EU/mL Operating Conditions(2) P050 0.5 – 0.85 46 < 0.02 EU/mL Maximum Operating 80 °C (176 °F) P100 1.5 – 3.5 45 < 0.02 EU/mL Temperature P080 1.5 – 4.0 49 < 0.02 EU/mL Maximum Operating 2.4 bard (35 psid) P200 2.8 – 6.0 43 < 0.02 EU/mL Pressure P250 4.0 – 9.0 44 < 0.02 EU/mL (2) With compatible fluids, which do not soften, swell or adversely affect the products or their material of construction. P700 6.0 – 15.0 45 < 0.02 EU/mL P900 10.0 – 22.0 45 < 0.02 EU/mL Plastic Parts of Construction of Supradisc Modules (3) After Flushing with 50 L/m2 WFI. Supradisc Components Polypropylene O-rings Silicone elastomer The FDA (Food and Drug Administration) in the USA has registered Supradisc modules under DMF (Drug Master File) No. 14325. Sterilization With regard to total extractables P-grade depth filter sheets and Steam in place 125 °C (257 °F), for 30 minutes at 0.3 bard (4.3 psid) Supradisc modules meet the specifications according to FDA maximum. guideline CFR part177.2260 e, f, g, h, I, j, k, l, volume 21 chapter 1, applicable for depth filters with resins. The Quality Management Nominal Dimensions – Supradisc Modules System of Pall has been certified according to DIN EN ISO 9001 by TÜV Cert (Certification Office TÜV Rheinland, Sicherheit und Nominal Total Length Double O-ring Execution: 332 mm (13.1 in.) Umweltschutz GmbH). With regard to food law conformity the manufacture of depth filter sheets is also subject to ongoing analysis Flat Gasket Execution: 272 mm (10.7 in.) by the German ISEGA Forschungs-und Untersuchungsgesellschaft mbH, Aschaffenburg. Nominal Diameter 284 mm (11.2 in.) 410 mm (16.1 in.) Technical Service Flat Sheets For best possible results and maximum reliability we recommend a Available in all common sizes test run under real-life conditions.
Part Numbering and Ordering Information
3
Code Filter Code Filter Code Gasket Code Filter Code Gasket Code Plastic Parts Spacing Type Option Area Material
00 Standard PEKS EKS-P S Double 205 0.5 m2(4) (5.9 ft2) S Silicone P Polypropylene O-ring elastomer 30 Increased PEKM EKM-P 209 1.0 m2 (10.7 ft2) cell C Flat PEK1 SUPRA 216 1.8 m2 (19.3 ft2) distance EK 1 P Gasket 409 2.1 m2 (22.6 ft2) P050 KS 50 P 2 2 P100 K 100 P 416 3.7 m (39.8 ft ) P080 SUPRA 421 5.0 m2 (53.8 ft2) 80 P (4) Only available with double P200 K 200 P O-ring. P250 K 250 P P700 K 700 P P900 K 900 P
18 K–Series Depth Filter Sheets Bioburden Reduction and Fluid Clarification
With 13 different retention rates, the To obtain assurance of sterile filtrate K series represents the standard depth through a sterilizing membrane filter filter sheet series from Pall. cartridge, downstream of depth filter sheets is essential. They are classified as microorganism- reducing depth filters. They can produce filtrate with low organism counts or even Typical LRV Figures zero counts for the EKS, EK 1 and EK (Log Reduction Value) grades if the influent bioburden is low. EKS > 8.5(1) Grades K 100 through to K 900 cover the EK 1 > 7.5(1) entire range from fine filtration through EK > 7.0(2) clarifying filtration to coarse filtration. KS 50 > 6.5(2) High Efficiency Bioburden KS 80 > 6.0(2) Reduction (1) Test organisms: Brevundimonas diminuta. (2) Test organisms: Serratia marcescens. Successful bioburden reduction to achieve very low organism counts necessitates knowledge of the microbiological status of the product. The filtration procedure has to be adapted in such a way that the organism challenge limit validated for a particular depth filter sheet is not exceeded. Differential pressure must be limited to a maximum of 1.5 bar (14.5 psi) The flow velocity should not exceed 500 L/m2 /h. These figures may be lower in the case of difficult or demanding products.
1800 1700 25
1600
1400 20 1275 1200 /min) 2 15 1000 925
800 785 10 600
510 Retention rates (µm) Permeability (L/m
400 213 5 200 146 185 93 113 29 41 68 0 0 EKS EK1 EK KS50 KS80 K100 K150 K200 K250 K300 K700 K800 K900 EKS EK1 EK KS50 KS80 K100 K150 K200 K250 K300 K700 K800 K900
19 K–Series Depth Filter Sheets Technical Specifications
Technical Data
Sheet Weight per Area Thickness Ash Content Extractable Ions Soluble in 0.025 µm H2 SO4 (g/m2) (mm) (%) (mg/m2)
Ca Fe Al EKS 1400 3.7 58 1800 15 150 EK1 1400 3.7 51 1600 15 140 EK 1350 3.7 46 1400 10 120 KS50 1350 3.7 46 1400 10 120 KS80 1350 3.7 46 1200 15 120 K100 1350 3.7 46 1400 15 120 K150 1350 3.9 46 1300 15 120 K200 1350 3.9 46 1200 15 110 K250 1300 4.0 46 1000 15 70 K300 1300 4.2 46 900 15 50 K700 1300 4.1 46 900 15 50 K800 1300 4.1 46 900 15 45 K900 1300 4.3 46 900 25 40 Heavy metals < 50 ppm (according to the Recommendation XXXVI/1 BgVV-German Federal Institute for Health Protection of Consumers and Veterinary Medicine).
Sheet
EKS Vaccines, pharmaceuticals and BioPharmaceuticals, phytopharmaceuticals (sterile filtration), plasma fractionation, serum, aqueous cosmetics (clarifying and fine filtration)
EK 1 Aqueous cosmetics (clarifying and fine filtration), pharmaceuticals and BioPharmaceuticals, plasma fractionation
EK Pharmaceuticals and BioPharmaceuticals.
KS 50 Phytopharmaceuticals (clarifying filtration)
KS 80 Antibiotics (clarifying filtration), vaccines, infusion solutions, plant extracts (clarifying filtration), plasma fractionation K 100 Clarifying filtration K 150 Pharmaceuticals and BioPharmaceuticals (clarifying filtration), serum (pre-filtration) K 200 Vaccines (prefiltration), phytopharmaceuticals (clarifying filtration) K 250 K 300 Antibiotics (clarifying filtration), cosmetics (clarifying filtration) K 700 Antibiotics (clarifying filtration), serum (prefiltration), cell harvest K 800 Vaccines (prefiltration), cell harvest K 900 Infusion solutions (prefiltration), cosmetics (particle filtration), cell harvest
The following Certificates are available: • Certificate of Compliance according to DIN 50049-2.1/EN 10204-2.1 • Materials Safety Data Sheet The depth filters conform to the Recommendation XXXVI/1 BgVV (German Federal Institute for Health Protection of Consumers and Veterinary Medicine) and meet the requirements of the Lebensmittel- und Bedarfsgegenständegesetz – LMBG – (Foodstuff and other Commodities Act), in particular §§ 5, 30 and 31.
20 T–Series Depth Filter Sheets High Output with Long Filtration Cycles
The T series depth filter sheets from Pall includes 10 different retention rates. Grades T 120 to T 950 are used for clarifying filtration. Due to their positive ZETA potential, these depth filters possess a high adsorption capacity. In contrast, grades T 1000 to T 5500 are designed for coarse filtration. They are characterized by a more open structure and combine very high outputs with long in-service life due to their high dirt-holding capacity. Grades T 1000 to T 5500 have proved successful in the filtration of viscous media, for the retention of gel particles and coarse dispersed substances at low differential pressures. Furthermore, they can be inserted into plate and frame kieselguhr filters to retain the pre-coat filter material.
80 30000
70 25000 25000
60
20000 50 /min) 2
40 15000 12750
30 10200 10200 10000 Retention rates (µm) 20 Permeability (L/m 7285
5000 3400 10 1700 213 465 565 0 0 T 120 T500 T750 T950 T1000 T1500 T2100 T2600 T3500 T5500 T 120 T500 T750 T950 T1000 T1500 T2100 T2600 T3500 T5500
∆p = 1 bar (14.5 psi) with water at 20 °C (68 °F).
21 T–Series Depth Filter Sheets Technical Specifications
Characterization The tests are carried out according to the methods of the Technical and Analytical Work Group within the European Depth Filtration Association or in accordance with in-house test methods.
Technical Data
Sheet Weight per Area Thickness Ash Content Extractable Ions Soluble in 0.025 µm H2 SO4 (g/m2) (mm) (%) (mg/m2)
Ca Fe Al T 120 900 2.8 43 1250 20 75 T 500 850 2.7 38 1000 15 45 T 750 850 2.7 40 770 15 45 T 950 850 2.8 40 600 13 25 T 1000 950 3.6 35 570 15 30 T 1500 850 3.7 33 500 12 25 T 2100 700 3.3 15 350 11 20 T 2600 700 2.9 <1 300 1 5 T 3500 880 4.6 15 450 15 30 T 5500 750 4.5 <1 300 1 5 Heavy metals < 50 ppm (according to the Recommendation XXXVI/1 BgVV-German Federal Institute for Health Protection of Consumers and Veterinary Medicine). The figures quoted in the diagrams and tables should be regarded as guidelines.
The following Certificates are available: Sheet Typical Application • Certificate of Compliance according to T 120 Fine clarification DIN 50049-2.1/EN 10204-2.1 T 500 T 750 • Materials Safety Data Sheet
T 950 General prefiltration The Depth Filters conform to the Recommendation XXXVI/1 BgVV T 1000 (German Federal Institute for Health Protection of Consumers and T 1500 Veterinary Medicine) and meet the requirements of the Lebensmittel - T 2100 und Bedarfsgegenständegesetz – LMBG – (Foodstuff and other T 2600 Pharmaceuticals and Commodities Act), in particular §§ 5, 30 and 31. T 3500 BioPharmaceuticals (solid/liquid T 5500 separation) Serum (prefiltration), vaccines (prefiltration)
22 Z–Series Depth Filter Sheets Positive Zeta Potential for Adsorptive Removal from Aqueous Suspensions
Z series depth filters have been developed for applications demanding excellent filtration removal efficiency with maximum filtration throughput. Due to the pronounced positive Zeta potential, these grades of filter sheets are particularly suited for adsorptive removal of negatively-charged particles from aqueous suspensions. As opposed to standard filter sheets, depth filter sheets with an adsorptive effect exhibit a considerably improved clarifying effect without a sacrifice in output. The grades Z 200 and Z 400 are characterized by a high bacteria retention capability; provided that they are suitably conditioned, they are capable of removing endotoxins from aqueous solutions. For endotoxin removal, see also special documentation on Supra EK 1P Depth Filter. Z–Series adsorptive filter sheets are compatible with most solvents as well as acids and alkalis provided that their concentration is low.
10 400
350 9 350
8 300 7 250 /min)
6 2
5 200
4 150
3 Permeability (L/m 100 Retention rates (µm) 80 2 65 50 1
0 0 Z 200 Z 400 Z 2000 Z 200 Z 400 Z 2000
∆p = 1 bar (14.5 psi) with water at 20 °C (68 °F).
23 Z–Series Depth Filter Sheets Technical Specifications
Characterization The tests are performed in accordance with the methods of the Technical and Analytical Work Group within the European Depth Filtration Association or in accordance with in-house test methods.
Technical Data
Sheet Weight per Area Thickness Ash Content Extractable Ions Soluble in 0.025 µm H2 SO4 (g/m2) (mm) (%) (mg/m2)
Ca Fe Al Z 200 1360 3.8 46 2450 35 125 Z 400 1320 3.8 46 2050 45 135 Z 2000 1220 3.9 45 1400 30 80 Heavy metals < 50 ppm (according to the Recommendation XXXVI/1 BgVV-German Federal Institute for Health Protection of Consumers and Veterinary Medicine). The figures quoted in the diagrams and tables should be regarded as guidelines.
The following Certificates are available: Sheet Typical Application • Certificate of Compliance according to Z 200 Enzyme solutions, fermenter broths, DIN 50049-2.1/EN 10204-2.1 water • Materials Safety Data Sheet Z 400 Pharmaceuticals Z 2000 Pharmaceuticals The depth filters conform to the Recommendation XXXVI/1 BgVV (German Federal Institute for Health Protection of Consumers and Veterinary Medicine) and meet the requirements of the Lebensmittel- und Bedarfsgegenständegesetz – LMBG – (Foodstuff and other Commodities Act), in particular §§ 5, 30 and 31.
24 E-Series Depth Filter Sheets Filter Paper with Depth Filter Properties for Solid and Liquid Separation or Clarifying Filtration
Introduction Main Applications
E-Series is a new filter paper with depth • Blood plasma fractionation filter properties for use in the • Therapeutic proteins pharmaceutical industry. It substitutes for conventional filter paper in solid and liquid • Biomass separation separation or clarifying filtration. Compared • Antibiotics production with conventional filter paper, the E-Series • Vaccines has the following advantages: • Natural plant extracts and transgenics • Better clarifying results due to depth filter properties The high wet strength of the E-Series enables filtration at higher operating • Better mechanical stability due to higher pressures compared to conventional filter wet strength papers, without the risk of breakthrough or • Very easy discharge of proteins or damage (tearing). The stiffness of the protein cake due to special surface E-Series sheets enables easier and safer treatment handling. The high wet strength combined with the Due to a special manufacturing method, low weight per area allows for the best the E-Series has a very smooth surface separation results, even in pre-coat with extremely low adhesion of proteins. filtration for the separation of pastes. The special surface treatment ensures an easy and complete discharge of both Features and Benefits protein and protein cakes. Because of the very small loss of product on the filter E-Series is a filter paper with depth filter surface, high product yield is obtained in properties, which is obtained by the solid and liquid separation applications. thickness of the filter medium. In comparison with filter papers having the same retention rates, the E-Series provides significantly better clarification than conventional filter papers.
Advantages
• Safe operation due to high wet strength • High mechanical stability (filtration at high operating pressure is possible) • Easy removal of protein cakes due to the very smooth, low adhesive surface • Higher clarity and retention due to the depth filter properties • High dirt-holding capacity
25 E-Series Depth Filter Sheets Technical Specifications
Technical Data Components E-Series is available in all common sheet sizes • Cellulose ∆ 2 Permeability p 340 L/m /min • Resin (< 3%) 0.2 bar (2.9 psi) Weight per Area 550 g/m2 • Resins according to the recommendations XXXVI and XXXVI/1 in connection with the German Foodstuff and Consumer Good Act Thickness 1.4 mm resp. Chapter 21 of Federal regulation (CFR) § 177.2260 Ash Content < 1 %
Extractables Soluble in Acetic Acid (5%) Quality (mg/m2) (mg/Kg) • The manufacture of E-Series is carried out under stringent quality Ca 250 450 control using specially developed equipment. Fe 11• E-Series complies with recommendations XXXVI and XXXVI/1 of Al 55 the German Foodstuff and Consumer Goods Act §§5, 30 and 31 (LMBG). Heavy metals < 50 ppm (according to the Recommendation XXXVI/1 BgVV-German Federal Institute for Health Protection of Consumers and Veterinary Medicine). • E-Series meets the specification of extractables 21 CFR, part 177.2260 e, f, g, h j, k, l, for depth filter with resin Comparison of Technical Data
Wet Strength Thickness Specific Weight per Area The following Documents are available:
E-Series 350 N/cm2 1.4 mm 550 g/m2 • Data Sheet
Filter Papers 20 N/cm2 0.2 – 0.8 mm 60 – 200 g/m2 • Certificate of Compliance
Technical Support Fast and reliable technical support is essential. Our Scientific and Laboratory Services (SLS) teams are at your disposal for technical service on site, or if you have further questions.
26 Supradisc™ Depth Filter Modules Benefits of Depth Filter Sheets in Module Form
The Supradisc module design concept combines the advantages of conventional depth filter sheets with the positive features of enclosed filters.
Module Concept Features and Benefits Each module consists of three major • Permits filtration without product losses components: due to the enclosed design • Filter cells or lenticles • Requires less space than classical • Tubular filtration systems due to its vertical design • Adapters SD Range • Offers maximum reliability against The individual filter cells comprising two product contamination Standard range for numerous applications. filter media layers and a drainage plate are SDP Range edge-sealed in an injection-molding • Affords maximum operational safety due to the exclusion of emissions A filter material low in endotoxins for process. applications in the pharmaceutical industry. Up to 21 cells are stacked on a tubular • Very simple to handle due to rapid module change and ease of cleaning BIO Range (Kieselguhr-free) core, compressed and joined to form a module. • Modules with double O-ring adapters Highly pure natural and modified grades of This design results in reliable sealing guarantee maximum reliability during cellulose – ideal for applications where the entire process minimum ion extraction and low protein between the filter cells, even if the module adsorption are of major concern. is in a dry state, which eliminates the need • A depth filter system with an extremely for retightening after wetting. high retention capability for solids SDT Range • Long service life: due to the mechanical This series is characterized by open Filter Media depth filter effect and the ZETA construction and reduced thickness to give Depth filters, which prove highly successful potential, particles are retained by both a low filtration resistance and high flow in a vast range of applications, are mechanical and electrokinetic rates. Therefore it is ideally suited for incorporated as filter media. Due to their adsorption viscous media, for the removal of gel excellent mechanical strength, they can be • Grades for the retention of yeast, particles and coarsely dispersed readily incorporated into modules. components. bacteria, and colloids are available Almost all grades of depth filters available SH Range • Supplied as a ready-to use unit, in Pall sheet format are also available in subsequent retightening after wetting is Permits reliable filtration up to 160 °C modular configuration, so that change-over not necessary, simplifying handling (320 °F) and has been specially developed from open sheet filter systems to closed • Highly efficient in the protection of for application in APIs. systems is relatively easy. downstream membrane filters with SD AKS Range (Activated Carbon) The Complete Filter System “police filter” duties, media and Due to the incorporation of activated media-difficult filter The proven adapter is fitted with two carbon into the matrix of the filter this • Can be sterilized by autoclaving or O-rings and a bayonet lock, a successful range possesses an extremely high steam-sterilization or disinfected with concept, adopted by the pharmaceutical adsorption capacity and is therefore hot water or by chemical means amongst others recommended industry for filter cartridges. Consequently, for decolorization, deodorization, and Supradisc modules can be mounted into • Can be disposed of with common dechlorination tasks and removal of lipids filter housings rapidly and easily. industrial waste and can be incinerated from protein solutions. Due to their specific design, Supradisc Note: For used depth filters, the disposal regulations modules are characterized by a very high applicable for the filtered product must be considered. mechanical stability. A range of module types with different permeabilities, filter media, and diameters – 284 and 410 mm (11.2 and 16.1 in.) – permits precise optimization of the filter system to specific filtration tasks. Modules to retrofit most commercial housings are available.
27 Supradisc Depth Filter Modules Technical Specifications
Operating Conditions(1) Sterilization
Maximum Operating 85 °C (185 °F) Steam in Place 125 °C (257 °F), for 30 minutes at Temperature 0.3 bard (4.3 psid) maximum.
Maximum Operating 2.5 bard (36 psid) Pressure Nominal Dimensions – Supradisc Modules
(1) With compatible fluids, which do not soften, swell or adversely affect the products or Nominal Total Length Double-O-ring Execution: its material of construction. 332 mm (13.1 in.) Flat Gasket Execution: Plastic Parts of Construction of Supradisc Modules 272 mm (10.7 in.)
Supradisc Components Polypropylene Nominal Diameter 284 mm (11.2 in.) Polyamid (high temperature version) 413 mm (16.3 in.) O-rings Silicone elastomer
Table 1
Sheet Depth Filter Weight per Ash Content Extractable Ions Soluble in 0.025 µm H2 SO4 Type Area (g/m2) (%) (mg/m2)
Ca Fe Al B010 BIO 10 1400 < 1 0.28 ppm(1) < 0.05 ppm(1) < 5 ppb(1) B020 BIO 20 1400 < 1 0.17 ppm(1) < 0.05 ppm(1) < 5 ppb(1) B040 BIO 40 1200 < 1 0.48 ppm(1) < 0.05 ppm(1) < 5 ppb(1) XEK1 EK 1 1400 51 1600 15 140 XEK0 EK 1350 46 1400 10 120 X050 KS 50 1350 46 1400 10 120 X080 KS 80 1350 46 1200 15 120 X100 K 100 1350 46 1400 15 120 X150 K 150 1350 46 1300 15 120 X200 K 200 1350 46 1200 15 110 X250 K 250 1300 46 1000 15 70 X300 K 300 1300 46 900 15 50 X700 K 700 1300 46 900 15 50 X900 K 900 1300 46 900 25 40 C100 K 100 IR 1400 51 200 20 75 C250 K 250 IR 1250 46 150 15 50 C800 K 800 IR 1250 46 120 10 30 C900 K 900 IR 1200 46 120 10 30 T950 T 950 850 40 600 13 25 T100 T 1000 950 35 570 15 30 T150 T 1500 850 33 500 12 25 T210 T 2100 700 15 350 11 20 T260 T 2600 700 < 1 300 1 5 T350 T 3500 880 15 450 15 30 T550 T 5500 750 < 1 300 1 5
(1) Soluble after 50 L/m2 flushing with WFI.
Part Numbering and Ordering Information
3
Code Filter Code Filter Code Gasket Code Filter Code Gasket Code Plastic Parts Spacing Type Option Area Material
00 Standard See Above Table 1 S Double 203 0.3 m2 (3.2 ft2) S Silicone P Polypropylene O-ring elastomer 01 High 205 0.5 m2 (5.9 ft2) A Polyamide(2) Temperature C Flat Other Gaskets available on 2 2 (2) Gasket 209 1.0 m (10.7 ft ) request High Temperature only. 30 Increased 2 2 cell 216 1.8 m (19.3 ft ) distance 509 2.3 m2 (24.7 ft2)
516 4.0 m2 (43.0 ft2)
28 520 5.0 m2 (53.8 ft2) Supradisc™ II Modules Next Generation Rigid Interlocked Depth Filter Module
Supradisc II depth filter modules have a Application Benefits design that eliminates direct operator • Higher flow rates handling of the discs to prevent damage and to ensure uniform performance. As • Eliminates contamination bypass part of this unique design, the Supradisc II • More resistant to temperature and modules have a clip-seal interlock that pressure shocks holds the filter sheet in place with an outside and inside separator. In addition, • Superior sealing in module housing the filter sheet is fastened during • Proprietary seal eliminates manufacture to both the polypropylene contamination bypass core and the outer casing to provide • Retrofits existing hardware maximum stability without the need for welds or resins. This ensures that the • Provides optimal filtration performance system will not fail under changing • Exceptional chemical compatibility pressures. • Steam-sterilizable The new depth filter module can be used with either a double O-ring or flat gasket • Consistent and reproducible filtration filter housing. By using a double O-ring results seal, the Supradisc II depth filter module • Polypropylene parts and silicone achieves the highest degree of safety in O-rings meet all USP, Class VI – 121 °C preventing contaminants from entering the criteria. filter stream. The ability to fit either type of P-grade media meets all USP, housing maximizes utilization of investment Class V – 121 °C criteria in existing equipment. The Supradisc II depth filter module provides optimal See The Difference In The Design filtration performance with a wide range of media grades. • Highly rigid module construction maintains structural integrity after Features and Benefits multiple steam-sterilization even cycles
The unique design of the Supradisc II depth filter module provides increased process safety, reliability, and performance. • More effective filter area per cell • Multiple flow channels • Proprietary clip connection • Highly rigid module construction • Available with nearly all grades of depth filter media • All-polypropylene molded parts • Steam-sterilizable for multiple cycles • FDA-listed materials of construction • Produced under an ISO 9001 quality system • Reverse-flow capabilities 29 Supradisc II Modules Technical Specifications
Materials of Construction Chemical Compatibility
Filter Media Composition Cellulose, Diatomaceous Earth, Perlite Resistant over a wide pH range of 3 – 10 and Binders (Polyolefin fibers in certain media types) Toxicity Core and Molded Parts Polypropylene Polypropylene parts and silicone O-rings meet all USP, Class VI – 121 °C Adapter Polypropylene with Stainless Steel Insert (250 °F) criteria. P-grade media meets all USP, Class V – 121 °C (250 °F) O-rings Standard: criteria. Silicone Elastomer
Optional: Nominal Dimensions and Weights Viton* 1 A, EPDM Diameter 284 mm (11.2 in.) Gaskets Standard: Buna N Height (Standard) Flat Gasket: Approx. 272 mm (11 in.) Optional: Silicone, PTFE, Viton A, EPDM O-ring: Approx. 332 mm (13 in.) * Viton is a registered trademark of DuPont Dow (non-FDA materials). Dry Weight 5 – 6 kg (11 – 13 lbs) depending on filter media Maximum Differential Pressure Filter Area 1.8 m2 (19.4 ft2) Forward Flow 3.5 bard (50 psid) @ 90 °C (195 °F ) Reverse Flow 0.45 bard (6 psid)
Ordering Information
Pall Part Number
Code Filter Media Code Adapter Code Sealing Materials Code Filter Area Code Molded Parts 200 S Double O-ring S Silicone 232 1.8 m2 (19.4 ft2) P Polypropylene (White; MVQ) C Flat gasket V Viton A E EPDM P Buna N T PTFE F FEP Encapsulated Silicone
Code Filter Media Code Filter Media XEKO EK C100 K 100 IR XEK1 EK 1 C250 K 250 IR X050 KS 50 C800 K 800 IR X080 KS 80 D120 Permadur X100 K 100 PEKS EKS P X150 K 150 PEK1 Supra EK 1 P X200 K 200 P050 KS 50 P X250 K 250 P080 Supra 80 P X300 K 300 T100 T 1000 X700 K 700 T150 T 1500 X900 K 900 T210 T 2100 B010 BIO 10 T260 T 2600 B020 BIO 20 T350 T 3500 B040 BIO 40 T550 T 5500
30 Supracap™ 60 Depth Filter Capsules Capsules for Process Development and Scale-up Studies
The Pall Supracap™ 60 filter capsule is Applications specifically designed for applications where • Cell harvest the use of a depth filter with a small surface area and low hold-up volume is • Clarification of fermentation broth critical. • Antibiotics Supracap 60 capsules are especially • Serum useful for the development and optimization of a process during scale-up • Blood products and scale-down studies. • Vaccines The special manufacturing process • Plant extracts provides a highly permeable media, with an extremely high dirt-holding capacity. Pall’s UpscaleSM Program
Features and Benefits From drug discovery and basic research, through process development and The key benefits of Supracap 60 filters production, Pall Corporation is the single include: source for all your filtration and separation • Scale-up to Pall Supradisc® modules needs. Our UpScale program provides and depth filter sheets you with the scalable products and the support you need to bring new products to • Disposable format with luer-lok* market faster. connections for ease of use • Upstream vent valve for easier process control • Available in a wide range of Pall depth filter media for optimum grade selection • Easy and economic process optimization • Broad chemical compatibility for use with a wide range of solutions found in the BioPharmaceutical industry High Quality Standards • Batch-tested in order to meet all quality requirements • Manufactured under a Quality Management System certified to ISO 9000 • Constructed from plastics which meet USP Class VI
* Luer-Lok is a trademark of Becton-Dickenson & Co.
31 Supracap 60 Depth Filter Capsules Technical Specifications
Materials of Construction Typical Filtration Area Media Cellulose base(1) 0.26 cm2 (0.040 in2) Capsule Polycarbonate Sterilization Luer-Lok* Vent Fitting Polypropylene Autoclaving at 125 °C (275 °F) 1 cycle x 30 minutes Sealing Technology Thermal bonding (1) See ordering information. * Luer-Lok is a trademark of Becton-Dickenson & Co. Dimensions
A Maximum: Operating Parameters 32 mm (1.26 in) Depends on thickness of sheet Maximum Operating 3 bar (44 psi) at 40 °C (104 °F) Pressure and Temperature B 70 mm (2.76 in)
Maximum Differential 1.5 bar (22 psi) Pressure
Typical Values for Ions after Flushing with 50 L/m2 WFI(2) Ca Mg Fe Cu Al Ni A 0.5 ppm < 0.1 ppm < 0.1 ppm < 0.1 ppm < 50 ppb < 10 ppb (2) The tests are carried out according the methods of the Technical and Analytical Work Group within the European Depth Filter Association or in accordance with in-house tests methods.
B
Ordering Information Code Type of Sheet Retention Range Ash Content Endotoxin Level(4) (SC060*) (µm) (%)
P-series: Produced under specific manufacturing and control procedure for low endotoxin content. Well balanced composition including cellulose fibers as well as kieselguhr and perlites PEKS EKS-P 0.1 – 0.3 58 < 0.02 EU/mL PEKM EKM-P 0.2 – 0.4 48 < 0.02 EU/mL PEK1 SUPRA EK 1 P 0.25 – 0.45 47 < 0.02 EU/mL P050 KS 50 P 0.5 – 0.85 46 < 0.02 EU/mL P100 K 100 P 1.5 – 3.5 45 < 0.02 EU/mL P080 SUPRA 80 P 1.5 – 4.0 49 < 0.02 EU/mL P200 K 200 P 2.8 – 6.0 43 < 0.02 EU/mL P250 K 250 P 4 – 9 44 < 0.02 EU/mL P700 K 700 P 6 – 15 45 < 0.02 EU/mL P900 K 900 P 10 – 22 45 < 0.02 EU/mL Supradur: Depth filter sheets with perlites up to 40 % w/w of selected polyolefin microfibers D50P Supradur 50 P 0.6 – 3.8 23 < 0.02 EU/ml BIO Series: Depth filter sheets with highly purified and modified cellulose with very low extractables and low protein adsorption B010 BIO 10 0.1 – 0.3 < 1 < 0.02 EU/mL B020 BIO 20 0.5 – 1.0 < 1 < 0.02 EU/mL B040 BIO 40 6 – 18 < 1 < 0.02 EU/mL Activated Carbon containing depth filter sheet for decolourization of blood products, glucose solution and antibiotics XAK5 AKS 5 Methylene blue adsorption < 1 < 0.02 EU/mL > 170 g/m2
(4) After flushing with 50 L/m2 WFI.
32 Supracap™ 200 Encapsulated Depth Filter Modules First Encapsulated Single-use Depth Filter Module for Process-scale Applications
The Supracap 200 depth filter capsule Design Features provides all the features and benefits of the • No contact between operator and Supradisc and Supradisc II modules in a fluids, means reduced exposure risks single-use, disposable design. • Less product loss due to less void The advantages of encapsulated volume means higher yields disposable systems are tied to highly reduced operator exposure risks, less • Better handling of difficult and toxic cleaning effort, increased yields, and products optimized handling. These are the main • Lower process times due to reduced reasons why disposable capsules are used cleaning throughout the pharmaceutical industry. Capsule filters can help eliminate cleaning • No cross-contamination risks problems, especially where biological • All Pall Supracap 200 modules are products are to be filtered. In applications 100% pressure-tested after production where hazardous materials are being • Pall Supracap 200 modules are filtered, such as cytotoxic drugs, or where sterilizable at 125 °C (257 °F) for 60 toxic materials like catalysts or minutes contaminated activated carbon has to be removed, Pall Supracap 200 capsules • All plastic components used in offer better operator protection and simplify construction meet the specifications for process-handling. Pall Supracap 200 the biological tests listed in the current capsules are the first encapsulated version of the USP class VI at 121 °C single-use depth filter modules for • Pall Supracap 200 modules as well as large-scale process filtration. all their components are fully traceable The capsule design provides a lower by serial number hold-up volume than Supradisc modules in stainless steel housings, allowing greater product recovery. The encapsulated modules are installed in a Pall Advanta Supracap 200 housing. The housing functions as a means of secondary pressure containment and does not require cleaning. The inlet and outlet pipes are removable and cleanable. The Supracap 200 housing can also be used wih Supradisc modules.
Applications • Filtration of fermenter broth • Serum filtration • Blood plasma filtration Supracap 200 modules in a Pall • Removal of mammalian cells prior to Advanta Supracap 200 housing downstream processing • Filtration of toxic products • Removal of filter aids • Removal of catalysts 33 • Removal of activated carbon Supracap™ 200 Encapsulated Depth Filter Modules Technical Specifications
Material of Construction Sterilization
Pall Supracap 200 Capsule Polypropylene Steam-In-Place 125 °C (140 °F), for 60 minutes Components O-rings Silicone elastomer Nominal Dimensions Total Length 324 mm (12.7 in.) (1) Operating Conditions Total Diameter 298 mm (11.7 in.) Maximum Operating 60 °C (140 °F) Temperature
Maximum Operating 6 barg (87 psig) at 60 °C (140 °F) Pressure
(1) With compatible fluids, which do not soften, swell or adversely affect the products or its material of construction.
Filter Media Specifications
Code Depth Filter Type Water Flow in Retention Rate Ash Content Positively- L/m2/min @ ∆p 1 bar (14.5 psi) in µm in % Charged Media PEKS EKS-P 29 0.1 – 0.3 58 no PEKM EKM-P 41 0.2 – 0.4 48 no PEK1 SUPRA EK 1 P 64 0.25 – 0.45 47 yes P050 KS 50 P 93 0.5 – 0.85 46 no P100 K 100 P 130 1.5 – 3.5 39 no P080 SUPRA 80 P 159 1.5 – 4.0 49 yes P200 K 200 P 240 2.8 – 6.0 43 no P250 K 250 P 600 4 – 944no P700 K 700 P 980 6 – 15 45 no P900 K 900 P 2200 10 – 22 45 no B010 BIO 10 30 0.1 – 0.3 < 1 no B020 BIO 20 75 0.5 – 1.0 < 1 no B040 BIO 40 1125 6 – 18 < 1 no X150 K 150 185 2.5 – 5.0 46 no X300 K 300 785 5 – 12 46 no T950 T 950 1700 8 – 20 40 no T100 T 1000 3400 10 – 25 35 no T150 T 1500 7285 11 – 30 33 no T210 T 2100 10200 13 – 35 15 no T260 T 2600 10200 15 – 40 < 1 no T350 T 3500 12750 19 – 50 15 no T550 T 5500 25500 25 – 70 < 1 no XAK5 AKS 5 310 – 1no XAK6 AKS 6 250 – 1no
Part Numbering and Ordering Information
C SP
Code Module Code Inter Disc Code Filter Code Filter Area Code Gasket Type Spacing Media Material
2 Supradisc II 00 Standard See above table 209(2) 1.0 m2 (10 ft2) S Silicone elastomer
3 Supradisc I 30 Increased cell 214(3) 1.6 m2 (17.2 ft2) F FEP coated silicone distance(1) 216(2) 1.8 m2 (19.4 ft2) (1) Supradisc I design only. 232(4) 1.8 m2 (19.4 ft2) (2) Supradisc I design only. (3) AKS 5/6 in Supradisc I design only. (4) Supradisc II design only. 34 Direct Flow Liquid Filtration Membrane and Depth Filter Cartridges, Capsules, and Disposable Systems Membrane and Depth Filter Cartridges, Capsules, and Disposable Systems
Pall offers a wide range of filter media and • Profile®, HDC® II, and MarksmanTM filter configurations to serve your liquid polypropylene filters filtration needs. • Emflon® FM PTFE filters for solvent Membranes have been developed to meet polishing specific application requirements. Pall provides the broadest array of membranes, including: Pall filters for liquid service are available in a variety of cartridge configurations that can be • Supor® PES (polyethersulfone) used in filter housings. In addition, Pall liquid sterilizing-grade 0.2 µm filters, which are filters are available in disposable capsule filter ideal for applications that require broad formats of all sizes with surface areas from pH compatibility. 0.02 m2 (31 in.2) to to 4.8 m2 (50 ft2). These capsules can be used in disposable systems*. • Low-binding Fluorodyne® II DBL (0.45 µm) One of Pall’s most convenient products, the DFL (0.2 µm sterilizing-grade) KleenpakTM connector can be used to make DJL (0.1 µm sterilizing-grade), which aseptic connections in any process have a PVDF (polyvinylidenedifluoride) environment. These connectors can be membrane and provide excellent flow incorporated in disposable filter assemblies. rates Note: It is important to maintain the integrity • Ultipor® N66 filters, which provide of 0.2 µm and 0.1 µm sterilizing grade filters excellent wettability and are available in and virus filters. Pall recommends bioburden reduction, prefiltration, and integrity-testing of all sterilizing-grade filters sterilizing grades prior to steaming, after steaming, and after the filtration process to ensure that the integrity of • Ultipor VF Grade DV 20 and DV50 for the filter has been maintained. virus removal applications (50 and 20 nm) Contact Pall for recommended procedures and integrity test parameters. Pall also offers process-optimized prefilters, to
protect sterilizing-grade filters, as well as for * Capsules supplied with sanitary flanges are Tri-Clamp clarification and bioburden reduction including; compatible. Tri-Clamp is a trademark of Alfa-Laval, Inc.
• PreFlow® and Ultipor GF resin-bonded glass fiber filters
36 Disposable Systems Improving Choice, Flexibility, and Operational Costs for System Designs
Managing the issues of cleaning and Disposable filters can be offered with a cleaning validation is one of the major wide range of filter media for: challenges facing the BioPharmaceutical • Prefiltration and clarification industry. This has resulted in the use of disposable equipment being the preferred • Sterilization option wherever possible. Using disposable • Virus removal equipment offers many benefits. They are made from a range of materials such as: Features and Benefits • PES (polyethersulfone) • Reduced assembly costs • PVDF (polyvinylidenedifluoride) • Reduced cleaning costs • Nylon 66 • Reduced cleaning validation • PTFE (polytetrafluoroethylene) • Reduced costs for capital equipment – capsule filters have a typical installation • Polypropylene cost that is 80% lower than a similar • Resin-bonded glass fiber sized stainless steel housing system • Cellulose-based depth media • Reduced risk of lost production time In addition to single-use capsule filters for due to simpler procedures direct flow clarification, sterilization and viral In applications where hazardous materials clearance, Pall provides single-use are being processed, such as cytotoxic chromatography and tangential flow (TFF) drugs, disposable equipment can play an products. important additional role in helping protect operators. Hazardous liquids can be Scaling Up and Scaling Down contained during processing with minimal risk of operator exposure. Pall is well-equipped to support processes as they are scaled up. Different size Choice and Flexibility capsules for each specific Pall filter grade contain identical filter materials. This Pall supplies a wide range of disposable feature ensures that scale-up and filter assemblies and disposable filtration scale-down studies yield relevant sets, such as capsule filters with information and minimum requalification for customized tubing systems attached. Pall various batch sizes. also supports the use of filters attached to The availability of a variety of capsules for disposable bag-based processing small scale operations is beneficial, systems. Disposable capsule filters of all particularly for new product developments. sizes with surface areas from a few cm2 to Capital investment can be a concern since as much as 4.8 m2 (50 ft2) are available and not all new BioPharmaceutical products can be used in disposable systems. Filters become commercialized. Single-use join together in series for protection of the capsules and systems make it possible to final filter or in parallel for increased area, produce new products during the early making it possible to have unlimited development stages, without a large filtration area in disposable systems. capital investment. Capital deferment and Flexibility of system design facilitates risk avoidance makes it easy to produce changes in product to process tests batches for early clinical trials and development. toxicity studies without capital equipment. 37 Disposable Systems Technical Specifications
Filter and Tubing Sets
Pall is able to supply a wide range of filtration and purification products with flexible tubing and connectors for your specific process requirements, preassembled and pre-sterilized.
Disposable Processing Systems
Fully integrated, single-use systems can include a filter, bag, tubing and other components. These systems are manufactured and sterilized as one, thereby eliminating the contamination risks associated with aseptic connections during coupling of a non-integrated system. Assembly and cleaning, as well as cleaning validation are eliminated for disposable process systems. Additionally, since the system is used only once, cross-contamination risks for facilities that produce many different BioPharmaceutical products are minimized. Fully integrated single-use systems bring other benefits for multi-product facilities by offering flexibility, and allowing the modification of batch sizes as required. Pall has a close working relationship with all the major disposable polymeric container suppliers. We can work with you and the company of your choice to provide a disposable processing system that is supplied pre-assembled and pre-sterilized by gamma-irradiation. These systems are typically custom-designed to include the flexible tubing of your choice in the configuration to best fit into your process and with the most appropriate connection devices, including Pall’s Kleenpak connectors. For more information please contact your local Pall representative.
38 Kleenpak™ Connectors For Simple Sterile Connections between Components
The single use, Kleenpak™ Connector allows for the simple dry connection of two separate pre-sterilized fluid pathways, while maintaining the sterile integrity of both. The connector consists of a male and a female connector, each covered by a vented peel away strip that protects the port and maintains the sterility of the sterile fluid pathway.
Applications 4. With one hand, hold the barrel of the male connector. Using the other hand, • Transfer of inocula to reactors grasp both white peel away strips and • Sampling during fermentation or cell pull them out simultaneously in a culture smooth continuous motion. Do not use • Connection of small sterile equipment if only one white peel away strip is to large equipment (e.g. bioreactors) removed accidentally instead of two; this will affect the sterility of the • Handling of bulk material in a pathway. non-sterile environment 5. Rotate the thumb rest on the male • Connection to a disposable system connector one full turn. The rotation (systems that contain capsule filters or serves to bend the anti-actuation tabs, bags) which prevent inadvertant engagement before this step. The thumb rest can be Features and Benefits turned one full turn back to re-align • No capital equipment required tubing, as required. • Connection is made in seconds 6. Push the thumb rest of the male • Easy to make connection – even in a connector down towards the base of cramped environment the barrel until they meet. • Maintains a sterile fluid pathway upon 7. Start the fluid transfer. activation of device High Quality Standards • Peel-away strip maintains sterility until ready to use • Manufactured under clean conditions in a controlled environment • Vented to allow steam penetration and to prevent tubing collapse after • Manufactured under a Quality autoclaving Management System certified to ISO 9000 • Shape coding and locking mechanism prevents incorrect assembly • Supplied with a Certificate of Test confirming the quality standards and • Device makes audible snap when quality control tests performed by Pall engaged • A detailed validation guide is available Making the Connection The fluid path materials of construction 1. Lift and pull tab of protective caps to meet remove caps from connectors. • USP Biological Reactivity Test, in vivo, 2. Hold the barrel of the larger (male) for Class VI-121 °C Plastics connector above the base. Align the smaller (female) connector with the larger (male) connector, so that the white peel away strips are facing each other as they exit the flat sides of the connectors.
3. Once aligned correctly, press the two connectors together firmly until both clips snap together tightly.
Step 1. Step 2. Step 3. Step 4. Steps 5 – 6. Step 7. 39 Kleenpak Connectors Technical Specifications
Materials of Construction Typical Flow Rate Connector Body(1) Polycarbonate 4.0 250 Plunger Polycarbonate 3.5 Rubber Grommets Thermoplastic Elastomer 3.0 200 O-ring Internally Lubricated Ethylene Propylene (EPDM) 2.5 Protective Cap Polypropylene 150 Peel-away Strip Hydrophobic Polyethersulfone (PES) 2.0
(1) Fluid path. 1.5 100 Differential Pressure (psi) Pressure Differential Sterilization Methods 1.0 (mbar) Pressure Differential 50 Gamma-irradiation Maximum Dosage: 50 kGy 0.5 Autoclave (121 °C) 1 cycle, 30 minutes 0 0 Consult with Pall Corporation on sterilization methods. 0 10 20 30 40 50 Flow Rate (L/min) Operating Conditions
Maximum Operating Pressure 3 bar (43.5 psi) at 40 °C (104 °F) and Temperature
Operating and Storage 3 °C to 40 °C Temperature Range (37 °F to 104 °F) Female Part Actuated Connector 13 mm (0.5 inch) hose barb Nominal Dimensions D A Internal Diameter 12.2 mm (0.48 in.) Locking clips C (on both sides) B Length when Actuated 123 mm (4.8 in.) A C Female Connector Length 55 mm (2.17 in.) Protective Caps with Cap
D Maximum Diameter of 37.64 mm (1.48 in.) Female Connector Barrel Plunger
B E Male Connector Length 100 mm (3.94 in.) O-ring E with Cap Base
F Maximum Diameter of 37.64 mm (1.48 in.) Thumb Rest Male Connector Male Part 13 mm (0.5 inch) hose barb Connections (Male and Female Connectors) F
1 13 mm ( ⁄2 in.) hose barb
Ordering Information Part Number Description Quantity
1 ACD02S6 Male plus Female Connector with 13 mm ( ⁄2 in.) hose barb 1
1 ACD02F6 Female Connector with 13 mm ( ⁄2 in.) hose barb 25 per box, double-bagged
1 ACD02M6 Male Connector with 13 mm ( ⁄2 in.) hose barb 25 per box, double-bagged
40 KleenpakTM Nova Particulate and Prefilter Capsule Filters Improving Choice, Flexibility and Operating Costs for the Prefiltration and Clarification of Liquids
The issues of effective cleaning and Kleenpak Nova capsules are used in a cleaning validation result in disposable wide range of critical applications including equipment being the preferred option. the filtration of BioPharmaceuticals, For many processes, disposable filters can biologicals, diagnostic reagents, serum, help eliminate cleaning problems, tissue culture media, and culture media especially where biological products are to components. be filtered. In applications where hazardous materials are being filtered, such as Kleenpak Nova Filters Reduce cytotoxic drugs, capsule filters can play an Operating Costs important role in helping protect operators. Kleenpak Nova filters have a typical Kleenpak Nova capsule filters are installation cost that is 80% lower than a designed to provide choice, similar sized stainless steel housing cost-effectiveness and flexibility, while system. Therefore, they offer an extremely ensuring ease of use for the operator. cost-effective alternative to housing and cartridge systems. Kleenpak Nova filters Designed to Provide Choice and can also provide further cost savings: Flexibility • No housing maintenance — Kleenpak Nova capsule filters are available Lower maintenance costs with either in-line or T-style configurations. • No housing cleaning or cleaning The T-style configuration is ideal for validation — manipulating multiple filters in series or Lower labor costs parallel configuration. • Filter is pre-assembled — Kleenpak Nova capsule filters incorporate Lower labor costs either a 10 in. (254 mm), 20 in. (508 mm) or 30 in. (762 mm) length standard Pall • Filter can be provided pre-sterilized — cartridge filters which have traditionally Lower energy costs been installed in stainless steel housings. In applications where a particular filter is already specified, the user can switch from a stainless steel housing to a fully disposable assembly with minimal requalification. This means the extensive range of cartridges currently available from Pall for clarification, bioburden reduction and prefiltration can easily be provided as a capsule filter. These include: • PreFlow™ Filters
• Ultipor® GF Plus Filters
• Profile® Filters Kleenpak Nova capsules are especially suited to pilot- and process-scale applications. They can be autoclaved or sterilized by gamma-irradiation and can be supplied as part of pre-sterilized processing systems such as a filter/tubing/bag set. 41 Kleenpak Nova Particulate and Prefilter Capsule Filters Technical Specifications
Operating Conditions(1) Kleenpak Nova NP Capsule — Maximum Operating 40 °C (104 °F) Typical Water Flow Rates at 20 °C (68 °F) Temperature Flow Rate (Gal/min) 5 10 15 20 25 Maximum Operating 3 barg (43.5 psig) at 40 °C (104 °F). 600 Pressure 8 500 (1) 7 With compatible fluids which do not soften, swell or adversely affect the product or its P6 materials of construction. 6 400 5 Capsule Materials of Construction 300 4 Housing Bowl Polypropylene 3 200 Housing Head(2) Polypropylene P9 2 Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential O-rings Silicone elastomer 100 1 (2) P1 Formulated with TiO2 whitener which does not contribute to organic extractables. 0 0 20 40 60 80 100 Sterilization Flow Rate (L/min) 1 • P6 Capsules (13 mm ( ⁄2 in.) hose barb) Autoclave (Maximum) single-cycle, 3 x 20 minutes • P9 Capsule (25 mm (1 in.) hose barb) 135 °C, for 1 hour • P1 Capsules (sanitary flange) Gamma-irradiation Maximum Dosage: 50 kGy Kleenpak Nova NT Capsule — Typical Water Flow Rates at 20 °C (68 °F) Consult Pall for procedures. Flow Rate (Gal/min) 510152025 2.5 Nominal Dimensions 160 P9
In-line NP6 NP7 NP8 140 P19 2 F (psi) ° Maximum Diameter 154 mm 154 mm 154 mm C (mbar) ° 120 (including Valves) (6.1 in.) (6.1 in.) (6.1 in.) 100 P1 1.5 Length with Hose Barb 397 mm 644 mm 895 mm Inlet and Outlet (15.6 in.) (25.4 in.) (35.2 in.) 80 1 Length with Sanitary 335 mm 584 mm 834 mm 60 Inlet and Outlet (13.2 in.) (23.5 in.) (32.8 in.) 40 0.5 T-style NT6 NT7 NT8
20 @ 68 Pressure Differential Maximum Diameter 240 mm 240 mm 240 mm @ 20 Pressure Differential 0 0 (including Valves) (9.5 in.) (9.5 in.) (9.5 in.) 0 20 40 60 80 90 100 Length 349 mm 598 mm 848 mm Flow Rate (L/min) (13.7 in.) (23.5 in.) (33.4 in.) • P1 Capsules (sanitary flange) • P19 Capsules (sanitary flange inlet, 25 mm (1 in.) hose barb outlet) • P9 Capsule (25 mm (1 in.) hose barb) Note: Empty Kleenpak Nova Capsule Housings for water at 20 °C (68 °F), 1 cP. For other liquids, multiply pressure times the viscosity in centipoise. For complete assembly, including AB-Style filter cartridge, add housing, and cartridge media pressure-drop values, contact Pall for assistance. Ordering Information NP – In-Line NT – T-style
Code Filter Size Code Filter Type Code Filter Grade Code Connection Options Code Sterilization 1 6 AB1 10 in. Pre-filter Grades P Pharmaceutical 11 – 1 ⁄2 in. sanitary flange inlet Status (254 mm) UUA 0.2 µm rated with Certificate and outlet G Non-sterilized 7 AB2 20 in. UUAP PreFlow filter of Test and Full 9 25 mm (1 in.) single-barb S Pre-sterilized (508 mm) UB 0.45 µm rated Traceability hose barb inlet and outlet 1 8 AB3 30 in. UBP PreFlow filter Omit Pharmaceutical 19 1 – 1 ⁄2 in. sanitary flange inlet (762 mm) U010Z 1.0 µm rated and 25 mm (1 in.) single-barb U010ZP Ultipor GF Plus filter hose barb outlet U2-20Z 2.0 µm rated Options for In-line Only 1 U2-20ZP Ultipor GF Plus filter 6 13 mm ( ⁄2 in.) single-barb A015P 1.5 µm rated hose barb inlet and outlet 1 Profile Star filter 16 1 – 1 ⁄2 in. sanitary flange inlet 1 Code Vent and Drain A030P 3.0 µm rated and 13 mm ( ⁄2 in.) single-barb – Stäubli(1) vent and Profile Star filter hose barb outlet stepped hose barb Options for T-style Only A050P 5.0 µm rated drain 1 Profile Star filter 1H 1 – 1 ⁄2 in. sanitary flange inlet (1) 1 AStäubli vent and and outlet, with 13 mm ( ⁄2 in.) UY045P 4.5 µm rated drain Profile filter with sanitary port on inlet ® 1 (1) Ultipleat construction 1H9 1 – 1 ⁄2 in. sanitary flange inlet Stäubli is a trademark of and 25 mm (1 in.) single-barb Stäubli AG. 42 Note: Partial list of part numbers. hose barb outlet, with 13 mm Contact Pall for specific part numbers. 1 ( ⁄2 in.) sanitary port on inlet PreFlow™ Capsule Filters Scalable Prefilters with PreFlow UUA and UB Media
PreFlow capsule filters have been Applications designed for small volume production and The PreFlow range of filters has been scale-up evaluation. specifically designed for the filtration of Pall PreFlow media provide bioburden biological fluids including: reduction, clarification, and prefiltration for • Serum sterilizing-grade filters when processing biological fluids. The fixed pore structure • Vaccines and proprietary resin-bonded glass fiber • Cell Culture Media composite media provide exceptional capacity for fine contaminants and long • Protein Solutions service life. Pall’s UpScaleSM Program PreFlow filters have the following properties: From drug discovery and basic research, through process development and • Fixed pore construction production, Pall Corporation is the single • Resistant to contaminant unloading source for all of your filtration and • Meets USP Biological Reactivity Test, separation needs. Our UpScale program in vivo, for Class VI – 121 °C Plastics provides you with the scalable filtration products and support you need to bring Features and Benefits new products to market faster.
The key benefits of DFA PreFlow capsules for prefiltration applications include: • Scalablity to production filters • Capsule format for ease of use • Effective and reliable protection of final filters, including 0.2 µm and 0.1 µm sterilizing-grade — providing higher throughputs and longer filter life • Low hold-up volumes • High-strength design allows for multiple autoclave cycles • Supplied with Certificate of Test giving batch traceability
43 PreFlow Capsule Filters Technical Specifications
Materials of Construction Typical Liquid Flow Rates at 20 °C (68 °F)(3) Filter Medium Resin-bonded glass fiber 20 3 Core and End Caps Polypropylene DFA3001UBC Support and Drainage Polypropylene 15 Shell Polypropylene 2
Operating Conditions(1) DFA3001UUAC 10 Maximum Operating 40 °C (104 °F) Temperature 1 Maximum Operating 3.5 barg (50 psig) Differential Pressure (psid) Pressure Differential Pressure (mbar) Pressure Differential 5
(1) In compatible fluids which do not soften, swell or adversely affect the filter or its materials of construction.
0 0 Typical Extractables in Water at 20 °C (68 °F) 0 2 4 6 8 after 4 hours Extraction Flow Rate (L/min)
DFA3001UUAC < 10 mg (3) Typical initial clean media ∆P; water at 20 °C (68 °F) viscosity 1cP. DFA3001UBC < 30 mg For assistance in sizing, contact your local pall representative.
Autoclave Sterilization(2) 3 x 1-hour cycles at 125 °C (257 °F) Nominal Filtration Area (2) Warning: This product must not be sterilized in situ by passing steam through under 0.1 m2 (1.0 ft2) pressure. Nominal Dimensions Length 124 mm (4.9 in.) Maximum Diameter 72 mm (2.8 in.)
3 Connections 10 mm ( ⁄8 in.) hose barb
Ordering Information Part Number Absolute Removal Rating DFA3001UUAC 0.2 µm DFA3001UBC 0.45 µm
44 Mini Profile® Capsule Filters Scalable Depth Filters with Profile II and Profile Star Media
Pall Mini Profile Capsule Filters have been • Excellent gel removal designed for small volume production and • Higher flows and throughputs scale-up evaluation. These scalable capsule filters are available in two media • Easy to use self-venting format types to complement and extend the range • Pharmaceutical P optimized grades of depth filters available in the Pall with Certificate of Test provides batch UpScaleSM Program. traceability They can be used for a wide range of • Low extractables and low applications including clarification of protein-binding biological products. • Manufactured under clean conditions in Pall Profile II filters are all-polypropylene a controlled environment depth filter elements, featuring tapered • Rating range from 0.5 µm to 5 µm pores that narrow to an inner (downstream) absolute-rated section. This thick depth SM structure provides high-capacity for larger Pall’s UpScale Program solids and gels as well as for fine particles. From drug discovery and basic research, Profile Star filter cartridges feature through process development and high-area star-shaped pleat construction. production, Pall Corporation is the single The patented design combines the source for all of your filtration and advantages of depth filters with the high separation needs. Our UpScale program flow rates of high-area pleated filters. provides you with the scalable filtration products and the support you need to Features and Benefits bring new products to market faster.
• Can be used in scale-up evaluation • Capsule format for ease of use • Choice of high void-volume depth medium or high-area pleated depth filter • Absolute particle-rated for reliability • Low hold-up volumes • Broad chemical compatibilities • Optimized for viscous fluids
45 Mini Profile® Capsule Filters Technical Specifications
Materials of Construction Typical Liquid Flow Rates(3)
Filter Medium 3500 5 Polypropylene BYY005P6 BYY010P6 Core and End Caps Polypropylene 3000 Housing Polypropylene 4
1 2500 13 mm ( ⁄2 in.) Single Polypropylene Hose Barb Adapter 3 2000
1500 BYA015P6 Absolute Removal Ratings (Liquid) 2 Profile II 1 µm and 0.5 µm(1) 1000
(1) (psi) Pressure Differential Profile Star 5 µm, 3 µm and 1.5 µm (mbar) Pressure Differential BYA030P6 1 BYA050P6 (1) Extrapolated. 99.98% by modified OSU-F2 Beta test. For further details, contact Pall. 500
0 0 Nominal Filtration Area 0 1 2 3 4 5 Flow Rate (L/min) Profile II 46 cm2 (7.1 in2) (3) Typical initial clean media ∆P; water at 20 °C (68 °F) viscosity 1cP. Profile Star 90 cm2 (14.5 in2) For assistance in sizing, contact your local Pall representative. Connections (Inlet and Outlet)
Operating Conditions 1 13 mm ( ⁄2 in.) hose barb Maximum operating pressure and temperatures in compatible(4) fluids
Temperature Maximum 85 mm Differential Pressure (3.35 in.) Profile II 30 °C (86 °F) 4.1 bard (60 psid) 37 mm 50 °C (122 °F) 3.4 bard (49 psid) (1.45 in.) Profile Star 50 °C (122 °F) 5.0 bard (72 psid) (4) Fluids which do not adversely affect the filter or materials of construction.
76.5 mm Maximum Accumulated Autoclave Time (3.07 in.) Up to 125 °C 3 x 30-minute cycles 50 mm (1.97 in.) Warning: Mini Profile Capsule filters must not be in situ steam-sterilized by passing steam through under pressure. The figures given are maximum allowable figures determined by testing under controlled laboratory conditions to the length of time indicated. Actual operating conditions may affect the filter’s long-term response to sterilization. Filters should be qualified for each process application.
77.5 mm (3.05 in.)
Ordering Information(2)
Part Number Medium Removal Rating BYA015P6 Profile Star 1.5 µm BYA030P6 Profile Star 3 µm BYA050P6 Profile Star 5 µm BYY005P6 Profile II 0.5 µm BYY010P6 Profile II 1 µm (2) This is a guide to the part number structure only. For availability of specific options, please contact Pall or your local Pall distributor.
46 Kleenpak™ Capsules with HDC® II Filter Assemblies High Dirt Retention Polypropylene Liquid Filters in the most Convenient Form
Pall Kleenpak filters combine the widest • A total absence of glues, binder resins available range of filter media and specially and surfactants results in very low filter designed self-contained assemblies extractables and extremely clean filtrate to satisfy the very highest standards of • All filter materials of construction have filtration security and user convenience. met the specifications for USP Class VI biological tests for plastics at 121 °C HDC II Filter Medium and meet FDA requirements for food At the heart of every Kleenpak filter with contact use 21 CFR parts 170-199 HDC II media is a high-performance pleated cartridge with polypropylene filter Quality and Bio-Safety medium. The HDC II medium is produced Biological Tests by a proprietary technique, varying the fiber diameter continuously to provide a • Meets USP Biological Reactivity, pore-size distribution from coarse In Vivo, for Class VI-121 °C plastics (upstream) to fine (downstream) while Effluent Quality Tests* maintaining constant void-volume • Meets Cleanliness per USP Particulates throughout the depth of the filter medium. in Injectables • The varied fiber diameter means • Non-Fiber-Releasing extraordinary contaminant-holding capacity, maximum flow rate, and low • Non-Pyrogenic per USP Bacterial costs per liter of filtered fluid Endotoxins (< 0.25 EU/mL) • The fixed pore structure means that • Meets Total Organic Carbon and Water contaminants will not unload under Conductivity per USP Purified Water, variations in flow or pressure differential, pH per USP Sterile Purified Water and fibers will not migrate or become * Per lot sample soak or rinse-up flush aliquots. dislodged to contaminate process fluids Convenience to Suit All Needs
Clean and Robust Design The self-contained design of each The Kleenpak filter uses well-proven Kleenpak filter means that operator proprietary Pall techniques for filter intervention and exposure during filter construction and heat sealing. installation and change-out are minimized. • The highest possible security against • Integrally molded inlet and outlet filter bypass is ensured, even under connections conditions of pulsed flow Maximum convenience and security • High-strength design allows multiple • Vent and drain connections with seal autoclave cycles for extended use and protected threads and precision molded maximum filter economy valves
• Polypropylene outer shell is designed to Exceptionally simple and reliable provide long-term assurance of operation pressure and temperature ratings • Available in three standard sizes. • Internal hold-up volume and dead Flexibility in batch size or flow rate space is minimized for maximum requirements product recovery
47 Kleenpak Capsules with HDC II Filter Assemblies Technical Specifications
Materials of Construction Typical Liquid Flow Rates(2) Medium Polypropylene Flow Rate (L/min) 0 1 2 3 4 Support, Drainage, Core, Polypropylene 1 Cage, End Caps and Shell KA1J012 KA2J012 KA1J045 60 Vent and Drain Valve O-rings Ethylene Propylene (EPDM)
Nominal Dimensions KA3J012 KA2J045 40 KA1J100 Size Code KA1 KA2 KA3 0.5 Maximum Diameter of 94 mm 94 mm 109 mm Bowl (including Valves) (3.7 in.) (3.7 in.) (4.2 in.) KA3J045 20
Differential Pressure (psid) Pressure Differential KA2J100 Nominal Length (including 117 mm 158 mm 174 mm (mbar) Pressure Differential 1 1 ⁄2 in. Sanitary Flange (4.6 in.) (6.2 in.) (6.8 in.) KA3J100 Connection) 0 0 Nominal Length (including 158 mm 199 mm – 0 0.2 0.4 0.6 0.8 1.0 Stepped Hose Barb (6.2 in.) (7.8 in.) – Flow Rate (Gal/min) Connection) Flow Rate (L/min) Nominal Length (including ––210 mm 0 1 2 3 4 Hose Barb Connection) ––(8.2 in.) 0.5
30 KA1J 060 KA2J025 KA3J025 Nominal Filter Areas KA1J025
Effective Size Code KA2J060 Filter Area KA1 KA2 KA3 20 0.25 J012, J025 0.06 m2 (0.6 ft2) 0.1 m2 (1.0 ft2) 0.2 m2 (2.0 ft2) KA3J060 J045 0.06 m2 (0.6 ft2) 0.11 m2 (1.2 ft2) 0.22 m2 (2.3 ft2) 10 2 2 2 2 2 2 Differential Pressure (psid) Pressure Differential
J060 0.03 m (0.3 ft ) 0.05 m (0.5 ft ) 0.10 m (1.0 ft ) (mbar) Pressure Differential
J100 0.03 m2 (0.3 ft2) 0.07 m2 (0.7 ft2) 0.13 m2 (1.4 ft2) 0 0 0 0.2 0.4 0.6 0.8 1.0 (1) Removal Ratings (Liquids) Flow Rate (Gal/min) (2) Typical initial clean ∆P, water at 20 °C (68 °F). Values shown are for 38 mm J100 J060 J045 J025 J012 1 (1 ⁄2 in.) sanitary flange connections. Values with other connections are 10 µm 6 µm 4.5 µm 2.5 µm 1.2 µm available on request. For assistance in filter sizing, contact your local Pall representative. (1) > 99.98% by modified OSU-F2 Beta test. Operating Conditions(2)
Connections (Inlet and Outlet) Maximum Operating 5.2 barg (75 psig) at 40 °C (104 °F) Pressure and Temperature 1 KA1 and KA2 Styles 38 mm (1 ⁄2 in.) sanitary flange 1 1 Maximum Differential 4.1 bard (60 psid) at 40 °C (104 °F) 6 – 13 mm ( ⁄4 – ⁄2 in.) stepped hose barb Pressure and Temperature 1 KA3 38 mm (1 ⁄2 in.) sanitary flange (2) 9 Using compatible liquids. Maximum 3.5 barg (50 psig) in air and gas service. 14 mm ( ⁄16 in.) stepped hose barb
Steam Autoclaving Cumulative Autoclave Time(3) 50 hours at 140 °C (3) Laboratory tests (1-hour cycles) establish multi-cycle resistance. Filters should be qualified in actual use.
Warning: Kleenpak filters must not be steamed in situ by passing steam through under pressure.
Ordering Information
K A P
Code Grade Removal Ratings in Liquids(4) Code Connectors
1 1 J012 1.2 µm 1 38 mm (1 ⁄2 in.) sanitary flange 2 J025 2.5 µm 2 6 to 13 mm 3 J045 4.5 µm 1 1 ( ⁄4 to ⁄2 in.) J060 6.0 µm stepped hose barb
9 J100 10 µm 6 14 mm ( ⁄16 in.) (4) Based on modified OSU F-2 test. 48 Contact Pall for further details. HDC® II Junior Style Filter Cartridges HDC II High Dirt Capacity Polypropylene Filters
HDC II Junior Style Filter Cartridges Features and Benefits (including Sealkleen™ cartridges) are high Varied Fiber Diameter dirt capacity pleated polypropylene filters constructed with a proprietary technique: • Extraordinarily high dirt-holding capacity varying the fiber diameter instantaneously Fixed Pore Structure and continuously to produce a pore-size • No solids unloading under variations in distribution from coarse (upstream) to fine flow or pressure differential (downstream) while maintaining constant void-volume throughout the depth of the • Fibers will not migrate or become filter medium. This unique construction dislodged and contaminate process means that more contaminants are fluid trapped in the outer and inner layers of the Pure Polypropylene Construction medium, thereby substantially increasing its • Extremely good chemical compatibility dirt-holding capacity, and the service life of with a wide range of fluids the filter. • No surfactants or binder resins Sealkleen and Junior HDC II style filters are available in absolute removal ratings • Cartridges can be in situ from 0.6 µm to 40 µm. steam-sterilized The all-polypropylene construction of these filters make them compatible with an Quality and Bio-Safety extremely wide range of fluids. Cartridges Biological Tests with a P option are optimized for pharmaceutical applications. • Meets USP Biological Reactivity, In Vivo, for Class VI-121 °C plastics All materials of construction are FDA-listed materials per 21 CFR. Effluent Quality Tests* • Meets Cleanliness per USP Particulates in Injectables • Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) • Meets Total Organic Carbon and Water Conductivity per USP Purified Water, pH per USP Sterile Purified Water
* Per lot sample soak or rinse-up flush aliquots.
49 HDC II Junior Style Filter Cartridges Technical Specifications
Operational Limits Typical Liquid Flow Rates for SLK7002 and MCY4463 Styles 500 Operating 50 °C (122 °F) 80 °C (176 °F) 7 Temperature (Maximum) J006 J012 J025 Maximum Differential 5.5 bard (80 psid) 4.1 bard (60 psid) 400 6 Pressure 5 Nominal Filter Area 300 J045 4 Grade SLK7001 Style MCY4463 and J060 SLK7002 Styles 200 3 J006 0.11 m2 (1.2 ft2) 0.22 m2 (2.4 ft2) J100
2 2 2 2 2 (psi) Pressure Differential J012 0.12 m (1.3 ft ) 0.25 m (2.7 ft ) (mbar) Pressure Differential J200 100 J025 0.14 m2 (1.6 ft2) 0.25 m2 (2.7 ft2) J400 1 J045 0.14 m2 (1.6 ft2) 0.25 m2 (2.7 ft2) J060 0.07 m2 (0.8 ft2) 0.15 m2 (1.7 ft2) 0 0 0 10 20 30 40 50 60 J100 0.09 m2 (1.0 ft2) 0.19 m2 (2.1 ft2) Flow Rate (L/min) J200 0.09 m2 (1.0 ft2) 0.19 m2 (2.1 ft2) Sterilization
2 2 2 2 J400 0.06 m (0.7 ft ) 0.25 m (2.7 ft ) Steam-sterilizing Up to 140 °C (284 °F) in situ Temperature or autoclave
Note: Differential pressures are for liquids with a viscosity of 1 cP. Differential pressures for liquids at other viscosities can be conservatively estimated by multiplying the indicated differential pressure by the viscosity in cP. To obtain the total pressure drop of a complete filter assembly the housing pressure drop must be added. Please refer to the relevant housing literature or contact Pall.
Ordering Information
Sealkleen Style Single open-ended 57 mm (2.25 in.) diameter element (excluding flange). Incorporates a patented sealing arrangement that eliminates any chance of fluid bypass via the seal, from the upstream side of the filter element to the downstream side. The housing elastomeric O-ring is placed on a special flange, which is an integral part of the element outlet end cap.
SLK
Code Nominal Length HDC II Filter Grade Removal Rating Code Filter Grade 7001 2.5 in. (66 mm) J006 0.6 µm(1) P Pharmaceutical 7002 5.2 in. (133 mm) J012 1.2 µm Omit Other J025 2.5 µm J045 4.5 µm J060 6.0 µm J100 10.0 µm J200 20.0 µm J400 40.0 µm Junior Style (MCY) Single open-ended 57 mm (2.25 in.) diameter element with single external O-ring seal contained in the outlet end cap. Cartridge nominal length of 133 mm (5.25 in.).
MCY
Code Nominal Length HDC II Filter Grade Removal Rating Code Filter Grade Code O-ring Option 4463 5.2 in. (133 mm) J006(1) 0.6 µm(1) P Pharmaceutical* H4 Silicone J012 1.2 µm Other O-ring options on request. J025 2.5 µm Omit General Use J045 4.5 µm * Pall pharmaceutical-grade J060 6.0 µm filters are designed for use in conformance with CGMP in J100 10.0 µm Manufacturing, Processing, Packing or Holding of Drugs J200 20.0 µm (21CFR210) and CGMP for J400 40.0 µm finished Pharmaceuticals (21CFR211.72) including (1) Extrapolated value. batch release certificate and 50 full traceability. Profile® II Filter Cartridges Absolute-rated Depth Filters with Excellent Chemical Compatibility and Long Service Life
Pall Profile II filters provide: Applications
• Absolute removal ratings for reliability Profile II polypropylene filters have a wide • Built in prefiltration for economy range of applications including filtration of fermentation broths, lysates, biological • Revolutionary new construction for long fluids, blood products, ophthalmics, service life and high flow-rates organic solvents, pH adjusters, buffers, purified water, parenterals and many other Features and Benefits fluids. Based on the widely accepted modified F-2 Filter Performance Test(1), Profile II Other Profile II filters available filters can be expected to yield longer Profile II nylon filters — for applications service life, in many cases by factors of six where polypropylene Profile II filters are or more, and higher flow rates when chemically or physically incompatible, such compared with existing products of similar as for the filtration of hot vegetable and physical appearance at equal efficiency. mineral oils and aromatic solvents. The specific features include: Profile II Plus filters — these • Excellent compatibility with a wide all-polypropylene filters have a positive range of chemicals charge to provide enhanced removal • Continuous operating temperatures up efficiency for small particles, bacteria and to 82 °C (180 °F) viruses. • Wide choice of particulate removal Profile II capsule filters — disposable efficiencies from 0.3 µm to 120 µm assemblies for ease of use. absolute to optimize filter ratings for each application • No media migration — the fibers are continuous and fixed by intertwining during the manufacturing process • Very low extractables — no binders, lubricants or surfactants are used during manufacture • Choice of cartridge length to match flow rates • Choice of three cartridge styles — AB, RMF and RF style to suit different housing styles and applications
(1) For additional information on the complete range of Profile II filters and the F-2 Filter Performance Test, please contact Pall.
Note: These filters are also available in Kleenpak Nova capsule format.
51 Profile II Filter Cartridges Technical Specifications
Operating Conditions(1) Extractables Extractables (non-volatile residues) of less than 10 mg per 10 in. Operating 30 °C 50 °C 70 °C 82 °C Temperature (86 °F) (122 °F) (158 °F) (180 °F) (250 mm) cartridge were found in a standard 24 hour reciprocating test in water at 20 °C (68 °F). Maximum 4.0 bar 3.4 bar 2.0 bar 1.0 bar Differential Pressure (58 psi) (49 psi) (29 psi) (15 psi)
(1) In fully compatible liquids which do not soften, swell or attack the filter. AB Code 7 style elements can be heated to 125 °C (257 °F), for example during in situ steam-sterilization or autoclaving and subsequent cooling to ambient temperatures prior to use. If RF or RMF style elements are heated in situ for any reason, and the filter is then used at a temperature lower by 20 °C (68 °F) or more, sealing of the element within the housing may be marginal.
Retention Ratings and Flow Rates Liquids Flow Rates for a 10 in. (254 mm) Element with water (1 cP) Code Absolute Retention Rates(2) ß ≥ 5000 (> 99.98%) ß = 1000 (99.9%) ß = 100 (99%) ß = 10 (90%) ∆P = ∆P = 100 mbar (1.45 psi) 50 mbar (0.75 psi) 003 0.3 µm(3) < 0.3(3) < 0.3(3) < 0.3(3) 1.6 – 005 0.5 µm(3) < 0.5(3) < 0.5(3) < 0.5(3) 1.8 – 010 1.0 µm 0.5(3) < 0.5(3) < 0.5(3) 2.1 – 020 2.0 µm 1.5 1.0 < 1.0(3) 2.9 – 030 3.0 µm 2.5 1.8 < 1.0(3) 3.7 – 050 5.0 µm 4.0 3.0 2.0 6.7 – 100 10.0 µm 9.0 7.5 6.5 – 8.3 150 15.0 µm 13.0 10.0 8.0 – 16.7 200 20.0 µm 18.0 14.0 10.0 – 27.7 300 30.0 µm 26.0 18.0 14.0 – 33.3 400 40.0 µm 35.0 30.0 20.0 – 50.0 700 –(4) 70.0 50.0 32.0 – 50.0 900 –(4) 90.0(3) 78.0(3) 50.0 – 50.0 1200 –(4) 120.0(3) 100.0(3) 60.0 – 50.0
(2) Modified OSU-F2 test. (3) Extrapolated data. (4) Not measurable.
Ordering Information and Selection Guide
RF Style: R F AB Style RMF Style RF Style Code 7 63.5 mm 63.5 mm 70 mm (2.5 in.) (2.5 in.) RMF Style: RM F (2.75 in.) diameter diameter diameter Flat gasket crush seal Double 226 seal O-ring seal
AB Style: AB Y
Code Nominal Length Code Removal Code Removal Code Cartridge Code Filter Code O-ring Rating(5) Rating(5) Style Grade Option 1 10 in. (254 mm) 003 0.3 µm 150 15 µm 7 Double 226 P Pharmaceutical* H4 Silicone 2 20 in. (508 mm) O-ring 005 0.5 µm 200 20 µm Omit General Use J Ethylene 3 30 in. (762 mm) with bayonet Propylene 010 1 µm 300 30 µm lock and * Pall pharmaceutical-grade 4 40 in. (1016 mm) fin end filters are designed for use in Other materials available on 020 2 µm 400 40 µm conformance with CGMP in request. Manufacturing, Processing, 030 3 µm 700 – Packing or Holding of Drugs (21CFR210) and CGMP for 050 5 µm 900 – finished Pharmaceuticals 100 10 µm 1200 – (21CFR211.72) including batch release certificate and (5) The removal rating is the value in microns at full traceability. which the modified OSU-F2 test gives a Beta value of ≥ 5000. 52 Profile® Star Filter Cartridges Absolute-rated Pleated Depth Filters combining Long Service Life and High Flow-rates
To keep pace with advancing technologies, Features and Benefits Pall continues its tradition of filtration Pleated High-area innovations with the Profile Star filter: a state-of-the-art concept for pleated • Extraordinarily high dirt-holding capacity polypropylene filters. The proven and • Long service life successful Pall technique of varying the • High flow-rates fiber diameter produces a pore-size gradient from coarse (upstream) to fine • Excellent gel removal capability (downstream) while maintaining constant Fixed Pore Structure high void-volume throughout the depth of the filter medium. Profile Star filters offer • No solids unloading under variations in longer life than many competitive pleated flow or pressure differential filters. Due to their proprietary construction, • Fibers will not migrate or become Profile Star filters deliver the benefits of dislodged and contaminate process both traditional pleated polypropylene and fluid depth style filters — the ideal combination. All-polypropylene Construction The pressure drop and flow capability is comparable to competitive pleated • Extremely good chemical compatibility polypropylene filters while also providing with a wide range of fluids excellent removal of soft contaminants, • Very low extractables such as gels, because of the depth of the • No surfactants or binder resins are medium. used during manufacture Profile Star filters are available in absolute • Continuous construction without side removal ratings from 1.0 µm to 90 µm and seam in four nominal cartridge lengths: • Media melt-sealed to solid components • 10 in. (254 mm) to ensure maximum integrity • 20 in. (508 mm) • 30 in. (762 mm) Quality and Bio-Safety • 40 in. (1016 mm) Biological Tests Their all-polypropylene construction makes • Meets USP Biological Reactivity, them compatible with an extremely wide In Vivo, for Class VI-121 °C plastics range of fluids. Cartridges are available in a Effluent Quality Tests* P grade which is optimized for • Meets Cleanliness per pharmaceutical applications. USP Particulates in Injectables Note: These filters are also available in Kleenpak Nova capsule format. • Non-Fiber-Releasing • Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) • Meets Total Organic Carbon and Water Conductivity per USP Purified Water, pH per USP Sterile Purified Water
* Per lot sample soak or rinse-up flush aliquots.
55 Profile Star Filter Cartridges Technical Specifications
Typical Liquid Flow Rates Materials of Construction 120
Filter Medium, Cage, Core, Polypropylene End Caps and Adapters 1.5 100 O-rings Silicone or Ethylene Propylene (EPDM) as standard A010 A015 A050 A030 80 Operating Conditions – Maximum Operating Differential Pressures and Temperatures in Compatible(1) Liquids 1 A100 Maximum Operating 50 °C (122 °F) 80 °C (176 °F) 60 Temperature A150 Maximum Differential 5.0 bar (72 psi) 3.4 bar (49 psi) Pressure
40 (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential Steam-sterilizing Temperature 125 °C A200 0.5 (in situ or Autoclave) A400
Cartridge Style AB Code 3 P grade and AB Code 7 20 Maximum Recommended 10 hours A700/900 Cumulative Steam Life at 125 °C 0 0 (1) Fluids which do not soften, swell or adversely affect the filter or materials of 0 20 40 60 80 100 120 construction. Flow rate (L/min) per 10 in. (254 mm) nominal length cartridge Note: Differential pressures are for liquids with a viscosity of 1 cP. Differential pressures for liquids at other viscosities can be conservatively estimated by multiplying the indicated differential pressure by the viscosity in cP. For cartridges of 20 in. (508 mm), 30 in. (762 mm) and 40 in. (1016 mm) nominal length, divide the differential pressure by 2, 3 and 4 respectively. To obtain the total pressure drop of a complete filter assembly the housing pressure drop must be added. Please refer to the relevant housing literature or contact Pall. Ordering Information
MCY 1000 Style Double open-ended 70 mm (2.75 in.) diameter element with gaskets on both ends. Sealing is assured by using a tie rod and seal nut. MCY 1000
Code Nominal Code Removal Code Filter Code Gasket Cartridge Sealing Length Rating(2) Grade Option Arrangements 1 10 in. A010 1.0 µm(3) P Pharmaceutical* H4 Silicone MCY1000 AB Style (254 mm) A015 1.5 µm(3) Omit General Use J Ethylene propylene Style (Other materials are available on request) 2 20 in. A030 3 µm (508 mm) * Pall pharmaceutical-grade filters Other materials available on request. 70 mm 70 mm 70 mm A050 5 µm are designed for use in 3 30 in. conformance with CGMP in diameter diameter diameter (762 mm) A100 10 µm Manufacturing, Processing, A150 15 µm Packing or Holding of Drugs 4 40 in. (21CFR210) and CGMP for (1016 mm) A200 20 µm finished Pharmaceuticals A400 40 µm (21CFR211.72) including batch release certificate and full Flat gasket Code 7 Code 3 A700 70 µm traceability. Double O-ring seal A900 90 µm AB Style Single open-ended element with double O-rings at one end.
AB
Code Nominal Code Removal Code Cartridge Code Filter Code Gasket Length Rating(2) Style Grade Option 1 10 in. A010 1.0 µm(3) 3 Double 222 O-ring P Pharmaceutical* H4 Silicone (254 mm) A015 1.5 µm(3) with flat end Omit General Use J Ethylene propylene 70 mm (2.75 in.) 2 20 in. A030 3 µm (508 mm) diameter * Pall pharmaceutical-grade filters Other materials available on request. A050 5 µm are designed for use in 3 30 in. 7 Double 226 O-ring conformance with CGMP in (762 mm) A100 10 µm with bayonet lock Manufacturing, Processing, A150 15 µm and fin end. Packing or Holding of Drugs 4 40 in. 70 mm (2.75 in.) (21CFR210) and CGMP for finished (1016 mm) A200 20 µm diameter Pharmaceuticals (21CFR211.72) including batch release certificate (2) A400 40 µm Absolute rating in this and full traceability. publication means the A700 70 µm value in microns at which the modified OSU-F2 test A900 90 µm gives a Beta value of 56 > 5000. (3) Extrapolated value. Starclear™ Filter Cartridges The Only Composite Pleated Depth Filters with Positive Zeta Potential
Revolutionary New Construction • Positive zeta potential for the removal of fine contaminants such as Starclear pleated filters are constructed using a totally new technique based on a bacteria composite design. viruses
• The unique built-in depth prefiltration endotoxins layer, constructed from pleated Profile haze particles Star filter medium provides:
Graded pore-size distribution from Total Commitment to Quality and coarse (upstream) to fine Excellence (downstream) Starclear filters are manufactured under a Constant void-volume Quality Management System certified to Exceptionally high dirt-holding ISO 9000. capacity • The inner section, constructed from Quality and Bio-Safety Ultipor GF Plus glass fiber filter Biological Tests medium with a fine pore structure, ensures high removal efficiency and • Meets USP Biological Reactivity, long service life. In Vivo, for Class VI-121 °C plastics Effluent Quality Tests* Exceptional Performance • Meets Cleanliness per USP Particulates in Injectables Starclear filter cartridges provide reliable and cost effective sub-micron filtration with • Non-Fiber-Releasing the following benefits: • Non-Pyrogenic per USP Bacterial • Absolute filtration, ensuring Endotoxins (< 0.25 EU/mL)
consistent, reproducible performance • Meets Total Organic Carbon and Water Conductivity per USP Purified Water, no fiber shedding pH per USP Sterile Purified Water no unloading * Per lot sample soak or rinse-up flush aliquots. • Built-in prefiltration for
high dirt-holding capacity
long-life
smaller installations • High flow-rates enabling
faster production times
smaller installations with less product loss and lower costs
57 Starclear Filter Cartridges Technical Specifications
Materials of Construction Extractables(2)
Filter Medium Prefiltration Layer: Typical Aqueous Extractables 40 mg Polypropylene per 10 in. (254 mm) Module
Final Filtration Layer: (2) Non-volatile residues from autoclaved elements after 4 hours reciprocation in deionized Positively-charged glass fiber water. Support and Drainage Layers Polypropylene Microbial and Particulate Removal Efficiency Core and Cage Polypropylene Challenge Contaminant Typical Removal Efficiency Adapter and End Cap Polypropylene (3) 2 Pseudomonas diminuta TR > 10 O-rings Silicone or ethylene propylene 5 as standard Serratia marcescens TR > 10
8 Lactobacillus brevis TR > 10
Liquid Flow vs. Differential Pressure 10 Saccharomyces cerevisiae TR > 10
Filter Size 10 in. (254 mm) nominal length Aqueous Suspension of ß ≥ 5000 (> 99.98%) at 0.5 µm(5) Flow Rate(1) at 16.7 L/min AC Fine Test Dust(4) 100 mbar (1.45 psi) ∆P (3) Titer reduction (TR) = No. organisms incident on filter The relationship between flow rate and differential pressure is linear. The ∆P at other flow No. organisms detected in effluent rates can therefore be calculated using the above data e,g. for a flow rate of 50 L/min, (4) Performance measured using Pall F2 test. Contact Pall for additional details. the clean ∆P will be 300 mbar (4.4 psi). (5) ß = No particles ≥ given size in influent (1) For fluids of 1 cP viscosity. As a general guide, for other viscosities, multiply differential No particles ≥ given size in effluent pressure by viscosity in cP. For cartridges of 5 in. (127 mm), 20 in. (508 mm), 30 in. (762 mm) and 40 in. (1016 mm) nominal length, divide differential pressure by 0.5, 2, and 4 respectively. Operating Limits(6) Maximum Operating Up to 40 °C Up to 60 °C Steam-sterilization Temperature (104 °F) (140 °F) Steam-sterilizing Temperature 125 °C Maximum Differential 5 bar (72 psi) 3.4 bar (49 psi) (in situ or autoclave) Pressure
Maximum Recommended 10 hours (6) In compatible liquids which do not soften, swell or adversely affect the filter or its Cumulative Steam Life materials of construction.
Additional details on steam-sterilization are available by contacting Pall.
Ordering Information
AB HAZ
Code Nominal Length Code Cartridge Style Code Filter Grade Code Seal Material 05(7) 5 in. (127 mm) 7 Double 226 O-ring with P Code outside US H4 Silicone bayonet lock and Omit Code in US only 1 10 in. (254 mm) fin end J Ethylene propylene 2 20 in. (508 mm) Supplied with Certificate of Test and Full 2(8) Double 226 O-ring with Traceability 3 30 in. (762 mm) bayonet lock and flat end
4 40 in. (1016 mm) (8) Available in cartridge type AB05 only. Other cartridges available on request. (7) Available with cartridge option code 2 only.
58 Profile® Filter Cartridges with Ultipleat® Construction Advanced Technology, Unsurpassed Performance
Profile Filters with Ultipleat construction Applications are an upgrade from pleated depth filter Profile Filters with Ultipleat construction technology pioneered by Pall, and have advantages in the filtration of viscous incorporate a revolutionary new liquids or for high flow-rates when there crescent-shaped pleat geometry which may be significant sizing and economic enables a 30% increase in effective benefits. filtration area.
The crescent-shaped pleat construction, Quality and Bio-Safety which is unique to Pall, combined with Profile depth filter medium provides a very Biological Tests low clean pressure drop and an • Meets USP Biological Reactivity, unsurpassed service life. In Vivo, for Class VI-121 °C plastics Effluent Quality Tests* Process Improvements • Meets Cleanliness per USP Particulates • Reduced operating costs and in Injectables downtime resulting from the • Non-Fiber-Releasing crescent-shaped pleat construction allows optimization of filter area, giving • Non-Pyrogenic per USP Bacterial unsurpassed service life — thus Endotoxins (< 0.25 EU/mL) reducing the frequency of changeout • Meets Total Organic Carbon and Water and providing substantial savings in the Conductivity per USP Purified Water, costs of maintenance and consumables pH per USP Sterile Purified Water
• Consistent and reliable performance * Per lot sample soak or rinse-up flush aliquots. is a benefit of the absolute and 100% efficient removal rating along with the fixed pore structure that prevents both unloading of contaminants and media
migration Diagrammatic Comparison of • Excellent chemical compatibility and Various Filter Constructions ease of disposal due to the Conventional Pleat Ultipleat Laid-over all-polypropylene construction which Geometry Pleat Geometry leads to lower filter inventories and allows complete incineration* of the spent cartridge.
Note: In the Code 7 style there is a metal insert in the adapter.
* Consult local and national regulations
Note: These filters are also available in Kleenpak Nova capsule format.
Depth Filter
59 Profile Filter Cartridges with Ultipleat Construction Technical Specifications
Operating Conditions in Compatible(1) Liquids Typical Liquid Flow Rates(2) 160 Maximum Differential 4.1 bar 3.4 bar 2.0 bar 1.0 bar Pressure (60 psi) (49 psi) (29 psi) (15 psi) 140 2.0 µm 4.5 µm Operating 30 °C 50 °C 70 °C 80 °C 2 Temperatures (86 °F) (122 °F) (158 °F) (176 °F) 120
(1) Fluids which do not soften, swell, or adversely affect the filter or materials of 100 construction.
80 Steam-sterilization 1 60 Up to 140 °C (284 °F) for AB style filter elements 6.0 µm
10 µm (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential 40 20 µm
40 µm 20 70 µm 100 µm 0 0 0 25 50 75 100 Flow Rate (L/min) – 10 in. (254 mm) nominal length cartridge (2) Typical initial clean media ∆P 10 in. (254 mm) element, water at 20 °C (68 °F), viscosity 1 cP. For assistance with filter assembly, sizing and housing selection, contact your local Pall representative.
Ordering Information
PUY Style Double open ended 63mm (2.5in) diameter cartridge with gaskets both end. Cartridge sealed with tie rod and seal nut. PUY Style: PUY UY 7
AB Style: AB UY 7
Code Nominal Code Removal Cartridge Style Code Filter Code Seal Options Length Rating(3) Grade
1 10 in. (254 mm) 020 2.0 µm Double 226 O-ring P Pharmaceutical* J Ethylene (extrapolated value) with bayonet lock propylene 2 20 in. (508 mm) and fin end Omit General Use (Standard) 045 4.5 µm 3 30 in. (762 mm) * Pall pharmaceutical-grade filters H4 Silicone 060 6.0 µm 4 40 in. (1016 mm) are designed for use in conformance with CGMP in H13 Buna-N 100 10 µm Manufacturing, Processing, Packing or Holding of Drugs 200 20 µm (21CFR210) and CGMP for 400 40 µm finished Pharmaceuticals (21CFR211.72) including batch 700 70 µm release certificate and full traceability. 1000 100 µm (3) Absolute rating in this publication means the value in microns at which the modified OSU-F2 Test gives a Beta Value of ≥ 5000 (> 99.98% removal efficiency).
60 HDC® II Filter Cartridges High Dirt Retention All-polypropylene Prefilters
Pall HDC II all-polypropylene filter Quality and Bio-Safety cartridges incorporate proprietary HDC II Biological Tests tapered pore polypropylene depth media. The single open-ended (SOE) AB filter • Meets USP Biological Reactivity Test, cartridge style features a high-area pleated in vivo, for Class VI-121 °C Plastics modular element construction designed to Effluent Quality Tests* fit in sanitary filter housings. • Meets Cleanliness per USP Particulates HDC II filter cartridges are well-suited for a in Injectables broad range of fine particle and prefiltration • Non-Fiber-Releasing applications where purity, economy and Non-Pyrogenic per USP reliability are critical. Typical applications include biologicals, pharmaceuticals, • Bacterial Endotoxins (< 0.25 EU/mL) fermentation feeds and intermediates, and • Meets Total Organic Carbon and Water vaccines. Conductivity per USP Purified Water, pH per USP Sterile Purified Water Features and Benefits * Per lot sample soak or rinse-up flush aliquots. • All-polypropylene construction • Resin-free, melt-sealed • Constant density tapered pores • High-capacity for long-life • Fixed pore, non-shedding • Low protein binding • Low extractables • Broad chemical compatibilities • Autoclavable and steamable in situ • Manufactured for use in conformance with cGMP • ISO 9000 Certified Quality System • Pharmaceutical P optimized grades with Certificate of Test provided • FDA-listed materials per 21 CFR
Note: These filters are also available in Kleenpak Nova capsule format.
61 HDC II Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates(6) Medium Polypropylene Flow Rate (L/min) 0 10 20 30 40 50 60 70 Support and Drainage Layers Polypropylene 0.8 Core, Cage and End Caps Polypropylene J025 J045 J060 J100 50 P Grade Code 7 Adapters Polypropylene with encapsulated stainless steel ring 0.6 40 O-ring Silicone(1) (1) Other polymers available J200 30 0.4 Removal Ratings (Liquid)(2) J400 70 µm, 40 µm, 20 µm, 10 µm, 6 µm, 4.5 µm, 2.5 µm, 1.2 µm, 0.6 µm(3) 20
(2)
> 99.98% by modified OSU-F2 test. 0.6 to 20 µm in water, 40 and 70 µm in oil. (psid) Pressure Differential
0.2 (mbar) Pressure Differential (3) Extrapolated value. J500 10
Nominal Dimensions 0 0 Lengths 10 in. (254 mm), 20 in. (508 mm), 0 3 6 9 12 15 18 30 in. (762 mm), 40 in. (1016 mm) Flow Rate per 10 in. (254 mm) Filter (Gal/min) Diameter 70 mm (2.75 in.) Flow Rate (L/min) 0 10 20 30 40 50 60 Operating Conditions 8 AB1J006 Maximum Differential 5.5 bard (80 psid) to 50 °C (122 °F) 500 Pressure and Temperature(4) 4.1 bard (60 psid) to 80 °C (176 °F)
(4) Using compatible fluids. 6 400
Autoclaving and Steaming in situ(5) 300 Maximum Steam Temperature 140 °C (284 °F) 4 AB1J012 (5) Filters should be qualified in actual use. Contact Pall for recommended procedures. 200 Differential Pressure (psid) Pressure Differential
2 (mbar) Pressure Differential 100
0 0 2 4 6 8 10 12 14 16 Flow Rate per 10 in. (254 mm) Filter (Gal/min)
(6) Typical initial media ∆P 10 in. (254 mm) element; water at 20 °C (68 °F); viscosity 1 cP. For assistance in filter assembly sizing and housing selection, contact your local Pall representative.
Ordering Information
AB 7
Code Nominal Code Removal Nominal Filter Cartridge Code Filter Code Gasket Length Rating Area(7) Style Grade Option
1 10 in. J006 0.6 µm 0.63 m2 (6.7 ft2) Double 226 O-ring P Pharmaceutical* H4 Silicone (254 mm) with bayonet lock J012 1.2 µm 0.70 m2 (7.5 ft2) Omit General Use and fin end(8) Other materials available on 2 20 in. request. J025 2.5 µm 0.88 m2 (9.5 ft2) * Pall pharmaceutical-grade filters (508 mm) (8) Other adapter codes are designed for use in J045 4.5 µm 0.88 m2 (9.5 ft2) available. conformance with CGMP in 3 30 in. Manufacturing, Processing, (762 mm) J060 6 µm 0.42 m2 (4.5 ft2) Packing or Holding of Drugs
2 2 (21CFR210) and CGMP for 4 40 in. J100 10 µm 0.55 m (6.0 ft ) finished Pharmaceuticals (1016 mm) J200 20 µm 0.55 m2 (6.0 ft2) (21CFR211.72) including batch release certificate and full J400 40 µm 0.38 m2 (4.0 ft2) traceability. J700 70 µm 0.38 m2 (4.0 ft2) (7) Per 10 in. (254 mm) element.
62 Ultipor® GF Plus Filter Cartridges Positive Zeta Potential for Enhanced Efficiency
Pall Ultipor GF Plus filter cartridges are Features and Benefits made with positive Zeta modified glass • Positive Zeta enhances efficiency fiber media for enhanced efficiency. The single open-ended (SOE) AB style • High-area pleated medium cartridges feature a high-area pleated • High void-volume element construction designed to fit in sanitary style filter housings. A bio-safe low • Low differential pressure extractables binder resin covalently • High-capacity for long-life immobilizes the glass fibers and imparts a • Fixed pore structure strong positive charge in aqueous service. In addition to the high particulate removal • Melt-sealed construction efficiency and low pressure drops • Broad chemical compatibility consistent with glass fiber media, the added positive Zeta charge enables • Manufactured for use in conformance Ultipor GF Plus filters to effectively remove with cGMP submicron haze particles or endotoxins • IS0 9000 Certified Quality System from a wide variety of aqueous biological and pharmaceutical solutions.
Pharma Quality (P grade) for Highest Quality Requirements
Ultipor GF Plus filters are manufactured in accordance with ISO 9000 and GMP requirements. Each P grade filter is supplied with a certificate of test that confirms suitability for use in pharmaceutical applications. Samples are tested for effluent quality to meet the USP requirements regarding • Total Organic Carbon • pH shift • Endotoxins All components meet the specifications for biological tests listed in the USP for Class VI plastics at 121 °C. Each box contains a certificate which confirms the quality standards in manufacturing, the traceability of all components, and the above mentioned safety tests.
Note: These filters are also available in Kleenpak Nova capsule format.
63 Ultipor GF Plus Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates(5)
Medium Bonded glass fiber, Flow Rate (L/min) 0 5 10 15 20 positive Zeta potential 0.3 20 Support and Drainage Polyester
U010Z U030Z U6-40Z Core, Cage and End Caps Polypropylene U2-20Z
(1) O-Ring Silicone 15
(1) Other polymers available. 0.2
(2) Removal Ratings (Liquid) U100Z 10 1 µm, 2 µm, 3 µm, 6 µm, 10 µm, 20 µm, 40 µm (2) > 99.98% by mod. OSU-F2 Beta test. 0.1 U200Z
Differential Pressure (psid) Pressure Differential U400Z 5 Differential Pressure (mbar) Pressure Differential Endotoxin Removal Efficiency(3) U010Z (1 µm) 99.998% U2-20Z, U030Z 99.97% 0 0 0 1 2 3 4 5 6 (3) Efficiency in deionized water with up to 55 – 70 mg E. coli 055-B5 endotoxin per Flow Rate per 10 in. (254 mm) Filter (Gal/min) 10 in. (254 mm) modular element. (5) Typical initial clean media ∆P 10 in. (254 mm) element; water at 20°C (68°F); viscosity 1 cP. For assistance in filter assembly, sizing and housing Latex Bead Removal Efficiency(4) selection, contact your local Pall representative. U010Z (1 µm) ≥ 99.99% for 0.29 µm beads to 2.8 gm U2-20Z (20/2 µm) ≥ 99.99% for 0.8 µm beads to 22 gm Operating Conditions(6)
U030Z (3 µm) ≥ 99.99% for 1.1 µm beads to 22 gm Maximum Differential Pressure 5.5 bard (80 psid) to 50 °C (122 °F) (4) Efficiency in deionized water per 10 in. (254 mm) modular element. and Temperature 3.8 bard (55 psid) to 82 °C (180 °F)
(6) Using compatible fluids. Nominal Dimensions (7) Lengths 10 in. (254 mm), 20 in. (508 mm), Autoclaving and Steaming in situ 30 in. (762 mm), 40 in. (1016 mm) Maximum Temperature to 140 °C (284 °F) Diameter 70 mm (2.75 in.) (7) Contact Pall for recommended procedures.
Ordering Information
AB Z 7
Code Nominal Code Removal Filter Cartridge Code Filter Code Gasket Length Rating Area(8) Style(10) Grade Option
1 10 in. U010 1 µm 0.50 m2 (5.4 ft2) Double 226 O-ring P Code outside US H4 Silicone (254 mm) with bayonet lock U2-20(9) 2 µm 0.65 m2 (7.0 ft2) Omit Code in US only and fin end Other materials available on 2 20 in. request. U030 3 µm 0.56 m2 (6.0 ft2) Supplied with Certificate of Test and (508 mm) (10) Other adapter codes Full Traceability U6-40(9) 6 µm 0.56 m2 (6.0 ft2) available. 3 30 in. (762 mm) U100 10 µm 0.49 m2 (5.3 ft2)
2 2 4 40 in. U200 20 µm 0.40 m (4.4 ft ) (1016 mm) U400 40 µm 0.39 m2 (4.2 ft2)
(8) Nominal filter area per 10 in. (254 mm) filter element. (9) Multi-layered graded composites; 20 to 2 µm and 40 to 6 µm respectively. Z in part number designates positive zeta in aqueous service.
64 PreFlow™ Filter Cartridges Effective Protection for 0.2 µm and 0.1 µm Filters in Biological Fluids
Pall PreFlow filters have been expressly Quality and Bio-Safety designed to bring a significant Biological Tests improvement to prefiltration technology. The filter media utilized is based on our • Meets USP Biological Reactivity Test, expertise in manufacturing rugged in vivo, for Class VI-121° C Plastics resin-bonded glass fiber composites. Effluent Quality Tests* These sanitary-style filter cartridges are • Non-Pyrogenic per USP Bacterial manufactured with pleated high-area Endotoxins (< 0.25 EU/mL) construction for long service life. PreFlow filters are designed to reduce • Meets Total Organic Carbon and Water costs and are especially suited for Conductivity per USP Purified Water; biological prefiltration applications, pH per Sterile Purified Water including serum, vaccines, tissue culture * Per lot soak or rinse-up flush aliquots. media, and protein solutions. Features and Benefits • Unparalleled protection of final membrane filters • Fixed pore construction • No unloading or media migration • High-capacity for economy • High-strength design • A choice of particulate removal efficiencies • Autoclavable and steamable • Manufactured for use in conformance with cGMP • ISO 9000 Certified Quality System
Note: These filters are also available in Kleenpak Nova capsule format.
65 PreFlow Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rate(1) at 20 °C (68 °F) 3.0 200 Medium Resin-bonded glass fiber UUA UB Support and Drainage Polyester (nonwoven) 2.5 Core, Cage and End Caps Polypropylene
Adapters Polypropylene with encapsulated 2.0 reinforcing ring
O-ring Silicone elastomer 2.0 100 Removal Ratings (Liquid) 1.5 Grade UUA 0.2 µm (nominal)
Differential Pressure (psi) Pressure Differential 1.0 Grade UB 0.45 µm (nominal) (mbar) Pressure Differential
0.5 Nominal Filter Area per 10 in. (254 mm) Element Grade UUA 0.57 m2 (6.2 ft2) 0 0 0 10 20 30 40 50 60 70 Grade UB 0.65 m2 (7.0 ft2) Flow Rate (L/min) (1) Typical initial clean media ∆P 10 in. (254 mm) element; water at 20°C (68°F); viscosity 1 cP. For assistance in filter assembly, sizing and housing Nominal Dimensions selection, contact your local Pall representative. Lengths 10 in. (254 mm), 20 in. (508 mm), 30 in. (726 mm), 40 in. (1016 mm) Operating Conditions Diameter 70 mm (2.75 in.) Maximum Operating 5.0 bard (72 psid) to 25 °C (77 °F) Pressure and Temperature(2) Extractables (2) Using compatible fluids. Compatible fluids are fluids which do not soften, swell, attack Grade UUA Typically < 100 mg per 10 in. or adversely affect the filter or materials of construction (254 mm) element
Grade UB Typically < 150 mg per 10 in. Steam and Autoclaving Sterilization(3) (254 mm) element Recommended Exposure 3 x 1-hour @ 125 °C (257 °F) (3) Laboratory tests establish resistance. Filters should be qualified in actual use. Contact Pall for recommended procedures.
Ordering Information
AB 7
Code Nominal Length Code Removal Cartridge Code Filter Grade Code Gasket Rating Style(4) Option
1 10 in. (254 mm) UUA 0.2 µm Double 226 O-ring P Code outside US H4 Silicone with bayonet lock 2 20 in. (508 mm) UB 0.45 µm Omit Code in US only Other materials available and fin end on request 3 30 in. (762 mm) Supplied with Certificate of Test and (4) Alternate AB adapter codes Full Traceability 4 40 in. (1016 mm) available Note: Contact Pall for assistance with part numbers.
66 Marksman™ Elements with Nexis® A Series Filters High-capacity Wide Diameter Depth Filters
Marksman elements with Nexis A Series Features and Benefits Filters contain high-capacity melt-blown Biological Tests depth filter media in a 152 mm (6 in.) wide diameter cartridge with in-to-out flow. They All components meet the specifications for offer high flow and long filter life. The biological safety as per the USP Biological unique push-in adapters enable direct Reactivity test, in vivo, for Class VI-121 °C replacement of bag filters into most Plastics (gaskets excluded). commercially available bag housings to Purity give reduced filter changeouts, improved Cartridges are free of adhesives. filtrate quality and lower costs. Rinse-up The main features can be summarized as: Rinse-up to 18 Megohm-cm with a • New, large cartridge geometry minimum of throughput. ® • Proprietary CoLD fiber technology Sanitization • Gradient pore structure Cartridges may be sanitized in hot water, • Absolute retention-rated at 99.9% 77 – 79 °C (170 – 175 °F) for 20 minutes efficiency with retention ratings from 3 (minimum). to 70 µm • Directly fits into bag housings with no hardware changes • Inside-out flow traps contaminant inside the cartridge • Unique sealing device adjusts to fit cartridge into most bag filter housings • Quick, easy changeouts • Short length option to accommodate shorter baskets
67 Marksman Elements with Nexis A Series Filters Technical Specifications
Materials of Construction Liquid Flow Specifications
Filter Media Polypropylene with polyethylene winding Filter Grade Psid/gal/min Psid/gal/min Hardware Polypropylene (mbard/L/min) – (mbard/L/min) – Water @ 20 °C (68 °F) Fluid with 40 cP Gaskets Ethylene Propylene (EPDM) Viton(1) A, 1 cP viscosity Buna N Size 1 Size 2 Size 1 Size 2 Sealing Thermal Bond NXAM 10 (1) Registered trademark of DuPont Dow (non-FDA material). 0.047 0.021 1.17 0.35 (0.86) (0.38) (21.3) (6.4)
Nominal Dimensions NXAM 70 0.004 0.0014 0.1 0.04 (0.07) (0.03) (1.82) (0.73) Outside Flange Diameter 184 mm (7.25 in.) Note: For kPa, multiply mbard by 0.1 (equal to Size 1 and Size 2 Bags) Lengths Size 1 Bag, Size 2 Bag Filter Diameter 152 mm (6 in.) Surface Area Size 1: Up to 0.16 m2 (1.7 ft2) Size 2: Up to 0.31 m2 (3.3 ft2)
Flow Capacity Size Maximum Recommended(2) 1 114 L/min (30 gal/min) 95 L/min (25 gal/min) 2 227 L/min (60 gal/min) 189 L/min (50 gal/min) (2) For maximum filter life.
Performance Specifications
Maximum Forward To 2.9 bard (42 psid) @ 20 °C (68 °F) Differential Pressure To 1.8 bard (26 psid) @ 54 °C (130 °F) To 1.0 bard (15 psid) @ 79 °C (175 °F)
Recommended Changeout 2.4 bard (35 psid) Differential Pressure(3)
(3) Provided that the maximum differential pressure is not exceeded based on temperature limits defined above.
Note: Stainless steel flange required for temperatures in excess of 43 °C (110 °F).
Part Numbering and Ordering Information
NXAM
Code Length Code Filter Code Nominal Code Gasket Code End Code Flange and Grades Length Materials Configurations Gasket Styles
Blank Standard 33 µm 1 Size 1 Blank NF version PF Plastic self- A FSI side entry, Bag adjusting Flange Rosedale, S Short 55 µm N Buna N Strainrite, Krystal, 2 Size 2 SF Stainless steel 10 10 µm E EPDM Pall Bag (peroxide self-adjusting BGAF 20 20 µm cured) flange (required for temperatures 40 40 µm C FSI over the top, V Viton A > 43 °C [110 °F]) Hayward over 70 70 µm NF No flange (For the top use with reusable SS flange)
68 Marksman™ Elements with Poly-Fine® XLD Series Filters High-capacity Wide Diameter Pleated Polypropylene Filters
Marksman Elements with Poly-Fine XLD Features and Benefits Series Filters contain pleated polypropylene Biological Tests depth media in a wide diameter 152 mm (6 in.) cartridge with in-to-out flow. They All components meet the specifications for offer high flow and long filter life. The biological safety as per the USP Biological unique push-in adapters enable direct Reactivity test, in vivo, for Class VI-121 °C replacement of bag filters into most Plastics (gaskets excluded). commercially available bag housings to FDA-listed Materials give reduced filter changeouts, improved All materials are FDA-listed for food filtrate quality and lower costs. contact, except Viton* A gaskets. The main features can be summarized as: Purity • New, wide diameter cartridge geometry Cartridges are free of surfactants, resins, • Innovative combination of depth media binders, and adhesives. and pleated cartridge technologies Rinse-Up • High surface area, high-flow capacity Rinse-up to 18 Megohm-cm with a • Excellent retention of deformable minimum of throughput. contaminants Sanitization • Proprietary gel guard media Cartridges may be sanitized in hot water, • Absolute rated at > 99.9% efficiency 77 – 82 °C (170 – 180 °F), for 20 minutes with retention ratings from 1.5 to 90 µm (recommended). • Directly fits into bag housings with no * Viton is a registered trademark of DuPont Dow (non-FDA materials). hardware changes • In-to-out flow traps contaminant inside the element • Quick, easy changeouts • All-polypropylene construction • Short length option to accommodate shorter baskets
69 Marksman Elements with Poly-Fine XLD Series Filters Technical Specifications
Materials of Construction Liquid Retention Ratings (µm) (by ASTM F-795 Test)
Filter Media Polypropylene Cartridge 90% > 99.9% Hardware Polypropylene Designation Efficiency Efficiency Support Material Polypropylene XLDM 1.5 0.7 1.5 Gaskets Ethylene Propylene (EPDM), XLDM 3 13 Viton* A, Buna N XLDM 4.5 3.5 4.5 Sealing Thermal Bond XLDM 10 510 * Registered trademark of DuPont Dow (non-FDA material). XLDM 20 15 20
Nominal Dimensions XLDM 30 18 30 XLDM 40 20 40 Outside Flange Diameter 184 mm (7.25 in.) (equal to Size 1 and Size 2 Bags) XLDM 70 30 70 Outside Filter Diameter 152 mm (6 in.) XLDM 90 45 90 Lengths Size 1 Bag, Size 2 Bag Surface Area: Size 1: Liquid Flow Specifications 2 2 Up to 0.93 m (10 ft ) Psid per 3.8 L/min Psid per 3.8 L/min Size 2: (1 gal/min) – (1 gal/min) – Up to 2.04 m2 (22 ft2) Water @ Fluid with 20 °C (68 °F) 40 cPs viscosity Flow Capacity Filter Grade Size 1 Size 2 Size 1 Size 2 Size Maximum Recommended(1) 1.5 0.051 0.026 1.200 0.600 1 189 L/min (50 gal/min) 95 L/min (25 gal/min) 3 0.020 0.010 0.400 0.200
2 379 L/min (100 gal/min) 189 L/min (50 gal/min) 4.5 0.013 0.007 0.400 0.200 (1) For maximum filter life. 10 0.009 0.005 0.310 0.160
Performance Specifications 20 0.006 0.003 0.240 0.120
Filter Grades 1.5, 3, 4.5, 10, 20, 30, 40, 70, 90 µm 30 0.006 0.003 0.180 0.090 (> 99.9% Retention Rating 40 0.006 0.003 0.150 0.080 by ASTM F-795 Test) 70 0.006 0.003 0.026 0.013 Maximum Differential Polypropylene Cage: Pressure To 5.1 bard (75 psid) @ 20 °C (68 °F) 90 0.006 0.003 0.026 0.013 To 2.4 bard (35 psid) @ 54 °C (130 °F) Note: For mbar values, multiply psid by 69 Stainless Steel Cage: To 1.7 bard (25 psid) @ 80 °C (175 °F)
Recommended Change Out 2.4 bard (35 psid) Differential Pressure(2)
(2) Provided that the maximum differential pressure is not exceeded, based on temperature limits defined above. Note: Stainless steel flange required for temperatures in excess of 43 °C (110 °F). Part Numbering and Ordering Information
XLDM
Code Length Code Filter Code Nominal Code Support Code Gasket Grades Length Cage Materials
Blank Standard 1.5 1.5 µm 1 Size 1 Bag U Poly- Blank For NF version propylene S Short 33 µm 2 Size 2 Bag N Buna N S Stainless 4.5 4.5 µm E EPDM (peroxide Steel cured) 10 10 µm V Viton A 20 20 µm 40 40 µm 70 70 µm Code End Configurations Code Flange and Gasket Styles 90 90 µm PF Plastic self-adjusting flange A Rosedale, Strainrite, SF Stainless steel self-adjusting Krystal, Pall flange (required for B GAF, FSI side entry temperatures > 43 °C (110 °F) C FSI over the top, NF No flange (For use with Hayward over the top 70 reusable SS flange) Marksman™ Elements with Poly-Fine® II Series Filters High-capacity Wide Diameter Pleated Polypropylene Filters
Marksman Elements with Poly-Fine II Features and Benefits Series Filters contain pleated polypropylene Biological Tests media in a wide diameter 152 mm (6 in.) cartridge with in-to-out flow. They offer All components meet the specifications for high flow and long filter life. The unique biological safety as per the USP Biological push-in adapters enable direct Reactivity test, in vivo, for Class VI-121 °C replacement of bag filters into most Plastics (gaskets excluded). commercially available bag housings to FDA-listed Materials give reduced filter changeouts, improved All materials are FDA-listed for food and filtrate quality and lower costs. beverage contact, except Viton* A gaskets. • New, wide diameter cartridge geometry Purity • High-flow capacity Cartridges are free of surfactants, resins, • Proprietary media for highly consistent binders, and adhesives. filtration Rinse-Up • In-to-out flow traps contaminant inside Rinse-up to 18 Megohm-cm with a the cartridge minimum of throughput. • Directly fits into bag housings with no Sanitization changes Cartridges may be sanitized in hot water, 77 – 82 °C (170 – 180 °F) for 20 minutes Changes minimum.
• Unique sealing device adjusts to fit into * Viton is a registered trademark of DuPont Dow most bag filter housings (non-FDA materials). • High surface area for filter stream life • All-polypropylene construction • Wide chemical compatibility • Short length option to accommodate shorter baskets
71 Marksman Elements with Poly-Fine II Series Filters Technical Specifications
Materials of Construction Liquid Retention Ratings (µm) (by ASTM F-795 Test)
Filter Media Polypropylene Cartridge 90% > 99.9 % Hardware Polypropylene Designation Efficiency Efficiency Support Material Polypropylene PFTM 1 0.5 1.2 Gaskets Ethylene Propylene (EPDM), PFTM 3 1 2.5 Viton* A, Buna N PFTM 5 25 Sealing Thermal Bond PFTM 10 510 * Registered trademark of DuPont Dow (non-FDA material). PFTM 20 10 20
Nominal Dimensions PFTM 40 20 40 PFTM 70 30 70 Outside Flange Diameter 184 mm (7.25 in.) (equal to Size 1 and Size 2 Bags) PFTM 90 60 90 Outside Filter Diameter 152 mm (6 in.) PFTM 150 102 150 Lengths Size 1 Bag, Size 2 Bag Liquid Flow Specifications Surface Area Size 1: 2 2 Up to 2.32 m (25 ft ) Psid per 3.8 L/min Psid per 3.8 L/min Size 2: (1 gal/min) – (1 gal/min) – Water @ Fluid with Up to 5.57 m2 (60 ft2) 20 °C (68 °F) 40 cPs viscosity
Flow Capacity Filter Grade Size 1 Size 2 Size 1 Size 2 Size Maximum Recommended(1) 1 0.0470 0.0240 0.790 0.400 1 227 L/min (60 gal/min) 189 L/min (50 gal/min) 3 0.0130 0.0070 0.660 0.330 2 454 L/min (120 gal/min) 379 L/min (100 gal/min) 5 0.0070 0.0040 0.430 0.220 (1) For maximum filter life. 10 0.0040 0.0020 0.260 0.130 20 0.0020 0.0010 0.230 0.120 Performance Specifications 40 0.0010 0.0005 0.070 0.035 Filter Grades 1, 3, 5, 10, 20, 40, 70, 90, 150 µm 70 0.0008 0.0004 0.030 0.015 (> 99.9% Retention Rating by ASTM F-795 Test) 90 0.0008 0.0004 0.015 0.008
Maximum Forward 5.1 bard (75 psid) @ 20 °C (68 °F) 150 0.0006 0.0003 0.010 0.005 Differential Pressure 2.4 bard (35 psid) @ 54 °C (130 °F) Note: For mbar values, multiply psid by 69
Recommended Changeout 2.4 bard (35 psid) Differential Pressure(2)
(2) Provided that the maximum differential pressure is not exceeded based on temperature limits defined above. Note: Stainless steel flange required for temperatures in excess of 43 °C (110 °F)
Part Numbering and Ordering Information
PTFM
Code Length Code Filter Code Nominal Code Gasket Code End Configurations Grades Length Materials
Blank Standard 11 µm 1 Size 1 Bag Blank For NF PF Plastic self-adjusting flange version S Short 33 µm 2 Size 2 Bag SF Stainless steel self-adjusting N Buna N flange (required for 55 µm E EPDM temperatures > 43 °C (110 °F) 10 10 µm (peroxide NF No flange (For use with 20 20 µm cured) reusable SS flange) 40 40 µm V Viton A
70 70 µm Code Flange and Gasket Styles 90 90 µm 150 150 µm A Rosedale, Strainrite, Krystal, Pall B GAF, FSI side entry C FSI over the top, Hayward over the top 72 Emflon® FM Filter Cartridges Designed for Cost-effective Solvent Polishing
Pall Emflon FM filters are designed for Compatibility cost-effective clarification of solvents used This filter was specifically designed for in the manufacture of antibiotics and other improved compatibility and optimized active pharmaceutical ingredients (APIs). economics in polishing a broad array of These pharmaceutical grade filters contain challenging solvents, including: a proprietary PTFE membrane and are compatible with a broad range of • Acetic Acid, Glacial chemicals. • Acetone They can also be used to ensure the • Acetonitrile cleanliness of high-purity solvents. Applications include removal of carbon or • Dimethylacetamide (DMAC) catalyst fines, and these filters are often • Dimethylformamide (DMF) used downstream of bulk solids removal • Dimethylsulfoxide (DMSO) systems. • Ethanol Features and Benefits • Ethyl Acetate • Broad chemical compatibility • Hexane • Very high flow-rates • Hydrochloric mAcid 38% • Low extractables • Isopropyl Alcohol (IPA) • Tolerant of high operating temperatures • Methanol • No cage option further reduces • Methylene Chloride potential extractables • Methyl Isobutyl Ketone (MIBK)
High Quality Standards • Methyl Tertiary Butyl Ether (MTBE) • n Heptane • Each filter supplied with a certificate of test • Pyridine • Lot number traceable • Sodium Hydroxide, 50% • Meets USP Biological Reactivity Test, • Tetrahydrofuran (THF) in vivo, for Class VI-121 °C Plastics • Toluene • FDA-listed materials per 21 CFR • Water Compatibility at 20 °C • Xylene
This partial list is provided for general guidance only.
Note: Because so many factors (such as elevated temperatures) can affect the chemical resistance of a given product, you should pre-test under your own operating conditions observing applicable safety practices such as those given in the Material Safety Data Sheet for each chemical. Pall Corporation can provide specific compatibility guidance, testing and data upon request.
73 Emflon FM Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rate(2)
Membrane Polytetrafluoroethylene (PTFE) 1000 14 Support and Drainage Layers Polypropylene Core, Cage and End caps Polypropylene
O-ring (single open-end [SOE] Fluorinated Ethylene Propylene 750 11 AB-style) (FEP) – encapsulated silicone Other materials available
Gasket (for double open-end Polytetrafluoroethylene (PTFE) industrial-style) Other materials available 500 7 AB1FM7PH15
Operating Parameters Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential 250 3.5 Maximum Differential 4.1 bard (60 psid) @ 23 °C (74 °F) Pressure (∆P) 2.1 bard (31 psid) @ 60 °C (140 °F)
Maximum Operating 95 °C (203 °F) at 1.0 bar (15 psi) Temperature 0 0 0 100 200 300 400 500 600 Extractables(1) Flow Rate (L/min) (2) Typical initial clean media ∆P 10 in. (254 mm) element; water at 20 °C Water < 5 mg (68 °F); viscosity 1 cP. For assistance in filter assembly, sizing and housing selection, contact your local Pall representative. 95% Ethanol 20 mg Acetone 90 mg Ethyl acetate 240 mg Removal Ratings Methylene chloride 575 mg Particle Size Beta Ratio Efficiency Toluene 515 mg 0.6 µm 100 99.0% (1) These typical extractables are based on tests of sampled 10 in. (254 mm) modules 1 µm 1000 99.9% with cages at 20 °C (68 °F). 2 µm 5000 99.98%
Nominal Filter Area per 10 in. (254 mm) Element 3 µm > 5000 > 99.98% 4 µm > 5000 > 99.98% 0.58 m2 (6.2 ft2) > 5 µm > 5000 > 99.98%
Ordering Information (Part number denotes one filter, minimum order quantity 12)
AB Style: A FM P
MCY 1000 Style: MCY100 FM P
Code Cage Option Code Nominal Length Code Cartridge Style Code Seal Option B Polypropylene cage 1 10 in. (254 mm) 47 Single 226 O-ring with bayonet H15(3) FEP/Silicone lock and fin end (4) BA No cage 2 20 in. (508 mm) (Fits in all code 7 housings) H2 PTFE 3 30 in. (762 mm) (3) AB style only. 7 Double 226 O-ring with bayonet (4) MCY1000 style only. 4 40 in. (1016 mm) lock and fin end
74 Ultipor® N66 Particulate and Bioreduction Filter Cartridges Ideal Prefilters for Ultipor N66 Sterilizing Filters
Pall Ultipor N66 particulate/bioreduction Quality and Bio-Safety filter cartridges are specifically engineered Biological Tests for fine filtration, prefiltration and bioburden reduction of a wide range of • Meets USP Biological Reactivity test, pharmaceutical and biological liquids. They in vivo, for Class VI-121 °C Plastics incorporate versatile Ultipor N66 pure Effluent Quality Tests (AB Style)* Nylon 6,6 membranes which are high-area • Meets Cleanliness per USP Particulates pleated into single open-ended (SOE) AB in Injectables style cartridges to fit in sanitary filter housings, and provide reliable, economical • Non-Fiber-Releasing and efficient particulate and bioburden • Non-Pyrogenic per USP removal. • Meets Total Organic Carbon and Water Conductivity per USP Purified Water, Features and Benefits pH per USP Sterile Purified Water • Intrinsically water wettable * Per lot sample soak or rinse-up flush aliquots. • Fixed pores, non-shedding • Resin and surfactant-free • Low filter extractables • High-area for long-life • Broad solvent compatibility • High protein recovery from most protein solutions • Repeatedly steamable in situ • Manufactured for use in conformance with cGMP • ISO 9000 Certified Quality System • Pharmaceutical P optimized • Certificate of Test provided • Double open-ended (DOE) available • FDA-listed materials per 21 CFR
Note: These filters are also available in Kleenpak Nova capsule format.
75 Ultipor N66 Particulate and Bioreduction Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates(4)
Membrane Nylon 6,6 Flow Rate (L/min) 0 5 10 15 2 Support, Drainage and Polyester NX NL NA End Caps 120 Core and Cage Polypropylene O-rings Silicone(1) (1) Other polymers available. 90 NB
Microbial Removal Ratings 1 60 NK 0.65 µm particulate rated NK NB 0.45 µm microbial-rated 4 – 6
(Typical Serratia marcescens TR > 10 ) (psid) Pressure Differential 30 (mbar) Pressure Differential NX, NL 0.45 µm microbial-rated (Lot samples retain > 107/cm2 Serratia marcescens) 0 0 NA 0.2 µm microbial-rated (Typical 0 1 2 3 4 4 – 6 Brevundimonas diminuta TR > 10 ) Flow Rate per 10 in. (254 mm) Filter (Gal/min) (4) Typical initial clean media ∆P 10 in. (254 mm) element; water at 20 °C (68 °F); viscosity 1 cP. For assistance in filter assembly sizing and Nominal Dimensions housing selection, contact your local Pall representative. Lengths 10 in. (254 mm), 20 in. (508 mm), 30 in. (762 mm), 40 in. (1016 mm) Autoclave and Steaming in situ(5) Diameter 70 mm (2.75 in.) Cumulative Steam Exposure 16 hours (1-hour cycles) at 121 °C Configuration (AB Code 7)(2) 4 hours (1-hour cycles) at Double 226 O-ring adapter 140 °C Fin end with bayonet lock. (5) Laboratory tests to establish multi-cycle resistance. Filters should be qualified in actual (2) Alternate adapter codes available. use. Contact Pall for recommended procedures.
Operating Conditions(3) Aqueous Extractables (NVR) per 10 in. (254 mm) Element(6)
Maximum Differential 5.5 bard (80 psid) to 50 °C (122 °F) Typically < 15 – 20 mg Pressure and Temperature 4.1 bard (60 psid) to 80 °C (176 °F) (6) In water at 20 – 25 °C (68 – 77 °F) after autoclaving. 2.1 bard (30 psid) to 125 °C (257 °F)
(3) Using compatible liquids.
Ordering Information
AB
Code Nominal Code Removal Nominal Forward Flow(8) Code Filter Code Gasket Length Rating Filter Area(7) mL/min at Grade Option (mbar) psi
1 10 in. NA7 0.2 µm 0.84 m2 (9.0 ft2) 85 at 2260 (30) P Pharmaceutical* H4 Silicone (254 mm) NX7 0.45 µm 0.46 m2 (5.0 ft2) 10 at 1720 (25) Omit General Use Other materials available on request. 2 20 in. NL7 0.45 µm 0.79 m2 (8.5 ft2) 15 at 1720 (25) * Pall pharmaceutical-grade filters (508 mm) are designed for use in NB7 0.45 µm 0.84 m2 (9.0 ft2) 85 at 1240 (18) conformance with CGMP in 3 30 in. Manufacturing, Processing, 2 2 (762 mm) NB7W 0.45 µm 0.86 m (9.2 ft ) 50 at 1240 (18) Packing or Holding of Drugs
2 2 (21CFR210) and CGMP for 4 40 in. NK7W 0.65 µm 0.84 m (9.0 ft ) 25 at 1100 (16) finished Pharmaceuticals (1016 mm) (7) Per 10 in. (254 mm) cartridge. (21CFR211.72) including batch (8) Forward Flow allowable limit for one 10 in. (254 mm) cartridge at given test release certificate and full pressure, water wet, air test gas. Please contact Pall for method details and test traceability. parameters.
76 Mini Kleenpak™ Sterilizing-grade Capsule Filters Ideal for Scale-up and Scale-down
Pall’s Mini Kleenpak sterilizing capsule High Quality Standards filters are compact pharmaceutical-grade • Validated with Brevundimonas diminuta capsule filters featuring very low hold-up (ATCC 19146) at a challenge level of volumes. They are expressly designed to 107 cfu/cm2 simplify scale-up and scale-down activities and eliminate the need for multiple filter • Fluorodyne II DJL validated with evaluations. Acholeplasma laidlawii (ATCC 28206) Typical titer reduction 108 cfu Supor PES and Fluorodyne II PVDF membranes are particularly suited for the • 100% integrity-tested during sterile filtration of a wide range of fluids, manufacturing including buffers, biological fluids, tissue • Manufactured for use under GMP culture media and ophthalmic products. • Pharmaceutical P optimized The low protein and preservative binding of the membranes ensures maximum • Each Filter supplied with a Certificate of transmission of active ingredients. Test • Comprehensive Validation Guide Features and Benefits available
• Smallest pleated membrane capsule filters available • Scalable to cartridges • High flow-rates and throughputs • Low protein and preservative binding • Low extractables • Gamma-irradiatable and autoclavable versions available as well as gamma-irradiated pre-sterilized versions for maximum flexibility • Minimal hold-up volume — typically < 6 mL • Fully integrity testable
77 Mini Kleenpak Sterilizing-grade Capsule Filters Technical Specifications
Materials of Construction Nominal Dimensions
Membrane Fluorodyne II: Overall Length 104 mm (4.1 in.) Hydrophilic polyvinylidenedifluoride Housing Length 49 mm (1.9 in.) (PVDF) Housing Diameter 50 mm (2.0 in.) Supor: Polyethersulfone (PES) Inlet and Outlet 27 mm (1.1 in.) Hose Barb Length Support and Drainage Polypropylene Capsule and Vent Polypropylene Extractables
(1) Filling Bell Polycarbonate < 1.0 mg in water at 20 °C (68 °F) (for non-irradiated filter capsule) Sealing Technology Thermal bonding without adhesives < 5.0 mg in water at 20 °C (68 °F) (for gamma-irradiated filter capsule) (1) Filling bell is removable for in-line use Nominal Filtration Area Operating Parameters(2) Fluorodyne II 0.02 m2 (0.21 ft2) Maximum Operating 4.1 bard @ 38 °C (60 psid @ 100 °F) Supor 0.022 m2 (0.23 ft2) Temperature and Pressure 2.1 bard @ 80 °C (30 psid @ 176 °F)
(2) In compatible fluids which do not soften, swell, or adversely affect the filter or its Typical Flow Rates(4) materials of construction. Supor EKV 350 mL/min/100 mbar (241 mL/min/psi) Sterilization(3) Supor EBV 322 mL/min/100 mbar (222 mL/min/psi)
Autoclave 3 x 30-minute cycles @ 140 °C (284 °F) Fluorodyne II DFL 225 mL/min/100 mbar (155 mL/min/psi) Fluorodyne II DJL Gamma-irradiation Maximum Dosage: 50 kGy 100 mL/min/100 mbar (69 mL/min/psi) (4) For fluids at 1 cP viscosity @ 20 °C (68 °F). For other viscosities, divide flow rate by (3) Warning: Pre-sterilized units should not be re-irradiated or autoclaved. This product viscosity in centipoise. For assistance, contact your local Pall representative. may not be sterilized by in situ steaming.
Ordering Information
KA02 P
Code Filter Type Code Inlet and Outlet Code Additional Options
(5) 1 1 EKV 0.2 µm rated Supor 2 6 – 13 mm ( ⁄4 – ⁄2 in.) G Non-sterilized version stepped hose barb EBV 0.2 µm rated Supor S Pre-sterilized version
(5) DFL 0.2 µm rated Bell on outlet is removable for in-line use. Fluorodyne II
DJL 0.1 µm rated Fluorodyne II
78 Kleenpak™ Capsules with Supor® EKV Membrane Assemblies Optimized for Filtration of Buffers and Biological Fluids
Pall Kleenpak capsule filters with Supor Every filter is: polyethersulfone membrane are validated, • Integrity-tested during manufacture with 0.2 µm sterilizing-grade filters with built-in results that are continually validated prefiltration to give longer filter life and against bacterial challenge lower filtration costs. The capsules are suitable for sterile filtration of a wide range • Identified by a lot number and unique of fluids including buffers, biological fluids, serial number for complete traceability tissue culture media, ophthalmic products of manufacturing history and for user’s and many others. They can be used for traceability system scale-up or scale-down studies. The low • Supplied with a Certificate of Test protein and preservative binding of the confirming the quality standards and Supor polyethersulfone membranes also quality control tests performed by Pall ensures maximum transmission of active • Manufactured under a Quality ingredients. Management System certified to ISO 9000 Features and Benefits
• Hydrophilic polyethersulfone membrane Quality and Bio-Safety for low adsorption and wide chemical Biological Tests compatibility • Meets USP Biological Reactivity test, • Easy to wet in vivo, for Class VI-121 °C Plastics • Built-in MachV prefilter layer with an Effluent Quality Tests* asymmetric membrane for long-life and • Meets Cleanliness per USP Particulates low filtration costs in Injectables • Low hold-up volumes (< 1 mL) • Non-Fiber-Releasing • Disposable format to avoid cleaning • Non-Pyrogenic per USP and cleaning validation Endotoxins (< 0.25 EU/mL) • Available pre-sterilized by • Meets Total Organic Carbon and Water gamma-irradiation or sterilizable by Conductivity per USP Purified Water, autoclaving or gamma-irradiation pH per USP Sterile Purified Water
High Quality Standards * Per lot sample soak or rinse-up flush aliquots.
Validated with Brevundimonas diminuta (ATCC 19146) at a challenge level of A comprehensive validation guide is 107 cfu/cm2. available upon request. Every production batch is routinely sampled for bacterial challenge.
79 Kleenpak Capsules with Supor EKV Membrane Assemblies Technical Specifications
Materials of Construction Nominal Dimensions
Membrane Hydrophilic Polyethersulfone (PES) Maximum Diameter of Bowl 109 mm (4.2 in.) Support and Drainage Layers Polypropylene (including Valves) End Cap, Core and Cage Polypropylene Length including 174 mm (6.8 in.) Sanitary Connector
Nominal Surface Area Length including 210 mm (8.3 in.) Hose Barb Connector 0.15 m2 (1.5 ft2) Typical Liquid Flow Rates Operating Conditions(1) Water @ 20 °C (68 °F) 3.2 L/min @ 100 mbar (1.5 psi) Maximum Differential 5.2 bard (75 psid) @ 40 °C (104 °F) Pressure and Temperature Typical Extractables (1) Using compatible fluids, which do not soften, swell or adversely affect the filter or its materials of construction < 10 mg in water at 20 °C (68 °F)
Sterilization
Autoclave 5 x 60-minute cycles @ 125 °C (257 °F)
Gamma-irradiation Maximum Dosage: 50 kGy
Warning: Kleenpak filters should not be sterilized in situ by passing steam under pressure.
Ordering Information
KA EKV
Code Size and Area Code Filter Grade Code Inlet and Outlet Code Sterilization Connections Grade
1 3 See above P Pharmaceutical* 1 38 mm (1 ⁄2 in.) G Non-sterilized version dimensions table sanitary flange * Pall pharmaceutical-grade filters are S Pre-sterilized version designed for use in conformance with 9 6 14 mm ( ⁄16 in.) CGMP in Manufacturing, Processing, single-barb hose barb Packing or Holding of Drugs (21CFR210)
and CGMP for finished Pharmaceuticals 1 16 38 mm (1 ⁄2 in.) (21CFR211.72) including batch release certificate and full traceability. sanitary flange inlet and 9 14 mm ( ⁄16 in.) single-barb hose barb outlet
80 Supor® EKV Sterilizing-grade Filter Cartridges Optimized for Filtration of Biological Fluids
Supor EKV polyethersulfone membrane Every filter is: cartridges are validated, 0.2 µm • Integrity-tested during manufacture sterilizing-grade filters with a unique combination of Pall Ultipleat filter • Identified by a lot number and a unique construction and optimized built-in serial number for complete traceability prefiltration to give longer filter life and of manufacturing history and for user’s lower filtration costs. The filters are suitable traceability system for sterile filtration of a wide range of fluids • Supplied with a certificate of test including buffers, biological fluids, tissue confirming the quality standards and culture media, ophthalmic products and quality control tests performed by Pall many others. The low protein and • Manufactured under a Quality preservative binding of the Supor Management System certified to polyethersulfone membrane also ensures ISO 9000 maximum transmission of active ingredients. Quality and Bio-Safety Features and Benefits Biological Tests
• Hydrophilic polyethersulfone membrane • Meets USP Biological Reactivity Test, for low adsorption and wide chemical in vivo, in accordance with USP Class compatibility Vl-121 °C Plastics • Easy to wet for a reliable integrity test Effluent Quality Tests* • Meets Cleanliness per USP Particulate • Patented Ultipleat filter construction for Matter in Injections high-area and good flow rates • Non-Fiber-Releasing • Built-in, MachV asymmetric prefilter layer for long-life and low filtration costs • Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) • High-strength construction tolerates up to 1 bard (14.5 psid) differential • Meets Total Organic Carbon and Water pressure during steam-in-place Conductivity per USP Purified Water, sterilization pH per USP Sterile Purified Water
• High-strength design allows for multiple * Per lot sample soak or rinse-up flush aliquots. autoclave cycles and extended use A comprehensive validation guide is High Quality Standards available upon request.
Forward Flow value correlated with sterile removal of Brevundimonas diminuta (ATCC 19146) at 107/cm2. A comprehensive validation guide is available upon request.
Note: These filters are also available in Kleenpak Nova capsule format.
81 Supor EKV Sterilizing-grade Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rate(3) Membranes Hydrophilic Polyethersulfone (PES) 300 4 Support and Drainage Polypropylene 250 Core and End Caps Polypropylene
Cage Polypropylene with TiO2 (white-colored) 3 200 Internal Adapter Support Ring Stainless steel AB1 O-rings Silicone elastomer 150 2 Sealing Technology Thermal bonding without adhesives
100 AB2 (1) Operating Parameters (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential 1 AB3 Maximum Differential 5.5 bar (80 psi) @ 40 °C (104 °F) 50 Pressure (Forward Direction) 3.0 bar (43.5 psi) @ 80 °C (176 °F)
Maximum Differential 2.0 bar (29 psi) @ 40 °C (104 °F) 0 0 Pressure (Reverse Direction) 0 5 10 15 20 25 30 Flow Rate (L/min) (1) In compatible fluids which do not soften, swell, or adversely affect the filter or its materials of construction. (3) Typical initial clean media ∆P 10 in. (254 mm) element; water at 20 °C (68 °F); viscosity 1 cP. For assistance in filter assembly sizing and housing selection, contact your local Pall representative. Sterilization(2) Typical Extractables(4) per 10 in. (254 mm) Element Autoclave 30 x 60 minutes cycles at 125 °C (261 °F) - slow exhaust < 25 mg in water at 20 °C (68 °F) after 4 hours extraction In Situ Steam 30 x 60 minutes cycles at (4) Tested on elements without pre-flushing 125 °C (261 °F) 5 x 60 minutes cycles at 142 °C (287 °F) Integrity Test Values for 10 in. (254 mm) Filter at 20 °C (68 °F)
(2) Contact Pall for confirmation of extended sterilization conditions ≤ Maximum differential pressure during steam sterilization is 1 bar (14.5 psi) in Maximum Allowable Water wet 17 mL/min forward direction for the 10 in. and 300 mbar (4.5 psi) for the 5 in. cartridges. Filter Forward Flow (Air Test Gas) at 2760 mbar (40 psi) must be fully wetted for sterilization. Contact Pall for multi-element integrity test values and recommended test procedures.
Nominal Dimensions Typical Effective Filtration Area(5) Lengths 10 in. (254 mm), 20 in. (508 mm), 0.6 m2 (6.5 ft2) per 10 in. (254 mm) module 30 in. (762 mm), 40 in. (1016 mm) 0.26 m2 (2.8 ft2) per 5 in. (125 mm) module Diameter 70 mm (2.75 in.) (5) 5 in. (125 mm) filters are standard pleated.
Ordering Information
AB
Code Nominal Code Removal Code Cartridge Style Code Filter Grade Code O-ring Length Rating Material
05 5 in. (125 mm) EKV 0.2 µm 2 Double 226 O-ring P Pharmaceutical* H4 Silicone elastomer sterilizing-grade bayonet lock, 1 10 in. (254 mm) * Pall pharmaceutical-grade filters are Other materials available without fin designed for use in conformance on request. 2 20 in. (508 mm) with CGMP in Manufacturing, 7 Double 226 O-ring Processing, Packing or Holding of 3 30 in. (762 mm) bayonet lock Drugs (21CFR210) and CGMP for 4 40 in. (1016 mm) and fin end finished Pharmaceuticals (21CFR211.72) including batch release certificate and full traceability.
82 Supor® EBV Sterilizing-grade Filter Cartridges Polyethersulfone (PES) Membrane Filter provides Broad pH Compatibility
Supor EBV polyethersulfone membrane Every filter is: cartridges are validated, 0.2 µm • Integrity-tested during manufacture and sterilizing-grade filters with a unique results are continually validated against combination of Pall Ultipleat filter bacterial challenge construction and built-in prefiltration to give longer filter life and lower filtration costs. • Identified by a lot number and a unique The filters are suitable for sterile filtration of serial number for complete traceability a wide range of fluids including buffers, of manufacturing history and for user’s biological fluids, tissue culture media, traceability system ophthalmic products and many others. • Supplied with a Certificate of Test The low protein and preservative binding of confirming the quality standards and the Supor polyethersulfone membranes quality control tests performed by Pall also ensures maximum transmission of • Manufactured under a Quality active ingredients. Management System certified to ISO 9000 Features and Benefits
• Hydrophilic polyethersulfone membrane Quality and Bio-Safety for low adsorption and wide chemical Biological Tests compatibility • Meets USP Biological Reactivity Test, • Patented Ultipleat filter construction for in vivo, in accordance with USP Class high-area and good flow rates Vl-121 °C Plastics • Built-in prefilter layer for long-life and Effluent Quality Tests* low filtration costs • Meets Cleanliness per USP Particulate • High-strength construction tolerates up Matter in Injections to 1 bard (14.5 psid) differential • Non-Fiber-Releasing pressure during steam-in-place sterilization • Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) • Low hold-up volumes • Meets Total Organic Carbon and Water • High-strength design allows for multiple Conductivity per USP Purified Water, autoclave cycles and extended use pH per USP Sterile Purified Water
High Quality Standards * Per lot sample soak or rinse-up flush aliquots.
Validated with Brevundimonas diminuta A comprehensive validation guide is (ATCC 19146) at 107/cm2. Every production available for inclusion with user’s validation batch is routinely sampled for bacterial documentation. challenge.
Note: These filters are also available in Kleenpak Nova capsule format.
83 Supor EBV Sterilizing-grade Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rate(3) Membranes Hydrophilic Polyethersulfone (PES) 300 4 Support and Drainage Polypropylene Core, Cage and End caps Polypropylene 250 Internal Adapter Support Ring Stainless steel 3 200 O-rings Silicone elastomer Sealing Technology Thermal bonding without adhesives 150 2 Operating Parameters(1) 100 Maximum Operating Pressure 5.5 bar (80 psi) @ 50 °C (122 °F) Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential (Forward Direction) 3.0 bar (43.5 psi) @ 80 °C (176 °F) 1 50 Maximum Operating Pressure 2.0 bar (29 psi) @ 50 °C (122 °F) (Reverse Direction) 0 0 (1) In compatible fluids which do not soften, swell, or adversely affect the filter or its 0 5 10 15 20 25 30 materials of construction. Flow Rate (L/min) (3) Typical initial clean media ∆P 10 in. (254 mm) element; water at 20 °C Sterilization(2) (68 °F); viscosity 1 cP. For assistance in filter assembly sizing and housing selection, contact your local Pall representative. Autoclave 5 x 60-minutes cycles at 125 °C Typical Extractables(4) per 10 in. (254 mm) Module In situ Steam 5 x 30-minutes cycles at 142 °C (287 °F) (2) Maximum differential pressure during steam-sterilization is 1 bar (14.5 psi). < 25 mg in water at 20 °C (68 °F) after 4 hours extraction (4) Tested on elements without pre-flushing, Nominal Dimensions Nominal Filtration Area per 10 in. (254 mm) Module Lengths 10 in. (254 mm), 20 in. (508 mm), 30 in. (762 mm), 40 in. (1016 mm) 0.66 m2 (7.1 ft2) Diameter 70 mm (2.75 in.) Integrity Test Values for 10 in. (254 mm) Filter at 20 °C (68 °F)
Maximum Allowable Water wet ≤ 23 mL/min Forward Flow (Air Test Gas) at 2760 mbar (40 psi)
Contact Pall for multi-element integrity test values and recommended test procedures.
Ordering Information
AB 7
Code Nominal Code Removal Cartridge Code Filter Grade Code O-ring Length Rating Style Material
1 10 in. (254 mm) EBV 0.2 µm Double 226 O-ring P Pharmaceutical* H4 Silicone elastomer sterilizing-grade bayonet lock 2 20 in. (508 mm) * Pall pharmaceutical-grade filters are Other materials available and fin end designed for use in conformance with on request. 3 30 in. (762 mm) CGMP in Manufacturing, Processing, Packing or Holding of Drugs (21CFR210) 4 40 in. (1016 mm) and CGMP for finished Pharmaceuticals (21CFR211.72) including batch release certificate and full traceability.
84 Kleenpak™ Capsules with Fluorodyne® II Membrane Assemblies Ideal for Sterile Filtration of Biopharmaceutical Fluids
Pall Kleenpak capsule filters with Quality and Bio-Safety hydrophilic PVDF Fluorodyne II membrane Biological Tests are rugged, self-contained sanitary filters Integrity designed for small-batch sterile filtration of most pharmaceutical solutions. They are • Every filter tested during manufacture. especially suitable for recovery of dilute Test correlated to microbial retention preservatives, proteins, or other critical Biological Tests components, or may be used where higher • Meets USP Biological Reactivity Test, throughput/higher flow rate PVDF in vivo, for Class VI-121 °C Plastics membranes are preferred. A wide range of sizes is available. Effluent Quality Tests* • Meets Cleanliness per USP Particulates Features and Benefits in Injectables
• Higher flow rates and throughputs • Non-Fiber-Releasing • Lowest binding membrane • Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) • 100% integrity and pressure tested • Meets Total Organic Carbon and Water • Lowest filter extractables Conductivity per USP Purified Water; • Compatible with caustic solutions pH per Sterile Purified Water • Sanitary vent and drain valves with Autoclave Resistance non-twist hose barbs • Lot samples multi-cycle autoclave • Low hold-up volumes (< 1 mL) challenged
• Repeatedly autoclavable * Per lot sample soak or rinse-up flush aliquots. • Manufactured for use in conformance with cGMP • ISO 9000 Certified Quality System • Pharmaceutical P optimized • Certificate of Test provided
85 Kleenpak Capsules with Fluorodyne II Membrane Assemblies Technical Specifications
Materials of Construction Typical Liquid Flow Rates for DFL Media(5) Flow Rate (L/min) Membrane Polyvinylidenedifluoride (PVDF), 0 1 2 3 4 5 6 7 8 Double-layer 8 KA1 KA2 Support, Drainage, Core, Polypropylene 500 Cage, End Caps and Shell KA3 Vent and Drain Valve O-ring Ethylene Propylene (EPDM) 6 400 Microbial Removal Ratings DBL(1) 0.45 µm, microbial-rated 300 4 DFL(2) 0.2 µm, sterilizing-grade
(3) 200 DJL 0.1 µm, mycoplasma-rated KA4 sterilizing-grade Differential Pressure (psid) Pressure Differential
2 (mbar) Pressure Differential (1) Typical Lactobacillus brevis titer reduction is > 106. 100 (2) Assembly lot samples retain > 107 CFU/cm2 of Brevundimonas diminuta per mod. ASTM F838-83 and FDA guidelines. (3) DJL grade filters have high removal efficiency for diminutive organisms (e.g., typical titer reductions for Acholeplasma laidlawii is > 108. 0 0 0 0.5 1 1.5 2 Flow Rate (Gal/min) Nominal Filter Areas (5) Typical initial clean media ∆P per 10 in. (254 mm) element; water at 20 °C (68 °F); viscosity 1 cP. For assistance in filter assembly sizing and Size Code KA1 KA2 KA3 KA4 housing selection, contact your local Pall representative. Effective 0.04 m2 0.08 m2 0.15 m2 0.34 m2 Aqueous Extractables (NVR)(6) Filter Area (0.4 ft2) (0.8 ft2) (1.5 ft2) (3.4 ft2) KA1 and KA2 1 mg
Operating Conditions(4) KA3 2 mg KA4 4 mg Maximum Pressure and 5.2 barg (75 psig) to 40 °C (104 °F) Temperature (6) Water at 20 – 25 °C (68 °F – 77 °F) after autoclaving.
Maximum Differential 4.1 bard (60 psid) at 40 °C (104 °F) Pressure Steam Autoclaving (Non-G and Non-S Grades)(7)
(4) Using compatible liquids. Maximum 3.5 barg (50 psig) in air/gas service. Cumulative Autoclave Time 30 hours at 125 °C (257 °F) 10 hours at 140 °C (284 °F)
Sterilization (7) Laboratory tests (1-hour cycles) establish multi-cycle.
Gamma-irradiation Maximum Dosage (G grade): 50 kGy Warning: Kleenpak filters must not be steam-sterilized in situ by passing steam through under pressure.
Nominal Dimensions Size Code KA1 KA2 KA3 KA4 Maximum Diameter of Bowl (including Valves) 94 mm (3.7 in) 94 mm (3.7 in) 109 mm (4.2 in.) 109 mm (4.2 in.) Length (including Sanitary Connection [Code 1]) 117 mm (4.6 in.) 158 mm (6.2 in.) 174 mm (6.8 in.) 286 mm (11.2 in.) Length (including Hose Barb Connection [Code 6]) 158 mm (6.2 in.) 199 mm (7.8 in.) 210 mm (8.2 in.) 325 mm(12.7 in.)
Ordering Information
KA P
Code Size and Area Code Removal Ratings Code Inlet and Outlet Connections Code Options
1 1 DBL 0.45 µm 1 38 mm (1 ⁄2 in.) sanitary flange Blank Autoclave service
9 2 See above DFL 0.2 µm sterilizing-grade 6 14 mm ( ⁄16 in.) hose barb G Unsterilized, dimensions Gamma-irradiatable 3 table DJL 0.1 µm sterilizing-grade S Pre-sterilized 4
Notes: Contact Pall for specific part number availability. DBL available in sizes KA1, KA2, KA3, and KA4 with Inlet and outlet 1 and 6 in autoclavable version. DBL is also available in KA2 size, G and S grade with 1 and 6 in inlet and outlet options. DFL available in sizes KA1 and KA2 with inlet and outlet options 1 and 2 for G, S and autoclavable versions. DFL available in sizes KA3 and KA4 with inlet and outlet options 1 and 6 for G, S and autoclavable versions. DJL available in sizes KA1, KA2, KA3, and KA4 with Inlet and outlet 1 and 6 in G and S versions.
86 Fluorodyne® II Hydrophilic PVDF Filter Cartridges Ideal for Large-volume Sterile Filtration
Pall Fluorodyne II filter cartridges feature a • Built-in PVDF prefiltration layers unique hydrophilic modified • Repeatedly steamable in situ polyvinylidenedifluoride (PVDF) membrane with ultra-low binding properties, broad • 100% integrity-tested chemical and temperature resistance, and • Individually serialized higher flows than competitive PVDF or • Manufactured for use in conformance other membrane cartridges. High-area with cGMP pleated into single open-ended (SOE) AB sanitary style cartridges, Fluorodyne II • ISO 9000 Certified Quality System filters are available 0.45 µm rated for Pharmaceutical P optimized stabilization, filtration of viscous fluids and • Certificate of Test provided membrane prefiltration, 0.2 µm rated for sterilization, and 0.1 µm rated for • Validation Guide available sterilization and mycoplasma removal. They are recommended for Quality and Bio-Safety pharmaceuticals including ophthalmics and Biological Tests other dilute preservative solutions, Integrity biologicals including dilute protein • Every filter tested during manufacture. solutions, cold and hot WFI, chemicals, Test correlated to microbial retention aggressive solvents and sanitizing agents. Biological Tests Features and Benefits • Meets USP Biological Reactivity Test, in vivo, for Class VI-121 °C Plastics • Higher flows per cartridge for smaller assemblies or reduced change-outs Effluent Quality Tests* • DJL provides 0.1 µm retention with • Meets Cleanliness per USP Particulates 0.2 µm flow in Injectables • Lower extractables • Non-Fiber-Releasing • Stable in 90 °C (184 °F) WFI • Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) • High protein recoveries • Meets Total Organic Carbon and Water • Rapid preservative recoveries Conductivity per USP Purified Water; • Inherently water wettable pH per Sterile Purified Water • Compatible with organic solvents, acids Steam Resistance (1) and chemicals . • Lot samples multi-cycle autoclave • Resin and surfactant-free challenged
• Melt-sealed, non shedding * Per lot sample soak or rinse-up flush aliquots.
(1) Except ketones and amides.
Note: These filters are also available in Kleenpak Nova capsule format.
87 Fluorodyne II Hydrophilic PVDF Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates(4) Flow Rate (L/min) Membrane Hydrophilic Polyvinylidenedifluoride 0 5 10 15 (PVDF) 4 DJ Support, Drainage, Core, Polypropylene 250 Cage and End Caps DF Code 7 Adapter Polypropylene with encapsulated 3 stainless steel reinforcing ring for 100 steaming in situ
(1) O-rings Silicone 150 2 (1) Other polymers available. DB 100 Microbial Removal Ratings(2) Differential Pressure (psid) Pressure Differential
1 (mbar) Pressure Differential DBL 0.45 µm microbial-rated 6 50 (Typical Serratia marcescens TR > 10 )
DFL 0.2 µm sterilizing-grade 0 0 DJL 0.1 µm mycoplasma-rated, 0 1 2 3 4 sterilizing-grade (Typical Flow Rate (Gal/min) 8 Acholeplasma laidlawii TR > 10 ) (4) Typical initial clean media ∆P per 10 in. (254 mm) element; water at 20 °C (68 °F); viscosity 1 cP. For assistance in filter assembly sizing and (2) Lot samples of sterilizing-grades retain >107 cfu/cm2 of Brevundimonas diminuta per mod. ASTM F838-83 and FDA guidelines. housing selection, contact your local Pall representative.
Aqueous Extractables (NVR)(6) per 10 in. (254 mm) Element Configuration (AB Code 2 and 7)(3) Typically < 5 mg Double 226 O-ring adapter (6) In water at 20 – 25 °C (68 °F – 77 °F) after autoclaving. Fin end with bayonet lock (3) Alternate adapter codes available. Autoclavable or Steamable in situ(7)
Cumulative Steaming 30 hours (1-hour cycles) at Nominal Dimensions Exposure 125 °C (257 °F) Lengths 5 in. (127 mm), 10 in. (254 mm), 10 hours (1-hour cycles) at 20 in. (508 mm), 30 in. (762 mm) 140 °C (284 °F) Hot Water Sanitization Diameter 70 mm (2.75 in.) To 90 °C (194 °F) at 0.5 bard (7 psid)
(7) Nominal Filter Area per 10 in. (254 mm) Element Forward Flow DBL 13 mL/min at 1240 mbar (18 psi) Size Code DBL DFL DJL DFL 12 mL/min at 2760 mbar (40 psi) Effective 0.55 m2 0.51 m2 0.51 m2 Filter Area (6 ft2) (5.5 ft2) (5.5 ft2) DJL 29 mL/min at 4475 mbar (65 psi) (7) Forward Flow allowable limit per 10 in. (254 mm) cartridge at given test pressure, water wet, air test gas. Operating Conditions(5)
Maximum Differential 5.3 bard (77 psid) to 50 °C (122 °F) Pressure and Temperature 3.4 bard (49 psid) to 90 °C (194 °F)
(5) Using compatible fluids.
Part Numbering and Ordering Information
AB
Code Nominal Code Removal Code Cartridge Code Filter Grade Code Gasket Length Rating Style Option
05 5 in. DBL 0.45 µm 7 Double 226 O-ring with P Pharmaceutical* H4 Silicone (127 mm) bayonet lock and fin end DFL 0.2 µm Omit General Use Other materials available on request. (8) 1 10 in. DJL 0.1 µm 2 Double 226 O-ring with * Pall pharmaceutical-grade (254 mm) bayonet lock and flat end filters are designed for use in conformance with CGMP 2 20 in. (8) AB05 size only. in Manufacturing, (508 mm) Processing, Packing or 3 30 in. Holding of Drugs (762 mm) (21CFR210) and CGMP for finished Pharmaceuticals (21CFR211.72) including batch release certificate and 88 full traceability. Kleenpak™ Capsules with Ultipor® N66 Membrane Assemblies 0.1 µm and 0.2 µm Capsules with Excellent Wettability
Pall Kleenpak sterilizing-grade capsule Quality and Bio-Safety filters with intrinsically hydrophilic Ultipor Biological Tests N66 membrane are self-contained sanitary Integrity filters designed for convenient small-batch sterile filtration of most pharmaceutical • Every filter tested during manufacture. solutions. Rugged, compact design Test correlated to microbial retention ensures reliability. Biological Tests • Meets USP Biological Reactivity test, Features and Benefits in vivo, for Class VI-121 °C Plastics • 100% integrity and pressure tested Effluent Quality Tests* • 0.2 micron NFP sterilizing-grade • Meets Cleanliness per USP Particulates • 0.1 micron NTP sterilizing-grade for in Injectables bacteria and mycoplasma removal • Non-Fiber-Releasing • Low filter extractables • Non-Pyrogenic per USP Bacterial • Excellent solvent compatibility Endotoxins (< 0.25 EU/mL) • Sanitary vent and drain valves with • Meets Total Organic Carbon and Water non-twist hose barbs Conductivity per USP Purified Water; pH per Sterile Purified Water • Low hold-up volumes (< 1 mL) Autoclave Resistance • Gamma-irradiatable, autoclavable, and • Lot samples multi-cycle autoclave pre-sterilized versions available for challenged maximum flexibility • Autoclavable versions can be * Per lot sample or rinse-flush aliquots. repeatedly autoclaved • Manufactured for use in conformance with cGMP • ISO 9000 certified Quality system • Pharmaceutical P optimized • Certificate of test provided
89 Kleenpak Capsules with Ultipor N66 Membrane Assemblies Technical Specifications
Materials of Construction Typical Liquid Flow Rates(4) Membrane Nylon 6,6 Flow Rate (L/min) 0 1 2 3 4 Support and Drainage Polyester 20 Core and Cage Autoclavable Version: 1250 Polypropylene KA1NFP
G and S Grades: 15 Polyester 1100 End Caps and Shell Polyester Valve O-rings Ethylene Propylene (EPDM ) 750 10 KA2NFP Microbial Removal Ratings(1) 600
NF 0.2 µm, sterilizing-grade, Brevundimonas diminuta. (psid) Pressure Differential
5 (mbar) Pressure Differential NT 0.1 µm, sterilizing-grade,(2) Brevundimonas diminuta. KA3NFP 250 (1) Assembly lot samples retain > 107 cfu/cm2 of Brevundimonas diminuta per modified ASTM F838-83 and FDA guidelines. (2) Also retains > 107/cm2 Acholeplasma laidlawii mycoplasma. 0 0 0 0.25 0.5 0.75 1 Nominal Filter Areas Flow Rate (Gal/min) (4) Typical initial clean ∆P; water at 20 °C (68 °F), 1 cP. Values shown are for Size Code KA1 KA2 KA3 KA4 1 38 mm (1 ⁄2 in.) sanitary flange connections. Values with other connections Effective Filter Area are available on request. For assistance, contact your local Pall representative. NF: 0.05 m2 0.1 m2 0.2 m2 0.5 m2 (0.5 ft2) (1 ft2) (2 ft2) (5 ft2) Aqueous Extractables (NVR)(5) NT: 0.045 m2 0.08 m2 0.2 m2 0.4 m2 (0.4 ft2) (0.8 ft2) (2 ft2) (4 ft2) Size Code KA1 KA2 KA3 KA4 Non-irradiated 7 mg 10 mg 12 mg 20 mg Nominal Dimensions Pre-sterilized 6 mg 12 mg 22 mg N/A Size Code KA1 KA2 KA3 KA4 (5) In water at 20 – 25 °C (68 – 77 °F) after autoclaving. Maximum Diameter 94 mm 94 mm 109 mm 109 mm N/A = Filter not available. of Bowl (including Valves) (3.7 in.) (3.7 in.) (4.2 in.) (4.2 in.) Steam Autoclaving(6) Length (including Sanitary 117 mm 158 mm 174 mm 286 mm Connection* [Codes 1 (4.6 in.) (6.2 in.) (6.8 in.) (11.2 in.) Cumulative Autoclave Time 16 hours at 125 °C (257 °F) and 8]) 4 hours at 140 °C (284 °F)
Length (including Stepped 158 mm 199 mm (6) Laboratory tests (1-hour cycles) establish multi-cycle resistance. Filters should be Hose Barb Connection (6.2 in.) (7.8 in.) qualified in actual use. Contact Pall for recommended procedures. [Code 2]) Warning: Kleenpak filters must be steamed in situ by passing steam through under Length (including Hose 158 mm 199 mm 210 mm 325 mm pressure. Barb Connection [Code 6]) (6.2 in.) (7.8 in.) (8.2 in.) (12.7 in.) Sterilization * Sanitary connection is Tri-Clamp compatible. Tri-Clamp is a trademark of Alfa Laval, Inc. Gamma-irradiation Maximum Dosage (G grade): 50 kGy Operating Conditions(3)
Maximum Pressure and 5.2 barg (75 psig) to 40 °C (104 °F) Note: Contact Pall for specific part number availability. Temperature S and G grades available in KA1 and KA2 with inlet and outlet options 1 and 2; KA3 with with inlet and outlet options 1 and 6. Maximum Operating 4.1 bard (60 psid) at 40 °C (104 °F) Autoclavable grades available in KA1 and KA2 with inlet and outlet options 1 and 2; KA3 and KA4 with with inlet and outlet options 1 and 6. Differential Pressure
(3) Using compatible liquids. Recommended maximum 3.5 barg (50 psig) in continuous air and gas service. KA*NT filters may be forward flow tested at 5171 mbar (75 psig) at ambient temperature.
Ordering Information
KA P
Code Size and Area Code Removal Ratings Code Inlet and Outlet Connections Code Options
1 1 NF 0.2 µm sterilizing-grade 11 – 1 ⁄2 in. sanitary flange Blank Autoclave service
See above 1 1 2 NT 0.1 µm sterilizing-grade 26 – 13 mm ( ⁄4 – ⁄2 in.) stepped G Unsterilized, dimensions hose barb Gamma-irradiatable 3 table 9 4 6 14 mm ( ⁄16 in.) hose barb S Pre-sterilized
1 3 8 ⁄2 – ⁄4 in. fractional sanitary flange 90 Option P8 available in KA2, autoclave service. Sealkleen™ Membrane Filter Cartridges Sterilizing and Microbial Grade Junior Style Filters
Pall Sealkleen membrane filter cartridges Quality and Bio-Safety are made with either Ultipor N66, Biological Tests Posidyne, or Fluorodyne II membranes Biological Tests with a choice of retention ratings in two high-area sizes. The unique Sealkleen • Meets USP Biological Reactivity Test, assembly features a patented sealing in vivo, for Class VI-121 °C Plastics design which eliminates the possibility of Effluent Quality Tests* fluid bypass from upstream to down- • Meets Cleanliness per USP Particulates stream. in Injectables Sealkleen membrane cartridges are ideal • Non-Fiber-Releasing for most small volume or low flow liquid prefiltration and sterilizing applications. • Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) Features and Benefits • Meets Total Organic Carbon and Water Conductivity per USP Purified Water; • Nylon 6,6 or PVDF membranes pH per Sterile Purified Water • Intrinsically water wettable * Per lot sample soak or rinse-up flush aliquots. • Range of surface properties • Low extractables • Broad chemical compatibilities • Sterilizing-grades per FDA Guidelines • Bioreduction and prefiltration grades • Manufactured for use in conformance with cGMP • IS0 9000 Certified Quality System • Pharmaceutical P optimized with Certificate of Test provided
91 Sealkleen Membrane Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates for SLK7002 Styles(4) Media (Double-layer except where noted) Flow Rate (L/min) 0 2 4 6 8 Ultipor N66 Nylon 6,6 4 NX NNXZ N66 Posidyne Nylon 6,6 with positive zeta potential 240 Fluorodyne II Hydrophilic polyvinylidenedifluoride (PVDF) NL Support, Drainage and End Caps 3 Ultipor N66 Polyester 160 N66 Posidyne Polyester 2 Fluorodyne II Polypropylene NB
Core and Cage Polypropylene 80 1 Differential Pressure (psid) Pressure Differential Differential Pressure (mbar) Pressure Differential Microbial Removal Ratings
Ultipor N66 0.45 µm and 0.2 µm microbial(1) 0 0 0.2 µm and 0.1 µm sterilizing(2) 0 0.5 1 1.5 2 Flow Rate (Gal/min) N66 Posidyne 0.45 µm microbial-rated Flow Rate (L/min) 0.2 µm and 0.1 µm sterilizing(2) 0 2 4 6 8 Fluorodyne II 6 0.45 µm microbial-rated NT, NTZ NR NF, NFZ 400 (2) 0.2 µm sterilizing DFL 5 1) 4 – 6 0.45 µm. NB: Typical Serratia marcescens TR 10 0.2 µm 4 – 6 NA: Typical Brevundimonas diminuta TR 10 300 NX, NL, NNXZ: Lot samples retain > 107 cfu/cm2 of Serratia marcescens 4 (2) Lot samples retain > 107 cfu/cm2 (0.45 µm) of Brevundimonas diminuta (0.2 µm and 0.1 µm) per mod. ASTM F838-83 and FDA guidelines. 0.1 µm NT also retains > 107 3 NA cfu/cm2 Acholeplasma laidlawii mycoplasma. 200
2 Configuration 100 Differential Pressure (psid) Pressure Differential Single open-ended cartridge 1 (mbar) Pressure Differential Integral flange on downstream End Cap 0 0 0 0.5 1 1.5 2 Nominal Dimensions Flow Rate (Gal/min) (4) Typical initial clean ∆P, air at 20°C (68°F). Values shown are for 38 mm Lengths SLK7001 SLK7002 1 (1 ⁄2 in.) sanitary flange connections. Values with other connections are 2.5 in. (64 mm) 5.2 in. (127 mm) available on request. For assistance in filter sizing, contact your local Pall representative. Diameter 57 mm (2.5 in.) 57 mm (2.5 in.) Autoclaving and Steaming in situ(5) (3) Operating Conditions Cumulative Exposure Time Ultipor N66, N66 Posidyne: Maximum Pressure Differential 5.5 bard (80 psid) at 50 °C (122 °F) 16 hours at 125 °C (257 °F) and Temperature 4.1 bard (60 psid) at 80 °C (176 °F) 4 hours at 140 °C (284 °F)
(3) Using compatible fluids. Fluorodyne II: 30 hours at 125 °C (257 °F) 10 hours at 140 °C (284 °F)
(5) Laboratory tests (1-hour cycles) establish multi-cycle resistance. Filters should be qualified in actual use. Contact Pall for recommended procedures.
Ordering Information
SLK
Code Nominal Code Removal Nominal Filter Code Filter Forward Flow integrity Test Parameters Length Rating Area(6) Grade 7001 2.5 in. NNXZ 1.2/0.45 µm 0.17 m2 (1.8 ft2) P Pharmaceutical* Part Number FF Test FF Limit Pressure* Value (64 min) NB 0.45 µm 0.30 m2 (3.2 ft2) Omit General Use mbar (psi) (mL/min) 7002 5.2 in. NL 0.45 µm 0.29 m2 (3.1 ft2) * Pall pharmaceutical-grade filters SLK7001NRP 2760 (40) 2.3 (133 mm) NX 0.45 µm 0.17 m2 (1.8 ft2) are designed for use in SLK7001NFP 2760 (40) 3.5 Note: NA 0.45 µm 0.30 m2 (3.2 ft2) conformance with CGMP in Manufacturing, Processing, SLK7001DFLP 2760 (40) 2 Ultipor N66 = NB, NL, NF 0.2 µm 0.27 m2 (2.9 ft2) NX, NA, Packing or Holding of Drugs SLK7001NTP 5175 (75) 3.6 NR 0.2 µm 0.17 m2 (1.8 ft2) (21CFR210) and CGMP for NF, NR, SLK7002NRP 2760 (40) 4.6 NT NFZ 0.2 µm 0.27 m2 (2.9 ft2) finished Pharmaceuticals (21CFR211.72) including batch SLK7002NFP 2760 (40) 7 Posidyne = NNXZ, NT 0.1 µm 0.25 m2 (2.7 ft2) NFZ, release certificate and full SLK7002DFLP 2760 (40) 4 NTZ 0.1 µm 0.25 m2 (2.7 ft2) traceability. NTZ SLK7002NTP 5175 (75) 5.9 Fluorodyne II = DFL DFL 0.2 µm 0.19 m2 (2.0 ft2) * Please contact Pall for method details and test 92 parameters. Ultipor® N66 Sterilizing-grade Filter Cartridges Sterilizing-grade Filters for Large-scale Applications
Pall Ultipor N66 sterilizing-grade filter Quality and Bio-Safety* cartridges feature high-strength pure Nylon Integrity 6,6 membranes for higher sterility assurance. In wide use for almost 20 • Every filter integrity tested during years, these filters have a proven record of manufacture. Test correlated to performance in the production of sterile microbial retention biologicals and pharmaceuticals. High-area Biological Tests pleated into single open-ended (SOE) AB • Meets USP Biological Reactivity Test, sanitary style cartridges, Ultipor N66 in vivo, for Class VI-121 °C Plastics sterilizing-grade filter cartridges are available with ratings from 0.45 µm for • Meets Cleanliness per USP Particulates LVPs, reagents and viscous fluids, in Injectables 0.2 µm for sterile products and • Non-Fiber-Releasing per 21 CFR intermediates, 0.1 µm for sterilization and mycoplasma removal from biologicals, to • Non-Pyrogenic per USP Bacterial 0.04 µm for sterilization and virus reduction Endotoxins (< 0.25 EU/mL) from biologicals. • Meets Total Organic Carbon and Water Conductivity per USP Purified Water, Features and Benefits pH per USP Sterile Purified Water
• Intrinsically water wettable Steam Resistance • Lot samples multi-cycle autoclave • Fixed pores, non-shedding challenged • Resin and surfactant-free * Per lot samples soak or rinse-up flush aliquots. • Broad solvent compatibility • Low filter extractables • High-area for long-life • High protein recovery from most protein solutions • Repeatedly steamable in situ
Note: These filters are also available in Kleenpak Nova capsule format.
93 Ultipor N66 Sterilizing-grade Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates(4)
Membranes Nylon 6,6, double-layer Flow Rate (L/min) 0 2 4 6 8 2 Supports, Drainage and Polyester ND, NT NR NF End Caps 120 Core and Cage Polypropylene O-ring Silicone(1) (1) Other polymers available. 90
(2) Microbial Removal Ratings 1 60 NR, NF 0.2 µm sterilizing-grade NT 0.1 µm mycoplasma sterilizing-grade Differential Pressure (psid) Pressure Differential
ND 0.04 µm rated, sterilizing-grade 30 (mbar) Pressure Differential 5 (Typical MuLV, HIV (retrovirus) TR 10 )
(2) Lot samples retain > 107 cfu/cm2 of an appropriate challenge organism per mod. ASTM F838-83 and FDA guidelines; NR, NF, NT, ND: Brevundimonas diminuta; 0 7 2 0 NT also retains > 10 cfu/cm Acholeplasma laidlawii mycoplasma. 0 0.5 1 1.5 2 Flow Rate (Gal/min) Nominal Dimensions (4) Typical initial clean media ∆P 10 in. (254 mm) element; water at 20 °C (68°F); viscosity 1 cP. For assistance in filter assembly sizing and housing Lengths 10 in. (254 mm), 20 in. (508 mm), selection, contact your local Pall distributor. 30 in. (762 mm), 40 in. (1016 mm) (5) Diameter 2.75 in. (70 mm) Configuration (AB Code 7) Double 226 O-ring adapter Operating Conditions(3) Fin end with bayonet lock Maximum Differential 5.5 bard (80 psid) to 50 °C (122 °F) (5) Alternate adapter codes available. Pressure and Temperature 4.1 bard (60 psid) to 80 °C (176 °F) 2.1 bard (30 psid) to 125 °C (257 °F) Autoclavable or steamable in situ(6)
(3) Using compatible fluids. Cumulative Steam Exposure 16 hours (1-hour cycles) at 121 °C (250 °F)
4 hours (1-hour cycles) at 140 °C (284 °F)
(6) Laboratory tests to establish multi-cycle resistance. Filters should be qualified in actual use. Contact Pall for recommended procedures.
Aqueous Extractables (NVR) per 10 in. (254 mm) Element Typically 15 – 25 mg
Ordering Information
AB
Code Nominal Code(7) Removal Nominal Forward Flow(9) Code Filter Code Gasket Length Rating Filter mL/min at Grade Option Area(8) mbar (psi)
05 5 in. NF 0.2 µm 0.79 m2 (8.5 ft2) 12 at 2760 (40) P Pharmaceutical* H4 Silicone (127 mm) NR 0.2 µm 0.46 m2 (5.0 ft2) 8 at 2760 (40) Omit General Use Other materials available 1 10 in. on request. NT 0.1 µm 0.79 m2 (8.5 ft2) 14 at 5175 (75) * Pall pharmaceutical-grade filters (254 mm) are designed for use in ND 0.4 µm 0.81 m2 (8.7 ft2) 25 at 3440 (50) conformance with CGMP in 2 20 in. Manufacturing, Processing, (7) Code 7 adapter is standard (except 05 length is Code 2 with flat cap). Packing or Holding of Drugs (508 mm) (8) Per 10 in. (254 mm) element. (21CFR210) and CGMP for (9) 3 30 in. Forward Flow allowable limit for one 10 in. (254 mm) cartridge at given test finished Pharmaceuticals (762 mm) pressure, water wet, air test gas. Please contact Pall for method details and test (21CFR211.72) including batch parameters. release certificate and full 4 40 in. traceability. (1016 mm)
94 Kleenpak™ Capsules with Posidyne® Membrane Assemblies Positive Zeta Potential for Enhanced Retention of Fine Particles
Pall Kleenpak capsule filters with Quality and Bio-Safety intrinsically hydrophilic positive zeta Biological Tests potential Posidyne membrane are rugged, self-contained sanitary filters designed for • Meets USP Biological Reactivity Test, small-batch sterile filtration of aqueous in vivo, for Class VI-121 °C Plastics pharmaceutical solutions. With a net Effluent Quality Tests* positive charge in most aqueous solutions • Meets Cleanliness per USP Particulates from pH 3 to 10, Kleenpak Capsules with in Injectables Posidyne Membrane Assemblies can be effective in removing contaminants such as • Non-Fiber-Releasing cell debris and endotoxin smaller than the • Non-Pyrogenic per USP Bacterial filter rating. Endotoxins (< 0.25 EU/mL) • Meets Total Organic Carbon and Water Features and Benefits Conductivity per USP Purified Water; • Positive Zeta potential for enhanced pH per Sterile Purified Water efficiency in aqueous solutions Autoclave Resistance: • Double-layer sterilizing membranes for • Lot samples multi-cycle autoclave high reliability challenged
• 100% integrity and pressure-tested * Per lot sample soak or rinse-up flush aliquots. • High protein recovery from serum and most protein solutions • 0.2 µm NF grade for sterilization • 0.1 µm NT grade for diminutive bacteria and mycoplasma removal • Low filter extractables • Sanitary vent and drain valves with non-twist hose barbs • Low hold-up volumes (< 1 mL) • Repeatedly autoclavable • Manufactured for use in conformance with cGMP • IS0 9000 Certified Quality System • Pharmaceutical P optimized • Certificate of Test provided
95 Kleenpak Capsules with Posidyne Membrane Assemblies Technical Specifications
Materials of Construction Typical Liquid Flow Rates(4) Flow Rate (L/min) Membrane Nylon 6,6, positively-charged 0 1 2 3 4 16 Support and Drainage Polyester KA1NTZ KA2NTZ KA1NFZ KA3NTZ 1000 Core and Cage Autoclavable Version: 14 Polypropylene G and S Grades: 12 Polyester 750 10 End Caps and Shell Polyester Vent and Drain Valve O-ring Ethylene Propylene (EPDM ) 8 KA2NFZ 500 6 Microbial Removal Ratings Differential Pressure (psid) Pressure Differential 4 (mbar) Pressure Differential NFZ 0.2 µm, sterilizing-grade(1) 250 KA3NFZ (2) NTZ 0.1 µm, sterilizing-grade 2 (1) Assembly lot samples retain > 107 cfu/cm2 of Brevundimonas diminuta per mod. ASTM F838-83 and FDA guidelines. 0 0 (2) Also retains > 107 cfu/cm2 Acholeplasma laidlawii mycoplasma. 0 0.25 0.5 0.75 1 Flow Rate (Gal/min) Nominal Filter Areas (4) Typical initial clean ∆P, water at 20 °C (68 °F), 1 cP. KA4NFZP ∆P flow is 37 mbard/L per min (2.1 psid/gpm). Pressure drops at other flows are 1 Size Code KA1 KA2 KA3 KA4 directly proportional to flow. Values shown for 38 mm (1 ⁄2 in.) sanitary flange connections. Values with other connections are available on request. For Effective 0.05 m2 0.1 m2 0.2 m2 0.5 m2 assistance, contact your local Pall representative. Filter Area (0.53 ft2) (1 ft2) (2.1 ft2) (5.3 ft2)
Nominal Dimensions Aqueous Extractables (NVR)(5) (Non G and S Grades)
Size Code KA1 KA2 KA3 KA4 Size Code KA1 KA2 KA3 KA4 Maximum Diameter 94 mm 94 mm 109 mm 109 mm 6 mg 12 mg 20 mg 40 mg of Bowl (including Valves) (3.7 in.) (3.7 in.) (4.2 in.) (4.2 in.) (5) Water at 20 – 25 °C (68 – 77 °F) after autoclaving. Length (including Sanitary 117 mm 158 mm 174 mm 286 mm Connection [Code 1]) (4.6 in.) (6.2 in.) (6.8 in.) (11.2 in.) Steam Autoclaving(6) (Non G and S Grades) Length (including Stepped 158 mm 199 mm –– Hose Barb Connection (6.2 in.) (7.8 in.) –– Cumulative Autoclave Time 16 hours at 125 °C (257 °F) [Code 2]) 4 hours at 140 °C (284 °F) Length (including Hose ––210 mm 325 mm Barb Connection [Code 6]) ––(8.2 in.) (12.7 in.) (6) Laboratory tests (1-hour cycles) establish multi-cycle. Warning: Kleenpak filters must not be steam-sterilized in situ by passing steam through under pressure.
Operating Conditions(3) Sterilization Maximum Pressure and 5.2 barg (75 psig) to 40 °C (104 °F) Temperature Gamma-irradiation Maximum Dosage (G Grade): 35 kGy
Maximum Differential 4.1 bard (60 psid) at 40 °C (104 °F) Pressure
(3) Using compatible liquids. Maximum 3.5 barg (50 psig) in air/gas service.
Ordering Information
KA P
Code Size and Area Code Removal Ratings Code Inlet and Outlet Connections Code Options
1 1 NFZ 0.2 µm sterilizing-grade 1 38 mm (1 ⁄2 in.) sanitary flange Blank Autoclave service
1 1 2 See above NTZ 0.1 µm sterilizing-grade 26 – 13 mm ( ⁄4 – ⁄2 in.) G Unsterilized, dimensions hose barb Gamma-irradiatable 3 table 9 6 14 mm ( ⁄16 in.) hose barb S Pre-sterilized 4
Note: Contact Pall for specific part number availability. S and G grades are available in KA2 with inlet and outlet option 1; KA3 with with inlet and outlet option 6. Autoclavable grades available in KA1 and KA2 with inlet and outlet options 1 and 2; KA3 and KA4 with with inlet and outlet options 1 and 6.
96 Posidyne® Filter Cartridges Positive Zeta Potential for Enhanced Retention of Fine Particles in Large-scale Processes
Pall Posidyne filter cartridges incorporate Quality and Bio-Safety a patented covalent charge-modified Biological Tests Nylon 6,6 membrane which exhibits a net positively-charged Zeta potential in • Meets USP Biological Reactivity Test, aqueous solutions. This positive Zeta in vivo, for Class VI-121 °C Plastics potential provides enhanced retention of Effluent Quality Tests* fine particles smaller than the membrane’s • Meets Cleanliness per USP Particulates rating, such as endotoxins in water, in a in Injectables direct flow mode without the higher pressure drop of finer filters. High-area • Non-Fiber-Releasing pleated into single open-ended (SOE) AB • Non-Pyrogenic per USP Bacterial sanitary-style cartridges, N66 Posidyne Endotoxins (< 0.25 EU/mL) filters are available in particulate and bioreduction grades and in • Meets Total Organic Carbon and Water sterilizing-grades. Conductivity per USP Purified Water, pH per USP Sterile Purified Water
Features and Benefits * Per lot sample soak or rinse-up flush aliquots.
• Inherently water wettable • Resin and surfactant-free • Positive Zeta potential • Enhanced retention of particles smaller than filter rating • Removes endotoxins from water • High protein recovery from sera and most protein solutions • Low filter extractables • 100% integrity-tested • Individually serialized • Manufactured for use in conformance with cGMP • ISO 9000 Certified Quality System • Pharmaceutical P optimized grades with Certificate of Test provided • Validation Guide available
Note: These filters are also available in Kleenpak Nova capsule format.
97 Posidyne Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rate(5)
Membrane Nylon 6,6, covalently-modified positive Flow Rate (L/min) Zeta 0 5 10 15 4 250 Supports, Drainage and Polyester NIZ End Caps NBAZ, NFZ Core and Cage Polypropylene NDZ, NTZ 3 200 O-ring Silicone(1) NNXZ (1) Other polymers available. 150 Microbial Removal Ratings(2) 2 NAZ, NLZ
NNXZ 0.45 µm microbial-rated 100 9 (Typical Serratia marcesens TR > 10 ) Differential Pressure (psid) Pressure Differential
1 (mbar) Pressure Differential NXZ, NLZ 0.45 µm microbial-rated 50 NBAZ, NAZ 0.2 µm microbial-rated (Typical 4 – 6 Brevundimonas diminuta TR > 10 ) 0 0 NIZ 0.1 µm microbial-rated (Typical 0 1 2 3 4 9 Brevundimonas diminuta TR > 10 ) Flow Rate (Gal/min) NFZ 0.2 µm sterilizing-grade (5) Typical initial clean media ∆P 10 in. (254 mm) element; water at 20°C (68°F); viscosity 1 cP. For assistance in filter assembly sizing and housing NTZ 0.1 µm sterilizing-grade selection, contact your local Pall representative.
NDZ 0.04 µm rated, sterilizing-grade (6) 5 Autoclavable or steamable in situ (Typical MuLV, HIV (retrovirus) TR 10 ) Cumulative Steam Exposure 16 hours (1-hour cycles) at (2) Lot samples retain > 107 cfu/cm2 of an appropriate challenge organism per mod. ASTM F838-83 and FDA guidelines; NXZ, NLZ: Serratia marcescens; NFZ, NTZ, NDZ: 121 °C (250 °F) Brevundimonas diminuta; NTZ also retains > 107 cfu/cm2 Acholeplasma laidlawii mycoplasma. 4 hours (1-hour cycles) at 140 °C (284 °F)
Nominal Dimensions (6) Laboratory tests to establish multi-cycle resistance. Filters should be qualified in actual use. Contact Pall for recommended procedures. Lengths 10 in. (254 mm), 20 in. (508 mm), 30 in. (762 mm), 40 in. (1016 mm) Aqueous Extractables (NVR) per 10 in. (254 mm) Element Diameter 2.75 in. (70 mm) Typically 15 – 25 mg Operating Conditions(3) Particle Removal Efficiencies Maximum Differential 5.5 bard (80 psid) to 50 °C (122 °F) Pressure and Temperature 4.1 bard (60 psid) to 80 °C (176 °F) Endotoxin Removal > 99.997% to 0.16 gm E. coli endotoxin 2.1 bard (30 psid) to 125 °C (257 °F) Efficiency(7)
(8) (3) Using compatible fluids. Polystyrene Bead Efficiency NLZ, NAZ, NIZ to > 1 gm loading: > 99.99% for 0.04 µm beads Configuration (AB Code 7)(4) NFZ, NTZ to > 2 – 10 gm loading: > 99.99% for 0.04 µm beads Double 226 O-ring adapter (7) Determined for 10 in. (254 mm) elements challenged in deionized water. No endotoxin Fin end with bayonet lock detectable in effluent using LAL reagent with sensitivity of < 0.5 EU/mL. (4) Alternate adapter codes available. (8) Determined for 10 in. (254 mm) elements challenged in deionized water. Capacity determined at breakthrough (effluent turbidity).
Ordering Information
AB 7
Code Nominal Code Removal Filter Forward Flow Code Filter Code Gasket Length Rating Area(7) mL/min at Grade Option mbar (psi)(8) 1 10 in. NNXZ 1.2/0.45 µm 0.82 m2 (8.8 ft2) 22 at 1240 (18) P Pharmaceutical* H4 Silicone (254 mm) NLZ 0.45 µm 0.82 m2 (8.8 ft2) 15 at 1725 (25) Omit General Use Other materials available on request. 2 20 in. NAZ 0.2 µm 0.85 m2 (9.0 ft2) 85 at 2060 (30) (508 mm) * Pall pharmaceutical-grade filters NBAZ 0.45/0.2 µm 0.82 m2 (8.8 ft2) 20 at 2060 (30) are designed for use in 3 30 in. conformance with CGMP in 2 2 (762 mm) NFZ 0.2 µm 0.78 m (8.5 ft ) 12 at 2760 (40) Manufacturing, Processing, NIZ 0.1 µm 0.85 m2 (9.0 ft2) 50 at 3440 (50) Packing or Holding of Drugs 4 40 in. (21CFR210) and CGMP for (1016 mm) NTZ 0.1 µm 0.70 m2 (7.5 ft2) 14 at 5175 (75) finished Pharmaceuticals (21CFR211.72) including batch NDZ 0.04 µm 0.81 m2 (8.7 ft2) 25 at 3440 (50) release certificate and full (7) Filter areas are per 10 in. (254 mm) element. All dimensions are nominal. traceability. 98 (8) Forward Flow allowable limit for one 10 in. (254 mm) cartridges at given test pressure, water wet, air test gas. Please contact Pall for method details and test parameters Novasip™ Liquid Sterilizing-grade Capsule Filters The Clear Choice for Steaming-In-Place
Novasip filters are unique. Novasip filters Features and Benefits combine Pall cartridge technology with • Low installation cost — up to 80% less advanced polymers to produce an than a comparable stainless steel all–plastic filter assembly that can provide system all of the benefits of a capsule filter and SIP (steam-in-place) capability. Novasip filters • Steam-in-place capability with no therefore provide an alternative to stainless housing cleaning or maintenance steel housings in many applications. This • Clear housing for easy venting enables filter users to reduce capital and labor costs and minimize cleaning • Laser-etched serial number for easy validation. identification Novasip filters consist of a • New design sanitary valves: standard-design filter cartridge Non-removable for safety permanently sealed in a clear Non-threaded for cleanliness polyetherimide housing. Polyetherimide is an advanced plastic selected for its • Integral Stäubli*-compatible vent valve high-strength at elevated temperatures and enables direct on-line connection to pressures. This ensures that Novasip electronic test equipment filters can be used under a wide range of • Non-rotating hose barb drain for safe operating conditions including and hygienic operation steaming–in–place at 142 °C (287 °F). • Available in a range of media and Novasip filters are supplied with sanitary removal ratings including Fluorodyne® II flange inlet and outlet connections and low-binding membrane integral vent and drain valves for immediate installation. *Stäubli is a trademark of Stäubli AG. Novasip filters for liquids are purpose-designed for the sterile filtration of pharmaceutical and biological products.
Comprehensive Validation Documentation
Novasip filters have been extensively tested to ensure consistent and reliable performance under a range of process conditions. Installation and operating instructions including information on steam-sterilization are available from Pall.
99 100 (5) Technical Specifications Novasip CP Note: (3) (2) (1) 300 mbar(4.3psi). NF Mediaonly. Part NumberingandOrdering Information materials ofconstruction. With fullycompatiblefluidswhichdonotsoften,swelloradverselyaffect thefilterorits Pressure Maximum Differential Pressure Maximum Operating Operating Conditions conditions ofuse. Maximum determinedinlaboratorytest.Actualsteamlifemayvarydependingonthe C3DFLP1/C3DJLP1 Validated using30-minutecycles. Exposure Time C05NFP1/C3NFP1 Cumulative Steam Temperature Part Number Maximum AccumulatedSteamLife O-rings Housing Head Housing Bowl Core andCage C3DFLP1/C3DJLP1 End Caps C05NFP1/C3NFP1 Support andDrainage Membrane Part Number Materials ofConstruction oeNmnlFle ra oeFilter Medium Code NominalFilterArea Code 05 0.15m 0.22m 3 3 0.15m 3 Maximum differential pressure duringsteam-sterilizationatupto142 (5) 0.056 m Liquid Sterilizing-gradeCapsuleFilters 2 2 2 (257 2 125 (1.62 ft (1.62 ft (2.37 ft or or or or or Hours Hours Hours Hours Hours Hours (0.60 ft 6423 02 10 30 2 4 16 (3) ° ° C135 )(275 F) iioeeatmrSiliconeelastomer Silicone elastomer 2 2 2 oyteiiePolyetherimide Polyetherimide Polyetherimide Polyetherimide J 0.1µmsterilizing-grade 0.2µmsterilizing-grade DJL 0.2µmsterilizing-grade DFL ) NF ) ) 2 oyrpln Polypropylene Polypropylene F0.2µmsterilizing-grade NF ) yo , Hydrophilic Nylon 6,6 oyse Polypropylene Polypropylene Polyester Polyester with TiO 5.3 bard (77psid)at40 6.5 barg (94psig)at40 ° ° 142 C )(287 F) 2 (1),(2) ° ° 125 C )(257 F) polyvinylidenedifluoride ° ° 135 C )(275 F) Fluorodyne Fluorodyne Ultipor Ultipor ° with TiO ° C (104 C (104 (PVDF) ° ° ° C (287 142 C )(287 F) N66 N66 ° ° 2 F) F) II II ° F) is ° ° C F) oeConnectionOptions Code Typical LiquidFlowRates (4) 26 1 Differential Pressure (mbar) 1000 Length (including Valves) Maximum Diameter Nominal Dimensions Refer tovalidationguidefortestconditions NF: Water at20 Extractables inDeionized Extractables 250 500 750 0 Note: 0 5101520 0 12345 tance, contactyourlocalPallrepresentative. multiplying theindicateddifferential pressure bytheviscosityincP. Forassis- pressures forliquidsatotherviscositiescanbeconservativelyestimatedby – Differential pressures are forliquidswithaviscosityof1cP. Differential sanitary clamp 38mm(1
° C05NFP1 C (68 (4) ° F) – 1 1 ⁄ 2 in.) Flow Rate(Gal/min) Flow Rate(L/min) C3NFP1 157 mm(6.1in.) 123 mm(4.8in.) < 5mg DFL/DJL: < 10mg *St oeVent, DrainandValve Code Blank C3DJLP1 ä B A ubli istrademarkofSt fitting) (compatible withSt disconnect coupling 4 fitting), novalve Vent anddrain: compatible) withvalve Vent anddrain: i.d. tube,withvalve Valve drain: Vent: ( coupling (St connect anddisconnect (compatible withTri-Clamp* 1 ⁄ 2 – in.) sanitaryflange 6m ( 6mm Quick connectand
C3DFLP1 1 ⁄ 8 ä C3EKV ä ubli AG. – Hose barbfor ubli*
1 ⁄ 4 in.) 13 mm Quick ä ubli* 0 2 4 6 8 10 12 14
Differential Pressure (psid) Kleenpak™ Nova Sterilizing-grade and Virus Removal Capsule Filters Improving Choice, Flexibility and Operation Costs for the Sterile Filtration of Liquids
The issues of effective cleaning and Kleenpak Nova capsules are especially cleaning validation result in disposable suited to pilot- and process-scale equipment being the preferred option for applications. They can be autoclaved or many processes. Disposable filters can sterilized by Gamma-irradiation and can be help eliminate cleaning problems, supplied as part of pre-sterilized especially where biological products are to processing systems such as a be filtered. In applications where hazardous filter/tubing/bag set. materials are being filtered, such as Kleenpak Nova capsules are used in a cytotoxic drugs, capsule filters can play an wide range of critical applications including important role in helping protect operators. the sterilization of BioPharmaceuticals, Kleenpak Nova capsule filters are biologicals, diagnostic reagents, serum, designed to provide choice, cost tissue culture media, and culture-media effectiveness and flexibility, while ensuring components. ease of use for the operator. Kleenpak Nova Filters Reduce Designed to Provide Choice and Operating Costs Flexibility Kleenpak Nova filters have a typical Kleenpak Nova capsule filters are available installation cost that is 80% lower than a with either in-line or T-style configurations. similar sized stainless steel housing The T-style configuration is ideal for system. Therefore, they offer an extremely manipulating multiple filters in series or in cost-effective alternative to housing and parallel configuration. cartridge systems. Kleenpak Nova filters can also provide additional cost savings: Kleenpak Nova Capsule filters incorporate either a 10 in. (254 mm), 20 in. (508 mm) • No housing maintenance — or 30 in. (762 mm) length standard Pall Lower maintenance costs cartridge filter which have traditionally been • No housing cleaning or cleaning installed in stainless steel housings. In validation — applications where a particular filter is Lower labor costs already specified, the user can switch from a stainless steel housing to a fully • Filter is pre-assembled — disposable assembly with minimal Lower labor costs requalification. This means the extensive • Filter can be provided pre-sterilized — range of sterilizing-grade and virus filters Lower energy costs currently available from Pall can easily be provided as a capsule filter, including: • Low binding, high-flow Fluorodyne II PVDF filters • Ultipor N66 and positively-charged Posidyne nylon 66 filters • Supor polyethersulfone filters • Ultipor VF DV20 and DV50 virus removal filters
101 Kleenpak Nova Sterilizing-grade and Virus Removal Capsule Filters Technical Specifications
Operating Conditions(1) Kleenpak Nova NP Empty Capsule – Typical Water Flow Rates at 20 °C (68°F) Maximum Operating 40 °C (104 °F) Flow Rate (Gal/min) Temperature 5 10 15 20 25 600 8 Maximum Operating 3 barg (43.5 psig) at 40 °C (104 °F). Pressure (6.2 barg (90 psig) at 40 °C (104 °F) for 7 up to a maximum of 10 hours)(2) 500 P6 6 (1) With compatible fluids which do not soften, swell or adversely affect the product or its 400 materials of construction. 5 (2) Integrity test purposes only. 300 4 Capsule Materials of Construction 3 200 P9 Housing Bowl and Head(3) Polypropylene 2 Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential 100 O-rings Silicone elastomer P1 1
(3) Formulated with TiO2 whitener which does not contribute to organic extractables. 0 0 0 20 40 60 80 100 Flow Rate (L/min) 1 Sterilization • P6 Capsules (13 mm ( ⁄2 in.) hose barb) • P9 Capsule (25 mm (1 in.) hose barb) Autoclave (Maximum) 135 °C, for 1 hour • P1 Capsules (sanitary flange)
Gamma-irradiation Maximum Dosage: 50 kGy Kleenpak Nova NT Capsule – Consult Pall for procedures. Typical Water Flow Rates at 20 °C (68 °F) Flow Rate (Gal/min) Nominal Dimensions 510152025 2.5 P9 In-line NP6 NP7 NP8 160
Maximum Diameter 154 mm 154 mm 154 mm 140 P19 2 (including Valves) (6.1 in.) (6.1 in.) (6.1 in.) 120 Length with Hose Barb 397 mm 644 mm 895 mm P1 1.5 Inlet and Outlet (15.6 in.) (25.4 in.) (35.2 in.) 100 80 Length with Sanitary 335 mm 584 mm 834 mm 1 Inlet and Outlet (13.2 in.) (23.5 in.) (32.8 in.) 60
T-style NT6 NT7 NT8 40 0.5 (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential Maximum Diameter 240 mm 240 mm 240 mm 20 (including Valves) (9.5 in.) (9.5 in.) (9.5 in.) 0 0 02040608090100 Length 349 mm 598 mm 848 mm Flow Rate (L/min) (13.7 in.) (23.5 in.) (33.4 in.) • P1 Capsules (sanitary flange) • P19 Capsules (sanitary flange inlet, 25 mm (1 in.) hose barb outlet) • P9 Capsule (25 mm (1 in.) hose barb)
Ordering Information NP – In-line NT – T-Style P
Code Filter Size Code Filter Type Code Connection Options Code Sterilization 1 6 AB1 10 in. (254 mm) Sterilizing State 1 25 – 38 mm (1 – 1 ⁄2 in.) State 7 AB2 20 in. (508 mm) DFL 0.2 µm rated Fluorodyne II filter sanitary flange inlet and outlet G Non-sterilized 8 AB3 30 in. (762 mm) DJL 0.1 µm rated Fluorodyne II filter 9 25 mm (1 in.) single-barb S Pre-sterilized NF 0.2 µm rated Ultipor N66 filter hose barb inlet and outlet 1 NT 0.1 µm rated Ultipor N66 filter 19 25 – 38 mm (1 – 1 ⁄2 in.) sanitary flange inlet and 25 mm (1 in.) NFZ 0.2 µm rated Posidyne filter single-barb hose barb outlet NTZ 0.1 µm rated Posidyne filter Options for In-line Only EKV 0.2 µm rated Supor filter 1 6 13 mm ( ⁄2 in.) single-barb (4) 92D 0.2 µm rated Suporlife filter hose barb inlet and outlet Virus Filters 1 (3) Note: Empty Kleenpak Nova 16 25 – 38 mm (1 – 1 ⁄2 in.) sanitary (4) 1 Code Vent and Drain Capsule Housings for water at 20 °C LUDV50 Ultipor VF grade DV50 virus filter flange inlet and 13 mm ( ⁄2 in.) (68 °F), 1 cP. For other liquids, LDV20(4) Ultipor VF grade DV20 virus filter single-barb hose barb outlet – Stäubli* vent and multiply pressure times the viscosity Options for T-style Only stepped hose barb in centipoise. For complete (4) L included in part number for in-line (NP) filters; 1 assembly, including AB-Style filter omitted for T-style filters (NT) 1H 25 – 38 mm (1 – 1 ⁄2 in.) sanitary drain cartridge, add housing, and flange inlet and outlet, with cartridge media pressure-drop 1 AStäubli* vent and 13 mm ( ⁄2 in.) sanitary port on drain values. Contact Pall for assistance. inlet 1 Note: Partial list of part numbers. 1H9 25 – 38 mm (1 – 1 ⁄2 in.) sanitary *Stäubli is trademark of Stäubli 1 Contact Pall for specific flange inlet and 1 ⁄2 in. AG. recommendations single-barb hose barb outlet, 1 with 13 mm ( ⁄2 in.) sanitary port 102 on inlet Novasip™ DV20 and DV50 Virus Removal Filter Capsules Steam-In-Place Capsules for Virus Filtration
Novasip Ultipor VF capsule filters are Quality and Bio-Safety disposable, Junior Style steamable Biological Tests assemblies designed to remove Integrity parvoviruses and other viruses from protein solutions. • Every filter integrity tested during manufacture. Test correlated to viral The Novasip DV20 grade capsule filter (phage) retention utilizes an Ultipor VF-grade DV20 grade pleated membrane cartridge to remove Biological Tests parvoviruses and other viruses as small as • Meets USP Biological Reactivity Test, 20 nm from protein solutions up to in vivo, for Class VI-121 °C Plastics 5 – 10 liters. Effluent Quality Tests* The Novasip DV50 grade capsule filter • Meets Cleanliness per USP Particulates incorporates an Ultipor VF DV50 grade in Injectables Ultipleat membrane cartridge for removal of viruses 40 – 50 nm and larger. • Non-Fiber-Releasing Novasip Ultipor VF capsule filters are • Non-Pyrogenic per USP Bacterial supplied non-sterile and can also be Endotoxins (< 0.25 EU/mL) Gamma-irradiated.* • Meets Total Organic Carbon and Water Conductivity per USP Purified Water, Features and Benefits pH per USP Sterile Purified Water
• ≥ 3 Log Titer Reduction (LTR) for 20 nm Autoclave Resistance viruses • Lot samples multi-cycle autoclave • ≥ 6 log LTR for ≥ 50 nm viruses challenged • Robust size exclusion mechanism * Per lot samples soak or rinse-up flush aliquots. • Narrow pore-size distribution • Low binding for high protein yields • Inherently water wettable • Very low extractables • Autoclavable or steamable in situ • Gamma-irradiatable • 100% integrity-tested • Individually serialized • Manufactured for use in conformance with cGMP • Pharmaceutical P optimized with certificate of test provided • Clear housing for easy venting • New design sanitary valves:
Non-removable for safety
Non-threaded for cleanliness 103 * For Gamma-irradiated products and maximum allowable dosage, please contact Pall. Novasip DV20 and DV50 Virus Removal Filter Capsules Technical Specifications
Materials of Construction Aqueous Extractables (NVR)
Filter Medium Hydrophilic polyvinylidenedifluoride < 5 mg/capsule (Deionized water at 20 °C [68 °F]) (PVDF) Support and Drainage Polyester Flow/Pressure (Water, 25 °C [77 °F]) Core, Cage and Endcaps Polypropylene Housing Shell Polyetherimide 3.2 mL/min at 5860 mbar (85 psi) for CLM05DV20P1G O-rings(1) Silicone 0.3 L/min @ 2 bar (29 psi) for CL3DV50P1G
(1) Other polymers available. Sterilization
Nominal Dimensions Autoclavable and Steamable in situ for 3 x 1-hour cycles at up to (2) CLM05DV20 C3DV50 125 °C (257 °F) (non-irradiated product only). Gamma-irradiatable .
(2) Length 84 mm (3.3 in.) 157 mm (6.18 in.) Contact Pall for recommended procedures. Diameter 123 mm (4.8 in.) 123 mm (4.8 in.) Effluent Quality Tests (P Tests) Nominal Filter Area 0.07 m2 (0.75 ft2) 0.4 m2 (4 ft2) Meets Cleanliness per USP Particulates in Injectables.
Inlet and Outlet Non-Fiber-Releasing
1 Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) 26 – 38 mm (1 – 1 ⁄2 in.) sanitary flange Meets Total Organic Carbon and Conductivity per USP Purified Water, pH per USP Sterile Purified waters. Virus Removal
3 DV20 TR > 10 for 25 nm PP7 bacteriophage 6 TR ≥ 10 for 53 nm PR772 bacteriophage
6 DV50 TR ≥ 10 for 50 nm PR772 bacteriophage
Operating Conditions
Recommended Operating 1 – 2 bard (15 – 29 psid) Pressure
Maximum Differential(1) 3 bard (43.5 psid). Pressure
(1) Note: Maximum assembly pressure is 6.0 bard (90 psid) for short-term integrity testing.
Ordering Information Part Number Media Type Rating CLM05DV20P1G Hydrophilic PVDF For viruses ≥ 20 nm CL3DV50P1G Hydrophilic PVDF For viruses ≥ 50 nm Note: For suggested qualification protocols, test/validation discs, sizing and sterilizing recommendations, multi-element forward flow values or other information, please contact Pall or your local Pall representative.
104 Ultipor® VF Grade DV50 Virus Filter Cartridges – SBF Junior Style Scaled-down Filter Cartridges for Virus Removal Filters
Pall Ultipor VF Grade DV50 virus removal Quality and Bio-Safety filters are a robust means to remove Biological Tests viruses from liquids by microfiltration, while Integrity permitting enhanced transmission of proteins. SBF Junior Style pleated • Every filter integrity tested during membrane mini-cartridges are designed for manufacture. Test correlated to viral small-scale qualification and validation (phage) retention studies and for small process batches up Biological Tests to 10 – 20 liters. Typical applications for • Meets USP Biological Reactivity Test, these easy-to-use direct flow filters include in vivo, for Class VI-121 °C Plastics purification of BioPharmaceuticals, plasma derivatives, protein or serum containing Effluent Quality Tests* cell-culture media and diagnostic reagents. • Meets Cleanliness per USP Particulates in Injectables Features and Benefits • Non-Fiber-Releasing • 6 log Titer Reduction (TR) for 50 nm • Non-Pyrogenic per USP Bacterial viruses Endotoxins (< 0.25 EU/mL) • Robust size exclusion mechanism • Meets Total Organic Carbon and Water • Narrow pore-size distribution Conductivity per USP Purified Water; pH per Sterile Purified Water. • Easy-to-validate direct flow use Autoclave Resistance • Linear scale-up to larger batches • Lot samples multi-cycle autoclave • Low protein binding challenged • Low filter extractables * Per lot samples soak or rinse-up flush aliquots. • 100% integrity-tested • Pre-use testable with WFI • Manufactured for use in conformance with cGMP • ISO 9000 Certified Quality System • Pharmaceutical P optimized • Certificate of Test provided • Validation Guide available • SBF style also available with 0.2 µm Ultipor N66, Posidyne, Fluorodyne II and Emflon PFR media
105 Ultipor VF Grade DV50 Virus Filter Cartridges – SBF Junior Style Technical Specifications
Materials of Construction Operating Conditions
Membrane Hydrophilic low protein binding Maximum Differential 3 bard (43.5 psid) polyvinylidenedifluoride (PVDF) Pressure(4)
Support and Drainage Polyester Recommended 1 – 2 bard (15 – 29 psid) Operating Pressure Core, Cage and End Caps Polypropylene O-ring Silicone(1) Maximum Differential 6.0 bard (90 psid) Pressure for Integrity (1) Other polymers available. Test Performance (Short-term)
(4) Viral TR pressure-independent. Virus Removal Ratings(2)
≥ 6 ≥ TR 10 for viruses 50 nm Aqueous Extractables (NVR) (2) Lot samples retain log 10 TR 6 of 53 nm spherical non-enveloped bacteriophage PR772. 1 mg per element in deionized water at 20 – 25 °C after autoclaving
Nominal Filter Area 0.074 m2 (0.8 ft2)
Nominal Dimensions Length 62 mm (2.4 in.) Diameter 43 mm (1.7 in.)
Configuration Single open-ended cartridge Sanitary style plug adapter Double 116 O-ring
Autoclave and Steaming in situ(3) Autoclavable at 125 °C (3) Contact Pall for recommended procedures.
Ordering Information(6) Part Number Media Type Removal Rating
6 SBF1DV50PH4 Hydrophilic PVDF TR ≥ 10 for viruses ≥ 50 nm
(6) H4 suffix = Silicone O-rings (standard). Ethylene Propylene and Fluoropolymer Elastomer O-rings available. See Appendix for alternate O-ring polymer codes. P in part number indicates optimized and qualified for pharmaceutical use including 100% integrity test and Certificate of Test.
Note: For suggested qualification protocols, test and validation discs, sizing and sterilizing recommendations, SBF style cartridges with 0.2 µm or other grade, please contact Pall.
106 Ultipor® VF Grade DV20 Virus Removal Filter Cartridges Removal of Viruses as small as 20 nm
Pall Ultipor VF grade DV20 filter cartridges Quality and Bio-Safety are integrity-testable, direct flow filters for Biological Tests size exclusion removal of viruses as small Integrity as 20 nm from biological solutions. The innovative DV20 hydrophilic PVDF • Every DV20 grade filter integrity tested microporous membrane also enables during manufacture. Test correlated to > 95% transmission of proteins up to 160 viral (phage) removal kiloDaltons. Using a standard single Biological Tests open-ended (SOE) AB sanitary style • Meets USP Biological Reactivity Test, cartridge design, Ultipor VF DV20 filters in vivo, for Class VI-121 °C Plastics achieve practical flows and pressure drops in process-scale purification of Effluent Quality Tests* BioPharmaceuticals, tissue and plasma • Meets Cleanliness per USP Particulates derivatives and protein additives. Where in Injectables required, suitable prefilters employing the • Non-Fiber-Releasing same PVDF membrane material are available, simplifying process optimization • Non-Pyrogenic per USP Bacterial and filtration system validation. Endotoxins (< 0.25 EU/mL) • Meets Total Organic Carbon and Features and Benefits Conductivity per USP Purified Water; pH per Sterile Purified Water • Sanitary direct flow cartridges Autoclave Resistance • Robust size exclusion mechanism • Lot samples multi-cycle autoclave • ≥ 3 log TR for > 20 nm viruses challenged • ≥ 6 log TR for > 50 nm viruses * Per lot sample or rinse-flush aliquots. • Low binding for high protein yields • High transmission of albumin and IgG Forward Flow Integrity Test • Very low extractables • Diffusional flow integrity test, carried out by standard upstream or downstream • Autoclavable and Steamable in situ methods (SIP) • Correlated to 3 log TR for 25 nm PP7 • 100% integrity-tested (correlated to phage and ≥ 6 log TR for 53 nm PR772 virus retention) phage • Manufactured for use in conformance • Test Wetting Fluid: 30% IPA (20% with cGMP EtOH values also available) • Pharmaceutical P optimized with • Water or buffer-wet values for Certificate of Test provided installation confirmation can also be • Validation Guide available provided
Claims based on challenges with bacteriophage (bacterial • Test Pressure: 85 psi (air test gas) viruses) PP7 (25 nm) and PR772 (53 nm) in 1% Bovine Serum Albumin in phosphate-buffered saline at pH 7.4, Contact Pall for cartridge values and 20 °C (68 °F). correlation data Note: These filters are also available in Kleenpak Nova • Validation Guide available capsule format.
107 Ultipor VF Grade DV20 Virus Removal Filter Cartridges
Technical Specifications
Materials of Construction Aqueous Extractables (NVR)
Membrane Hydrophilic modified < 5 mg per 10 in. (254 mm) element in deionized water at 20 °C (68 °F), polyvinylidenedifluoride (PVDF) process-ready (after integrity testing in 30% IPA/water, water flush and autoclaving). Support and Drainage Polyester Core, Cage and End Caps Polypropylene Autoclave and Steaming in situ(1) Code 7 Adapter Polypropylene with encapsulated stainless steel reinforcing ring Maximum Temperature 125 °C (257 °F) (1) Contact Pall for recommended procedures to qualify filters under actual conditions of O-rings Silicone use.
Configuration (AB Code 7) Typical Liquid Flow Rate(2) Double 226 O-ring adapter 15 L/h/10 in. (254 mm) module at 30 psid for 1% Bovine Serum Albumin in Fin end with bayonet lock. phosphate-buffered saline at pH 7.4, 20 °C (68 °F)
(2) Claims based on challenges with bacteriophage (bacterial viruses) PP7 (25 nm) and Nominal Dimensions PR772 (53 nm) in 1% Bovine Serum Albumin in phosphate-buffered saline at pH 7.4, 20 °C (68 °F). Lengths 10 in. (254 mm), 20 in. (508 mm), 30 in. (762 mm), 40 in. (1016 mm) Removal Ratings Diameter 70 mm (2.75 in.) 3 Log TR for viruses > 20 nm
Operating Conditions 6 Log TR for viruses > 50 nm Recommended Operating ∆P 1 – 2 bard (15 – 29 psid) Maximum Differential 6.0 bard (90 psid) during integrity testing Pressures 3.1 bard (45 psid) for continuous service
Nominal Filter Area 1.0 m2 (10.8 ft2) per 10 in. (254 mm) element
Part Numbering and Ordering Information Part Number Nominal Length AB1DV207PH4 10 in. (254 mm) AB2DV207PH4 20 in. (508 mm) AB3DV207PH4 30 in. (762 mm) AB4DV207PH4 40 in. (1016 mm)
Ordering Information for Recommended Prefilters
AB 7
Code Nominal Code Rating Filter Type Code Filter Code Gasket Length Grade Option
1 10 in. DV20 ≥ 3 log TR for viruses > 20 nm Ultipor VF P Pharmaceutical* H4 Silicone (254 mm) UDV50 ≥ 6 log TR for viruses > 50 nm Ultipor VF Omit General Use Other materials available 2 20 in. on request. DVD Sub 0.1 µm virus prefilter Ultipor VF * Pall pharmaceutical-grade filters (508 mm) are designed for use in DJL 0.1 µm (+ 0.2 µm prefilter layer) Fluorodyne II conformance with CGMP in 3 30 in. Manufacturing, Processing, (762 mm) DFL 0.2 µm (double-layer) Fluorodyne II Packing or Holding of Drugs (21CFR210) and CGMP for 4 40 in. DBL 0.45 µm (+ 0.65 µm prefilter layer) Fluorodyne II finished Pharmaceuticals (1016 mm) (21CFR211.72) including batch release certificate and full traceability.
108 Ultipor® VF Grade DV50 Virus Removal Filter Cartridges Optimized for Removal of 50 nm Viruses
Pall Ultipor VF virus removal filter • Manufactured for use in conformance cartridges feature innovative hydrophilic with cGMP PVDF microporous membranes to remove • ISO 9000 Certified Quality System significant levels of viruses from biological solutions, while enabling > 95% • Pharmaceutical P optimized transmission of proteins up to 300 kD or • Certificate of Test provided larger. Using patented Ultipleat • Validation Guide available crescent-shaped pleating technology, the filters to incorporate 1.6 m2 (17.5 ft2) of filter • Discs and mini-cartridges (SBF Junior area per 10 in. (254 mm) element in Style) available standard single open-ended (SOE) AB Note: These filters are also available in Kleenpak Nova sanitary style cartridges. Ultipor VF capsule format. cartridges achieve practical flows and pressure drops while effectively removing Quality and Bio-Safety nanometer-size viral contaminants with Biological Tests high protein yields. Integrity An optional sub-0.1 µm rated prefilter • Every DV50 grade filter integrity tested (Grade DVD) and Fluorodyne II filters during manufacture. Test correlated to enhance throughputs and employ the viral (phage) retention. same PVDF membrane material for ease of validation. Typical applications include Biological Tests purification of BioPharmaceuticals, tissue • Meets USP Biological Reactivity Test, and plasma derivatives, protein additives, in vivo, for Class VI-121 °C Plastics culture media, diagnostic reagents, buffers Effluent Quality Tests* and diluents. • Meets Cleanliness per USP Particulates in Injectables Features and Benefits • Non-Fiber-Releasing • Sanitary direct flow cartridges • Non-Pyrogenic per USP Bacterial • 6 log Titer Reduction (TR) for 50 nm Endotoxins (< 0.25 EU/mL) viruses (DV50 grade) • Meets Total Organic Carbon and • Robust size exclusion mechanism Conductivity per USP Purified Water; • PVDF microporous membranes pH per Sterile Purified Water • Narrow pore-size distribution Autoclave Resistance • Inherently water wettable • Lot samples multi-cycle autoclave challenged • Low binding for high protein yields * Per lot sample or rinse-flush aliquots. • Very low extractables • Steamable in situ • 100% integrity-tested • Individually serialized
109 Ultipor VF Grade DV50 Virus Removal Filter Cartridges Technical Specifications
Materials of Construction Operating Conditions(4)
Membrane Hydrophilic modified Maximum Differential 6.0 bard (90 psid) polyvinylidenedifluoride (PVDF) Pressure during Integrity Testing Support and Drainage Polyester Maximum Differential 3 bard (43.5 psid) Core, Cage and End Caps Polypropylene Pressure for Continuous Code 7 Adapter Polypropylene with encapsulated Service stainless steel reinforcing ring for steaming in situ Recommended Operating ∆P 1 – 2 bard (15 – 29 psid) O-rings Silicone(1) (4) Laboratory tests confirm viral TR is in independent of pressure differential to 3.1 bard (45 psid). (1) Other polymers available.
Autoclave and Steaming in situ(5) Removal Ratings Maximum Temperature 125 °C (257 °F) DVD Sub-0.1 µm prefilter (5) Laboratory tests confirm multi-cycle resistance. Filters should be qualified in actual 6 (2) DV50 TR 10 for 50 nm viruses use. Contact Pall for recommended procedures.
(2) 6 Lot samples retain log 10 TR of 53 nm spherical non-enveloped bacteriophage. Aqueous Extractables (NVR) per 10 in. (254 mm) Element(6) Configuration (AB Code 7) < 25 mg after autoclaving (water wet) Double 226 O-ring adapters. Fin end with bayonet lock. < 5 mg after installation integrity testing (30% IPA/water wet), water flush and autoclaving. Nominal Dimensions (6) In water at 20 – 25 °C ( 68 – 77 °F) after autoclaving. Lengths 10 in. (254 mm), 20 in. (508 mm), 30 in. (762 mm), 40 in. (1016 mm) Diameter 70 mm (2.75 in.)
Nominal Filter Area(3) DVD 0.9 m2 (9.5 ft2) UDV50 1.63 m2 (17.5 ft2) (3) Per 10 in. (254 mm) element.
Typical Flow Rate Clear water flow is 1 L/min @ 2 bard (29 psid)
Ordering Information for Recommended Prefilters
AB 7
Code Nominal Code Removal Code Filter Code Gasket Length Rating Grade Option 1 10 in. DVD sub-0.1 µm prefilter P Pharmaceutical* H4 Silicone (254 mm) UDV50 106 for 50 nm viruses * Pall pharmaceutical-grade filters Other materials available 2 20 in. are designed for use in on request. (508 mm) conformance with CGMP in Manufacturing, Processing, 3 30 in. Packing or Holding of Drugs (21CFR210) and CGMP for (762 mm) finished Pharmaceuticals 4 40 in. (21CFR211.72) including batch release certificate and full (1016 mm) traceability.
110 Air and Gas Filtration Air and Gas Filtration
Pall air and gas filters have been developed Coalescing filters protect downstream from a successful range of products that are equipment and processes from compressor widely used in the pharmaceutical and wear products, lubrication oil, water or other biotechnology industries. liquid droplets, corrosion products, and other particulate contaminants, while reducing Emflon filters have been designed and maintenance costs. liquid-validated for use as sterilizing filters for air, gas, and vent service in critical ambient Rigimesh® sintered metal mesh, PSS® sintered and high-temperature applications in metal powder and PMM® metal membrane BioPharmaceutical and bioprocess industries filter cartridges can be used for both gas and such as product or hot WFI tank vents, liquid service. Metal filters are also used for autoclaves, freeze dryers, and high-flow steam filtration. applications such as fermenter inlet and exhaust air. Note: It is important to maintain the integrity of 0.2 µm sterilizing-grade filters. Pall Pall capsule filters combine process and recommends integrity testing of all Junior-size cartridge technology with the latest sterilizing-grade filters prior to steaming, after polymers in an all-plastic filter assembly that steaming, and after the filtration process to offers the benefits of a disposable capsule for ensure that the integrity of the filter has been air, gas and vent filtration. Pall capsule filters maintained. Contact Pall for recommended can be autoclaved, even steamed-in-place or procedures and Integrity test parameters. gamma-irradiated, to provide a reliable, cost- effective alternative to stainless steel housings.
Several different particle removal filters have been designed for sanitary-style filter and industrial-style housings and are often recommended for clarification of air and gas feeds. Pall particle removal filters can also serve as an economical prefilter for high-flow fermentation and other air-sterilizing membrane cartridges.
112 Novasip™ Capsule with Emflon® PFR Membrane Assemblies The Clear Choice for Steam-in-Place of Air and Gas Filters
The unique Novasip capsule filter Features and Benefits combines Pall cartridge technology with • Low installation cost — up to 80% less the latest engineered polymers in an than a comparable stainless steel all–plastic filter assembly that can provide system all of the benefits of a capsule filter with SIP (steam-in-place) capability. Novasip • Integrity testable in situ using the water filters, therefore, provide an alternative to intrusion test (WIT) stainless steel housings in many • Integral Stäubli-compatible vent valve applications. This enables filter users to enables direct in-line connection to reduce capital and labor costs and to electronic test equipment minimize maintenance costs. • Repeatedly steam-sterilizable for long Novasip filters consist of a standard service life and low operating costs design filter cartridge permanently sealed in a clear polyetherimide housing. • Suitable for use in high pressure air systems up to 6.5 barg (94 psig) at Polyetherimide is an advanced plastic temperatures up to 40 °C (104 °F) selected for its high-strength at elevated temperatures and pressures. This ensures • Supplied with a numbered disc which that Novasip filters can be used under a can be fitted easily to the capsule and wide range of operating conditions used to help record the number of including multiple steam-in-place cycles. times the filter is sterilized Novasip filters are supplied with inlet/outlet connections compatible with sanitary High Quality Standards flange fittings. Vents and drains are • Validated in liquids with Brevundimonas available with integral valves. diminuta (ATCC 19146) at a challenge Novasip filters with Emflon PFR filter level of 107 organisms/cm2 of filter area membranes are purpose-designed for use • 100 % integrity tested during in critical air and vent applications. manufacturing
Comprehensive Validation • Identified by a lot number with a unique Documentation serial number for complete traceability of manufacturing history and for user Novasip filters with Emflon PFR filter traceability systems membrane have been extensively tested to • Each filter supplied with a Certificate of ensure consistent and reliable performance Test under a range of process conditions. • Comprehensive validation guide A full validation guide is available on available request. • Manufactured under a Quality Installation and operating instructions, Management System certified to including information on steam-sterilization, ISO 9000 are available from Pall. • Meets USP Biological Reactivity Tests in vivo, in accordance with USP Class VI plastics at 121 °C
113 Novasip Capsule with Emflon PFR Membrane Assemblies Technical Specifications
Materials of Construction Typical Air Flow Rates(4) Flow Rate (scfm) Membrane Hydrophobic PTFE 0 5 10 15 20 25 30 35 Membrane Support and Polypropylene 120 Drainage Layer Assembly 1.5 Endcaps Polypropylene 100 Vent mode Vent mode Core and Cage Polypropylene 2 barg (29 psig) inlet Housing Bowl Polyetherimide 80 2 barg (29 psig) inlet
Housing Head Polyetherimide with TiO2 1 O-rings Silicone elastomer 60
(1) 40 Maximum Accumulated Steam Life 0.5 Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential Temperature 125 °C (257 °F) 135 °C (275 °F) 142 °C (287 °F) 20 Maximum Steam 100 cycles 50 cycles 5 cycles Exposure(2) 0 0 (1) Validated using 30 minute cycles. 0 10 20 30 40 50 60 (2) Maximum values determined in laboratory tests. Actual steam life may vary with 3 conditions of use. Flow Rate (Nm /h)
= C3PFRP1 = C2PFRP1 Operating Conditions(3) (4) Typical initial clean ∆P, air at 20 °C (68 °F). Maximum Operating 6.5 barg (94 psig) at 40 °C (104 °F) Contact your local Pall representative for assistance. Pressure
Maximum Differential 5.2 barg (75 psig) at 40 °C (104 °F) Pressure Nominal Dimensions
Note: Maximum differential pressure during steam sterilization at up to 142 °C (287 °F) is Maximum Diameter 123 mm (4.84 in.) 300 mbar (4.3 psid). (Including Valves)
(3) With fully compatible fluids that do not soften, swell or adversely affect the filter or its Length 157 mm (6.18 in.) materials of construction.
Ordering Information
C P F R P 1
Code Nominal Filter Area Code Connection Code Vent, Drain and Valves
1 2 0.17 m2 (1.8 ft2) 1 25 – 38 mm (1 – 1 ⁄2 in.) Blank Vent: Quick connect and Sanitary flange fittings disconnect coupling (compatible 2 2 3 0.23 m (2.5 ft ) with Stäubli* fitting) with valve Drain: Hose barb for 4 – 6 mm 1 1 ( ⁄8 – ⁄4 in.) i.d. tube, with valve
A Vent and Drain: Quick connect and disconnect coupling (compatible with Stäubli fitting) with valve
1 B Vent and Drain: 13 mm ( ⁄2 in.) sanitary flange, no valve
*Stäubli is a trademark of Stäubli AG.
114 Kleenpak™ Capsules with Emflon® II Membrane Assemblies Gamma-irradiation Tolerant Air and Gas Filters for Disposable Systems
Kleenpak capsule filters containing with Features and Benefits hydrophobic polyvinylidenedifluoride (PVDF) • Highly retentive Emflon II membrane Emflon II membranes are especially designed for the sterile filtration of air and • High flow-rates associated with low gas. These compact filter capsules provide Delta P enable the use of small filters — high air flows, resist blocking in wet reduction of installation and operating applications, and provide 100% removal of costs bacteria and viruses from air and gases, • Gamma-irradiatable or pre-sterilized for even in the presence of high humidity and maximum convenience moisture. • Integral molded connections Kleenpak capsules are manufactured using gamma-irradiation tolerant materials • Fully integrity testable using the forward and offer the very highest standard of flow test filtration security and user convenience. These filters can be integrated within High Quality Standards gamma-irradiatable or gamma-sterilized • Validated in liquids with Brevundimonas complex systems such as bioreactors, filter diminuta (ATCC 19146) at a challenge assemblies, or transfer sets where venting level of 107 organisms/cm2 of filter area is required. • 100 % integrity tested during Pre-sterilized Option manufacturing • Identified by a lot number with a unique These Kleenpak filters can be supplied serial number for complete traceability sterilized by a validated gamma-irradiation of manufacturing history and for user process reducing time and costs. Filter traceability systems capsules are then double-bagged and the outlet is covered with a protective cap for • Each filter supplied with a Certificate of extra security. Test • Comprehensive validation guide Gamma-irradiatable Option available These capsules can also be supplied • Manufactured under a Quality non-sterile, allowing the connection to Management System certified to tubing or any other type of equipment prior ISO 9000 to gamma irradiation. This allows users to • Meets USP Biological Reactivity have a sterilized processing system without Tests in vivo, in accordance with the need for aseptic connections and the USP Class VI plastics at 121 °C associated risks of contamination.
Custom-made Sets
We are happy to work with end-users to provide custom-designed processing systems which will integrate one or more of our capsule ranges.
115 Kleenpak Capsules with Emflon II Membrane Assemblies Technical Specifications
Materials of Construction Typical Air Flow Rates(2) Flow Rate (Nm3/h) Membrane Hydrophobic PVDF 0 5 10 15 20 Support and Drainage Layers Polypropylene 4 KA1 KA2 KA1 End Cap Polypropylene 250 KA2 Core and Cage Polypropylene 3 Outer Shell Polypropylene 200 Vent and Drain – Valve O-rings Ethylene Propylene (EPDM)
KA3 150 Nominal Dimensions 2
KA02 KA1 KA2 KA3 100 Maximum Diameter 51 mm 94 mm 94 mm 109 mm Differential Pressure (psid) Pressure Differential (Including Valves) (2.0 in.) (3.7 in.) (3.7 in.) (4.2 in.) 1 (mbar) Pressure Differential KA3 50 Length with Hose Barb 104 mm NA NA NA Connections (Code 2) (4.1 in.) ––– 0 0 Length with Sanitary NA 11.7 cm 15.8 cm 17.4 cm 0 2 4 6 8 10 12 Connections – (4.6 in.) (6.2 in.) (6.8 in.) Flow Rate (scfm) Nominal Filtration Area 200 cm2 500 cm2 1000 cm2 1500 cm2 = Vent = 2.1 barg (30 psig) (0.21 ft2) (0.5 ft2) (1.0 ft2) (1.5 ft2) (2) For gases other than air or nitrogen, contact your local Pall representative.
Operating Conditions(1) Sterilization
KA02 KA1/KA2/KA3 Gamma-irradiation Maximum Dosage (G option only): Maximum Operating _ 40 °C Up to 50 kGy Temperature
Maximum Operating 4.1 barg (60 psig) 5.2 barg (78 psig) Autoclave Sterilization Pressure at 38 °C (100 °F) at 38 °C (100 °F) Gamma-irradiated Filters One 30-minute cycle at 125 °C Maximum Differential 2.1 bard (30 psid) _ Non Gamma-irradiated Filters 3 x 1 hour cycles at 125 °C Pressure at 80 °C (176 °F) Warning: Kleenpak filters must not be in situ steam-sterilized by passing steam through (1) In air/nitrogen gas service or other compatible fluids, which do not soften, swell, or under pressure. The figures are maximum allowable figures determined by testing under adversely affect the filter or its materials of construction. controlled laboratory conditions to the total number of hours indicated. Actual operating conditions may affect the filters long-term response to sterilization. Filters should be qualified for each process application.
Ordering Information
KA V 0 0 2 P
Code Nominal Length Code Connection Type Code Sterilization Status
(3) 1 02 1 38 mm (1 ⁄2 in.) S Gamma-irradiated sanitary flange 1 See above G Non-irradiated 1 1 dimensions 26 – 13 mm ( ⁄4 – ⁄2 in.) hose Barb 2 table (4) 1 3 8 13 mm ( ⁄2 in.) sanitary flange (3) For KA1, KA2 and KA3 sizes only. (4) For KA02 size only.
116 Kleenpak™ Capsules with Emflon® PFR Membrane Assemblies High-strength, Long-life Sterilizing Filters for Air and Gas
Pall Kleenpak filters combine the widest High Quality Standards available range of filter media with specially Every Pall Kleenpak filter is manufactured designed self-contained assemblies, to to a very high standard of quality satisfy the very highest standards of assurance and cleanliness, and in filtration security and user convenience. accordance to a quality system accredited to ISO 9000. Emflon PFR Filter Medium For pharmaceutical use, the P designation At the heart of every Kleenpak Emflon in the part number provides full traceability PFR Capsule filter is a high-performance supported by a certificate of test. pleated cartridge, containing proprietary PTFE membrane. The high-strength PTFE Quality and Bio-Safety membrane is inherently hydrophobic, chemically inert, and designed specifically Biological Tests for removal of contaminating bacteria and • Meets USP Biological Reactivity Test, viruses. Emflon PFR filters have a in vivo for Class VI-121 °C Plastics microbial removal rating of 0.2 µm in Effluent Quality Tests* liquids and a particulate removal rating of 0.003 µm in gases. • Meets Cleanliness per USP Particulates in Injectables Emflon PFR filters meet the ever-increasing demand for air filters with • Non-Fiber-Releasing greater strength and longer life. • Non-Pyrogenic per USP Bacterial Endotoxins (< 0.25 EU/mL) Clean and Robust Design • Meets Oxidizables and pH per USP The Kleenpak filter uses well-proven Sterile Purified Water proprietary Pall techniques for filter * Per lot sample soak or rinse-up flush aliquots. construction and heat sealing. • The highest possible security against Features and Benefits filter bypass is ensured, even under • Comprehensive validation assures conditions of pulsed flow highest removal efficiency and highest • High-strength design allows multiple safety margins (validation guide autoclave cycles for extended use and available on request) maximum filter economy • High flow-rates and low pressure drop • Polypropylene outer shell is designed to allow use of small systems, reducing provide long-term assurance of installation and running costs pressure and temperature ratings • Robust construction ensure integrity • A total absence of glues, binder resins and reliability and surfactants results in very low filter • Long autoclave life and long service extractables and extremely clean filtrate offer low-cost filtration
117 Kleenpak Capsules with Emflon PFR Membrane Assemblies Technical Specifications
Materials of Construction Typical Air Flow Rates(2)
Membrane Double-layer hydrophobic PTFE 50 0.7 Support and Drainage Layers Polypropylene 0.6 40 End Cap Polypropylene KA1PFRP6 0.5 Core and Cage Polypropylene 30 Outer Shell Polypropylene 0.4 KA1PFRP6 Vent and Drain - valve O-rings Ethylene Propylene Rubber 0.3 20 KA2PFRP6 0.2
Nominal Dimensions KA2PFRP6 (psi) Pressure Differential
Differential Pressure (mbar) Pressure Differential 10 KA1 KA2 KA3 0.1
Maximum Diameter 94 mm 94 mm 109 mm 0 0 (Including Valves) (3.7 in.) (3.7 in.) (4.2 in.) 0 1 2 3 4 5
3 Length with 38 mm 117 mm 158 mm 174 mm Flow Rate (Nm /h) 1 (1 ⁄2 in.) sanitary (4.6 in.) (6.2 in.) (6.8 in.) = Vent condition = 2 barg (29 psig) inlet connections
Length with hosetail 158 mm 199 mm 210 mm 250 connection (14 mm (6.2 in.) (7.8 in.) (8.2 in.) 9 ( ⁄16 in.) single–barb) 200 3 Maximum Cumulative Steam Autoclave Time 150 Up to 140 °C (284 °F) 50 hours 2 Warning: Kleenpak filters must not be in situ steam sterilized by passing steam through KA3PFRP1 KA3PFRP1 under pressure. The figures are maximum allowable figures determined by testing under 100 controlled laboratory conditions to the total number of hours indicated. Actual operating conditions may affect the filters long-term response to sterilization. Filters should be 1
qualified for each process application. (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential 50
(1) Operating Conditions 0 0 0 20 40 60 80 100 Maximum Operating 40 °C (104 °F) Temperature Flow Rate (Nm3/h) = Vent condition = 2 barg (29 psig) inlet Maximum Operating 3.5 barg (50 psig) (2) ∆ Pressure Typical initial clean P, air at 20 °C (68 °F). Values shown are for 38 mm 1 (1 ⁄2 in.) sanitary flange connections. Values with other connections are Maximum Differential 3.5 bard (50 psid) available upon request. For gases other than air or nitrogen, contact your Pressure local Pall representative.
(1) In compatible fluids which do not soften, swell or adversely affect the filter or materials Nominal Filter Area of construction. Size Code KA1 KA2 KA3 Filter Integrity Test Recommendation Filter Area 0.05 m2 0.1 m2 0.2 m2 (0.5 ft2) (1 ft2) (2 ft2) KA2 and KA3 Water Intrusion Test * KA1, KA2 and KA3 are also testable with Forward Flow test after wetting with suitable alcohol/water mixtures. Please contact Pall for test method parameters.
Ordering Information
KA P F R P
Code Nominal Length Code Connection Type
1 1 1 38 mm (1 ⁄2 in.) See above sanitary flange 2 dimensions 9 table 6 14 mm ( ⁄16 in.) 3 hose barb
118 Kleenpak™ Capsules with HDC® II Gas Filter Assemblies High-capacity Polypropylene Air and Gas Filters in the Most Convenient Form
Pall Kleenpak assemblies with HDC II Quality and Bio-Safety media are compact, self-contained filters Biological Tests with a rugged all-polypropylene construction. They provide up to • Meets USP Biological Reactivity Test, HEPA-quality air and gas filtration with a in vivo for Class VI-121 °C Plastics hydrophobic polypropylene graded-density Effluent Quality Tests* depth medium which, with with superior • Meets Cleanliness per USP Particulates flow rates, lower pressure drops, higher in Injectables capacity and longer filter life, outperforms other membrane filters. • Non-Fiber-Releasing • Non-Pyrogenic per USP Bacterial Features and Benefits Endotoxins (< 0.25 EU/mL) • Hydrophobic polypropylene media • Meets Oxidizables and pH per USP Sterile Purified Water • High efficiency in air and gases • HEPA filtration with J012 grade * Per lot sample soak or rinse-up flush aliquots. • No housing required • Absolute particle-rated for reliability • Low pressure loss • Melt-sealed construction • Repeatedly autoclavable • Manufactured for use in conformity with cGMP • FDA-listed materials per 21 CFR • ISO 9000 Certified Quality System • Pharmaceutical P optimized • Certificate of Test provided
119 Kleenpak Capsules with HDC II Gas Filter Assemblies Technical Specifications
Materials of Construction Typical Air Flow Rates (at 2 barg [30 psig] Inlet Pressure)(3) Flow Rate (scfm) Medium Polypropylene 0 5 10 15 Support, Drainage, Core, Polypropylene 250 KA1 KA1 KA2 KA2 Cage, End Caps and Shell Vent and Drain Valve O-ring Ethylene Propylene (EPDM) 3 200 Removal Ratings
Grade In Air(1) In Liquids(2) 150 2 J100 93% at 0.3 µm 10 µm
J060 99% at 0.3 µm 6 µm 100 J045 99.75% at 0.3 µm 4.5 µm
1 (psi) Pressure Differential J025 99.95% at 0.3 µm 2.5 µm (mbar) Pressure Differential KA3 50 J012 99.99% at 0.3 µm 1.2 µm (1) % removal 0.3 µm DOP droplet aerosol. KA3 Due to the enhanced particle removal efficiencies in gases, the approximate ratings for 0 0 gas service can be calculated by dividing the liquid rating in µm by between 5 and 10. 0 5 10 15 20 25 (2) > 99.98% by mod. OSU-F2 beta test. Flow Rate (Nm3/h) = J025P = J045P Nominal Filter Areas (3) Typical initial clean ∆P, air at 20 °C (68 °F). Values shown are for 38 mm 1 Effective Size Code (1 ⁄2 in.) sanitary flange connections. Values with other connections are Filter Area KA1 KA2 KA3 available on request. For gases other than air or nitrogen, contact your local Pall representative. J012, J025 0.06 m2 (0.6 ft2) 0.1 m2 (1.0 ft2) 0.2 m2 (2.0 ft2) Connections (Inlet and Outlet) J045 0.06 m2 (0.6 ft2) 0.11 m2 (1.2 ft2) 0.22 m2 (2.3 ft2) 1 KA1 and KA2 Styles 38 mm (1 ⁄2 in.) sanitary flange 2 2 2 2 2 2 1 1 J060 0.03 m (0.3 ft ) 0.05 m (0.5 ft ) 0.10 m (1.0 ft ) 6 – 13 mm ( ⁄4 – ⁄2 in.) hose barb
2 2 2 2 2 2 1 J100 0.03 m (0.3 ft ) 0.07 m (0.7 ft ) 0.13 m (1.4 ft ) KA3 Style 38 mm (1 ⁄2 in.) sanitary flange 9 14 mm ( ⁄16 in.) hose barb Nominal Dimensions Operating Conditions (Gases)(4) Size Code KA1 KA2 KA3 Maximum Diameter of 94 mm 94 mm 109 mm Maximum Operating 3.5 barg (50 psig) to 40 °C (104 °F) Bowl (Including Valves) (3.7 in.) (3.7 in.) (4.2 in.) Pressure and Temperature
Nominal Length (Including 117 mm 158 mm 174 mm Maximum Differential 3.5 bard (50 psid) at 40 °C (104 °F) 1 in. Tri-Clover Connection) (4.6 in.) (6.2 in.) (6.8 in.) Pressure and Temperature
(4) Nominal Length (Including 158 mm 199 mm – In air/N2 service or other compatible gases. Stepped Hose Barb (6.2 in.) (7.8 in.) – Connection) Steam Autoclaving Nominal Length (Including ––210 mm Cumulative Autoclave Time(5) 50 hours (1-hour cycles) at Hose Barb Connection) ––(8.2 in.) 140 °C (284 °F)
(5) Laboratory tests to establish multi-cycle resistance. Filters should be qualified in process conditions. Contact Pall for recommended procedures.
Warning: Kleenpak filters must not be steam sterilized in situ by passing steam through under pressure.
Ordering Information
KA J
Code Nominal Code Removal Rating Code Filter Grade Code Connection This is a guide to the part number structure Length in Liquids* Type and possible options
1 only. For availability of 1 012 1.2 µm P Pharmaceutical** 1 38 mm (1 ⁄2 in.) See above specific options, please sanitary flange 2 dimensions 025 2.5 µm Omit General Use contact Pall. table 26 – 13 mm 3 045 4.5 µm **Pall pharmaceutical-grade filters are 1 1 ( ⁄4 – ⁄2 in.) designed for use in conformance 060 6.0 µm with CGMP in Manufacturing, stepped hose barb Processing, Packing or Holding of 100 10 µm 9 Drugs (21CFR210) and CGMP for 6 14 mm ( ⁄16 in.) * Due to the enhanced particle finished Pharmaceuticals hose barb removal efficiencies in gases, the (21CFR211.72) including batch approximate ratings for gas service release certificate and full can be calculated by dividing the traceability. 120 liquid rating in µm by between 5 and 10. Emflon® PFR Junior Style Filter Cartridges High-flow, Hydrophobic Filters for Small-scale Sterile Gas and Vent Applications
Emflon PFR filters have been developed Scientific Validation from the successful Emflon filter range Emflon PFR filters have been extensively launched in 1981 and are widely used as scientifically validated using the most air and gas-sterilizing filters in the advanced methods and the most sensitive pharmaceutical and biotechnology equipment available. They have a microbial industries. The Pall PTFE membrane is removal rating of 0.2 µm in liquids and a inherently hydrophobic, chemically inert particulate removal rating of 0.003 µm in and designed specifically for removal of gases and have been validated by: contaminating bacteria and viruses. • Brevundimonas diminuta liquid Emflon PFR filters meet the challenge at 107/cm2 ever-increasing demand for air filters with greater strength, longer life and the ability • Brevundimonas diminuta aerosol to withstand the rigors of in situ steaming challenge in the forward or reverse direction. • PP7 and MS-2 bacteriophage aerosol challenge Superior Performance • Bacillus subtilus Var niger spores Emflon PFR filters provide high assurance aerosol challenge of filter integrity and long-life, even during • Airborne sodium chloride aerosol continuous use in hot air up to 60 °C challenge at 100 L/min flow (140 °F) and after repeated steamings for a giving a 0.003 µm rating in gases typical period of up to 12 months. This is combined with high flow-rates and excellent de-wetting characteristics resulting in very economical filtration through the use of smaller installations and reduced energy costs. In addition, the filters can be tested in situ by the Forward Flow integrity test or by a Water Intrusion test. Both tests are correlated to liquid bacterial challenge — the ‘worst case’ challenge.
121 Emflon PFR Junior Style Filter Cartridges Technical Specifications
Materials of Construction Differential Pressure at 50 Nm3/h (30 ft3/min) Air Flow and (2) Membrane Hydrophobic PTFE 2 barg (29 psig) Inlet Pressure Part Number Differential Pressure Support and Drainage Layers Polypropylene MCY1110PFRPH4 End Cap, Core and Cage Polypropylene 500 mbard (7.25 psid) O-rings Silicone elastomer MCY2230PFRPH4 200 mbard (2.9 psid) (excluding SLK Styles) MCY3330PFRPH4 160 mbard (2.3 psid) Internal Adapter Stainless steel MCY4440PFRPH4 120 mbard (1.7 psid) Support Ring (MCY2230/4463 Styles Only) MCY4463PFRPH4 180 mbard (2.6 psid) SBF1PFRPH4 790 mbard (11.4 psid) Cumulative Steam Life(1) SLK7001PFRP 175 mbard (2.5 psid) Up to 142 °C (288 °F) and 0.3 bar (4.3 psi) ∆P SLK7002PFRP 80 mbard (1.1 psid) MCY1110PFRPH4 100 hour (2) Pressure drops are for filter elements only. To obtain the total pressure drop of a complete assembly the housing pressure drop must be added. Please refer to the MCY4440PFRPH4 relevant housing literature or contact Pall for specific sizing information. MCY3330PFRPH4 MCY2230PFRPH4 50 hours Nominal Filter Area MCY4463PFRPH4 Part Number Surface Area
2 2 SBF1PFRPH4 MCY1110PFRPH4 0.05 m (0.53 ft )
2 2 SLK7001PFRP MCY2230PFRPH4 0.14 m (1.5 ft )
2 2 SLK7002PFRP MCY3330PFRPH4 0.17 m (1.82 ft )
2 2 (1) Steam life validated using 1 hour cycles. MCY4440PFRPH4 0.23 m (2.47 ft )
The steam life and service life data were determined by testing under controlled 2 2 laboratory conditions up to the time indicated. Actual operating conditions may affect MCY4463PFRPH4 0.28 m (3.01 ft ) the filters long-term resistance to steam sterilization and hot air service. SBF1PFRPH4 0.04 m2 (0.43 ft2) Filters should be qualified for each process application. SLK7001PFRP 0.14 m2 (1.5 ft2) Maximum Differential Pressure SLK7002PFRP 0.28 m2 (3.01 ft2) All Styles 4.1 bar (60 psi) up to 80 °C (176 °F)
Ordering Information See Also:
Part Numbers For details about cartridge and capsule configurations see MCY1110PFRPH4(1) Filter Configurations and Dimensions on page 272. MCY2230PFRPH4(1) MCY3330PFRPH4(1) MCY4440PFRPH4(1) MCY4463PFRPH4(1) SBF1PFRPH4 SLK7001PFRP SLK7002PFRP (1) H4 suffix refers to silicone O-ring.
122 Emflon® PFR Sterilizing-grade Filter Cartridges High-flow Hydrophobic Filters for Sterile Gas and Vent Applications
Pall Emflon PFR sterilizing-grade filter Quality and Bio-Safety cartridges feature Pall’s advanced 0.2 µm Biological Tests polytetrafluoroethylene (PTFE) double-layer membranes. They are designed to • Meets USP Biological Reactivity Test, completely remove bacteria, viruses and in vivo for Class VI-121 °C Plastics particles from air and gas streams, even in Effluent Quality Tests* the presence of humidity and moisture. • Meets Cleanliness per USP Particulates Pleated with very high area into sanitary in Injectables single open-ended (SOE) AB style cartridges, Emflon PFR filters are built to • Non-Fiber-Releasing withstand adverse in situ steaming • Non-Pyrogenic per USP Bacterial conditions in either the forward or reverse Endotoxins (< 0.25 EU/mL) direction. Suitable applications are fermenter inlet air and exhaust venting, • Meets Oxidizables and pH per USP sterile process air, and sterile venting of Sterile Purified Water tanks, lyophilizers, and autoclaves. Steam Resistance • Lot samples multi-cycle autoclave Features and Benefits challenged
• Pall PTFE membranes * Per lot sample soak or rinse-up flush aliquots. • Inherently hydrophobic • Oxidation resistant hardware • High-flow and low pressure drop • 100% bacteria retentive in liquids • 100% virus retentive in gases • Melt-sealed construction • Enhanced steaming resistance • 100% Forward Flow tested • Water intrusion testable • Individually serialized • Manufactured for use in conformance with cGMP • FDA-listed materials per 21 CFR • ISO 9000 Certified Quality System • Pharmaceutical P optimized • Certificate of Test provided • Validation Guide available
123 Emflon PFR Sterilizing-grade Filter Cartridges Technical Specifications
Materials Typical Air Flow Rates(5) Flow Rate (scfm) Membranes Double-layer PTFE 0 50 100 150 Support and Drainage Polypropylene, oxidation resistant 250 Core, Cage, End Caps and Polypropylene, oxidation resistant Adapters 3.0 200 O-rings(1) Silicone (1) Other polymers available 2.5 150 2.0 Removal Ratings Air and Gases < 0.003 µm, particulate(2) 100 1.5 Liquids 0.2 µm, sterilizing(3)
1.0 (psi) Pressure Differential (2) By NaCl CNC particle analysis. Also retains 100% of Brevundimonas diminuta bacteria, (mbar) Pressure Differential bacteriophage and virus aerosols. 50 (3) Lot samples of assemblies retain > 107 cfu/cm2 of Brevundimonas diminuta in liquid per 0.5 mod. ASTM F838-83 and FDA guidelines.
0 0 Nominal Dimensions 0 80 160 240 320 Flow Rate (Nm3/h) Lengths 127 mm (5 in.), 10 in. (254 mm), = Vent = 2.1 barg = 4.1 barg 20 in. (508 mm), 30 in. (762 mm), (30 psig) inlet (60 psig) inlet 40 in. (1016 mm) (5) Typical initial clean medium ∆P per 254 mm (10 in.) element, air at 20 °C Diameter 2.75 in. (70 mm) (68 °F). For multi-element cartridges, divide pressure drop by number of 254 mm (10 in.) elements. Non-linear cartridge turbulence factors are incorporated into housing pressure drop values. For complete assembly Nominal Filter Area pressure drop, add filter cartridge medium value to housing value at
2 2 specified flow rate. For gases other than air or nitrogen, contact your local 0.8 m (8.6 ft ) per 10 in. (254 mm) element Pall representative. 0.4 m2 (4.1 ft2) per 5 in. (127 mm) element Autoclave and Steaming Operating Conditions(4) Cumulative Steaming Time Maximum Differential Pressure and Temperature 165 hours (1-hour cycles) to 140 °C (287 °F) 5.3 bard (77 psid) at 20 °C (68 °F) Maximum Forward Steaming Conditions 4.1 bard (60 psid) to 80 °C (176 °F) 1.0 bard (15 psid) at 125 °C (257 °F)
Typical Continuous Air Service Life(4) 0.3 bard (4.3 psid) at 142 °C (287 °F) 12 months to 60 °C (166 °F) Maximum Reverse Steaming Conditions Typical Vent Service Life 0.5 bard (7.3 psid) at 125 °C (257 °F) 6 months to 80 °C (176 °F) 0.2 bard (3.0 psid) at 142 °C (287 °F)
(4) In air/N2 service or other compatible gases. (6) For continuous air flow above 60 °C (140 °F), Emflon CPFR filters are recommended. Integrity Test Values for one 10 in. (254 mm) Cartridge Emflon PFR can be operated at higher temperatures for shorter time periods. Forward Flow (Air/Test/Gas) 60:40 IPA: Water wet (v:v) 15 mL/min at 1035 mbar (15 psi) Aqueous Extractables (20 °C [68 °F]) Water Intrusion 0.33 mL/min at 2485 mbar (36 psi) < 5 mg per 10 in. (254 mm) element after 1-hour steam at 125 °C (257 °F) (6) Contact Pall for multi-element values. AB05PFR value is 7.8 mL/min at 2485 mbar (36 psi).
Ordering Information
AB PFR V
Code Nominal Length Code Cartridge Style Code Filter Grade Optimization Code O-ring Material 05 5 in. (127 mm) 2(7) Double 226 O-ring with P Pharmaceutical* Oxidation-resistant H4 Silicone bayonet lock and flat end polypropylene 1 10 in. (254 mm) Omit General Use hardware Other materials available. 7 Double 226 O-ring with 2 20 in. (508 mm) bayonet lock and fin end * Pall pharmaceutical-grade filters are designed for use in 3 30 in. (762 mm) (7) AB05 cartridges only. conformance with CGMP in 4 40 in. (1016 mm) Manufacturing, Processing, Packing or Holding of Drugs (21CFR210) and CGMP for This is a guide to the part number structure and possible options only. finished Pharmaceuticals For availability of specific options, please contact Pall. (21CFR211.72) including batch release certificate and 124 full traceability. Emflon® CPFR High-temperature Sterilizing-grade Filter Cartridges Air, Gas and Vent Service in Critical High-temperature Applications
Pall Emflon CPFR High-temperature filters Feature have been developed from the long-life Correlation of challenge test data with: and high-strength Emflon PFR filter range. They have been designed and • Forward Flow Test and liquid-validated as sterilizing filters for air, • Water intrusion test gas and vent service in critical Benefit high-temperature applications in the BioPharmaceutical and bioprocess • Allows a safe, easy and fast industry, like fermentation inlet air, aseptic confirmation of filter integrity for packaging, or hot WFI tank vents. assurance of sterile filtration in critical applications. The oxidation-resistant components typically allow extended use in air up to Feature 80 °C (176 °F) and for shorter periods up • Lot tests for multi-cycle autoclave to 120 °C (248 °F). The high-strength challenges cartridges can also withstand high Benefit differential pressures in forward or reverse • Repeat steamability in situ and robust direction during multiple steam-in-place construction optimized for air, gas and sterilization cycles. The filters incorporate a vent service with enhanced life at double-layer (0.2 µm) of inherently high-temperatures hydrophobic polytetrafluoroethylene (PTFE) membrane, manufactured by Pall. Emflon CPFR filters are identified by their unique Certified P Quality colored oxidation resistant components Emflon CPFR cartridges have been and the easy-to-read laser-etched part designed and qualified for pharmaceutical number and serial number. use. The provided P Certificate meets and confirms pharmaceutical requirements on Features and Benefits the effluent regarding: Feature: Effluent Quality Tests (P Tests) Validated in accordance with: • Cleanliness per USP Particulates in injectables • Brevundimonas diminuta in liquid at 107 per cm2 according to modified • Non Fiber-Releasing ASTM Standard Test Method F383-83 • Non-Pyrogenic per USP Bacterial and FDA Guidelines on Sterile Drug Endotoxins (< 0.25 EU/mL) Products Produced by Aseptic Processing (1987) • Meets oxidizables and pH per USP Sterile Purified Water Benefit: Biological Tests High validation standards ensure the highest removal efficiency and safety • Meets USP Biological Reactivity Test, margins even in processes with in vivo for Class VI-121 °C Plastics high-temperatures, humid conditions and The quality management system for variable bioburden. manufacturing of Emflon CPFR occurs in conformance with Certified Quality System ISO 9000. Each filter is 100% integrity tested and fully traceable by individual laser marked lot and serial number. 125 Emflon CPFR High-temperature Sterilizing-grade Filter Cartridges Technical Specifications
Materials of Construction Typical Air Flow at 20 °C (68 °F) and 2 barg (30 psig) Inlet Pressure(2) Membrane Double-layer proprietary hydrophobic PTFE Flow Rate (scfm) 0 50 100 150 200 250 Drainage Layers Specially developed, resin impregnated 300 polyaramid non-woven material 4.0
End Cap, Core and Cage Pigmented polypropylene 250 3.5 Adapter Pigmented polypropylene with encapsulated stainless steel 3.0 reinforcing ring 200 2.5 150 Nominal Filter Area 2.0 AB1CPFR7PVH4 0.72 m2 (7.7 ft2) 100 1.5 Differential Pressure (psi) Pressure Differential Maximum Differential Pressure (mbar) Pressure Differential 1.0 50 Maximum Forward Differential Pressures in Air, Nitrogen or other 0.5 Compatible Gas Service are: 0 0 5.4 bard at 50 °C (80 psid at 122 °F) 0 100 200 300 400 500 4.1 bard at 80 °C (60 psid at 176 °F) Air Flow Rate (Nm3/h) (2) ∆ 3.4 bard at 90 °C (50 psid at 194 °F) Typical initial clean medium p per 254 mm (10 in.) element, air at 20 °C (68 °F). For multipleat cartridges, divide pressure drop by number of 254 mm (10 in.) elements. Contact Pall for assistance in sizing. Maximum Operating Temperature (In Compatible Gases) 120 °C (248 °F) Typical Service Life in Continuous Flowing Air Service(3) 1 year at 100 °C (212 °F) Maximum Forward Steaming Conditions 6 months at 110 °C (230 °F) 1 bard at 125 °C (15 psid at 257 °F) 2 months at 120 °C (248 °F) 0.3 bard at 142 °C (4.3 psid at 288 °F) (3) For continuous air flow above 60 °C (140 °F), in air/N2 service or other compatible gases, Emflon CPFR filters are recommended. Emflon CPFR can be operated at higher temperatures for longer time periods. Maximum Reverse Steaming Conditions
0.5 bard at 125 °C (7.3 psid at 257 °F) Typical Cumulative Steam Life(4) 0.2 bard at 142 °C (3.0 psid at 288 °F) 100 hours (1-hour cycles) at 140 °C (284 °F) (4) The steam life and service life data were determined by testing under controlled Integrity Test Values(1) laboratory conditions up to the time indicated. Actual operating conditions may affect the filter’s long-term resistance to steam sterilization and hot air service. Filters should Forward Flow Test With 60/40 IPA/Water wet (v:v) be qualified for each process application. and air as test gas 14 mL/min at 1040 mbar (15 psi) Water Intrusion Test 0.3 mL/min at 2500 mbar (36 psi) (1) Values are for one 10 in. (254 mm) filter at 20 °C (68 °F). Please contact Pall for multi-element integrity test values.
Ordering Information
AB CPFR V
Code Nominal Length Code Cartridge Style Code Filter Grade Optimization Code O-ring Material 05 5 in. (127 mm) 2(5) Double 226 O-ring with P Pharmaceutical* Oxidation resistant H4 Silicone bayonet lock and flat end polypropylene 1 10 in. (254 mm) * Pall pharmaceutical-grade hardware Other materials available. 7 Double 226 O-ring with filters are designed for use in 2 20 in. (508 mm) bayonet lock and fin end conformance with CGMP in Manufacturing, Processing, 3 30 in. (762 mm) (5) AB05 cartridges only. Packing or Holding of Drugs (21CFR210) and CGMP for finished Pharmaceuticals (21CFR211.72) including This is a guide to the part number structure and possible options only. batch release certificate and For availability of specific options, please contact Pall. full traceability.
126 Emflon® PFA Filter Cartridges High-flow Economical Filters for the Sterilization of Air and Gas
Emflon PFA filters are a further addition Optimized pleating configuration and to the successful Emflon filter range. membrane support, together with a wide The filters contain a proprietary bore cartridge core and adapter, ensure pleated hydrophobic PTFE membrane that this high-flow performance can be and are designed for the removal of exploited to the fullest. micro-organisms and particles from air and gases. Typical Applications
Emflon PFA filters: • Large-scale fermenter air • Offer exceptionally high-flow rates to • Intermediate product vessel venting ensure low installation and operating costs • Autoclave vacuum break • Have been validated for bacterial • Instrument air removal in air at an aerosol challenge • Air and gas service lines level of 107 Brevundimonas diminuta ATCC 19146 per 254 mm (10 in.) Features and Benefits length cartridge • High-flow rates and low pressure drop • Are integrity testable by the Water allow the use of smaller systems, Intrusion test or alcohol wet Forward minimizing installation, filter Flow test replacement, and energy costs • Can also be steam sterilized repeatedly • In situ integrity testable by Water in situ to provide long service life Intrusion or Forward Flow methods for maximum convenience and security Better by Design • Long steaming life offering low-cost The heart of the filter is a PTFE membrane filtration with exceptional flow properties. Equally important is Pall’s unrivalled expertise in cartridge construction drawing on many years experience in making PTFE membrane filters.
127 Emflon PFA Filter Cartridges Technical Specifications
Materials of Construction Typical Air Flow Rates – Vent Application(3)
Components Material 200 4 Membrane 180 Hydrophobic PTFE AB1 160 Support and Drainage Layers Polypropylene 3 140 End Cap, Core and Cage Polypropylene 120 Code 7 Adapter Polypropylene with encapsulated 100 2 stainless steel reinforcing ring 80 AB1 60 AB2 Nominal Filter Area 1 40 AB3 AB1PFA7PV 0.8 m2 (8.6 ft2) 20 AB2 Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential 0 Maximum Differential Pressure(1) AB3 Temperature Maximum Differential Pressure Forward Direction 0 50 100 150 200 250 300 350 400 Steam up to 125 °C (257 °F) 0.3 bar (4.3 psi) Air Flow Rate (1) Validated using 1-hour cycles. = Nm3/h = ft3/min
Cumulative Steam Life(2) Up to 125 °C (257 °F) 100 hours (3) Typical initial clean medium ∆p per 254 mm (10 in.) element, air at 20 °C (68 °F). For multipleat cartridges, divide pressure drop by number of 254 mm (10 in.) elements. Up to 140 °C (284 °C) 40 hours Contact Pall for assistance in sizing. (2) Validated using 1-hour cycles. The steam life and service life data were determined by testing under controlled laboratory conditions up to the time indicated. Actual operating conditions may affect the filters’ long-term resistance to steam sterilization and hot air service. Filters should be qualified for each process application
Service Life in Air Temperature Service Life 60 °C (140 °F) Pressurized Air Typically 12 months 80 °C (176 °F) Vent Service Typically 6 months
Ordering Information
AB PFA V
Code Nominal Length Code Cartridge Style Code Filter Grade Optimization Code O-ring Material 05 5 in. (127 mm) 2(4) Double 226 O-ring with P Pharmaceutical* Oxidation resistant H4 Silicone bayonet lock and flat end polypropylene 1 10 in. (254 mm) Omit General Use hardware 7 Double 226 O-ring with 2 20 in. (508 mm) bayonet lock and fin end * Pall pharmaceutical-grade filters are designed for use in 3 30 in. (762 mm) (4) AB05 cartridges only. conformance with CGMP in Manufacturing, Processing, Packing or Holding of Drugs (21CFR210) and CGMP for This is a guide to the part number structure and possible options only. finished Pharmaceuticals For availability of specific options, please contact Pall. (21CFR211.72) including batch release certificate and full traceability.
128 Ultipor® GF Plus Air and Gas Filters High Capacity, Long Life Filters for Air and Gas Service
Pall Ultipor GF Plus filter cartridges are Features and Benefits made with high voidage glass fiber media • High area pleated medium for enhanced filter life. The cartridges feature a high area pleated • Low differential pressures element construction designed to fit in • Absolute particle-rated in liquids sanitary-style filter housings. A bio-safe low extractables binder resin covalently • High-capacity for long-life immobilizes the glass fibers and imparts • Fixed pores prevent unloading high-strength and reliable removal • Choice of AB (SOE) sanitary or (DOE) efficiency. Due to the high particulate cartridge styles removal efficiency and low pressure drops consistent with glass fiber media, Ultipor • Manufactured for use in conformance GF Plus filters effectively protect with cGMP sterilizing-grade filters in air and gas • FDA-listed materials per 21 CFR applications. • ISO 9000 Certified Quality System Pharma Quality for Highest Quality Requirements
Ultipor GF Plus filters are manufactured in accordance with ISO9000 and GMP requirements. Each filter is supplied with a certificate of test that confirms suitability for use in pharmaceutical applications. Samples are tested for effluent quality to meet the USP requirements regarding • Total Organic Carbon • pH shift • Endotoxins All components meet the specifications for biological tests listed in the USP for Class VI plastics at 121 °C. Each box contains a certificate which confirms the quality standards in manufacturing, the traceability of all components, and the above mentioned safety tests.
129 Ultipor GF Plus Air and Gas Filters Technical Specifications
Materials of Construction Operating Conditions(1)
Filter Medium Resin-bonded glass-fiber Maximum Operating 4 bar (58 psi) at 80 °C (176 °F) Pressure Support and Drainage Polyester (1) In compatible liquids which do not soften, swell or adversely affect the filter or Core, cage and Endcaps Polypropylene materials of construction
Steam Sterilization Up to 140 °C (284 °F)
Ordering Information and Selection Guide(5)
AB
MCY100
Code Nominal Filter Removal Nominal Cartridge Code Filter Code O-ring Length Medium Rating in Liquids* Filter Area(6) Style Grade Option
1 10 in. (254 mm) U010Z 1 µm 0.50 m2 (5.3 ft2) Double 226 O-ring P Code outside US** H4 Silicone with bayonet 2 20 in. (508 mm) U2-20Z 2 µm 0.65 m2 (6.9 ft2) H13 Nitrile lock and fin end Omit Code in US only 2 2 Other materials available 3 30 in. (762 mm) U6-40Z 6 µm 0.55 m (5.9 ft ) **Supplied with Certificate of Test on request. and Full Traceability. 4 40 in. (1016 mm) U200Z 20 µm 0.49 m2 (5.2 ft2) * Due to the enhanced particle removal efficiencies in gases, the approximate ratings for gas service can be calculated by dividing the liquid rating in µm by between 5 and 10.
SLK
MCY4440
MCY4463
Code Filter Removal Nominal Code Filter Code O-ring Medium Rating in Liquids* Filter Area(6) Grade Option
7001 U010Z 1 µm 0.20 m2 (2.1 ft2) P Code outside US H4 Silicone
7002 U2-20Z 2 µm 0.22 m2 (2.3 ft2) Omit Code in US only H13 Nitrile
2 2 Other materials available U6-40Z 6 µm 0.20 m (2.1 ft ) Supplied with Certificate of Test on request. and Full Traceability U200Z 20 µm 0.18 m2 (1.9 ft2) (5) This is a guide to the part number structure only. (6) For SLK7002 and MCY4463 style.
130 HDC® II Gas Filter Cartridges High Dirt Retention All-polypropylene Filters
Pall HDC II filters are constructed using a Features and Benefits proprietary technique that varies the fiber High Removal Efficiency diameter instantaneously and continuously to produce a pore-size distribution from • 99.9998% efficiency at 0.3 µm for finest coarse (upstream) to fine (downstream) grade while maintaining constant void-volume Varied Fiber Diameter throughout the depth of the filter medium. • Extraordinarily high dirt-holding capacity This unique construction means that more contaminants are trapped in the outer and • Lowest cost per liter of filtered fluid inner regions of the medium, thereby Fixed Pore Structure substantially increasing the dirt-holding • No solids unloading under variations in capacity and the service life of the filter. flow or pressure differential HDC II AB style and MCY 1000 style filters • Fibers will not migrate or become are available in a range of removal ratings dislodged and contaminate the process and in four nominal cartridge lengths: fluid 10 in. (254 mm), 20 in. (508 mm), 30 in. (762 mm) and 40 in. (1016 mm). Their All-Polypropylene Construction all-polypropylene construction makes them • Extremely good chemical compatibility compatible with an extremely wide range with a wide range of gaseous fluids of gaseous fluids. Cartridges are also • No surfactants available as P option which are optimized for pharmaceutical applications. • Meets USP Biological Reactivity Tests (in vivo) in accordance with USP Class All materials of construction are FDA-listed VII Plastics at 121°C and all components have been tested according to USP Class VI biological tests • Cartridge can be in situ steam-sterilized for plastics at 121 °C. or autoclaved • Media melt-sealed to endcaps without the use of binder resins P Optimization for Pharmaceuticals • Statistical testing of filter effluent for:
particle and fiber counts
endotoxins using LAL test
pH shift test
Total organic carbon and water conductivity tests
131 HDC II Gas Filter Cartridges Technical Specifications
Operating Limits(1) Steam Sterilization
Operating Temperature Maximum Differential Pressure Maximum Cumulative Steam Sterilizing Temperature of AB 50 °C (122 °F) 5.5 bard (80 psid) Steaming Exposure Code 3 (P Grade Only) and AB Code 7 (In situ or Autoclave) 80 °C (176 °F) (Maximum) 4.1 bard (60 psid) 50 hours Up to 140 °C (284°F) (1) In compatible fluids which do not soften, swell or adversely affect the filter medium or materials of construction.
Retention Ratings Liquids Gas Flow Rates per 10 in. (254 mm) Cartridge(2) Code Absolute Retention (90%) Efficiency(3) Nominal Filter For Air Rating for 0.3 µm Aerosols Area(4) m3/h ∆P = 10 mbar (0.15 psi)(4) J006 0.6 µm(3) < 1.0 µm(3) 99.9998 % 0.62 m2 (6.67 ft2) 4.0 J012 1.2 µm < 1.0 µm(3) 99.996 % 0.69 m2 (7.43 ft2)10.0 J025 2.5 µm < 1.0 µm(3) 99.75 % 0.86 m2 (9.26 ft2)14.0 J045 4.5 µm 1.2 µm 99.95 % 0.86 m2 (9.26 ft2)17.0 J060 6.0 µm 3.0 µm 99 % 0.40 m2 (4.31 ft2)24.0 J100 10.0 µm 5.4 µm 93 % 0.52 m2 (5.6 ft2)39.0 J200 20.0 µm 10.0 µm – 0.53 m2 (5.7 ft2) – J400 40.0 µm 22.0 µm – 0.37 m2 (3.98 ft2) – J700 70.0 µm 35.0 µm – 0.37 m2 (3.98 ft2) – (2) For fluids of 1 cP viscosity. As a general guide for viscosities multiply pressure drop by viscosity in cP. For cartridges of 508, 762 and 1016 mm nominal length, divide differential pressure by 2, 3, and 4 respectively. (3) Based on mineral oil test. (4) For 10 in. (254 mm) nominal length cartridge (5) Extrapolated value. Ordering Information(5)
MCY 1000 style Double open-ended 70 mm (2.75 in.) diameter element with gaskets on both ends. Sealing is assured by using a tie rod and seal nut. MCY 100
Code Nominal Length Code(4) Removal Rating(5) in Liquids* Code Gasket Options Cartridge Sealing Arrangements 1 10 in. (254 mm) J006 0.6 µm H13 Nitrile 1000 style AB style 2 20 in. (508 mm) J012 1.2 µm J Ethylene 3 30 in. (762 mm) J025 2.5 µm propylene 4 40 in. (1016 mm) J045 4.5 µm Other materials available on request.
(5) For availability of specific options, J060 6.0 µm Flat Code 7 Code 3 contact Pall J100 10.0 µm Gasket Double O-ring seal (6) Absolute rating means the value in microns at which the OSU-F2 test J200 20.0 µm gives a beta value of > 5000. J400 40.0 µm * Due to the enhanced particle removal efficiencies in gases, the approximate J700 70.0 µm ratings for gas service can be calculated by dividing the liquid rating in µm by between 5 and 10.
AB style Single open-ended 70 mm (2.75 in.) diameter element with double O-ring at one end
AB
Code Nominal Code Removal Rating Code Cartridge Code Filter Code O-ring Length in Liquids* Style Grade Option 1 10 in. (254 mm) J006 0.6 µm 3 Double 222 O-ring P Pharmaceutical* H4 Silicone with flat end 2 20 in. (508 mm) J012 1.2 µm Omit General Use J Ethylene 3 30 in. (762 mm) J025 2.5 µm 7 Double 226 O-ring propylene with bayonet * Pall pharmaceutical-grade filters 4 40 in. (1016 mm) J045 4.5 µm lock and fin end are designed for use in Other materials available on request. J060 6.0 µm conformance with CGMP in Manufacturing, Processing, J100 10.0 µm Packing or Holding of Drugs (21CFR210) and CGMP for J200 20.0 µm finished Pharmaceuticals J400 40.0 µm (21CFR211.72) including batch release certificate and full 132 J700 70.0 µm traceability. Pallcell® Air and Gas Filter Cartridges Economical Air Prefiltration for High-flow Fermentation Applications
Pallcell filter cartridges for air and gas Features and Benefits service feature a binder-free pure cellulose • Absolute (liquid) rated for reliability filter medium which is pleated with all-polypropylene hardware into either • Fixed pore structure for consistent single open-ended (SOE) modular AB style effluent quality cartridges designed for sanitary-style filter • Low pressure drop housings, or economical double open-ended (DOE) modular cartridges • High-capacity for long-life designed for industrial DOE style housings. • Non-fiber-releasing Pallcell filters are recommended for • Resin-free melt-sealed construction clarification of air and gas feeds and as an economical prefilter for high-flow • Broad chemical compatibility fermentation air-sterilizing membrane • Low extractables cartridges. • Choice of AB (SOE) sanitary or (DOE) cartridge styles • ISO 9000 Certified Quality System • Manufactured for use in conformance with cGMP • FDA-listed materials per 21 CFR
133 Pallcell Air and Gas Filter Cartridges Technical Specifications
Materials of Construction Typical Air Flow Rates(4) Medium 100% pure cellulose Flow Rate (scfm) 0 30 60 90 Support and Drainage Layers Polypropylene 6 DC DE DC DG DE Core, Cage and End Caps Polypropylene 0.08 5 0.07 Seals(1) 0.06 AB Style Silicone O-rings 4 DG DOE style Ethylene Propylene gaskets 0.05 (1) Other polymers available. 3 0.04
(2) Removal Ratings (Liquid) 2 0.03 Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential 8 µm, 14 µm and 35 µm 0.02 (2) > 99.98% by mod. OSU-F2 Beta test 1 Due to the enhanced particle removal efficiencies in gases, the approximate ratings for 0.01 gas service can be calculated by dividing the liquid rating in µm by between 5 and 10. 0 0 0 40 80 120 160 Configurations Flow Rate (Nm3/h) AB Code 7 Style(3) Single open-end, Double 226 O-ring = 3.4 barg = 6.9 barg adapter with bayonet lock and (50 psig) inlet (100 psig) inlet finned end (4) Typical initial clean medium ∆P per 10 in. (254 mm) element, air at 20 °C Uni Cap Cartridge Double open-end, male and female (68 °F). For multi-element cartridges, divide pressure drop by number of end caps and flat gasket seal 10 in. (254 mm) elements. Non-linear cartridge turbulence factors are incorporated into housing pressure drop values. For complete assembly (3) Alternate adapter codes available. pressure drop, add filter cartridge medium value to housing value at specified flow rate. For gases other than air or nitrogen, contact your local Pall representative. Nominal Filter Area per 10 in. (254 mm) Element Operating Conditions 0.44 m2 (4.7 ft2) Maximum Differential 5.5 bard (80 psid) at 50 °C (122 °F) Pressure and Temperature(5) Nominal Dimensions AB Style 4.1 bard (60 psid) at 80 °C (176 °F) Lengths 10 in. (254 mm), 20 in. (508 mm), 30 in. (762 mm), 40 in. (1016 mm) DOE Style 3.1 bard (45 psid) at 82 °C (180 °F)
(5) In air/N2 service or other compatible gases. Diameters AB Style: 70 mm (2.75 in.) DOE Style: 64 mm (2.5 in.)
Ordering Information
AB
PUY
Code Nominal Code Removal Ratings Code Filter Code O-ring Length in Liquids* Grade Option
1 10 in. (254 mm) DC 8 µm P Pharmaceutical* H4 Silicone 2 20 in. (508 mm) DE 14 µm Omit General Use J Ethylene propylene 3 30 in. (762 mm) DG 35 µm * Pall pharmaceutical-grade filters are designed for use in 4 40 in. (1016 mm) Other materials available conformance with CGMP in on request. Manufacturing, Processing, Note: AB Style is recommended if cartridges are to be heated and then cooled by 20 °C Packing or Holding of Drugs (68 °F) before filtration. For sizing assistance, or for steaming in situ, requiring AB style P (21CFR210) and CGMP for finished option with stainless steel ring reinforced adapter option, contact your local pall Pharmaceuticals (21CFR211.72) representative. including batch release certificate * Due to the enhanced particle removal efficiencies in gases, the approximate ratings for and full traceability. gas service can be calculated by dividing the liquid rating in µm by between 5 and 10.
134 LG Liquid and Gas Coalescing Filter Cartridges Removal of Oil and Water Droplets in Critical Gas Service
Pall LG coalescing filter cartridges are Features and Benefits designed for critical air or gas service • Remove oil and water droplets from air applications where high-efficiency removal and gas streams of oil or water droplets and particulate solids is required. Via a series of graded • Fixed-pore and non-shedding media non-wettable media, droplets are captured, • High separation efficiency coalesced, and drained to the bottom of the housing, preventing filtered droplet • HEPA-quality air effluent re-entrainment into the downstream gas • Prevents wet-out blockage of flow. downstream membranes LG coalescing filters protect downstream • High filter area for prolonged life equipment and processes from • Low saturated pressure drop reduces compressor wear products, lubrication oil, operating costs water or other liquid droplets, corrosion products and other particulate • Rapid from liquid surges recovery contaminants, while reducing maintenance • Range of sizes for most applications costs. • Protects equipment and processes • Reduces downtime and labor costs • Manufactured for use in conformance with cGMP • ISO 9000 Certified Quality System
135 LG Liquid and Gas Coalescing Filter Cartridges Technical Specifications
Materials Nominal Dimensions
Medium Specially-treated resin-bonded glass Lengths CC05 CC1 CC3 CS fiber–hydrophobic and oleophobic 5 in. 10 in. 30 in. 40 in. Support and Drainage CC05, CC1, CC3LGA, CC3LG0, CS: (127 mm) (254 mm) (762 mm) (1016 mm) Polyester Diameters CC05 CC1 CC3 CS
CC3LGB: 57 mm 70 mm 70 mm 152 mm Polypropylene (2.25 in.) (2.75 in.) (2.75 in.) (6 in.) Core 304 Stainless Steel Cage CC1, CC3: Operating Conditions and Sizing(5) PVC coated glass mesh Changeout Differential 0.83 bard (12 psid) + CC05, CS: Pressure Clean Differential Pressure Stainless Steel Maximum Gas Temperature Side Seal Polypropylene CC05, CC1, CC3LGA, CC3LG0, CS: End Caps CC1, CC3 (Single open-end, SOE): Polypropylene, glass filled With water droplets/vapor 60 °C (140 °F) CC3 (Double open-end, DOE): Water droplet/vapor-free 82 °C (180 °F) Acetal CC3LGB: CC05, CS (SOE): Water droplet/vapor-free 82.2 °C (180 °F) Stainless Steel (5) Note: Assembly pressure drop designed to customer specification using Pall O-rings and gaskets Buna-N(1) LGSIZER2™ software program. Contact Pall for part number and assembly sizing recommendations. (1) Other polymers available.
Liquid (Oil) Coalescing Efficiency < 0.01 ppmw of oil in effluent(2) (2) Based on standard Pall Liquid Aerosol Separation Efficiency (LASE) test.
Particle Removal Rating (Air and Gas) 0.3 µm particulate(3),(4) (3) CC05: > 99.99% removal of 0.3 µm DOP aerosol. (4) CC1, CC3, CS: > 99.99% removal of 0.2 µm NaCl aerosol. > 99.97% removal of 0.3 µm DOP aerosol.
Ordering Information(5)
Part Nominal Length Nominal Configuration, Operating Service Number Filter Area Adapter and Seal Design Pressure
CC05LGH13 5 in. (127 mm) 0.08 m2 (0.84 ft2) SOE, Internal O-ring Low/High > 17.2 barg (250 psig) CC1LGA7H13 10 in. (254 mm) 0.26 m2 (2.8 ft2) SOE, Piston O-ring Low > 17.2 barg (250 psig) CC3LGA7H13 30 in. (762 mm) 0.88 m2 (9.5 ft2) SOE, Piston O-ring Low > 17.2 barg (250 psig) CC3LGB7H13 30 in. (762 mm) 0.80 m2 (8.6 ft2) SOE, Piston O-ring Low/High > 17.2 barg (250 psig) CC3LG02H13 30 in. (762 mm) 0.88 m2 (9.5 ft2) DOE, Gasket seals Low/High > 17.2 barg (250 psig) CS604LGH13 40 in. (1016 mm) 2.60 m2 (28 ft2) SOE, Piston O-ring Low/High > 17.2 barg (250 psig) (5) CC05LGH13 replaces PFS4463ZMH13; CC3LGB7H13 is recommended in amine/ammonia gas service. H13 suffix indicates Buna-N O-ring material (standard). See Appendix for alternate polymers and codes. Note: For sizing coalescer assemblies or other information, please contact your local Pall representative.
136 Rigimesh® Sintered Metal Mesh Filter Cartridges High-flow Pleated Metal Cartridges for Liquid and Gas Service
Pall Rigimesh sintered metal mesh filter Features and Benefits cartridges are constructed from fine-woven • All-stainless steel construction stainless steel wire mesh which is sintered at each wire contact point in a • Sintered mesh screen media Pall-patented process to produce an • Pleated for high-capacity extremely strong surface-sieving porous material with extremely narrow pore size • Consistent and fixed pore size distribution. Unlike unsintered meshes, • Corrosion resistant Rigimesh media will not shift under stress. • High pressure resistant Sintering also enables the use of finer wires to produce more pores per unit area for • Withstands high reverse-flows higher flow rates and higher contaminant • High-temperature capabilities loading capacity. Rigimesh media is pleated to form double open-ended (DOE) • Repeatedly cleanable MBS1000 style filter cartridges with • No soluble polymeric extractables applications in bulk active pharmaceutical • No unloading or shedding chemical purification processes such as catalyst solids recovery and decolorizing • Absolute rated for reliable performance carbon removal. • ISO 9000 Certified Quality System Single open-ended (SOE) AB sanitary and • Manufactured for use in conformance threaded styles are also available. with cGMP • FDA-listed materials per 21 CFR
137 Rigimesh Sintered Metal Mesh Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates(6) Flow Rate (L/min) Medium 304 L stainless steel(1) 0 25 50 75 100 125 150 (1) 0.4 Core and End Caps 304 stainless steel RZ 25 Gaskets Buna-N(2) (1) Also available with type 316 L medium and type 316 hardware or with other alloys 0.3 20 (special order). RK (2) Other polymers available. 15 (3) 0.2 Configuration RJ Double open-ended (DOE) 10 Flat gasket seals 0.1 Differential (psid) Pressure 5 Differential (mbar) Pressure (3) Single open-ended sanitary AB and threaded styles available.
0 0 Nominal Dimensions 0 10 20 30 40 Flow Rate (gpm) Diameters 64 mm (2.5 in.) Flow Rate (L/min) 0 25 50 75 100 125 150 0.008 Operating Conditions RM RR 5 Maximum Differential Pressure and Temperature(4)
Forward Flow Direction 8.6 bard (125 psid) to 232 °C (450 °F) 0.006 4 RS Reverse Flow Direction 0.7 bard (10 psid) to 232 °C (450 °F) (4) Minimum collapse differential pressure. Temperature limit with Buna-N gaskets: 3 0.004 121 °C (250 °F). Other gasket materials to 232 °C (450 °F). For Reinforced for 50 psid (3.4 bard) Reverse-flow option, temperatures to 316 °C (600 °F), or in other alloys to 677 °C (1250 °F), contact your local Pall distributor. 2 0.002 Differential (psid) Pressure Differential (mbar) Pressure Recommended Maximum Flow Densities(5) 1
Grade Aqueous Air 0 0 L/min (gal/min) Nm3/hr (acfm) 0 10 20 30 40 RA 14 (3.7) 47 (300) Flow Rate (gpm) (6) Typical initial clean medium ∆P per 10 in. (254 mm) element, water at RT 11 (2.9) 38 (240) 20 °C (68 °F), 1 cp. For assistance in sizing and housing selection, contact RS 8.8 (2.3) 32 (200) your local Pall representative. RR 7.0 (1.8) 24 (150) RM 3.3 (0.8) 16 (100) RJ 3.5 (0.9) 13 (80) RK 2.8 (0.7) 11 (69) RZ 1.8 (0.5) 6.3 (40) (5) Aqueous (water, 1 cp) and air flows per 10 in. (254 mm) cartridge.
Ordering Information
MBS100
Code Nominal Length Filter Area Code Liquid Ratings(7) Gas Ratings(7) Code Gasket Options 1 10 in. (254 mm) 0.9 m2 (1.0 ft2) RA 450 µm 350 µm H13 Buna-N gaskets (Standard) 2 20 in. (508 mm) 0.19 m2 (2.0 ft2) RT 225 µm 175 µm H Viton* 3 30 in. (762 mm) 0.28 m2 (3.0 ft2) RS 105 µm 85 µm J Ethylene Propylene 4 40 in. (1016 mm) 0.37 m2 (4.0 ft2) RR 70 µm 55 µm J7 Ethylene Propylene (Steam Service) RM 45 µm 25 µm Other materials available on request. * Viton is a registered trademark of DuPont Dow RJ 25 µm 18 µm (non-FDA materials). RK 18 µm 13 µm RZ(8) 15 µm 2 µm (7) Liquids: > 99.98% by mod. OSU-F2 test. Gases: 100% for hard spherical particles. (8) Supramesh® (Sintered powdered metal and mesh composite 138 medium). PSS® Porous Metal Filter Cartridges Sintered Metal Powder Filters for Liquid and Gas Service
Pall PSS porous metal filter cartridges are Features and Benefits made from fine stainless steel powders • All-stainless steel construction sintered to form rugged high voids and fixed pore filters with high-temperature, • Controlled and fixed pore size pressure, and solvent resistance. P Series • PH grade for clean steam cartridges begin as flat porous sheets which are shaped and welded into • Up to 2x life of competitive filters cylindrical elements. S Series cartridges • High pressure and corrosion resistant are produced in cylindrical form with higher • Withstands high reverse-flows voids and narrower pore size distributions for greater flows at comparable ratings. • High-temperature capabilities Double open-ended (DOE) style cartridges • Repeatedly cleanable are standard. They are recommended for steam service and well suited for liquid or • No soluble polymeric extractables gas applications including solvents, • No unloading or shedding chemical intermediates, heat transfer and • Absolute rated for reliable performance cryogenic fluids, polymers, pharmaceuticals, and high-temperature • ISO 9000 Certified Quality System gases. Single open-ended (SOE) AB • Manufactured for use in conformance sanitary and threaded styles are also with cGMP available. • FDA-listed materials per 21 CFR
139 PSS Porous Metal Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates(6) Flow Rate (L/min) Medium Type 316L stainless steel(1) 0 5 10 15 20 25 30 (1) 3.2 End Caps Type 316 stainless steel P05 P09 PH 200 Gasket Buna-N (Standard)(2)
(1) Other grades and alloys available 2.4 (2) Other Polymers available. 150
(3) Configuration 1.6 100 Double open-ended (DOE), flat gasket seals (3) Single open-ended AB sanitary and threaded styles available. PF 0.8
Differential (psid) Pressure 50 Differential (mbar) Pressure
Nominal Dimensions PD, PE
Diameters P Series: 2.5 in. (64 mm) 0 0 0 2 4 6 8 S Series: 2.38 in. (60.5 mm) Flow Rate (gpm) Flow Rate (L/min) 0 8 16 24 32 Operating Conditions 3.6 S050 S100 Maximum Differential Pressure(4) 240 Forward and Reverse 3.4 bard (50 psid) to 232 °C (450 °F) 200 Flow Direction 2.7
(4) Minimum collapse differential pressure. Temperature limit with Buna-N gaskets: 160 121 °C (250 °F). Other gasket materials to 232 °C (450 °F). For temperatures to 316 °C (600 °F), or in other alloys to 677 °C (1250 °F), contact your local Pall distributor. 1.8 120
Recommended Maximum Flow Densities(5) 80 0.9 S200 Differential (psid) Pressure Grade Aqueous Air Differential (mbar) Pressure 40 3 L/min (gal/min) Nm /hr (acfm) S350 P Series 0 0 0 1 2 3 4 5 6 7 8 9 PD 3.5 (0.9) 13 (80) Flow Rate (gpm) per 10 in. (254 mm) filter
PE 2.5 (0.7) 9.5 (60) (6) Typical initial clean medium ∆P per 10 in. (254 mm) element, water at 20 °C (68 °F), 1 cp. For assistance in sizing and housing selection, contact PF 2.1 (0.6) 7.9 (50) your local Pall representative. PH 1.4 (0.4) 6.3 (40) P09 1.1 (0.3) 4.7 (30) P05 0.7 (0.2) 1.6 (10) S Series S350 3.5 0.9) 13 (80) S200 2.5 (0.7) 7.9 (50) S100 1.8 (0.5) 6.3 (40) S050 1.1 (0.3) 3.2 (20) (5) Ratings are absolute particulate in liquids and gases. Aqueous water, 1 cp and air flows per 10 in. (254 mm) cartridge.
Ordering Information
MBS100
Code Nominal Length Filter Area Code Liquid Ratings(7) Gas Ratings(7) Code Gasket Options 1 10 in. (254 mm) 0.05 m2 (0.5 ft2) PD 55 µm 20 µm H13 Buna-N gaskets (Standard) PE 35 µm 11 µm 2 20 in. (508 mm) 0.09 m2 (1.0 ft2) H Viton* PF 20 µm 2.8 µm 3 30 in. (762 mm) 0.14 m2 (1.5 ft2) J Ethylene Propylene PH 13 µm 1.3 µm J7 Ethylene Propylene (Steam Service) P09 9 µm 0.8 µm Other materials available on request. P05 5 µm 0.4 µm * Viton is a registered trademark of DuPont Dow S35 35 µm 11 µm (non-FDA materials). S200 20 µm 2.8 µm S100 10 µm 0.8 µm S050 5 µm 0.4 µm
140 (7) Liquids: > 99.98% by mod. OSU-F2 test. Gases: 100% for hard spherical particles. PMM® Metal Membrane Filter Cartridges Pleated Composite Metal Media for High-removal Efficiency
Pall PMM metal membrane media Features and Benefits combine the best qualities of Pall’s PSS • All-stainless steel construction and Rigimesh media by incorporating a thin matrix of ultra-fine stainless steel • Controlled and fixed pore size powders sintered within the pore structures • High area pleated cartridges of fine sintered stainless steel woven wire mesh. This combination of technologies • Efficiencies to 2 µm absolute in liquids enables production of highly permeable • Ultra-clean steam service metal membranes with greater strength • Efficient cake formation and solids and finer grades than either method alone. recovery PMM media can be pleated to form double open-ended (DOE) MBS1000 style • Corrosion resistant membrane filter cartridges with high area • High pressure resistant and fine ratings making it an excellent choice for steam service and other fine • Withstands high reverse-flows solids recovery/removal applications in • High-temperature capabilities both liquid and gas applications. • Repeatedly cleanable • No soluble polymeric extractables • No unloading or shedding • Absolute rated for reliable performance • ISO 9000 Certified Quality System • Manufactured for use in conformance with cGMP • FDA-listed materials per 21 CFR
141 PMM Metal Membrane Filter Cartridges Technical Specifications
Materials of Construction Typical Liquid Flow Rates(6) Flow Rate (L/min) Medium Type 316L stainless steel(1) 0 3 6 9 12 15 End Caps Type 304 stainless steel(1) 0.54 M020 M050 M100 35 Gasket Buna-N (standard)(2) M150 (1) Other grades and alloys available. 30 (2) Other polymers available. 0.405 25 Configuration(3) 20 Double open-ended (DOE), flat gasket seals 0.27
(3) Single open-ended AB sanitary and threaded styles available. 15 M200
Differential (psid) Pressure 10 Nominal Dimensions 0.135 Differential (mbar) Pressure Diameters 2.5 in. (64 mm) 5
Operating Conditions 0 0 0 1 2 3 4 Maximum Differential Pressure and Temperature(4) Flow Rate (gpm) Forward Flow Direction 8.6 bard (125 psid) to 232 °C (450 °F) (6) Typical initial clean medium ∆P per 10 in. (254 mm) element, water at Reverse Flow Direction 0.7 bard (10 psid) to 232 °C (450 °F) 20 °C (68 °F), 1 cp. For assistance in sizing and housing selection, contact your local Pall representative. (4) Minimum collapse differential pressure. Limit with Buna-N gaskets: 121 °C (250 °F). Other gasket materials to 232 °C (450 °F). For Reinforced for 3.4 bard (50 psid) Reverse Flow option, temperatures to 316 °C (600 °F), or in other alloys to 677 °C (1250 °F), contact your local Pall distributor.
Recommended Maximum Flow Densities(5)
Grade Aqueous Air L/min (gal/min) Nm3/hr (acfm) M200 1.4 (0.37) 4.7 (30) M150 1.1 (0.29) 3.9 (25) M100 0.4 (0.1) 3.2 (20) M050 0.3 (0.08) 1.6 (10) M020 0.3 (0.08) 1.6 (10) (5) Ratings are absolute particulate in liquids and gases. Aqueous (water, 1 cp) and air flows per 10 in. (254 mm) cartridge.
Ordering Information
MBS100
Code Nominal Length Filter Area Code Liquid Ratings(7) Gas Ratings(7) Code Gasket Options 1 10 in. (254 mm) 0.14 m2 (1.5 ft2) M200 20 µm 55 µm H13 Buna-N gaskets (Standard) 2 20 in. (508 mm) 0.28 m2 (3.0 ft2) M150 15 µm 25 µm H Viton* 3 30 in. (762 mm) 0.42 m2 (4.5 ft2) M100 10 µm 18 µm J Ethylene Propylene 4 40 in. (1016 mm) 0.56 m2 (6.0 ft2) M050 5 µm 13 µm J7 Ethylene Propylene (Steam Service) M020 2 µm 2 µm Other materials available on request. * Viton is a registered trademark of DuPont Dow (7) Liquids: > 99.98% by mod. OSU-F2 test. (non-FDA materials). Gases: 100% for hard spherical particles.
142 Filter Housings Filter Housings
Pall has over 35 years of successful • Junior Style and SealkleenTM stainless experience in designing and manufacturing steel filter housings for laboratory use filter housings for a wide range of applications. and process development All Pall housings allow optimal product flow at TM minimal pressure drop to offer users the • Pall Advanta Junior housings for small advantages of reduced energy costs, safer to medium volume sanitary applications operation, and the longest possible filter • Pall Advanta single-round sanitary service life. housings with aseptic design and The Pall AdvantaTM line of sanitary housings is engineered for the filtration of gases and specially designed for applications in the fluids in today’s manufacturing pharmaceutical and biotechnology industries. processes There are no removable tube sheets in these • Pall Advanta multi-round sanitary housings, therefore enabling Clean-in-Place housings for high-flow liquid applications operation. The housing design is flexible, providing various inlet and outlet options and • VeladiscTM filter housings for Supradisc vent and drain configurations. The number of depth filter modules welds is minimized to reduce the chances of residual deposit. The interior and exterior • Junior Style industrial housings for small surfaces are electro-polished to meet the flow applications most stringent surface requirements. • IOL and IDL industrial single cartridge Pall’s expertise in BioPharmaceutical filtration filter housings and separation ensures that Advanta housings meet all GMP requirements. • PCY polypropylene housings for liquid filtration applications Supported by the state-of-the-art manufacturing technology, Pall is the leader in • MegaplastTM plastic housings that can be providing the most reliable and technologically utilized safely at high pressures for advanced filter housings to the industry. In this high-flow rate applications section, you will find complete product data for following Pall air/gas and liquid service filter housings.
144 Junior B series Filter Housings Small-scale Stainless Steel Housings for High-flow Gas or Liquid Filtration
To meet the increasing demand for Applications small-scale filters for laboratory use and • Small batches of biological and process development, Pall has developed biochemical fluids the the Junior B series housings. These are some of the smallest stainless stainless • Filtration of compressed gases steel housings on the market, yet they can • A variety of processes requiring filtration achieve very high-flow rates using specially Above: BLS7001G23J of small flows of liquids or gases developed Pall SBF-style pleated cartridges. For small-scale filtration this • Sterile air for small and medium Junior range is less cumbersome than fermentation systems larger housings or difficult-to-use disc • Sterile venting of small tanks and holders. All styles are suitable for in situ vessels steam-sterilization in sterile processes.
Features and Benefits
• Minimal size and weight makes these filter housings ideal for bench-top use, or for installing into processing equipment, for both gas and liquid filtration up to 10 bar (145 psi) operating pressure • The electropolished crevice-free surfaces give maximum cleanliness for sterile processes. In situ steam-sterilization and steam autoclaving up to 140 °C (284 °F) can be employed • Housings are made of 316L stainless steel, and are therefore resistant to a wide variety of chemicals • Maximizes product recovery, particularly important when filtering small-batch or high value products. • Plug-in double O-ring cartridges in a selection of Pall filtration media are available to give maximum filtration quality, economy and performance for individual applications • Available in T-flow or inline styles with butt weld or sanitary inlet and outlet connections
145 Junior B series Filter Housings Technical Specifications
Materials of Construction Typical Liquid Flow Rates for Typical Air Flow Rates for BLS/BTS 7001 Housing* BLS/BTS 7001 Housings* Housing 316L stainless steel except the 10000 10000 closure ring which is 431 stainless steel Seal Material Ethylene Propylene Vessel Closure Closure ring
Surface Finish Electro-polishing 1000 1000 Inlet and Outlet a) 1 in. Sanitary flange Connection Options b) 15 mm Butt weld Vent Connection BTS Housing: Male Stäubli* 100 100 Differential Pressure (mbar) Pressure Differential Drain Connection BTS Housing: (mbar) Pressure Differential Hose barb BLS Housing: Hose barb 10 10 1 10 100 1 10 100 Design Code Designed and manufactured to Pall Flow Rate (L/min) Flow Rate (Nm3/h) industrial standards which includes: a) A minimum design capability of * 1 bar = 14.5 psi, 1 Nm3/h = 0.59 scfm 5 x maximum operating pressure b) Hydrostatically testing each unit to at least 1.5 x maximum operating Nominal Dimensions pressure BLS7001G23J BLS7001G22J BTS7001G23J * Stäubli is a registered trademark of Stäubli AG. Dimension A 121 mm 218 mm 218 mm (4.76 in.) (8.6 in.) (8.6 in.)
Operating Conditions Dimension B 64 mm 64 mm 64 mm Maximum Operating -1(1) to 10 barg (2.52 in.) (2.52 in.) (2.52 in.) (1) Pressure (-14.5 to 150 psig) Dimension C 75 mm 75 mm 75 mm Maximum Operating and 140 °C (284 °F) (2.95 in.) (2.95 in.) (2.95 in.) Steaming Temperature Dimension D 49 mm 49 mm 49 mm (1) Full vacuum. (1.93 in.) (1.93 in.) (1.93 in.)
Use with Steam: This housing may be steam-sterilized and used for steam filtration up Dimension E – 66 mm 66 mm to a temperature of 140 °C (284 °F). Operating limits for steam service may be (2.60 in.) (2.60 in.) influenced by filter cartridge specifications. Refer to appropriate literature for Pall filter cartridges. Weight 1.3 kg 1.3 kg 1.3 kg (2.87 lbs) (2.87 lbs) (2.87 lbs) Pressure Drop Volume 0.1 L 0.1 L 0.1 L
The water flow and pressure drop characteristics refer to the empty housing only for (3) Length across. water flow at 20 °C (68 °F). For other liquids multiply pressure drop by the relative density. The air flow and pressure drop characteristics refer to the empty housing only for air flow at 20 °C (68 °F). Flow rates relate to air (in Nm3/hour/scfm) at 2 bar gauge (3 bar (43.5 psi) absolute). Pressure drops for other pressures may be obtained by multiplying BLS 7001 Housing BTS 7001 Housing the figure taken from the bar gauge graph with the factor shown in the following table: Working Pressure (Barg)(2) 12345
Factor to Apply 1.50 1.00 0.75 0.60 0.50 Required Clearance C Required Clearance C for Cartridge Removal for Cartridge Removal Working Pressure (Barg) 6 7 8 9 10 Factor to Apply 0.42 0.37 0.33 0.30 0.2 ØD To obtain the total pressure drop of a complete filter assembly, the cartridge pressure drop must be added. Please refer to the relevant filter cartridge literature or contact Pall. A (2) 1 bar = 14.5 psi. ØD
A
Ordering Information Inlet and Outlet Connection
B S7001G J B E
Code Housing Type Code Inlet and Outlet B L In-Line 22 15 mm Butt weld
T T-flow 23 1 in. sanitary flange Housings use Pall SBF1 style filter cartridges, and are supplied without cartridges
146 Sealkleen™ Filter Housings Versatile In-line Filter Housings for Small-scale Production
Sealkleen filter housings are versatile in- Features and Benefits line filter housings for small-scale • Aseptic design — with electropolished production. In-line filter housings are ideally surfaces giving typical internal suited for bench top applications and Ra-values of ≤ 0.4 µm (≤ 15 µin.) processes where minimal hold-up volumes without crevices or deadlegs are required to maximize product yields. The Pall Sealkleen housing combines this • High product yields by low hold-up Left: ZLK702G10NKH4 Right: ZLK702G23LHKH4 key requirement with a unique production volumes safety concept. • Valve designed for easy operation, Its patented sealing mechanism ensures maintenance and filter integrity testing that the downstream section of the filter • Variants for integration into automated is essentially never contaminated with systems unfiltered fluid. Designed for GMP use, these housings are easy to use and benefit • Wide range of connection options from low installation and maintenance costs. Pall Sealkleen filter housings are made from stainless steel grade AISI 316L. Advanced manufacturing technologies including CNC machining and orbital welding ensures a robust and highly sanitary design. Features of this housing range include high quality electropolished internal surfaces, a design optimized for CIP/SIP requirements, design variants for easy automation, as well as convenient filter integrity testing.
147 Sealkleen Filter Housings Technical Specifications
Materials of Construction Typical Gas Flow Rates All Product Wetted Parts AISI 316L Flow Rate (scfm) 0306090 V-Clamp AISI 316L, Nitronic 60 300 4.0 Seals Silicone elastomer GNW15 and G10 Surface Finish All electropolished 250 Internal: 3.0 Ra ≤ 0.4 µm (≤ 15 µin.) (typical) 200 External: Ra ≤ 0.8 µm (≤ 32 µin.) (typical) 150 2.0 Documentation Certificate type 2.3 to EN10204 100 1 Differential Pressure (psi) Pressure Differential Operating Conditions (mbar) Pressure Differential 50 G23L Maximum Operating -1(1) to 10 barg (1) Pressure (-14.5 to 150 psig) 0 0 0204060 Maximum Operating 150 °C (300 °F) Flow Rate (Nm3/h) Temperature
(1) Full vacuum. Typical Water Flow Rates Flow (gal/min) Nominal Dimensions 01 23 45 200 (2) (3) Part Number A BCWeight Volume GNW15 and G10
ZLK702G23LHKH4 202 mm 63.5 mm 135 mm 1.1 kg 0.5 L 2.5 ZLK702G23LDDH4 (8.0 in.) (2.5 in.) (5.3 in.) (2.42 lbs) 150 ZLK702GNW15NKH4 2.0 ZLK702G10NKH4 270 mm 63.5 mm 135 mm 1.1 kg 0.5 L (10.7 in.) (2.5 in.) (5.3 in.) (2.42 lbs) 100 1.5 (2) SLK7001 variant may be possible, please contact Pall for details. (3) For use with Sealkleen SLK7002 filter elements. Where SLK7001 type filters are used, 1 the clearance requirement reduces to 75 mm (3.0 in.). 50 Differential Pressure (psi) Pressure Differential
Differential Pressure (mbar) Pressure Differential G23L Gas flow and differential pressure characteristics refer to the empty housing only for air at 0.5 2 barg pressure and 20 °C (68 °F). Pressure drops for other pressure ratings may be obtained by multiplying the pressure drop at 2 barg by the factors shown in table below. 0 0 0 5 10 15 20 Pressure Comparisons Flow Rate (L/min) Working Pressure (barg) 1 2 3 4 5 6 Working Pressure (psi)(3) 15 30 45 60 75 90 Filter Styles and Dimensions
Factor to Apply 1.50 1 0.75 0.60 0.50 0.42 C (3) psi rounded figure. Clearance for Cartridge removal
Main Accessories and Spares B Part Number(4) Description
1 ACS0598CM Diaphragm valve for ⁄2 in. sanitary flange connections including clamp and silicone gasket A ACS0272EU Silicone housing gasket Overall Height Overall SLK1VG23H4 Downstream gasket (silicone)
ACS0718EU Housing valve gasket (silicone)
ACS0224DA V – Clamp housing closure ZLK702G23LHKH4 ZLK702G23LDDH4 ZLK702GNW15NKH4 ZLK702G10NKH4
ORH4P-335 Silicone housing closure gasket
(4) For steam jacketed housing option, please contact Pall. Ordering Information
ZLK 702 G H4(5)
Code Inlet and Outlet Code Vent Code Drain
1 (5) 1 (5) 1 (6) 23L For 1 ⁄2 in. sanitary flange D For ⁄2 in. sanitary flange DFor ⁄2 in. sanitary flange NW15 Dairy fitting NW15 to DIN 11851 H Sanitary valve with quick release K Sanitary hose barb valve (6) 1 (7) 1 fitting for Stäubli* couplings for 6 mm ( ⁄4 in.) I.D. tubing 10 Hosetail for 13 mm ( ⁄2 in.) i.D. tubing K Sanitary hose barb valve (5) Gasket material silicone, other materials available on request. 1 (7) for 6 mm ( ⁄4 in.) i.D. tubing (6) Available for sanitary flange inlet and outlet connections only. (7) N No vent Care should be taken to fit hoses to the housing in a secure manner suitable to withstand the maximum 148 *Stäubli is a trademark of Stäubli AG. operating pressure of 10 barg (150 psig). Pall Advanta™ Junior Filter Housings Advanced Sanitary Housings for Small to Medium Applications
Pall Advanta Junior filter housings are designed for small to medium volume sanitary applications. Four complete series — AGT, ALI, ALT and AVL — provide optimal performances for gas filtration of up to 100 Nm3/hour (60 SCFM) and liquid filtration of up to 7.5 L/min (2 gal/min). Pall Advanta Junior housings are made from stainless steel grade AISI 316L and are available in in-line, L flow and T flow configurations. Developed for GMP implementation, these low upstream volume housings enable high product yields, low installation costs, low maintenance costs and operational simplicity. Advanced manufacturing technologies including CNC machining, automatic orbital welding and electro-polishing ensure a robust and highly sanitary design that meets the most stringent requirements. Top: Pall Advanta Junior Housing — Liquid Bottom: Pall Advanta Junior Housing — Gas
Applications Series AGT ALI ALT AVL Applications Air and Gas Air and Gas, Air and Gas, Air and Gas, Liquid Liquid Liquid
Filter MCY4463 MCY 1110 – MCY 4440 MCY 1110 – Cartridges MCY4440 MCY4440 MCY 4440 Configurations T Flow Inline Flow T Flow L Flow
Specification
Maximum Operating Pressure -1 to 10 barg (-14.5* to 150** psig)
Maximum Operating Temperature 150 °C (300 °F)
Materials of Construction All Product Wetted Parts AISI 316L V-Clamp AISI 316L, Nitronic 60 Seals Silicone elastomer Surface Finish All electropolished Internal: Ra ≤ 0.4 µm (≤ 15 µin.) (typical) External: Ra ≤ 0.8 µm (≤ 32 µin.) (typical)
Inspection Documentation Certificate type 2.3 to EN10204
* Full vacuum. ** With compatible fluids, which do not soften, swell or adversely affect the gasket materials. 149 Pall Advanta Junior Gas Filter Housings Technical Specifications
High quality sanitary T-style housings for general purpose small-scale Typical Air Flow Rates(4) gas filtration. Flow Rate (Nm3/h) 0 20 40 60 80 100 120 140 160 300 Features of this housing range for use in sanitary gas applications are 4.4 A B • A: Vent high quality electropolished internal surfaces, a design optimized for • B: 1 barg (15 psig) CIP/SIP requirements, design variants for easy automation, as well as • C: 2 barg (29 psig) • D: 3 barg (44 psig) C convenient filter integrity testing with the Water Intrusion Test method for hydrophobic filters. 2.9 200
Features and Benefits D • Aseptic design — with electropolished surfaces giving typical internal Ra-Values of ≤ 0.4 µm (≤ 15 µin.) without crevices or 1.5 100 Differential Pressure (psi) Pressure Differential
deadlegs and fully self draining (mbar) Pressure Differential • In situ water intrusion test without additional upstream gas buffer volumes 0 0 • New valve design for easy operation, maintenance and filter 0 10 20 30 40 50 60 70 80 90 integrity testing Flow Rate (scfm) (4) Gas flow and differential pressure characteristics refer to the empty • Variants for integration into automated systems housing only for air at 20 °C (68 ° F). Pressure drops for other pressure ratings may be obtained by multiplying the pressure drop at the pressure • Cartridge fixes to internal spigot and sealed by single O-ring stated by the factors shown in the table. • Every housing supplied with a quality certificate and manufactured to ATEX Directive 94/9/EC (Group ll Category 2) Pressure Comparisons Working Pressure (barg) 1 2 3 4 5 6 Nominal Dimensions Working Pressure (psi)(3) 15 30 45 60 75 90 Factor to Apply 1.50 1 0.75 0.60 0.50 0.42 Part Number(1) Face to Face Overall(2) Clearance Width Height Required (3) Psi rounded figure.
AGT463G05HKH4 151 mm 308 mm 112 mm AGT463G23HKH4 (5.9 in.) (12.1 in.) (4.4 in.) Main Accessories and Spares AGT463GNW15HKH4 AGT463GB21HKH4 Part Number Description
1 AGT463G05DDH4 151 mm 226.5 mm 112 mm ACS0598CM Diaphragm valve for ⁄2 in. sanitary flange (5.9 in.) (8.9 in.) (4.4 in.) connections to ISO 2852 including clamp and silicone gasket AGT463GB21NEH4 151 mm 211 mm 112 mm (5.9 in.) (8.3 in.) (4.4 in.) ORH4P-150 Silicone housing closure gasket ACS0718EU Housing valve gasket kit AGT463GB21NNH4 151 mm 187 mm 112 mm (5.9 in.) (7.3 in.) (4.4 in.) ACS0224DA V Clamp housing closure
(1) Pall Advanta Junior AGT463 housings are not designed to be fitted with MCY2230 Further spares and accessories available upon request. filter elements. For special Pall Advanta Junior housings accepting MCY2230 filter elements, please contact Pall. (2) When MCY2230 elements are used, please consult Pall.
Ordering Information
AGT 463 G H4(5)
Code Design Code Inlet and Outlet Code Vent Code Drain
3 1 1 – To European Pressure 05 For ⁄4 in. sanitary flange D For ⁄2 in. sanitary flange D For ⁄2 in. sanitary flange Equipment Directive to ISO 2852 to ISO 2852 to ISO 2852
D To European Pressure 23 For 1 in. sanitary flange E Butt weld H Sanitary valve with Equipment Directive with to ISO 2852 13.5 x 1.6 mm to ISO 1127 quick release fitting for enhanced documentation Stäubli couplings including 3.1b stamped NW15 Dairy fitting NW15 to H Sanitary valve with material and certification DIN11851 quick release fitting for K Sanitary valve with Stäubli* couplings hose barb for 6 mm B21 Butt weld 21.3 x 1.6 mm 1 ( ⁄4 in.) i.D. tubing to ISO1127 N No vent E Butt weld 13.5 x (5) Gasket material silicone, other gasket 1.6 mm to ISO 1127 materials available on request. Please contact Pall. N No drain *Stäubli is a trademark of Stäubli AG. 150 Pall Advanta Junior F Liquid Filter Housings Technical Specifications
High quality versatile sanitary T-style housings for all small-scale gas Typical Water Flow Rates(3) filtration. Typical Water Flow Rate (gpm) Features of this housing range are high quality electropolished internal 0 5 10 15 20 7 surfaces, a design optimized for CIP/SIP requirements, design 500 variants for easy automation, as well as convenient filter integrity 6 testing. 400 5 Features and Benefits 300 4 • Aseptic design — with electropolished surfaces giving typical internal Ra-Values of ≤ 0.4 µm (≤ 15 µin.) without crevices or 3 deadlegs and fully self draining 200
• New valve design for easy operation, maintenance and filter 2 (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential integrity testing 100 1 • Variants for integration into automated systems
0 0 • Wide range of connection options 0 20 40 60 80 • Cartridge retained by built-in flanges and double O-ring seal Typical Water Flow Rate (L/min)
• Housings accept up to four cartridge sizes for flexibility (3) Water flow and differential pressure drop characteristics refer to the empty housing only for water at 20 °C (68 °F). For other liquids please multiply • Every housing supplied with a quality certificate and manufactured pressure drop by specific gravity. to ATEX Directive 94/9/EC (Group ll Category 2)
Nominal Dimensions
Part Number(1) Face to Face Overall(2) Clearance Main Accessories and Spares Width Height Required Part Number Description
1 ALT440G05HKH4 151 mm 314 mm 112 mm ACS0598CM Diaphragm valve for ⁄2 in. sanitary clamp ALT44GNN15HKH4 (5.9 in.) (12.4 in.) (4.4 in.) compatible connections to ISO 2852 ALT440GA15HKH4 including clamp and silicone gasket ALT440GB21HKH4 ALT440G23HKH4 ORH4P-150 Silicone housing closure gasket ACS0718EU Housing valve gasket kit ALT440G05DDH4 151 mm 227 mm 112 mm (5.9 in.) (8.9 in.) (4.4 in.) ACS0224DA V Clamp housing closure
(1) MCY2220 and MCY1110 variants may be possible, refer to Pall. Further spares and accessories available upon request. (2) For MCY4440 filters, where smaller filter elements are used, please consult for nominal length information.
Ordering Information
ALT 440 G H4*
Code Design Code Inlet and Outlet Code Vent Code Drain
3 1 1 – To sound engineering 05 For ⁄4 in. sanitary D For ⁄2 in. Tri-Clamp* D For ⁄2 in. sanitary practice clamp to ISO 2852 to ISO 2852 clamp to ISO 2852
D To sound engineering 23 For 1 in. sanitary H Sanitary valve with K Sanitary valve with practice with enhanced clamp to ISO 2852 quick release fitting for hose barb for 6 mm 1 documentation including Stäubli* couplings ( ⁄4 in.) i.D. tubing 3.1b stamped material A15 Aseptic thread connections and certification to DIN11864-1 * Gasket material silicone, other gasket materials available on request. NW15 Dairy fitting NW15 to Please contact Pall. DIN11851 *Stäubli is a trademark of Stäubli AG.
B21 Butt weld 21.3 x 1.6 mm to ISO1127
151 Pall Advanta Junior F Gas Filter Housings Technical Specifications
Versatile high quality sanitary T-style housings for all small-scale gas Typical Air Flow Rates(4) filtration. Flow Rate (Nm3/h) 0 20 40 60 80 100 120 140 160 300 Features of this housing range for use in sanitary gas applications are 4.4 A B • A: Vent high quality electropolished internal surfaces, a design optimized for • B: 1 barg (15 psig) CIP/SIP requirements, design variants for easy automation, as well as • C: 2 barg (29 psig) • D: 3 barg (44 psig) C convenient filter integrity testing with the Water Intrusion Test method for hydrophobic filters. 2.9 200
Features and Benefits D • Aseptic design — with electropolished surfaces giving typical internal Ra-Values of ≤ 0.4 µm (≤ 15 µin.) without crevices or 1.5 100 Differential Pressure (psi) Pressure Differential
deadlegs and fully self draining (mbar) Pressure Differential • In situ water intrusion test without additional upstream gas buffer volumes • New valve design for easy operation, maintenance and filter 0 0 0 10 20 30 40 50 60 70 80 90 integrity testing Flow Rate (scfm) • Variants for integration into automated systems (4) Gas flow and differential pressure characteristics refer to the empty housing only for air at 20 °C (68 ° F). Pressure drops for other pressure • Wide range of connection options ratings may be obtained by multiplying the pressure drop at the pressure • Cartridge retained by built in flanges and double O-ring seal stated by the factors shown in the table. • Housings accept single cartridges in four different lengths for increased flexibility Pressure Comparisons • Every housing supplied with a quality certificate and manufactured to ATEX Directive 94/9/EC (Group ll Category 2) Working Pressure (barg) 1 2 3 4 5 6 Working Pressure (psi)(3) 15 30 45 60 75 90 Nominal Dimensions Factor to Apply 1.50 1 0.75 0.60 0.50 0.42 (3) Psi rounded figure. Part Number(1) Face to Face Overall(2) Clearance Width Height Required
AGT440G05HKH4 151 mm 312.5 mm 112 mm AGT440G23HKH4 (5.9 in.) (12.3 in.) (4.4 in.) Main Accessories and Spares AGT440GNW15HKH4 AGT440GA15HKH4 Part Number Description
1 AGT440G05DDH4 151 mm 228.5 mm 112 mm ACS0598CM Diaphragm valve for ⁄2 in. sanitary flange (5.9 in.) (8.9 in.) (4.4 in.) compatible connections to ISO 2852 including clamp and silicone gasket AGT440GB21ENH4 151 mm 213 mm 112 mm (5.9 in.) (8.4 in.) (4.4 in.) ORH4P-150 Silicone housing closure gasket
AGT440GB21NNH4 151 mm 190.5 mm 112 mm ACS0718EU Housing valve gasket kit (5.9 in.) (7.5 in.) (4.4 in.) ACS0224DA V Clamp housing closure
(1) MCY2220 and MCY1110 variants may be possible, refer to Pall. * Further spares and accessories available upon request. (2) For MCY4440 filters, where smaller filter elements are used, please consult for nominal length information Ordering Information
AGT 440 G H4(5)
Code Design Code Inlet and Outlet Code Vent Code Drain
3 1 1 – To sound engineering 05 For ⁄4 in. sanitary flange D For ⁄2 in. sanitary flange D For ⁄2 in. sanitary flange practice to ISO 2852 to ISO 2852 to ISO 2852
D To sound engineering 23 For 1 in. sanitary flange E Butt weld H Sanitary valve with practice with enhanced to ISO 2852 13.5 x 1.6 mm to ISO 1127 quick release fitting for documentation including Stäubli couplings 3.1b stamped material A15 Aseptic thread connections H Sanitary valve with and certification to DIN11864-1 quick release fitting for K Sanitary valve with Stäubli* couplings hose barb for 6 mm NW15 Dairy fitting NW15 to 1 ( ⁄4 in.) i.D. tubing DIN11851 N No vent E Butt weld 13.5 x B21 Butt weld 21.3 x 1.6 mm *Stäubli is a trademark of Stäubli AG. 1.6 mm to ISO 1127 to ISO1127 N No drain (5) Gasket material silicone, other gasket materials available on request. Please 152 contact Pall. Pall Advanta™ ALT Liquid Filter Housings Advanced Sanitary T-Style Filter Housings for Liquid Applications
The Pall Advanta range of filter housings Features and Benefits has been specifically designed and • Aseptic design engineered for today’s manufacturing processes. These advanced housings are Crevice-free electropolished surfaces manufactured from 316L stainless steel with an internal Ra value of ≤ 0.4 µm and are engineered to meet the (≤ 15 µin.) requirements of the BioPharmaceutical Fully self draining industry. State-of-the-art manufacturing technologies are used to construct a No dead legs housing ideal for the most critical of • Low hold-up volumes for maximum applications. product recovery Fine filtration of liquids is a key part of • Quick fit Stäubli*-type connections for many production processes. These Pall easy filter integrity testing Advanta housings have been specifically • Easy to use low point sanitary drain designed to meet the many requirements valve of this demanding application. During the design process critical features were • Range of options to aid use in optimized to ensure trouble-free use and automated production systems low installation and maintenance costs. • CE marking shows design review to Areas such as surface finish, suitability for European Pressure Directive 97/9/EC CIP and SIP, integrity testing and incorporation into automated production • Every housing supplied with a quality processes are included: certificate and manufactured to ATEX Directive 94/9/EC (Group ll Category 2) • Variety of connection styles, vents and drains offer choice and convenience • Filter cartridge accepts single open-ended Pall Code 7 and Code 2 AB style 5 in. (127 mm), 10 in. (254 mm), 20 in. (508 mm), and 30 in. (762 mm) height filter cartridges
* Stäubli is a trademark of Stäubli AG.
153 Pall Advanta ALT Liquid Filter Housings Technical Specifications
Materials of Construction Typical Water Flow Rates(3) Flow Rate (Gal/min) Wetted Parts AISI 316L stainless steel 0 5 10 15 25 Clamp AISI Nitronic* 60 300 O-ring Silicone — FDA-listed 4 Steam-sterilizable Up to 150 °C (300 °F) 250 Surface Finish All electropolished 3 Internal: 200 Ra ≤ 0.4 µm (≤ 15 µin.) (typical)
External: 150 Ra ≤ 0.8 µm (≤ 32 µin.) (typical) 2
Inspection Documentation Test report type 2.3 to EN10204 100 (1)
Conformance to EC PED (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential 1 (1) With compatible fluids, which do not soften, swell or adversely affect the materials. 50 * Nitronic is a registered trademark of Armco Inc.
0 0 Nominal Dimensions 0 10 20 30 40 50 60 70 80 90 100 Part Number(2) Face to Face Overall Clearance Flow Rate (L/min) Width Height Required (3) The flow and pressure drop characteristics refer to the empty housing only for water at 20 °C (68 °F). For other liquids multiply pressure drop by relative ALT105G23CBH4 190 mm 378 mm 160 mm density. To obtain the total pressure drop of a complete filter assembly, the (7.4 in.) (14.8 in.) (6.2 in.) cartridge pressure drop must be added. Please refer to the relevant filter cartridge literature or contact Pall. ALT11G23CBH4 190 mm 514 mm 320 mm ALT11GNW25CBH4 (7.4 in.) (20.2 in.) (12.5 in.)
ALT11G23CDH4 190 mm 519 mm 320 mm (7.4 in.) (20.4 in.) (12.5 in.) Operating Conditions
ALT11G23DDH4 190 mm 437 mm 320 mm Maximum Operating -1 to 10 barg (7.4 in.) (17.2 in.) (12.5 in.) Pressure (-14.5(4) to 150(5) psig)
ALT11GA25ABH4 190 mm 517 mm 320 mm Maximum Operating 150 °C (300 °F) (7.4 in.) (20.3 in.) (12.5 in.) Temperature
ALT12G23CBH4 190 mm 765 mm 570 mm (4) Full vacuum. (7.4 in.) (30.1 in.) (22.4 in.) (5) With compatible fluids, which do not soften, swell or adversely affect the materials.
ALT13G23CBH4 190 mm 1039 mm 820 mm ALT13GNW25CBH4 (7.4 in.) (40.9 in.) (32.2 in.)
(2) These part numbers represent the most commonly used housing variants with the shortest lead times. Many other variants are available (see ordering information). Please contact Pall for further information.
Ordering Information
ALT 1 G H4(6)
Code Design Code Cartridge Type Code Inlet and Outlet Code Vent Code Drain – To European Pressure 05 AB05 code 2 23 1 in. sanitary A Sanitary valve B Sanitary valve with Equipment Directive flange to ISO 2852 fitting for Stäubli hosebarb 1 AB1 code 7 type couplings 1 D To European Pressure NW25 Dairy fitting NW 25 D ⁄2 in. sanitary flange 2 AB2 code 7 1 Equipment Directive to DIN 11851 C11⁄2 in. sanitary flange connection to with enhanced 3 AB3 code 7 connection to ISO 2852 documentation A25 Aseptic thread ISO 2852 with side N No drain including 3.1b connection sanitary valve with stamped material and NW 25 to quick release fitting (6) Silicone elastomer seal material. certification DIN 11864-1 for Stäubli type other materials available upon request. 95 ISO butt weld couplings
33.7 x 2.0 mm 1 D1⁄2 in. sanitary flange to ISO 1127 compatible with side sanitary valve with fitting for Stäubli type couplings
E ISO butt weld 13.5 x 1.6 mm to ISO 1127
*Stäubli is a trademark of Stäubli AG. 154 Pall Advanta™ In-Line Liquid and Gas Filter Housings Advanced Sanitary In-Line Filter Housings for Liquid and Gas Applications
The Pall Advanta range of filter housings Features and Benefits has been specifically designed and • Aseptic design engineered for today’s manufacturing processes. These advanced housings are Crevice-free electropolished surfaces manufactured from 316L stainless steel with an internal Ra value of ≤ 0.4 µm and are engineered to meet the (≤ 15 µin.) requirements of the BioPharmaceutical Fully self draining industry. State-of-the-art manufacturing technologies are used to construct a No dead legs housing ideal for the most critical of • Low hold-up volumes for maximum applications. product recovery Fine filtration of liquids and gases is a key • Quick fit Stäubli* type connections for part of many production processes. These easy filter integrity testing Pall Advanta housings have been • Easy to use low point sanitary drain specifically designed to meet the many valve requirements of these demanding applications. Optimization of critical • Range of options to aid use in features during the design process has automated production systems provided a housing range which ensures • Every housing supplied with a quality trouble-free use and low installation and certificate and manufactured to ATEX maintenance costs. Areas included in this Directive 94/9/EC (Group ll Category 2) process were: • CE marked in accordance with • Surface finish Pressure Equipment Directive 97/23/EC • Suitability for CIP and SIP *Stäubli is a trademark of Stäubli AG. • Integrity testing • Incorporation into automated production processes
155 Pall Advanta In-Line Liquid and Gas Filter Housings Technical Specifications
Materials of Construction Typical Air Flow Rates(3) Flow Rate (scfm) Housing AISI 316L Stainless Steel 0 11 23 35 47 58 0.04 1 Clamp 431 Stainless Steel • 1 barg (15 psig) Seals Silicone elastomer • 2 barg (29 psig) • 4 barg (58 psig) Surface Finish All electropolished 0.03 0.75 Internal: Ra ≤ 0.4 µm (≤ 15 µin.) (typical) 0.02 0.5 External: Ra ≤ 0.8 µm (≤ 32 µin.) (typical)
Documentation Certificate type 2.3 to EN10204 0.01 0.25 Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential Operating Conditions 0 0 Maximum Operating -1(1) to 10 barg 0 10 20 30 40 50 60 70 80 90 100 Pressure (-14.5(1) to 150(2) psig) Flow Rate (Nm3/h)
Maximum Operating 150 °C (300 °F) (3) Temperature Typical Water Flow Rates
(1) Full vacuum. Flow Rate (gal/min) (2) With compatible fluids, which do not soften, swell or adversely affect the gasket 0 6 11 16 20 27 70 1 materials. 60
Nominal Dimensions 0.75 50 Part Number Overall Clearance Weight Height Required 40 0.5 ALI105G23LABH4 301 mm 150 mm 2.2 kg 30 ALI105G23LDDH4 (11.8 in.) (5.9 in.) (4.8 lbs) 20 0.25
ALI11G23LAAH4 437 mm 310 mm 2.6 kg (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential ALI11G23LABH4 (17.2 in.) (12.2 in.) (5.7 lbs) 10 ALI11GA23LDDH4 0 0 ALI12G23LABH4 688 mm 564 mm 3.5 kg 0 10 20 30 40 50 60 70 80 90 100 ALI12G23LDDH4 (27 in.) (22.2 in.) (7.7 lbs) Flow Rate (L/min) ALI13G23LABH4 961 mm 818 mm 4.3 kg ALI13G23LDDH4 (37.8 in.) (32.2 in.) (9.47 lbs) Main Accessories and Spares
(3) The flow and pressure drop characteristics refer to the empty housing only for water at Part Number Description 20 °C (68 °F). For other liquids multiply pressure drop by relative density. To obtain the 1 total pressure drop of a complete filter assembly, the cartridge pressure drop must be ACS5098CM Diaphragm valve kit for ⁄2 in. sanitary added. flange connections including clamp and silicone gasket Gas Filtration: This housing style is suitable for use in the filtration of gases and the in- line design ensures that the pressure drops are exceptionally low. Pall recommend using ORH4P-238 Silicone housing closure gasket the cartridge pressure drop when calculating the system pressure drops. Please refer to the relevant cartridge literature or contact Pall. ACS0602EM Silicone housing valve gasket kit Contact your Pall representative or local representative for other spares and accessories.
Ordering Information
ALI 1 G H4(4)
Code Design Code Filter Height Code Inlet and Outlet Code Vent Code Drain – To European Pressure 05 AB05 code 2 23L 1 in. Tri-clamp* A Sanitary valve A Sanitary valve Equipment Directive fittings to ISO2852 coupling to coupling to Stäubli 1 AB1 code 7 Stäubli** type type RBE.03 D To European Pressure 94 33.7 mm (1.33 in.) 2 AB2 code 7 RBE.03 Equipment Directive O.D x 2.0 mm B Sanitary valve with 1 with enhanced 3 AB3 code 7 (0.079 in.) wall butt D ⁄2 in. sanitary hosetail for 6 mm 1 documentation weld to ISO 1127 flange connection ( ⁄4 in.) ID tubing including 3.1b to ISO 2852 1 stamped material and * Tri-Clamp is a trademark of D ⁄2 in. sanitary flange Alfa-Laval, Inc. certification ** Stäubli is a trademark of connection to Stäubli AG. ISO 2852
(4) Gasket material — silicone, other gasket materials available on request. Please contact Pall.
156 Pall Advanta™ Jacketed Housings T-Style and In-Line Housings with Jacket for Temperature Control
Jacketed Filter Housings are fabricated • Fewer welds — results in an extremely with either T-Type or In-Line flow designs sanitary design and AB style Code 7 fitting configurations • Automated orbital welding — produces for single open-ended (SOE) sanitary AB consistent high quality welds style filter cartridges. They offer the added feature of a 316L stainless steel jacket for • Non-rotating vent and drain — prevent temperature control using hot water or twisted hoses and allow hard piping steam, and are suitable for gas service or • Manufactured for use in conformance liquid flows to 20 gal/min (75 L/min) with with cGMP minimal pressure drops. • 3-A Sanitary Standard Symbol for optimized CIP/cleanable design Features and Benefits • Manufacturing Quality System Certified • Corrosion resistant 316 L Stainless to ISO 9000 Standards steel jacket for temperature control • In-Line or T-Type flow designs • Entire housing electropolished • Internal surfaces with ≤ 0.4 µm (≤ 15 µin.) Ra surface finish Top: T-Line Style Filter Housing • External surfaces with ≤ 0.8 µm Bottom: In-Line Style Filter Housing (≤ 32 µin.) Ra surface finish • Low hold-up volume — maximizes product recovery • Easy-draining features, including downward sloping internal contour and low-point drain — allows easy removal of CIP solution or product
157 Pall Advanta Jacketed Housings Technical Specifications
Materials of Construction Typical Water Flow Rates(3)
Housing 316L Stainless Steel Flow Rate (gal/min) 0 6 11 16 20 27 Design Pressure and 10 barg at 140 °C (150 psig at 284 °F) 70 1 Temperature Jacket: 4.9 barg at 140 °C (72 psig at 284 °F) 60
1 Nominal Diameter 114.5 mm (4 ⁄2 in.) 0.75 50 Number of Cartridges 1 40 Cartridge Style AB Code 7 0.5
1 30 Inlet and Outlet Connections 1 ⁄2 in Sanitary coupling Jacket: 1 20 ⁄2 in. NPT 0.25 Differential Pressure (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential Standard Gasket Ethylene Propylene 10 O-ring Material 0 0 Legs and Support ALT: 0 10 20 30 40 50 60 70 80 90 100 Stand available Flow Rate (L/min) ALI: None Closure Style Vee-band clamp Flow Configuration ALT: Tee ALI: In-Line
Operating Conditions
Maximum Operating -1(1) to 10 barg Pressure (-14.5(1) to 150(2) psig)
Maximum Operating 150 °C (300 °F) Temperature
(1) Full vacuum. (2) With compatible fluids, which do not soften, swell or adversely affect the gasket materials.
Ordering Information
ALT1 J23 H4
ALI1 J23L H4
Code Cartridge Type Code Vent Code Drain 1 AB1 code 7 A Sanitary valve with B Sanitary valve with 8 mm quick-release coupling (0.314 in.) hosetail 2 AB2 code 7 1 B Sanitary valve with 8 mm D ⁄2 in. sanitary coupling 3 AB3 code 7 (0.314 in.) hosetail N None
4 AB4 code 7 1 C1⁄2 in. Sanitary flange connection to ISO2852
1 D ⁄2 in. Sanitary coupling N None
158 Pall Advanta™ AGT Gas Filter Housings Advanced T-style Housings for Sanitary Applications
This range of Pall filter housings has been Features and Benefits specifically designed and engineered for • Crevice-free internal surface finish of the filtration of air and gases. The design ≤ 0.4 µm (≤ 15 µin.) Ra is ideal for all complements the high-flow capacities of sanitary applications the Pall Emflon range of sterilizing gas filter cartridges to ensure reliable and cost • Designed for in-line steaming and efficient filtration. integrity testing with Water Intrusion and Forward Flow These advanced gas filter housings are from the Pall Advanta range of housings. • Non-rotation valve connections for easy Manufactured from 316L stainless steel, condensate draining Pall Advanta housings are engineered to • Optional vent valve with integrated meet the requirements of the Stäubli* compatible connector for easy BioPharmaceutical industry. Advanced connection to Palltronic test equipment manufacturing technologies are used to construct a robust housing, incorporating a • Low dynamic pressure drop to assist in high degree of automated orbital welding. energy conservation Features of this advanced sanitary housing • CE marking shows design review to such as the surface finish, steam European Pressure Directive 97/9/EC sterilizability, and ease of filter integrity • Every housing supplied with a quality testing have been tuned to match today’s certificate and manufactured to ATEX exacting requirements both technically and Directive 94/9/EC (Group ll Category 2) economically. • Variety of connection styles, vents and drains offer choice and convenience • Filter cartridge accepts single open-ended Pall Code 7 and Code 2 AB style 5 in. (127 mm), 10 in. (254 mm), 20 in. (508 mm), and 30 in. (762 mm) height filter cartridges
*Stäubli is a trademark of Stäubli AG.
Main Accessories and Spares Part Number Description
1 ACS5098CM Diaphragm valve kit for ⁄2 in. sanitary flange connections including clamp and silicone gasket
ORH4P-238 Silicone housing closure gasket
ACS0602EM Silicone housing valve gasket kit
1 ACS0457FA Pressure gauge kit -1 to 10 barg for 1 ⁄2 in. sanitary clamp connection to ISO 2852 (includes clamp and gasket)
Contact your Pall representative or local representative for other spares and accessories.
159 Pall Advanta AGT Gas Filter Housings Technical Specifications
Materials of Construction Typical Flow Rates(3) Wetted Parts AISI 316L stainless steel 150 NW50 Clamp AISI Nitronic 60 NW25 2 O-ring Silicone — FDA-listed
Steam-sterilizable Up to 150 °C (300 °F) 100 Surface Finish All electropolished Internal: Ra ≤ 0.4 µm (≤ 15 µin.) (typical) 1 External: 50 Ra ≤ 0.8 µm (≤ 32 µin.) (typical) Differential Pressure (psi) Pressure Differential
Inspection Documentation Test report type 2.3 to EN10204 (mbar) Pressure Differential Conformance to EC PED(2)
0 Operating Conditions
Maximum Operating -1 to 10 barg 0 100 200 300 400 500 Pressure (-14.5(1) to 150(2) psig) Flow Rate (Nm3/hour) Vent mode 2 barg inlet 4 barg inlet Maximum Operating 150 °C (300 °F) (29 psi) (58 psi) Temperature NW25 NW50 (1) Full vacuum. (2) With compatible fluids, which do not soften, swell or adversely affect the materials. (3) The flow pressure drop characteristics refer to empty housings only for air at 20 °C (68 °F). To obtain the pressure drop of a complete assembly, the cartridge pressure drop must be added. 1 Nm3/h = 0.59 scfm. Nominal Dimensions Part Number Face to Face Width Overall Height Clearance Required Weight Volume AGT105G94EEH4 240 mm 9.4 in. 345 mm 13.6 in. 180 mm 7.08 in. 2.5 kg 5.5 lbs 1.5 L AGT11G95EEH4 240 mm 9.4 in. 528 mm 20.7 in. 340 mm 13.3 in. 3.6 kg 7.9 lbs 3.0 L AGT12G95EEH4 240 mm 9.4 in. 779 mm 30.6 in. 590 mm 23.3 in. 4.4 kg 9.6 lbs 4.6 L AGT13G95EEH4 240 mm 9.4 in. 1054 mm 41.4 in. 840 mm 33.0 in. 5.3 kg 11.6 lbs 6.2 L AGT105GNW25ABH4 190 mm 7.4 in. 431 mm 16.9 in. 180 mm 7.08 in. 2.5 kg 5.5 lbs 1.5 L AGT11GNW50ABH4 190 mm 7.4 in. 591 mm 23.2 in. 340 mm 13.3 in. 3.6 kg 7.9 lbs 3.0 L AGT12GNW50ABH4 190 mm 7.4 in. 842 mm 33.1 in. 590 mm 23.2 in. 4.4 kg 9.7 lbs 4.6 L AGT13GNW50ABH4 190 mm 7.4 in. 1117 mm 43.9 in. 840 mm 33.0 in. 5.3 kg 11.6 lbs 6.2 L AGT105G23ABH4 190 mm 7.4 in. 431 mm 16.9 in. 180 mm 7.08 in. 2.5 kg 5.5 lbs 1.5 L AGT11G31ABH4 190 mm 7.4 in. 591 mm 23.2 in. 340 mm 13.3 in. 3.6 kg 7.9 lbs 3.0 L AGT12G31ABH4 190 mm 7.4 in. 842 mm 33.1 in. 590 mm 23.2 in. 4.4 kg 9.7 lbs 4.6 L AGT13G31ABH4 190 mm 7.4 in. 1117 mm 43.9 in. 840 mm 33.0 in. 5.3 kg 11.6 lbs 6.2 L AGT105G23CDH4 190 mm 7.4 in. 365 mm 14.3 in. 180 mm 7.08 in. 2.5 kg 5.5 lbs 1.5 L AGT11G31CDH4 190 mm 7.4 in. 521 mm 20.5 in. 340 mm 13.3 in. 3.6 kg 7.9 lbs 3.0 L AGT12G31CDH4 190 mm 7.4 in. 776 mm 30.5 in. 590 mm 23.3 in. 4.4 kg 9.7 lbs 4.6 L AGT13G31CDH4 190 mm 7.4 in. 1051 mm 41.3 in. 840 mm 33.0 in. 5.3 kg 11.6 lbs 6.2 L
Ordering Information
AGT 1 G H4(4)
Code Design Code Cartridge Type Code Inlet and Outlet Code Vent Code Drain – To European Pressure 05 AB05/AB02 23 1 in. sanitary flange A Sanitary valve with A Sanitary valve with Equipment Directive Code 2 to ISO 2852 fitting for Stäubli fitting for Stäubli* D To European Pressure 1 AB1 Code 7 NW25 NW25 to DIN 11851 type couplings couplings Equipment Directive 2 AB2 Code 7 94 ISO butt weld B Sanitary hose barb B Sanitary hose barb with enhanced valve for 8 mm valve for 8 mm i.D. 3 AB3 Code 7 33.7 x 2.0 mm to documentation ISO 1127 i.D. tubing tubing including 3.1b 1 31 2 in. sanitary flange C 1 in. sanitary flange D ⁄2 in. sanitary flange stamped material and with side sanitary certification to ISO 2852 E Butt weld valve with fitting for 13.5 x 1.6 mm NW50 NW50 to DIN 11851 Stäubli* type (4) Seal Material — Silicone 95 ISO butt weld couplings elastomer. Other materials 60.0 x 2.3 mm to E Butt weld available upon request. ISO 1127 13.5 x 1.6 mm Please contact Pall. to ISO 1127 *Stäubli is a trademark of Stäubli AG. 160 Pall Advanta™ AVL Liquid and Gas Filter Housings L-Flow Sanitary Filter Housings
Pall Advanta AVL series filter housings are Features and Benefits L-flow pattern (in the side, out the bottom) • Convenient L-flow pattern facilitates sanitary stainless steel housings. They piping and solves many head-space accommodate one single open-ended limitations Code 7 filter cartridge of 5, 10, 20, or 30 inches (127 mm, 254 mm, 508 mm or • Low-point drain facilitates drainage of 762 mm) nominal length. The Pall Advanta steam-condensate, product or CIP AVL series housings are used for either gas fluids or liquid applications, and are designed to • Crevice-free internal surface finish of meet the stringent requirements of the ≤ 0.4 µm (≤ 15 µin.) Ra is ideal for BioPharmaceutical industry. These sanitary applications housings are commonly used for venting applications because of their convenient • Purpose-design enables inline flow pattern and low pressure-loss. steaming and integrity testing (by water intrusion — WIT — and forward flow) • CE marking shows design-review to European Pressure Equipment Directive 97/23/EC (housings with volumes > 2.5 L) • Every housing supplied with a quality certificate and manufactured to ATEX Directive 94/9/EC (Group ll Category 2) • Variety of connection-styles, vents and drains offers choice and convenience
161 Pall Advanta AVL Liquid and Gas Filter Housings Technical Specifications
Materials Typical Air Flow Rates at 20 °C (68 °F) Housing AISI 316L stainless steel Flow Rate (scfm) 0 50 100 150 180 V-band Clamp AISI 316L Nitronic* 60 • A: Vent C A B D 2.5 O-ring Seal FDA-listed silicone • B: 1 barg (15 psig) 150 • C: 2 barg (29 psig) (other elastomers also available) • D: 3 barg (44 psig) E 2.0 • E: 4 barg (58 psig) Surface Finishes Internal: 120 • F: 7 barg (102 psig) Polished to 0.4 µm (15 µin.) Ra (typical) 1.5 External: 90 F Polished to 0.8µm (32 µin.) Ra (typical) 1.0 60 Interior and Exterior Electropolished
* Nitronic is a registered trademark of Armco, Inc. 30 0.5 Estimated Differential Pressure (psid) Pressure Estimated Differential Estimated Differential Pressure (mbard) Pressure Estimated Differential (1) 0 0 Nominal Dimensions of Selected Housings 0 50 100 150 200 250 Flow Rate (Nm3/hour) Part Number Overall Clearance Weight Volume Height Required(2) (Empty) Typical Liquid Flow Rates at 20 °C (68 °F) Flow Rate (Gal/min) AVL105G23LABH4 364 mm 150 mm 2.5 kg 1.5 L 0 5 10 15 20 25 AVL105G23LDDH4 (14.3 in.) (5.9 in.) (5.5 lbs) (0.4 US gal) 200 AVL105G94ABH4 AVL105G94DDH4 2.5
AVL11G23LABH4 500 mm 340 mm 3.0 kg 2.3 L 150 AVL11G23LDDH4 (19.7 in.) (13.4 in.) (6.6 lbs) (0.6 US gal) 2.0 AVL11G94ABH4 AVL11G94DDH4 100 1.5
AVL12G23LABH4 751 mm 590 mm 3.9 kg 3.8 L 1.0 AVL12G23LDDH4 (29.6 in.) (23.2 in.) (8.6 lbs) (1.0 US gal) AVL12G94ABH4 50 AVL12G94DDH4 0.5 Estimated Differential Pressure (psid) Pressure Estimated Differential AVL13G23LABH4 (mbard) Pressure Estimated Differential 1025 mm 840 mm 4.8 kg 5.4 L 0 0 AVL13G23LDDH4 (40.3 in.) (33.1 in.) (10.6 lbs) (1.4 US gal) 0 10 20 30 40 50 60 70 80 90 100 AVL13G94ABH4 Flow Rate (L/min) AVL13G94DDH4 Main Accessories and Spares (1) All dimensions are nominal. Sales drawings showing +/- tolerances are available on Part Number Description request. Please contact your Pall representative or local distributor for current sales 1 drawings. ACS5098CM Diaphragm valve kit for ⁄2 in. sanitary (2) 1 Suggested clearance is based on completely lifting the bowl over the top of an flange connection. Compatible with ⁄2 in. installed filter. Alternative methods of filter change-out allow operation with more fractional sanitary flange connection. limited “head-space”. Contact Pall for assistance. Includes clamp and gasket. ACS0602EM Valve seal kit (contains ten silicone Operating Conditions O-rings and ten PTFE O-rings) CC41608C00 Valve stem Maximum Operating -1 to 10 barg Pressure (-14.5(3) to 150(4) psig) LY00381 Valve knob cap ACS0609DA Closure clamp Maximum Operating 150 °C (300 °F) Temperature ACS0428EX EPR closure seal ORH4P-238 (3) Full vacuum. Silicone housing closure gasket (4) With compatible fluids, which do not soften, swell or adversely affect the materials. Contact your Pall representative or local representative for other spares and accessories.
Ordering Information
AVL 1 G
Code Design Code Cartridge Code Inlet and Code Vent Code Drain Code Seal Type Outlet Material(5)
1 – To European 05 AB05 23L For 1 ⁄2 in. A Quick-connect and A Quick-connect and H4 FDA- Pressure code 2 sanitary disconnect male disconnect male listed Equipment 1 AB1 code 7 flange to connector connector Silicone Directive ISO2852 (compatible with (compatible with (5) 2 AB2 code 7 Stäubli* coupling) Stäubli* coupling) Other elastomer D To European 94 33.7 mm materials are Pressure 3 AB3 code 7 (1.33 in) with valve with valve available. Contact Equipment O.D. x B Valve with 8 mm B Valve with 8 mm Pall for information. Directive with 2.0 mm (0.31 in.) hose barb (0.31 in.) hose barb *Stäubli is a trademark of enhanced (0.079 in.) 1 1 D For ⁄2 in. sanitary DFor ⁄2 in. sanitary Stäubli AG. documentation wall butt flange connection flange connection including 3.1b weld to stamped ISO1127 N None N None 162 material and certification Pall Advanta™ ALT4 Multi-round Housings Advanced Multi-round Sanitary Filter Housings for Liquid Applications
The Pall Advanta filter housings have been Features and Benefits specifically designed and engineered for • Aseptic design today’s manufacturing processes. These advanced housings are manufactured from Crevice-free electropolished surfaces 316L stainless steel and are engineered to with an internal Ra value of ≤ 0.4 µm meet the requirements of the (≤ 15 µin.) BioPharmaceutical industry. Fully self draining State-of-the-art manufacturing technologies are used to construct a No dead legs housing ideal for the most critical of • Low hold-up volumes for maximum applications. product recovery This multi-round version of the Pall • Quick fit Stäubli-type* connections for Advanta housing range is designed to easy filter integrity testing allow up to four filter elements in parallel • Easy to use low-point sanitary drain arrangement. valve During the design process, critical features • Range of options to aid use in were optimized to ensure trouble-free use automated production systems and low installation and maintenance costs. Areas included in this process were: • Options available for use with CIP spray cleaning device • Surface finish • Every housing supplied with a quality • Suitability for CIP and SIP certificate and manufactured to ATEX • Integrity testing Directive 94/9/EC (Group ll Category 2) • Incorporation into automated • Design variants to ASME and European production processes Pressure Equipment Directive, CE marking available
*Stäubli is a trademark of Stäubli AG.
163 Pall Advanta ALT4 Multi-round Housings Technical Specifications
Materials of Construction Typical Water Flow Rates(2) Flow Rate (Gal/min) Housing AISI 316L Stainless Steel 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Clamp AISI 316L and Nitronic* 60 700 10 Stainless Steel Seals Silicone elastomer 600 Surface Finish Internal: 8 Ra ≤ 0.4 µm (≤ 15 µin.) (typical) 500 External: 400 6 Ra ≤ 0.8 µm (≤ 32 µin.) (typical)
Inspection Documentation Certificate type 2.3 to EN10204 300 4 * Nitronic is a registered trademark of Armco, Inc.
200 (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential Operating Conditions 2 100 Maximum Operating -1 to 10 barg Pressure (-14.5(1) to 150 psig) 0 0 Maximum Operating and 150 °C (300 °F) 0 100 200 300 400 500 Steaming Temperature Flow Rate (L/min)
(2) (1) Full vacuum. The flow and pressure drop characteristics refer to the empty housing only for water at 20 °C (68 °F). For other liquids multiply pressure drop by relative density. To obtain the total pressure drop of a complete filter assembly, the Nominal Dimensions cartridge pressure drop must be added. Please refer to the relevant filter cartridge literature or contact Pall. Part Number Width Overall Clearance (Face to Face) Height Required ALT41G31ABH4 319 mm 528.5 mm 310 mm Main Accessories and Spares (12.6 in.) (20.8 in.) (12.2 in.) Part Number Description ALT41G31CBH4 319 mm 486.5 mm 310 mm 1 ALT41G31CDH4 (12.6 in.) (19.2 in.) (12.2 in.) ACS0598CM Diaphragm valve for ⁄2 in. sanitary flange compatible connections including clamp ALT41G31DDH4 319 mm 476.5 mm 310 mm and silicone gasket (12.6 in.) (18.8 in.) (12.2 in.) ACS0457FA Pressure gauge kit -1 to 10 barg for ALT41GNW50ABH4 319 mm 528.5 mm 310 mm 1 1 ⁄2 in. sanitary flange connection to ALT41GA50ABH4 (12.6 in.) (20.8 in.) (12.2 in.) ISO 2852 (includes clamp and gasket) ALT41G95ABH4 368 mm 528.5 mm 310 mm ORH4P-676 Silicone housing closure gasket (14.5 in.) (20.8 in.) (12.2 in.) ACS0602EM Silicone housing valve gasket kit ALT42G31ABH4 319 mm 777.5 mm 564 mm (12.6 in.) (30.6 in.) (22.2 in.) LY00381 Valve knob cap ALT43G31ABH4 319 mm 1025.4 mm 818 mm CC41608CC00 Valve stem (12.6 in.) (40.4 in.) (32.2 in.) ACS0364DA V-clamp housing closure ALTA41G31ABH4 373 mm 526 mm 310 mm ALTA41G31CBH4 (14.7 in.) (20.7 in.) (12.2 in.) ACS0814AS CIP Spray Device ALTA41G31CDH4 * Further spares and accessories available upon request. ALTA41G31DDH4 373 mm 487 mm 310 mm (14.7 in.) (19.2 in.) (12.2 in.)
Ordering Information
ALT 4 G H4
Code Design Code Cartridge Code Inlet and Outlet Code Vent Code Drain Type
– To European 05 AB05 code 2 G31 50 mm (2 in.) OD A Sanitary valve with B Sanitary valve with Pressure Equipment tubing with sanitary quick release fitting for hosebarb for 8 mm Directive 1 AB1 code 7 flange to ISO 2852 Stäubli* type couplings ID tubing
1 1 A To ASME Code 2 AB2 code 7 GNW50 Dairy fitting NW50 C For 1 ⁄2 in. sanitary flange D For ⁄2 in. sanitary to DIN 11851 connection to ISO 2852 flange connection D To European 3 AB3 code 7 Pressure Equipment GA50 Aseptic thread with side sanitary valve N No drain Directive with 4 AB4 code 7 connection NW50 with quick release fitting (3) enhanced to DIN 11864-1 for Stäubli* type couplings Wall thickness as specified in 1 ISO1127. documentation G95 Butt weld D For ⁄2 in. sanitary flange *Stäubli is a trademark of including 3.1b 60.3 x 2.3 mm(3) E Butt weld 13.5 x 1.6 mm(3) Stäubli AG. stamped material 1 and certification G34 50 mm (2 in.) S For 1 ⁄2 in. sanitary flange NB SCH10 connection to ISO 2852 with side connection for 1 ⁄2 in. sanitary flange 164 N No vent Veladisc™ Depth Filter Module Housings Filter Housings for Supradisc™ Depth Filter Modules
Features and Benefits Finishes and Customization
Pall Veladisc housings have been Pharmaceutical Version Surface developed for Supradisc Depth Filter Finishes Modules. These housings are fabricated Crevice-free construction with internal inner from stainless steel with different heights to surface: accommodate modules in 300 mm (12 in.) or 400 mm (16 in.) diameter Standard: Ra < 0.65 µm (< 25 µin.) Option: ≤ ≤ • 316L Stainless Steel Construction Ra 0.4 µm ( 15 µin.) • 8.6 barg/860 kPa (125 psig) @ 120 °C Customization (250 °F) maximum operating pressure Housings can be engineered to meet the • Single or split dome option specific needs of the process and • Closed system insures product purity installation including ASME Code • Electropolished surface finish as Certification. Please contact our Technical standard Services Department for assistance. • V-band clamp — 300 mm (12 in.) — only or bolt closure sealing system available for 300 mm (12 in.) to 400 mm (16 in.) • Models Available for Filter Areas from 0.46 m2 (5 ft2) to 14.8 m2 (160 ft2)
165 Veladisc Depth Filter Module Housings Technical Specifications
Materials of Construction Nominal Dimensions
Housing Standard: Model Overall Dome Clearance 316L Stainless Steel Height Height Required
Inlet and Outlet Connections 300 mm (12 in.) Housing: P12-01 768 mm 464 mm 330 mm 1 1 ⁄2 in. sanitary flange (30.25 in.) (18.25 in.) (13 in.)
406 mm (16 in.) Housing: P12-02 1073 mm 768 mm 635 mm 2 in. sanitary flange (42.25 in.) (30.25 in.) (25 in.)
1 Drain on Inlet and Outlet ⁄2 in. sanitary flange on P12-03 1378 mm 1073 mm 940 mm 300 mm (12 in.) and 400 mm (16 in.) (54.25 in.) (42.25 in.) (37 in.)
1 Dome Vent 1 ⁄2 in. sanitary flange on P12-04 1683 mm 1378 mm 1270 mm 300 mm (12 in.) and 400 mm (16 in.) (66.25 in.) (54.25 in.) (50 in.)
O-rings Standard: P16-02 1132 mm 805 mm 686 mm EPDM (food grade) (44.56 in.) (31.68 in.) (27 in.)
Optional: P16-03 1437 mm 1110 mm 1003 mm Viton* 1 A (56.56 in.) (43.68 in.) (39.5 in.)
* Viton is a registered trademark of DuPont Dow (non-FDA material). P16-04 1741 mm 1414 mm 1321 mm (68.56 in.) 55.68 in.) (52 in.) Operating Conditions
Maximum Operating 8.6 barg/860 kPa (125 psig) Pressure @ 120 °C (250 °F)
Housing Weights and Flow Rates
Model Dome Maximum Weight Flow Rate P12-01 7.3 kg (15 lbs) 72 L/min (19 gal/min) P12-02 13.6 kg (30 lbs) 144 L/min (38 gal/min) P12-03 22.7 kg (50 lbs) 216 L/min (57 gal/min) P12-04 31.8 kg (70 lbs) 288 L/min (76 gal/min) P16-02 52.6 kg (116 lbs) 303 L/min (80 gal/min) P16-03 64.9 kg (143 lbs) 454 L/min (120 gal/min)
P16-04 76.7 kg (169 lbs) 606 L/min (160 gal/min)
Ordering Information
Code Application Code Nominal Code Number of Code Closing Code Adapter Module Diameter Modules System Style
P Pharmaceutical 284 300 mm (12 in.) 00 Half Height C V-band clamp 00 Flat gasket Module 300 mm (12 in.) 410 400 mm (16 in.) 88 Double O-ring 01 1 Module H Rathmann Clamp closure 02 2 Modules 03 3 Modules Bolt closure 400 mm (16 in.) 04 4 Modules (Standard) 300 mm (12 in.) (Engineered Option)
ASME code stamped with bolt closure
Code Connections Code Inlet and Outlet
TC Sanitary flange 040 DN40 DIN 32676 connection 050 DN50 DIN 32676 166 Pall Advanta™ Electrical Trace Heater For Enhanced Temperature Control
The ability to control the temperature of a • Large LED display of actual filter system is beneficial in many temperature — measured by PT100 applications. These include: thermocouple • Hot water tank vents-elimination of • Separate IP54 rated control box allows condensate to comply with current full control independent of the housing GMP location • Freeze dryer vacuum break filters — • Low overall installation cost — no removal of residual water after steaming expensive steam valves, piping and or integrity testing pressure regulators required • Filtration of ointment bases-reduction of • Easy removal or access for changeout viscosity or liquidification of filter elements
• Bulk active ingredient * Please contact Pall for further details. production-temperature control to avoid crystalization during filtration Ordering Information Advanta Trace Heater System for Housings In these and many other applications, the to hold 10 in. (254 mm) Filter Elements electrical trace heaters for Pall Advanta Part Number Description housings offer a number of advantages. ACS0681AM 240 V (50 Hz), UK Plug • Easy installation — allowing simple ACS0682AM 250 V (50 Hz), upgrade of existing housings — the European Plug preformed cylindrical silicone jacket is ACS0685AM Extension Lead set (10 m [33 ft]) with the Pall Advanta housing bowl. It Advanta Trace Heater System for Housings can also be used on housings with to hold 20 in. (508 mm) Filter Elements 100 mm nominal diameter bowls* Part Number Description • Simple temperature adjustment — ACS0677AM 240 V (50 Hz), UK Plug control box has a digital input from ACS0678AM 250 V (50 Hz), ambient to 140 °C European Plug ACS0685AM Extension Lead set (10m [33 ft])
Heating Jacket Temperature Control Unit Jacket Material Silicone Rubber Housing Material Polycarbonate Insulation Material Silicone Foam Operating Voltage 240 V (50 Hz) or 110 V (60 Hz) Operating Voltage 240 V (50 Hz) or 110 V (60 Hz) Recommended Temperature Ambient to 140 °C (284 °F)(3) Power Output 305 mm (11.8 in.) long = 300 W(1) Setting Range 559 mm (22 in.) long = 600 W(2) Maximum Environmental 55 °C (131 °F) Maximum Temperature 200 °C (392 °F) Temperature for Controller De-energized Maximum Output — Current 7A Temperature Sensor PT100 Over Current Protection @ 4 seconds @ 12A Thermal Cut-out 150 °C ± 5 °C (302 °F ± 41 °F) 23 °C Ambient 1 seconds @ 24A Temperature Setting Set Temperature Display 8 mm (0.31 in.) red LED display Testing Voltage 1500 VΩ Actual Temperature Display 10 mm (0.39 in.) green LED display Insulation Value Greater than 100 MΩ PID (Proportional Integral Derivative control via Autotune parameters Protection Rating IP65 set by the user) Design Standard EN 60519-1 and EN 60519-2 Protection Rating IP54 Lead Length 1 m (3.3 ft) Design Standards EN61010-1
(1) For 10 in. (254 mm) filter elements. (3) Consult filter element specifications for maximum operating temperatures. (2) For 20 in. (508 mm) filter elements. 167 MDS Junior Style Industrial Housings Junior Style Industrial Housings for 4463- and 2230-style Cartridges
Pall MDS filter housings are recommended for small flow applications involving filtration of either liquids or gases. MDS series housings accommodate MC* or MD* 4463- and 2230-style cartridges with liquid flow rates up to 7.5 L/min (2 gal/min) and gas flows up to 100 Nm3/hour (60 scfm).
Features and Benefits
• High-temperature rated • High pressure rated • Easy mounting and change-out • Electropolished stainless steel for ease of cleaning • Manufacturing Quality System Certified to ISO 9000 Standards
Materials of Construction Housing 316L Stainless Steel Standard Gasket Silicone O-ring Material
Design Pressure and Temperature 5.1 barg (75 psig) and full vacuum at 93 °C (200 °F)
Other Specifications Number of Elements Around 1 Number of Elements High 1 Cartridge Style 4463 Legs and Support None
1 Vent 3 mm ( ⁄8 in) NPT
Ordering Information 1 Drain 6 mm ( ⁄4 in.) NPT
MDS4463 MFH4 Closure Style Vee band clamp ASME Code No Code Inlet and Outlet Connections Flow Configuration Tee
1 N4 6 mm ( ⁄4 in.) NPT Replaceable Tube Sheet No
1 N8 13 mm ( ⁄2 in.) NPT Davitor No
168 IOL and IDL Single-round Industrial Housings
Pall IOL and IDL Single-round Housings IDL Style - Features and Benefits are constructed of stainless steel and are • Single cartridge housings accepts designed for industrial applications (such Double open-end, RF and MCY 1000 as filtration of fluids in utilities areas). Style Filters IOL Style - Features and Benefits • All Stainless Steel materials of construction • Single cartridge housing accepts AB style, single open-end filter elements • Accepts 4 in. (102 mm), 10 in. (254 mm), 20 in. (508 mm) and 30 in. • All stainless steel materials of (762 mm) lengths construction • 2 Closure Styles offered — Through • Accepts 5 in. (127 mm), 10 in. Bolt or V-band Clamp (254 mm), 20 in. (508 mm) or 30 in. (7620 mm) Code 3, Code 7, Code 8 or • V-Band Clamp Style features a Quick Code 18 Filter Cartridges Opening T-Handle • Quick opening T-Handle V-Band Clamp • Variety of Inlet and Outlet sizes and facilitates Filter Change Out O-ring Seal Options Offered • Wide Choice of Inlet and Outlet sizes • Optional Mounting Brackets available and O-ring Seal options Top: IOL Series Filter Housing Bottom: IDL Series Filter Housing • Passivated for purity.
Nominal Dimensional Data Model Typical Height Clearance Required Volume Weight Empty Flow Rate(1) Threaded Nozzle Flanged Nozzle IOL Series IOL05 19 L/min (5 gal/min) 198 mm (7.8 in.) 102 mm (4 in.) 0.4 L (0.10 gals) 2.3 kg (5.1 lbs) 5.4 kg (11.9 lbs) IOL31 38 L/min (10 gal/min) 419 mm (16.5 in.) 321 mm (12.6 in.) 1.6 L (0.42 gals) 2.7 kg (5.9 lbs) 5.8 kg (12.8 lbs) IOL32 76 L/min (20 gal/min) 667 mm (26.3 in.) 572 mm (22.5 in.) 3.1 L (0.82 gals) 3.1 kg (6.9 lbs) 6.2 kg (13.7 lbs) IOL33 114 L/min (30 gal/min) 918 mm (36.1 in.) 822 mm (32.4 in.) 4.6 L (1.22 gals) 3.6 kg (7.9 lbs) 6.7 kg (14.7 lbs) IOL71 38 L/min (10 gal/min) 419 mm (16.5 in.) 321 mm (12.6 in.) 1.6 L (0.42 gals) 2.7 kg (5.95 lbs) 5.8 kg (12.8 lbs) IOL72 76 L/min (20 gal/min) 667 mm (26.3 in.) 572 mm (22.5 in.) 3.1 L (0.82 gals) 3.1 kg (6.9 lbs) 6.2 kg (13.7 lbs) IOL73 114 L/min (30 gal/min) 918 mm (36.1 in.) 822 mm (32.4 in.) 4.6 L (1.22 gals) 3.6 kg (7.9 lbs) 6.7 kg (14.7 lbs) IOL81/IOL181 38 L/min (10 gal/min) 419 mm (16.5 in.) 321 mm (12.6 in.) 1.6 L (0.42 gals) 2.7 kg (5.95 lbs) 5.8 kg (12.8 lbs) IOL82/IOL182 76 L/min (20 gal/min) 667 mm (26.3 in.) 572 mm (22.5 in.) 3.1 L (0.82 gals) 3.1 kg (6.9 lbs) 6.2 kg (13.7 lbs) IOL83/IOL183 114 L/min (30 gal/min) 918 mm (36.1 in.) 822 mm (32.4 in.) 4.6 L (1.22 gals) 3.6 kg (7.9 lbs) 6.7 kg (14.7 lbs) IDL Series IDLD04 15 L/min (4 gal/min) 203 mm (8 in.) 153 mm (6 in.) 0.4 L (0.11 gals) 2.3 kg (5.1 lbs) 5.4 kg (11.9 lbs) IDLD1 38 L/min (10 gal/min) 362 mm (14.2 in.) 321 mm (12.6 in.) 1.3 L (0.34 gals) 2.6 kg (5.7 lbs) 5.7 kg (12.5 lbs) IDLD2 76 L/min (20 gal/min) 516 mm (24.2 in.) 572 mm (22.5 in.) 2.8 L (0.74 gals) 3.1 kg (6.7 lbs) 6.1 kg (13.5 lbs) IDLD3 114 L/min (30 gal/min) 870 mm (34.2 in.) 822 mm (32.4 in.) 4.3 L (1.14 gals) 3.5 kg (7.7 lbs) 6.6 kg (14.5 lbs) IDL104 15 L/min (4 gal/min) 203 mm (8 in.) 153 mm (6 in.) 0.4 L (0.11 gals) 2.3 kg (5.1 lbs) 5.4 kg (11.9 lbs) IDL11 38 L/min (10 gal/min) 362 mm (14.2 in.) 321 mm (2.6 in.) 1.3 L (0.34 gals) 2.6 kg (5.7 lbs) 5.7 kg (12.5 lbs) IDL12 76 L/min (20 gal/min) 516 mm (24.2 in.) 572 mm (22.5 in.) 2.8 L (0.74 gals) 3.1 kg (6.7 lbs) 6.1 kg (13.5 lbs) IDL13 114 L/min (30 gal/min) 870 mm (34.2 in.) 822 mm (32.4 in.) 4.3 L (1.14 gals) 3.5 kg (7.7 lbs) 6.6 kg (14.5 lbs) IDLT04 15 L/min (4 gal/min) 200 mm (7.8 in.) 153 mm (6 in.) 0.4 L (0.11 gals) 2.3 kg (5.1 lbs) 5.4 kg (11.9 lbs) IDLT1 38 L/min (10 gal/min) 359 mm (14.1 in.) 321 mm (12.6 in.) 1.3 L (0.34 gals) 2.6 kg (5.7 lbs) 5.7 kg (12.5 lbs) IDLT2 76 L/min (20 gal/min) 613 mm (24.1 in.) 572 mm (22.5 in.) 2.8 L (0.74 gals) 3.1 kg (6.7 lbs) 6.1 kg (13.5 lbs) IDLT3 114 L/min (30 gal/min) 867 mm (34.1 in.) 822 mm (32.4 in.) 4.3 L (1.14 gals) 3.5 kg (7.7 lbs) 6.6 kg (14.5 lbs) 169 (1) Dependent on inlet and outlet selection. IOL and IDL Single-round Industrial Housings Technical Specifications
Materials of Construction Typical Air Flow Rates at 20 °C (68 °F) Head 316L Stainless Steel Flow Rate (scfm) 0 50 100 150 200 250 300 350 10 700 Bowl 316 Stainless Steel • A: 2.7 barg (40 psig) A BC • B: 4.1 barg (60 psig) • C: 5.5 barg (80 psig) 600 Design Ratings 8 500 IOL 27.5 barg (400 psig) @ 40 °C (100 °F) 6 24.1 barg (350 psig) @ 150 °C (300 °F) 400 IDL Through Bolt Design: 4 300 8.2 barg (120 psig) @ 40 °C (100°F) 200 V-band Clamp Design: Differential Pressure (mbar) Pressure Differential Differential Pressure (psid) Pressure Differential 2 27.5 barg (400 psig) @ 40 °C (100 °F) 100 24.1 barg (350 psig) @ 150 °C (300 °F) 0 0 Note: Above ratings apply to housing only. Cartridge and housing O-ring selection may 0 100 200 300 400 500 600 impose different and narrower limitations. Flow Rate (Nm3/h)
Connections Typical Liquid Flow Rates Flow Rate (Gal/min) at 20 °C (68 °F) Inlet and Outlet Both Styles: 0 5 10 15 20 25 30 35 19 mm (0.375 in.) NPT, 25 mm (1 in.) 10 700 NPT, 19 mm (0.375 in.) BSPT, 25 mm (1 in.) BSPT, 600 8 IOL Only: 500 25 mm (1 in.) BSPP 6 400 Flange Option 300 lbs. ANSI raised face flanges for 25 mm (1 in.) IOL and IDL 300 Housings or BS4504 flanges for 25 mm 4 (1 in.) IDL Housings 200 Differential Pressure (psid) Pressure Differential Vent and Drain 6 mm (0.25 in.) NPT, BSPT or BSPP 2 (mbar) Pressure Differential 100 Shell O-rings Viton* A, FEP Encapsulated Viton A, Silicone Elastomer, Buna N, Ethylene 0 0 Propylene, Ethylene 0 20 40 60 80 100 120 Flow Rate (L/min) Propylene for Steam Service Stainless steel brackets are available Bracket Option as a standard option
* Viton is a registered trademark of DuPont Dow Elastomers L.L.C (non-FDA material).
Ordering Information
IOL G
Code Cartridge Style Code Nominal Cartridge Code Inlet and Outlet Vent and Drain Code Seal Materials Length
3 3 Code 3 05 5 in. (127 mm) N12 19 mm ( ⁄4 in.) NPT 6 mm (0.25 in.) NPT H Viton A 7 Code 5 1 10 in. (254 mm) N16 25 mm (1 in.) NPT 6 mm (0.25 in.) NPT H1 FEP Encapsulated
3 Viton A 8 Code 8 2 20 in. (508 mm) B12 19 mm ( ⁄4 in.) BSPT 6 mm (0.25 in.) BSPT 18 Code 18 3 30 in. (762 mm) B16 25 mm (1 in.) BSPT 6 mm (0.25 in.) BSPT H4 Silicone B17 25 mm (1 in.) ANSI Flange 6 mm (0.25 in.) BSPT H13 Buna N N17 25 mm (1 in.) ANSI Flange 6 mm (0.25 in.) NPT J Ethylene Propylene P17 25 mm (1 in.) ANSI Flange 6 mm (0.25 in.) BSPP J7 Ethylene Propylene for Steam Service P19 25 mm (1 in.) BSPP 6 mm (0.25 in.) BSPP B35 25 mm (1 in.) BS4504 Flange 6 mm (0.25 in.) BSPT P35 25 mm (1 in.) BS4504 Flange 6 mm (0.25 in.) BSPP
IDL G
Code Cartridge Code Nominal Cartridge Code Inlet and Outlet, Code Housing Options Code Seal Materials Style Length Vent and Drain D DOE/RF V-band 04 4 in. (102 mm) See above IOL Style table – Blank See above IOL Style table 1 MCY 1001 V-band 1 10 in. (254 mm) C2 Passivated T DOE/RF 2 20 in. (508 mm) C9 Clean for Through Bolt 3 30 in. (762 mm) Oxygen Service 170 PCY Polypropylene Filter Housings
Pall PCY filter housings are manufactured Applications from reinforced polypropylene and For the filtration of a wide variety of liquids incorporate several innovative features. including water, acids, bases, compatible Four styles of cartridge fitting are available, solvents and deionized water, where each welded into the head to eliminate the corrosion resistance and economy of risk of bypass. The ability to utilize a range operation are required. of Pall filter cartridge styles incorporating secure sealing mechanisms together with a high pressure rating allows for flexibility and security in a wide range of process applications. Housing features include the following: • Flow rates up to 100 L/min (20 gal/min) • 25 mm (1 in.) connections for high-flow rates and low pressure drops • Pressure rating up to 150 psig (10 barg) • Welded fittings for different styles of Pall filter cartridges • Provision for drain, vent and mounting bracket Multi-cartridge Housings For larger flows, multi-cartridge housings in stainless steel and plastic are also available from Pall.
Features and Benefits
• Sturdy reinforced polypropylene designs for rugged liquid service and long-life • Broad chemical compatibility • Choice of filter cartridge styles and lengths
171 PCY Polypropylene Filter Housings Technical Specifications
Materials of Construction Typical Water Flow Rates Material Glass-reinforced polypropylene 1000 Seal Material Options Nitrile, FDA approved Viton* and general purpose Viton
Connection Options 25 mm (1 in.) BSPT or 25 mm (1 in.) BSP female
1 1 Vent and Drain 6 mm ( ⁄4 in.) BSPT or ( ⁄4 in.) BSP Connection Options with plug 100 Note: Polypropylene housings are not suitable for use with gases. * Viton is a registered trademark of DuPont Dow. 50
Nominal Dimensions (mbar) Pressure Differential
Length PCY1 Housing: 440 mm (17.3 in.) 10 PCY2 Housing: 10 50 100 688 mm (27 in.) Flow Rate (L/min) (log scale)
Diameter Both Styles: = RF/RMF and = AB Code 7 and 147 mm (5.7 in.) MCY 1000 styles Code 3 styles
Design Pressure and Temperature 10 barg (150 psig) @ 37 °C (100 °F) Main Accessories and Spares Part Number Description Other Specifications SAN1DV04H2 Stainless steel vent and drain valve 6 mm (0.25 in.) BSPTr Number of Cartridges 1 SAN1PG04 Stainless steel pressure gauge Connections 25 mm (1 in.) NPT ACS0018BA T-Piece: Standard Gasket Nitrile 6 mm (0.25 in.) BSPT female O-ring Material 6 mm (0.25 in.) BSPT female
1 6 mm (0.25 in.) BSPT male Vents 6 mm ( ⁄4 in.) NPT
1 Drain 6 mm ( ⁄4 in.) NPT Replacement Parts Closure Style Threaded Housing Gasket Kit ASME Code No GK1344PB01 Nitrile Flow Configuration Tee GK1344PH01 FDA approved Viton
ACS0284EE General purpose Viton Vent and Drain Plug Kit
ACS0067AY X Option
ACS0182AY Y Option
Ordering Information
PCY G
Code Cartridge Nominal Code Inlet and Outlet Code Seal Material Code Vent and Drain Style Length 1001 DOE MCY1000 10 in. (254 mm) 16 25 mm (1 in.) BSPT H13 Nitrile – No tappings H FDA approved Viton 1002 DOE MCY1000 20 in. (508 mm) 19 25 mm (1 in.) BSP Y Head and bowl tapped HB General purpose Viton 6 mm (0.25 in.) BSPT 1RF DOE RF/RMF 10 in. (254 mm) (female with plug) 2RF DOE RF/RMF 20 in. (508 mm) X Head and bowl tapped 13 SOE AB code 3 10 in. (254 mm) 6 mm (0.25 in.) BSP (female with plug) 23 SOE AB code 3 20 in. (508 mm) 17 SOE AB code 7 10 in. (254 mm) 27 SOE AB code 7 20 in. (508 mm) 172 Megaplast™ Plastic Filter Housings
Pall Megaplast housings are manufactured The housings accommodate either one Pall from PFA (Perfluoroalkoxy), PVDF AB Code 3 style filter cartridge which (Polyvinylidenedifluoride) or polypropylene. features a high security double O-ring This range represents a significant advance sealing mechanism, or the RF style in filter housing design. The housings are Profile II filter cartridge which employs a crevice-free and can be used at high knife edge seal, tie-rod and seal nut. PVDF pressures (with suitable safety measure housings are available in two lengths to implemented), and their filter cartridges can accommmodate either 10 in. (254 mm) or be installed and changed quickly and 20 in. (504 mm) nominal length filter easily. cartridges. PFA and natural polypropylene housings are designed to use one 10 in. As a result of computer-aided design and (254 mm) nominal length filter. high technology plastic molding techniques, Megaplast housings can be used for high flow-rate applications with Features and Benefits very low corresponding pressure drops. • Three part construction (head, collar All fluid contact surfaces are molded rather and bowl) than machined, to provide very smooth • DIN outlet and inlet connections (natural surfaces with a high level of particulate polypropylene and PVDF housings only) cleanliness when compared with other 1 currently available plastic filter housings. • 6 mm ( ⁄4 in.) butt weld inlet and outlet connections (PFA housings only) Easy to use, Megaplast housings are constructed from three parts – head, • Threads not wetted by process fluid bowl,and collar. The screw-threaded • All product wetted surfaces are molded closure provides a positive and effective (not machined), providing a very seal, and is not wetted by the fluid being smooth, high quality surface finish filtered (i.e., no potential contaminant are • Constructed from PFA, PVDF or natural traps introduced), and the design avoids polypropylene unnecessary stress being placed on the internal closure O-ring. The coarse collar • AB Code 3 fitting molded into head thread allows quick one-handed operation, design without thread galling. • Plug-in element secured in position by Easy to install, the inlet and outlet bowl connections are either non-wetted • Mounting bracket is part of the head international standard DIN, or butt weld. molding (PFA housings), or can be fitted DIN connections enable the housing to be (PVDF and natural polypropylene fitted to or removed from pipework housings) systems without disturbing existing • Choice of Pall AB Code 3 or RF style pipework. Megaplast housings also 1 filter cartridges incorporate a 6 mm ( ⁄4 in.) BSP parallel female vent and drain port as part of the bowl, complete with plug and seal. seal protected non-wetted threads eliminate potential sources of contamination.
173 Megaplast Plastic Filter Housings Technical Specifications
Materials of Construction Typical Water Flow Rates Vessel Closure Coarse thread closure ring 1000 Closure Seal Material Ethylene propylene (natural polypropylene and PVDF housings), FEP encapsulated fluorocarbon (PVDF and PFA housings) 100 Inlet and Outlet Natural Polypropylene and PVDF Connections Housings: DIN 25 male to DIN 8063 part 3 PFA Housings: 1 (1) 6 mm ( ⁄4 in.) butt weld 10
Vent and Drain Connections Bowl: (mbar) Pressure Differential 1 All materials — 6mm ( ⁄4 in.) BSP parallel female Head: 1 Polyproylene — supplied blank 1 10 100 1000 1 PVDF — supplied blank or 6 mm ( ⁄4 in.) BSP parallel female Flow Rate (L/min) 1 PFA — 6 mm ( ⁄4 in.) BSP parallel female = TAAC = TRX = TAX/TAV
(1) 3 A 18 mm ( ⁄4 in.) Flaretek* inlet and outlet connection option is also available. Please contact Pall for further details. * Flaretek is a registered trademark of Entegris, Inc.
Maximum Allowable Pressure and Temperature Material Applications Polypropylene Water: 5 barg (72.5 psig) at temperatures up to 40 °C (104 °F).
Chemical(2): Not suitable for use above 40 °C (104 °F). PVDF Water: (TAVW housing) 10 barg (145 psig) at temperatures up to 40 °C (104 °F). 7.5 barg (108 psig) at temperatures between 40 °C (104 °F) and 80 °C (176 °F). Not suitable for use above 80 °C (176 °F) Chemicals: (TAVC housings) 3.5 barg (50.7 psig) at temperatures up to 40 °C (104 °F). Not suitable for use above 40 °C (104 °F). PVA Water: Not applicable Chemical: 5.6 barg (81 psig) at temperatures up to 30 °C (86 °F) 2.8 barg (40.6 psig) at temperatures between 30 °C (86 °F) and 95 °C (203 °F). Not suitable for use above 95 °C (203 °F).
(2) Compatible chemicals are defined as those which do not soften, swell or attack any of the housing components.
Ordering Information
T 01 G
Code Cartridge Code Housing Code Application Code Nominal Code Inlet and Style Material Cartridge Length Outlet A AB Code 3 A* PFA C Compatible 1 10 in. (254 mm) 26 Din 25 to R RF Style V* PVDF chemicals 2 20 in. (508 mm) DIN 8063 part 3 (male)(3) X Polypropylene W Water 1 53 6 mm ( ⁄4 in.) * Only available in AB1 code 3. Butt weld(4)
Code Seal Material Code Vent and Drain J Ethlene Propylene(3) – Supplied blank(3) H1 FEP Encapsulated D Drilled, tapped Fluorocarbon(4) and plugged 1 6 mm ( ⁄4 in.) (3) Polypropylene and PVDF BSP parallel housings only (4) 174 (4) PFA housings only female Tangential Flow Filtration Tangential Flow Filtration (TFF)
Pall offers the most comprehensive selection MembraloxTM Ceramic Modules of tangential flow filtration platforms to meet the increasing diversity of biological and Ceramics are the preferred choice when biopharmaceutical processes and operating conditions are outside the limits applications. tolerable by plastics due to extremes of temperature, or chemical compatibility. In These platforms are: many high solids applications, such as natural extracts, the ability to clean ceramics with Membrane Cassettes and Hardware harsh cleaning agents can give required Ultrafiltration: Pall membrane cassettes and process cost advantages. their associated hardware and systems are PallsepTM Vibrating Membrane Filters the preferred choice in applications that require gentle processing and precise tailoring Pallsep membrane filters are an enabling of membrane characteristics to the technology for difficult processes where the application. Predominant use is biotechnology security of a polymeric barrier process is and biologicals for labile molecules. required, but where feed materials are very high in complex mixtures of biomolecules and Microfiltration: Open channel cassettes or viscosities may be elevated. Examples are cassettes with suspended screens can be direct processing of mycelial fermentation used in batch applications for the harvesting broths without pretreatment, recovery of cell of bacterial, mammalian, or insect cells. wall fractions from chemically lysed Microza Hollow Fiber Modules recombinant bacterial systems used to produce vaccines. Ultrafiltration: Hollow fibers are the preferred choice for larger volume processes with more Plate and Frame Sheet Membranes robust molecules such as enzymes,and for clarification of materials where small molecules Bulk processes in the manufacturing of APIs such as antibiotics are the target. Also the often require extensive membrane areas of choice for both pure water applications, and predominantly ultrafiltration membrane. Pall raw water treatment. membranes are available to retrofit most pre-existing systems. Microfiltration: Simple flow geometry and steam sterilizability make hollow fibers an excellent option for culture techniques such as perfusion culture.
176 Tangential Flow Filtration Technology
Pall has many years of experience in TFF is utilized to perform various steps on the design and manufacturing of a wide range of applications in the state-of-the-art systems. We work closely biopharmaceutical industry. Examples of a with our clients to evaluate and supply the few typical applications are listed below: best technical solution for each application • Concentrate and desalt solutions of using proven features, designs and proteins,peptides and oligonucleotides engineering know-how. • Purify and recover antibodies or For TFF applications, systems can be recombinant proteins from cell culture designed to automatically perform all media phases of a typical process including, flushing, sanitization, draining, buffer • Vaccine concentration and diafiltration conditioning, concentration, diafiltration, • Fractionate protein mixtures product recovery and clean-in-place (CIP) • Concentration and diafiltration in blood operations. See “Tangential Flow Filtration plasma fractionation and purification Automated Systems” on page 195 for additional details. • Clarify cell lysates or tissue homogenates Applications in TFF • Recover products expressed into the Tangential Flow Filtration (TFF) is an media from cell culture efficient method for concentrating, • Continuously perfuse out spent media desalting, or buffer exchanging solutions of and product from cell culture biomolecules ranging in volume from • Recover products from natural extracts several milliliters to thousands of liters. It of plants or animal origin can be used to fractionate large from small biomolecules,depyrogenate buffer • Depyrogenate water, buffers and media solutions, harvest cell suspensions, and solutions clarify fermentation broths and cell lysates. • Prepare samples (concentrate, desalt, or buffer exchange) prior to or following column chromatography
177 Ultrafiltration and Microfiltration TFF Cassette Membranes
Membranes for UF and MF TFF Features and Benefits Pall’s ultrafiltration (UF) membranes have • Low affinity and adsorption been developed and manufactured to give characteristics resulting in higher consistent performance. Products are product recovery available for laboratory, development, pilot, • Available in a wide variety of cassette and production-scale TFF applications. configurations, for easy and direct Pall’s microfiltration (MF) membranes are scale-up/scale down optimized for product clarification and Top: Maxisette Membrane Cassettes • Greatest selection of ultrafiltration Bottom: Centrasette Membrane Cassettes recovery in biotechnology and membrane rating available: pharmaceutical applications. 650 Da – 1000 kDa to fit specific Membrane Types application needs Pall offers four distinct membrane types • Compatible with acids, bases and a that provide superior performance and variety of other cleaning agents to stability to meet the challenges of each optimize for example cleaning unique TFF application. Membrane Types procedures include: Omega™, Alpha™, Regen™, and Alpha Membrane Supor® TFF membranes. Each membrane is available in a broad range of cassette Alpha membrane is a PES membrane types and configurations. modified to minimize the flux depression caused by antifoam agents (such as Omega Membrane silicone and polyglycols) that might effect Omega polyethersulfone (PES) membranes especially membranes with smaller cut offs. have been specifically modified to minimize Alpha membranes typically clean up protein binding to the surface and quicker and easier after contact with these interstitial structure of the membrane. This agents. polymeric membrane is stable against Features and Benefits biological and physical degradation due to • Proprietary membrane chemistry the unique chemical properties of PES. reduces non-specific adsorption, Omega membranes have an anisotropic minimizes membrane fouling and structure, a thin skin-like top layer with a increases product recovery highly porous underlying support. The • Exceptional membrane recovery and structure of the skin determines the stability after cleaning which results in a porosity and permeability characteristics of longer lifetime of the membrane the membrane. Anisotropic membranes have higher water permeability and can typically be cleaned quicker and easier than membranes with a uniform, sub-micron depth structure. Damage to the skin of anisotropic membranes is easily detected with an integrity test. This may not be the case for membranes with sub-micron porous underlayers.
178 Ultrafiltration and Microfiltration TFF Cassette Membranes
Regen Membrane Supor TFF Membrane Regen membrane is regenerated cellulose. This hydrophilic Supor TFF membrane is a micron-rated pore, modified membrane is characterized as low protein binding with a broad polyethersulphone membrane with a uniform depth structure. The chemical compatibility. Regenerated cellulose membranes have lower membrane is optimized for microfiltration TFF applications including water permeability compared to PES membranes but may give harvest, concentration and clarification of cell cultures and higher, consistent process flux rates especially if antifoam agents or fermentation broths. Use Supor TFF membranes to harvest bacterial, polysaccharides are present in the process fluid. mammalian, and insect cells; separate red blood cells from hemoglobin; and clarify yeast broth and bacterial lysates. Features and Benefits • Good for processing hydrophobic proteins where the low binding Features and Benefits characteristic increases the performance of the membrane • Low non-specific adsorption due to its hydrophilic chemistry which leads to higher product yields • Maintains high process flux rates in presence of antifoams and polysaccharides which can lead to shorter process time • Wide range of membrane pore sizes to optimize the process • Broad solvent compatibility to handle also applications where PES • Compatible with acids, bases, oxidizing agents and variety of membranes can not be used other cleaning agents to fit different application needs May be substituted where regenerated cellulose is specified and validated to minimize the effort of revalidation
179 Matching Membrane Cassettes to Applications
Pall offers a broad range of membrane cassettes for TFF to cover the Membrane Area Requirements growing range of potential applications and process volumes. The process volume and concentration, filtrate flux rate and time There are four cassette formats for UF and MF applications – requirements must all be considered in order to determine the Centramate™, Centrasette™, Maximate™ and Maxisette™. membrane area required for a specific process. Specify range of expected volumes and calculate area based on largest volume. It is important to consider your specific requirements in order to select the most appropriate cassette and format for your application. • Filtrate Volume – total filtrate volume collected from concentration and diafiltration steps. Filtrate volume can be estimated from the Choosing A Membrane Cassette total process volume, concentration factor and diafiltration volumes required. Process Objectives • Time Requirements – specify the maximum allowable process It is necessary to clearly define process requirements including the time following in order to be able to determine the required membrane molecular weight cut-off (MWCO) and area for a process: • Filtrate Flux Rate (FFR) – the rate of liquid passing through the membrane e.g. L/m2/h (LMH). Trials are required to determine the • Is Product in Concentrate or filtrate? actual FFR for a product under a specified set of operating • Total process volume parameters including transmembrane pressure (TMP), cross flow flux rate (CFF) and temperature. • Required concentration factor To estimate membrane area required for a process, use the following • Diafiltration requirement equation; • Process temperature Required Membrane Area = filtrate volume ÷ [average filtrate flux rate • Process time x process time] You must also evaluate the process fluid characteristics From the Required Membrane Area calculated, a cassette holder with (concentration, viscosity, impurities, additives, presence of sufficient capacity can be selected. particulates, etc) and how they may affect the process. Membrane Molecular Weight Cutoff (MWCO) vs.Molecular Scale-up/Scale-down weight of sample molecules to be retained/passed Processes are often developed on a scaled-down system to As a general rule to maximize product recovery, choose a MWCO conserve sample. It is best to develop a process using a cassette that is 3 – 6 times smaller than the MW of molecules to be retained. If format that has the same pathlength and channel configuration as the performing concentration only, a difference of 3 – 4 times is sufficient. full scale system. This allows direct scale-up following a simple rule – If process includes diafiltration, use 4 – 6 times, favoring the higher increase membrane area and retentate flow rate in direct proportion factor with increasing number of diafiltration volumes (DV). to increase in sample volume. If this is followed, the TMP,Cross Flow The same 3 – 6 times rule applies for product passage (transmission). Flux Rate and process time will not change appreciably. If pathlength In this case, choose a MWCO that is 3 – 6 times larger than the MW is changed, then additional optimization will be required. of molecules to be passed. The pH and ionic strength of the process fluid can have a significant affect on transmission of specific molecules, including low MW species. Fractionation – separation of large from smaller molecules – can be achieved by choosing a MWCO that is at least 2 times lower than the MW of molecules to be retained and 2 times greater than the MW of molecules to be passed. The higher MW molecules will be concentrated while the lower MW molecules have to be diafiltered out to affect a complete separation. There may have to be a compromise between recovery and complete separation when the difference in MW is too small.
180 Minimate™ Tangential Flow Filtration Capsules
The easy to use Minimate TFF capsule is • High Product Recovery – Optimized a valuable tool for any laboratory requiring flow path design coupled with low tangential flow filtration of small process protein binding Omega membrane volumes. Sample batch sizes of up to one minimize non-specific binding liter can be reduced to as low as 5 mL. • Efficient – Concentration and desalting Sample concentration and diafiltration processes can be performed on the (desalting) can take place sequentially same system with minimal user using the same device and system, saving intervention. Achieve high concentration time and avoiding product loss associated factors in a single processing step due with transfer steps. to the low hold-up volume of the device The Minimate TFF Capsules contain a • Disposable – This economically priced robust, polyethersulfone, ultrafiltration (UF) device can be dedicated to a single membrane. The Omega UF membrane batch or process eliminating the time offers low non-specific adsorption required for cleaning characteristics resulting in high product • Confidence – Each pharmaceutical recovery. The Minimate TFF capsules are grade Minimate capsule is 100% available with a wide range of molecular integrity tested during manufacture to weight cut-offs. They can be used in a ensure reliable performance. For critical variety of biological applications in applications the user can re-test the biotechnology, molecular biology, protein integrity after initial use. A Certificate of chemistry, microbiology and immunology. Quality is included with each capsule
Features Applications • Ready to use – Minimate TFF capsule • Concentrate and desalt proteins, includes all fittings and tubing to peptides, or nucleic acids (DNA, RNA, simplify installation into filtration setups. oligonucleotides) This versatile, self-contained device works with most laboratory pumps • Recover antibodies or recombinant proteins from clarified cell culture media • Cost-effective design – The plastic construction of the Minimate TFF • Process metal sensitive enzymes and capsule and chemical compatibility of other biomolecules the Omega membrane facilitate • Separate (fractionate) large from small cleaning and reuse biomolecules • Scalable – The Minimate TFF capsules • Concentrate viruses or gene therapy have the same path length and similar vectors materials of construction as larger • Prepare samples prior to column Centramate and Centrasette chromatography cassettes used in pilot and production scale. Several Minimate TFF capsules • Concentrate samples after gel filtration may be connected in parallel for • Depyrogenate water, buffers, and media increased membrane area Predictable solutions performance saves time when scaling up a process.
181 Minimate Tangential Flow Filtration Capsules Technical Specifications
Technical Data Materials of Construction
Effective Filtration Area 50 cm2 (0.05 ft2) Filter Media Omega membrane Recommended Crossflow 60 – 70 mL/min (polyethersulfone)
Operating Temperature 5 – 50 °C (41 – 122 °F) Housing Polypropylene, Glass reinforced Range Screens, Housing Sealing Polypropylene Ring and Fittings Maximum Operating Pressure 4 bar (400 kPa, 60 psi) Membrane Plate and Filtrate Polyethylene pH Range 1 – 14 Channels Product Hold-up Volume Approximately 1.6 mL Internal Gasket Ethylene Propylene Elastomer Forward Flow < 7/mL/min at 0.75 bar (10 psi) Air Integrity Value
Nominal Dimensions 200 mm x 38 mm x 18 mm (Length x Width x Height) (8 in. x 1.5 in. x 0.7 in.)
Ordering Information The Minimate TFF Capsule comes with threaded luer plugs in each of Part Number Description the four ports. A fitting package with the following components is OAD65C12 Minimate TFF Capsule included. with 650 Da Omega membrane OA001C12 Minimate TFF Capsule Accessories with 1 kDa Omega membrane Part Number Description OA003C12 Minimate TFF Capsule 88216 Minimate Fittings kit with 3 kDa Omega membrane Contains: 1 OA005C12 Minimate TFF Capsule 2 Male luer to 3.2 mm ( ⁄8 in.) with 5 kDa Omega membrane hose barb 1 2 Female luer to 3.2 mm ( ⁄8 in.) OA010C12 Minimate TFF Capsule hose barb 1 with 10 kDa Omega membrane 120 cm (3.9 ft) Tubing 3.2 mm ( ⁄8 in.) i.d. 1 Retentate screw clamp OA030C12 Minimate TFF Capsule 4 Tubing clamps with 30 kDa Omega membrane 1 Adhesive strips (loop and hook) OA050C12 Minimate TFF Capsule with 50 kDa Omega membrane
OA070C12 Minimate TFF Capsule with 70 kDa Omega membrane
OA100C12 Minimate TFF Capsule with 100 kDa Omega membrane
OA300C12 Minimate TFF Capsule with 300 kDa Omega membrane
OA500C12 Minimate TFF Capsule with 500 kDa Omega membrane
OA990C12 Minimate TFF Capsule with 1000 kDa Omega membrane
182 Minimate™ TFF System Streamlining Laboratory-scale Concentration, Desalting, and Buffer Exchange Processes
Designed to work with the Minimate TFF Features Capsule, this easy-to-use system can • Ready to Use – Plug in a Minimate process sample volumes up to 1L or more TFF capsule, add sample and turn on and efficiently concentrate samples to as the pump to start processing. The little as 5 mL. Subsequent desalting or Minimate TFF system includes all the buffer exchange steps can be run on the hardware, tubing and fittings needed to same system with minimal user get your TFF process up and running intervention. quickly The ready-to-use Minimate TFF System • High Concentration Factors – The low includes a variable speed peristaltic pump, system working volume achieved as well as a 0 – 4 bar (0 – 60 psi) pressure through the use of a conical bottom gauge, valves, 500 mL reservoir with reservoir and compact design enable magnetic stir bar, and stir plate all high concentration factors from up to assembled on a compact drip tray. The 1L or more of sample to be achieved. use of a peristaltic pump with disposable Concentrate your sample down to as tubing and fittings minimizes sample little as 5 mL cross-contamination while providing gentle processing for biomolecules. All wetted • Secure – All wetted components are parts meet USP Class VI testing. made from low protein-binding, chemically resistant, USP Class VI The reservoir is designed to hold up to materials The system has a very low 500 mL of sample and provides efficient volume and interior fluid contact area. mixing of product. The tapered bottom and Fluid does not pass through and is not optimally located feed and return ports retained in the pump mechanism, as it reduce the system hold-up volume, which does with diaphragm or piston pumps. allows high concentration factors to be If cross-contamination is a concern, achieved. The reservoir lid seals tightly simply change the tubing between allowing additional sample volume or samples. The Easy-Load® pump head diafiltration solution to be drawn into the makes it easy to replace the system reservoir by vacuum created as filtrate is tubing. generated through the TFF device. This allows continuous diafiltration to be • Gentle Processing – Roller head performed and eliminates the need for a peristaltic pumps are the choice for transfer pump. When it’s time to retrieve critical applications such as fragile your sample, simply open the valve on the biomolecules. Alternative pumps use reservoir outlet and pump out your sample. direct mechanical action on the fluids, and increase the possibility of damage to cells or proteins • Easy Cleaning and Maintenance – System components are designed for easy assembly and disassembly, no tools required. Tubing and fitting replacement is simple and quick. Slip See Also: nuts for luer locks eliminate tubing kinks Refer to “Matching Cassettes to Applications” on page 180 and “Tangential Flow Filtration Membrane Cassettes” on pages 185 – 189 for * Easy-Load is a trademark of Cole-Palmer. additional details. 183 Minimate TFF System Technical Specifications
All fittings are simple and inexpensive to replace. Three-way valves at Materials of Construction the reservoir inlet and outlet can be used for sample recovery or spill Reservoir Polysulfone free addition of rinse and cleaning fluids. Reservoir Cover Polypropylene • Efficient – Continuous diafiltration for desalting or buffer exchange Reservoir O-ring EP Rubber can be performed unattended. The diafiltration buffer container is Magnetic Stir Bar PTFE coated connected to the lid of the feed reservoir. By simply pulling a Gauge Wetted Parts 316L stainless steel vacuum on the feed reservoir, new buffer is drawn into the feed reservoir at the same rate filtrate is generated. The stir plate Gauge Mounting Block Polypropylene ensures adequate mixing of the buffer addition Luer Fittings Polypropylene and stainless steel • Compact Design – Saves valuable bench space, making the Tubing C-flex* and Pharmed* entire fluid path easily accessible for built-in flexibility Four-way Valves Polycarbonate body, polyethylene core • Process Monitoring – Pressure gauge enables monitoring of feed Drip Tray Urethane pressure to ensure reproducible process parameters for consistent * C-Flex is a registered trademark of Consolidated Polymer Technologies, Inc. Pharmed is a registered trademark of Saint-Gobain Performance Plastics Corp. runs
Applications
• Concentrate and desalt proteins, peptides or nucleic acids (DNA, RNA, oligonucleotides) • Recover antibodies or recombinant proteins from clarified cell culture media • Process metal sensitive enzymes and molecules • Separate (fractionate) large from small biomolecules • Concentrate viruses or gene therapy vectors • Prepare samples prior to column chromatography • Concentrate samples after gel filtration • Depyrogenate water, buffers, and media solutions
Ordering Information
Description Part Number Part Number
115V AC 50/60 Hz version OAPMP110 OARES110
230V AC 50/60 Hz version OAPMP220 OARES220
Minimate TFF System Minimate TFF Reservoir Assembly Only
Includes Peristaltic pump, pressure gauge, Pressure gauge, valves, valves, reservoir with stir bar, reservoir with stir bar, built in stir built in stir plate on a drip tray plate on a drip tray.(1)
Dimensions 307 mm wide x 482 mm deep 307 mm wide x 203 mm deep x 208 mm high x 208 mm high (12.1 in. wide x 19 in. deep (12.1 in. wide x 8.0 in. deep x 8.2 in. high) x 8.2 in. high) Weight 6.0 Kg (13.3 lbs.) 1.0 Kg (2.3 lbs.) Maximum Inlet Pressure 4.1 bar (410 kPa, 60 psi) 4.1 bar (410 kPa, 60 psi) Operating Temperature Range 0 – 50 °C (0 – 106 °F) 0 – 50 °C (0 – 106 °F) Recirculation Flow Rate 10 – 240 mL/min 10 – 240 mL/min Minimum System Working Volume < 5 mL < 5 mL (1) User will need to supply their own MasterFlex L/S Variable-Speed pump with Easy-Load pump head or equivalent. * Masterflex and L/S are registered trademarks of Cole-Parmer.
184 Tangential Flow Filtration Membrane Cassettes Centramate™, Centrasette™, Maximate™, and Maxisette™ Cassettes
Centramate Cassettes Centrasette and Centrasette II Cassettes Centramate cassettes are perfect for laboratory scale and development Centrasette cassettes,available in the applications in TFF. Small area formats with same range of membrane and screen 0.009 m2 and 0.018 m2 may be used with formats as the Centramate cassettes, the LV Centramate holder for process have been widely used for years in various volumes of a few liters down to a few process applications including milliliters. The 0.09 m2 format is used with concentration and diafiltration by the the Centramate Stainless Steel or biopharmaceutical industry. Centrasette
Top: Centramate Membrane Cassettes Centramate PE holders. Centramate cassettes are available with membrane Bottom: Centrasette Membrane Cassettes cassettes are available in a range of areas of 0.46, 1.9, and 2.3 m2 (5, 20, and channel formats and membranes to meet 25 ft2). Larger cassette areas simplify every application requirement. The installation in large TFF systems, reducing cassettes are supplied with the same the number of gaskets required and membrane and construction materials as minimizing risk of leakage used in the Centrasette Membrane Pall continues to improve membrane cassettes. cassettes to meet the more rigid Applications developed on a Centramate requirements of today’s applications. cassette can be easily scaled up by adding The Centrasette II membrane cassette cassettes to a Centramate holder or by uses the same components as in the switching to the Centrasette cassette original Centrasette. Therefore revalidation format with identical path length and may not be necessary. channel format. Feed ports in the Centrasette II have been Refer to Tables 1 – 4 on page 187 for a list enlarged to twice the size of the of membranes and formats available for Centrasette and membrane area has been Centramate cassettes increased by about 10%. The larger fluid Cassette Holders and approximate port design will enhance the membranes Membrane Area Capacity and Working performance by: Volumes are listed in the table Choosing a • Improving fluid flow distribution between Cassette Holder on page 188. and through cassettes • Allowing more efficient cleaning • Reducing the pressure profile across the feed/retentate channels Both types of Centrasette cassettes are available with 3 different membrane area options to meet small scale and larger process volume requirements. The Centrasette cassettes fit in a variety of Centrasette holders as well as similar
Centrasette and Centrasette II holders from other manufacturers. Feed Port Comparison
185 Tangential Flow Filtration Membrane Cassettes Technical Specifications
Maximate Membrane Cassette General Information
The Maximate membrane cassette offers the opportunity to simulate There are four cassette formats for UF and MF applications – the performance of the larger Maxisette membrane cassette on a Centramate, Centrasette, Maximate and Maxisette. smaller scale. The path length in Maximate membrane cassettes is Pall TFF membrane cassettes are available in a range of molecular identical to that used in the Maxisette format but the membrane weight cut-offs from 650 Da to 1000 kDa and pore sizes from 0.1 µm surface area and hold up volume are proportionately lower, meaning to 1.2 µm to meet every application requirement. Featured membrane that processing and optimization studies may be performed on types include: smaller batches. • Omega Maxisette • Alpha • Supor TFF The Maxisette format has some distinct benefits that make it advantageous for large volume processes. Most important is that the • Regen volumetric flow rate required is 40 % lower compared to cassette Cassette Channel Configurations formats like the Centrasette. This translates to a smaller pump and Cassettes are available in fine, medium and suspended screen piping diameter required for the same membrane area with a channel formats to best meet the specific requirements of each corresponding reduction in energy cost. The larger porting in the application. Maxisette (almost 50% larger feed and retentate ports than the Centrasette II Cassette) provides lower resistance to high feed flow Select a cassette channel configuration based on the following rates which results in lower pressure drops and easier cleaning. criteria:
Channel Configuration Selection Criteria Fine Screen Clarified, dilute solutions Final concentration below 2% (20 mg/mL) MWCO below 300K
Medium Screen Clarified solutions; low – medium viscosity Final concentration < 30% (300 mg/mL)
Suspended Screen/ Particles/cells/cell debris in solution Open Channel High viscosity
Maxisette Membrane Cassettes Storage Agents Omega, Alpha, Supor TFF and Regen cassettes are shipped wet, in liquid containing a humectant and bactericidal storage solution. This solution consists of 15 – 20% glycerin, and 0.05 – 0.1% sodium azide. The storage solution must be removed and the cassette flushed well with water prior to use to prevent product contamination. Cassettes are also available with circa 0.3N sodium hydroxide as the storage agent.
Traceability Each membrane cassette has a unique serial number for full traceability. Each cassette is supplied with: • Certificate of quality • Membrane Cassette Care and Use Procedures • Material Safety Date Sheet (MSDS) for cassette preservative • Two platinum cured silicon gaskets
Materials of Construction
Membrane Choice of 4: Omega, Alpha, Supor TFF or Regen Encapsulant Polyurethane Screens Polyester Spacers Polyolefin/PES 186 Cassettes pass current USP biological safety tests for Class VI plastics at 70 °C. Tangential Flow Filtration Membrane Cassettes Technical Specifications and Ordering Information
How to Order Membrane Cassettes Typical Examples:
1. Choose a membrane type from Table 1 (e.g. OS, AS, CS or PS). OS010F06AF PSM20G02XX 2. Choose a MWCO from Table 2 or a µm rating code from Table 3, as appropriate (e.g. 010 = 10 kD, M20 = 0.2 µm). Membrane Omega Membrane Supor 3. Choose a format code from Table 4 (e.g., C10, C11, or C12). MWCO/Rating 10 kD MWCO/Rating 0.2 µm Format Centrasette II Format Maximate Table 1 – Membrane Type Feed Channel Medium Screen Feed Channel Medium
2 2 2 2 Code Membrane Comments Area 0.5 m (5.4 ft ) Area 0.18 m (2 ft ) OS Omega Low protein-binding Special Format NaOH Special Format None modified polyethesulfone Storage Agent
AS Alpha Antifoam-resistant modified polyethersulfone
CS Regen Low protein-binding Table 2 – Available MWCOs for Ultrafiltration Membranes Regenerated Cellulose Code MWCO Omega Alpha Regen PS Supor TFF Microfiltration-optimized (kD) (OS) (AS) (CS) polyethersulphone D65 0.65 –– 001 1 –– Table 3 – Available Micron Ratings for Microfiltration Membranes 003 3 –– 005 5 –– Code Pore Size Supor Omega (µm) (PS) (OS) 010 10 M10 0.1 – 030 30 M20 0.2 – 050 50 – M45 0.45 – 070 70 –– M65 0.65 – 100 100 –– M80 0.8 – 200 200 –– M12 1.2 – 300 300 –– 994 0.16 – 500 500 –– 990 1000 ––
Table 4 – Cassette and Screen Formats
Nominal Area Fine Screen(1) Medium Screen Suspended Screen Code Code Code Cassette Format Centramate 0.01 m2 (0.1 ft2) – C12P1 C11P1 0.02 m2 (0.2 ft2) – C12P2 C11P2 0.1 m2 (1.0 ft2) C10 C12 C11 Centrasette 0.46 m2 (5.0 ft2) C05 C06 C07 1.86 m2 (20 ft2) C20 C21 C22 2.32 m2 (25 ft2) C25 C26 C27 Centrasette II 0.5 m2 (5.4 ft2) F05 F06 F07 2.0 m2 (22 ft2) F20 F21 F22 2.5 m2 (27 ft2) F25 F26 F27 Maximate 0.04 m2 (0.4 ft2) – G01P2 G02P2 0.19 m2 (2.0 ft2) G10 G01 G02 Maxisette 2.8 m2 (30 ft2) C50 C51 C52 (1) Fine Screen channel not available in any MWCOs greater than 200 kDa.
187 Tangential Flow Filtration Membrane Cassette Holders Choosing a Cassette Holder
Designed for optimum performance and Operators must use calibrated torque product recovery Pall TFF cassette holders wrenches (supplied with the holder) to are available in a variety of sizes to meet effect required compression of cassettes every application requirement. This way and gaskets in a manual torque cassette applications that are developed on a small holder. Auto-torque cassette holders Centramate Housing with 3-Gauge, 2-Valve Fitting system using a Centramate or Maximate automatically compensate for cassette Kit and Torque Wrench cassette can be easily scaled up, either by compression and temperature reduction. adding additional cassettes to the holder They also eliminate variability in technique or by scaling into a larger cassette format between operators. Auto-torque cassette and holder configuration with identical flow holders are recommended for path like the Centrasette/Centrastak or process-scale validated processes. Maxisette holders. Sanitary stainless steel holders may be TFF cassette holders for the medium and sterilized by steam or autoclaving without large-scale production environment have a cassettes installed. small footprint, yet still are capable of holding large areas of membrane. All Complete fittings kits consisting of stainless steel holders are engineered to pressure gauges, valves, filtrate manifold, precise specifications with a high standard connectors, gaskets and clamps are internal and external surface finish and are available for most cassette holders. available with either manual torque (MT) or Ordering a complete fitting kit with the auto torque (AT) compression systems for cassette holder simplifies installation into a Holder Fittings Kits ease of use. system and avoids potential delays in Complete fittings kits consisting of starting your process due to missing parts. pressure gauges, valves, filtrate manifold, connectors, gaskets and clamps are Choosing a Cassette Holder available for most cassette holders. The following table lists cassette holders with relative area capacities and working volumes. The Ordering a complete fitting kit with the Minimate TFF Capsule is also included to complete the range of lab scale products. cassette holder simplifies installation into a Product Membrane Area Working Volumes* system and avoids potential delays in Lab and Development Scale starting your process due to missing parts. (Scale-up and Scale-down studies) Starting Final Minimate TFF 0.005 m2 0.05 ft2 25 – 500 mL 25 mL Capsule Centramate LV 0.01 – 0.02 m2 0.1 – 0.2 ft2 25 – 2,000 mL 10 mL Centramate PE 0.01 – 0.37 m2 1 – 4 ft2 0.5 – 80 L 150 mL Centramate 0.01 – 0.46 m2 1 – 5 ft2 0.5 – 100 L 150 mL Maximate 0.19 – 1.11 m2 2 – 12 ft2 1 – 250 L 350 mL Pilot Scale (Process Development) Centrasette LV 0.46 – 2.3 m2 5 – 25 ft2 2.5 – 500 L 400 mL Centrasette P 0.46 – 2.3 m2 5 – 25 ft2 2.5 – 500 L 400 mL Centrasette 5 0.46 – 4.6 m2 5 – 50 ft2 2.5 – 1,000 L 1,000 mL Process Scale (Production) Centrastak 100 0.9 – 18.5 m2 10 – 200 ft2 10 – 4,000 4 L Centrastak 200 1.85 – 37.2 m2 20 – 400 ft2 20 – 8,000 10 L Centrastak 300 2.8 – 55.8 m2 30 – 600 ft2 30 – 12,000 15 L Centrastak 400 3.7 – 74.0 m2 40 – 800 ft2 40 – 16,000 20 L Maxisette 25 2.8 – 27.9 m2 30 – 300 ft2 30 – 6,000 15 L Maxisette 50 5.6 – 55.8 m2 60 – 600 ft2 60 – 12,000 30 L Maxisette 100 5.6 – 92.9 m2 60 – 1,000 ft2 60 – 20,000 40 L
(1) Fewer suspended screen cassettes will fit due to increased thickness. Some holders can fit more membrane area than can be operated at required cross flow rates due to high pressure drops. Do not use more than the recommended area in these holders.Manual (MT) and auto-torque (AT) version holders are available for Pilot and Process Scale applications. (2) Working Volumes are based on an average filtrate flux rate of about 50 LMH and process time of 5 hours. Starting Range covers minimum to maximum area installed for screen channel cassettes. Final process volume represents final concentration volume or minimum working volume for the system. Actual volumes depend on system hold-up volume and operating parameters. Piping (tubing) lengths and internal diameters significantly affect the final volume. 188 Tangential Flow Filtration Membrane Cassette Holders
Centramate LV Holder compensate for the height difference as additional cassettes are added to the The Centramate LV holder is fabricated holder. Sanitary fitting kits with either 2 or 3 from Stainless Steel (316L) with female luer pressure gauges are available. fittings for use with 0.01 m2 (0.1 ft2) and 0.02 m2 (0.2 ft2) Centramate cassettes. Centrasette LV Holder The holder can accommodate up to 0.04 m2 (0.4 ft2) of screen channel or The Centrasette LV Holder is 0.02 m2 (0.2 ft2) of open channel manufactured using highly polished 316L 3 Centramate cassettes at recommended stainless steel. This holder has ⁄4 in. cross flow rates. A range of luer fittings sanitary fractional fitting on the and valves are available as well as pressure feed/retentate and permeate ports which gauges or transducers to set-up a minimizes the hold-up volume. It is ideal for complete TFF system. use in systems that use Centrasette cassettes when total membrane area will Centramate PE Holder be less than 2.5 m2 (27 ft2) of screen channel cassettes or 1.5 m2 (16 ft2) of The Centramate PE holder has a suspended screen cassettes. 1 polyethylene manifold with ⁄4 in. NPT threaded ports sandwiched between 304 Centrasette P Holder stainless steel outer plates for support. It will accommodate up to 4 screen channel The Centrasette P Holder has a (3 suspended screen channel) 0.09 m2 polypropylene center manifold and end (1 ft2) cassettes. The use of several plate,for use when product contact with spacers on the tie rods makes it easy to metal is not desirable or prohibited by your apply and tighten the nuts with minimal application; for example when processing threading if only one cassette is installed. certain metal sensitive enzymes or As additional cassettes are added, spacers oligonucleotides. The manifold and end can be removed. The Centramate PE plate are housed between stainless steel holder is recommended for use in plates to supply the necessary rigidity applications where metal contact must be when operating at higher pressures.Luer 3 avoided. A plastic, NPT threaded fitting fittings on the ⁄4 in. sanitary polypropylene kit,with either 2 or 3 pressure gauges is ports can be used for connection to plastic available. pressure transducers for monitoring pressures, again without metal contact. Centramate Stainless Steel Holder The low-cost plastic manifold and end plate can be replaced to avoid cleaning The Centramate stainless steel cassette validation or dedicated to a specific 1 holder (316L) comes with ⁄2 in. sanitary application along with a set of cassettes to flanges on feed and filtrate ports. The prevent any risk of cross-contamination. holder is supplied with surface and weld The Centrasette P holder like the certification. Up to 5 screen channel (4 Centrasette LV holder is intended for use suspended screen channel) 0.09 m2 (1 ft2) with Centrasette cassettes when total cassettes can be accommodated. Holder membrane area will be less than 2.5 m2 is supplied with both 1 in. and 2 in. (27 ft2) of screen channel cassettes or spacers on the tie rods to simplify cassette 1.5 m2 (16 ft2) of suspended screen Top to Bottom: Centramate LV Holder installation and to apply the required cassettes. Centramate PE Holder torque. Spacers can be removed to Centramate Stainless Steel Holder Centrasette LV Holder Centrasette P Holder 189 Tangential Flow Filtration Membrane Cassette Holders
Centrasette 5 and Centrasette 5AT Holders Centrastak Holders
The Centrasette 5 holder is intended for use in pilot and process Processes developed at bench scale on Centramate and scale applications with up to 5 m2 (54 ft2) screen channel Centrasette Centrasette cassettes can be scaled up to process volumes in or Centrasette II cassettes or 4 m2 (43 ft2) of suspended screen excess of 10,000 L using a Centrastak system. The Centrastak cassettes. The feed/retentate channels have tapered bores range of cassette holders have been designed for optimal engineered to maintain uniform cross flow and pressure drops across performance in large-scale production environment. The small the membrane cassettes. Two permeate ports, one near the feed and footprint makes them ideal for use in process skids and the other near the retentate, are designed to reduce backpressure on manufacturing suites where space is at a premium. Each level in a the permeate side of the membrane. This is especially important Centrastak holder can hold up to 10 m2 (107 ft2) of Centrasette when operating at high flux rates. Pressure on the permeate side cassettes on each side of a central manifold or effectively 20 m2 effectively reduces transmembrane pressure and lowers filtrate flux [215 ft2] per level. A single center-manifold significantly reduces rates. The highly polished 316L stainless steel unit has ports that hold-up volumes. mate up with 1 in. sanitary connectors. A calibrated torque wrench Feed flow direction is from bottom to top allowing air to be easily and socket is supplied with the holder, as it is with other manual expelled from the system. Four Centrastak holders are available: torque holders. • Centrastak 100AT – 20 m2 (215 ft2) capacity
• Centrastak 200AT – 40 m2 (430 ft2) capacity
• Centrastak 300AT – 60 m2 (645 ft2) capacity
• Centrastak 400AT – 80 m2 (861 ft2) capacity All Centrastak holders are available in auto-torque format with a hydraulic system,including stainless steel pistons and pump,for maintaining optimal and uniform compression on the installed cassettes. A pressurized air supply is required to operate the hydraulic pump (60 psi minimum,125 psi maximum). All wetted surfaces are electropolished, 316L stainless steel. Holder is supplied with surface and weld certification to support I/Q validation.
Top : Centrasette Holder with Manual Torque Bottom: Centrasette Holder with Auto Torque
Top: Centrastak 200 AT Bottom: Hydraulic Pump for AutoTorque Holders
190 Tangential Flow Filtration Membrane Cassette Holders
Maximate Holders Maxisette holders are available in auto-torque format with a hydraulic Maximate holders are designed for use system, including six pistons and a pump, with Maximate membrane cassettes. The for maintaining optimal and uniform 3 316L stainless steel holder has ⁄4 in. compression on the installed cassettes. A 1 sanitary feed/retentate ports and ⁄2 in. pressurized air supply is required to permeate ports. Up to 6 screen channel operate the hydraulic pump (60 psi cassettes (4 suspended screen channel [4.1 bar] minimum, 125 psi [8.6 bar] cassettes), 0.19m2 (2ft2) will fit into the maximum). All wetted surfaces are holder accommodating process fluid electropolished, 316L stainless steel. volumes from a few hundred milliliters up to over a hundred liters. Maxisette holders are available in three different sizes: Maximate cassettes are chosen for scale-up studies when process-scale • Maxisette 25: 28 m2 (300 ft2) capacity, volumes will be processed using a screen channel Maxisette system that has the same • Maxisette 50: 56 m2 (600 ft2) capacity, feed/retentate channel path length. screen channel
• Maxisette 100: 89 m2 (960 ft2) capacity, Maxisette Holders screen channel The Maxisette holder has been designed All Maxisette Holders are supplied with for optimal performance in a large-scale surface and weld certification. production environment. The longer path length of a Maxisette cassette compared with a Centrasette cassette allows a 40% reduction in cross flow rate (retentate flow rate), therefore requiring a smaller pump with a corresponding reduction in heating, energy costs and space requirements. The small footprint makes it ideal for use in process skids and manufacturing suites where space is at a premium. Feed flow direction is from bottom to top allowing air to be easily expelled from the system. Port design in the Maxisette cassette results in a significant reduction in pressure drops and a more uniform pressure profile at operating cross flow rates compared to other cassette formats. This results in higher performance during production and more efficient cleaning. Processes developed at bench scale on Maximate cassettes can be efficiently scaled up to process volumes in excess of 10,000L.
191 Tangential Flow Filtration Membrane Cassette Holders Technical Specifications
Centramate Cassette Holders Cassette Holder Centramate LV Centramate PE Centramate
1 1 Feed and Retentate Ports Female luer SS ⁄4 in. NPT Fitting (female) ⁄2 in. Sanitary, 9.6 mm (0.38 in.) bore
1 1 Filtrate Port Female luer SS ⁄4 in. NPT Fitting (female) ⁄2 in. Sanitary, 8.1 mm (0.32 in.) bore Maximum Membrane Area Screen 0.04 m2 (0.4 ft2) 0.37 m2 (4 ft2) 0.46 m2 (5 ft2) Suspended Screen 0.02 m2 (0.2 ft2) 0.28 m2 (3 ft2) 0.37 m2 (4 ft2)
Nominal Dimensions 12 x 23 x 6.6 cm 9.4 x 24 x 19 cm 13 x 23 x 16 cm 1 1 3 1 1 1 1 (Width x Length x Depth) (4 ⁄2 x 9 x 2 ⁄2 in.) (3 ⁄4 x 9 ⁄2 x 7 ⁄2 in.) (5 ⁄4 x 9 x 6 ⁄4in.)
Weight 4 kg (8.75 lbs) 8.6 kg (19 lbs) 6.4 kg (14 lbs)
Maximum Operating Temperature(2) 50 °C (121 °F) 80 °C (175 °F) 80 °C (175 °F)(3)
Maximum Operating Pressure 5 bar (75 psi) 6 bar (90 psi) 6 bar (90 psi)
Centrasette Cassette Holders
Cassette Holder Centrasette LV Centrasette P Centrasette 5,* 5AT*
3 3 Feed and Retentate Ports ⁄4 in. sanitary SS ⁄4 in. sanitary PP 1 in. sanitary SS
3 3 Filtrate Port ⁄4 in. sanitary SS ⁄4 in. sanitary PP 1 in. sanitary SS
Maximum Membrane Area(1) Screen 2.0 m2 (22 ft2) 2.0 m2 (22 ft2)5 m2 (54 ft2) Suspended Screen 1.5 m2 (16 ft2) 1.5 m2 (16 ft2)4 m2 (43 ft2)
Nominal Dimensions 26 x 25 x 21 cm 30 x 20 x 34 cm 26 x 25 x 27 mm 1 1 1 1 3 (Width x Length x Depth) (10 ⁄4 x 10 x 8 ⁄2 in.) (12 x 8 x 13 ⁄2 in.) (10 ⁄4 x 10 x 10 ⁄4 in.)
Weight 28 kg (62 lbs) 25 kg (55 lbs) 30 kg (66 lbs)
Maximum Operating Temperature(2) 80 °C (175 °F)(3) 50 °C (121 °F) 80 °C (175 °F)(3)
Maximum Operating Pressure 6 bar (90 psi) 5 bar (75 psi) 6 bar (90 psi)
* Extended tie rods available to increase membrane capacity to 5 m2 (54 ft2) for suspended screen channel cassettes.
Centrastak Cassette Holders Cassette Holder Centrastak 100 Centrastak 200 Centrastak 300 Centrastak 400 Feed and Retentate Ports 2 in. sanitary 2 in. sanitary 2 in. sanitary 2 in. sanitary Filtrate Port 1 in. sanitary 1 in. sanitary 1 in. sanitary 1 in. sanitary Maximum Membrane Area(1) Screen 20 m2 (216 ft2) 40 m2 (430 ft2) 60 m2 (645 ft2) 80 m2 (860 ft2) Suspended Screen 15 m2 (161 ft2) 30 m2 (323 ft2) 45 m2 (484 ft2) 60 m2 (645 ft2)
Nominal Dimensions 39 x 91 x 59 cm 39 x 91 x 95 cm 39 x 91 x 107 cm 39 x 91 x 120 cm 1 1 1 1 1 1 1 (Width x Length x Height) (15 ⁄2 x 36 x 23 ⁄4 in.) (15 ⁄2 x 36 x 37 ⁄2 in.) (15 ⁄2 x 36 x 42 in.) (15 ⁄2 x 36 x 47 ⁄2 in.)
Weight 155 kg (340 lbs) 255 kg (560 lbs) 314 kg (690 lbs) 409 kg (900 lbs)
Maximum Operating 80 °C (175 °F) 80 °C (175 °F) 80 °C (175 °F) 80 °C (175 °F) Temperature(2, 3)
Maximum Operating 6 bar (90 psi) 6 bar (90 psi) 6 bar (90 psi) 6 bar (90 psi) Pressure
(1) Cassette blocks (2 m2 [21.6 ft2] or 2.5 m2 [26.9 ft2]) are recommended. If 0.5 m2 [5.3 ft2] cassettes are used, stabilizer plates must be used between every 5 cassettes (fine/medium screen) or 3 cassettes (suspended screen). (2) Maximum operating temperature may be restricted by cassette operating temperature limit. (3) Holder may be steamed with compatible cassettes, or without cassettes at up to 142 °C (287.6 °F).
192 Tangential Flow Filtration Membrane Cassette Holders Technical Specifications and Ordering information
Maximate and Maxisette Cassette Holders Cassette Holder Maximate Maxisette 25 Maxisette 50 Maxisette 100
3 1 1 Feed and Retentate Ports ⁄4 in. sanitary 2 in. sanitary 2 ⁄2 in. sanitary 2 ⁄2 in. sanitary
1 1 1 1 Filtrate Ports 1 ⁄2 in. sanitary 1 ⁄2 in. sanitary 1 ⁄2 in. sanitary 1 ⁄2 in. sanitary Maximum Membrane Area(1) Fine/Medium Screen 1.1 m2 (12 ft2) 28 m2 (300 ft2) 56 m2 (600 ft2) 89 m2 (960 ft2) Suspended Screen 0.74 m2 (8 ft2) 28 m2 (300 ft2) 56 m2 (600 ft2) 56 m2 (600 ft2) Dimensions 16 x 44 x 22 cm 47 x 105 x 57 cm 47 x 105 x 97 cm 47 x 105 x 117 cm 1 1 3 1 1 1 1 1 1 1 (Width x Length X Height) (6 ⁄4 x 17 ⁄2 x 8 ⁄4 in.) (18 ⁄2 x 41 ⁄2 x 22 ⁄2 in.) (18 ⁄2 x 41 ⁄2 x 38 in.) (18 ⁄2 x 41 ⁄2 x 46 in.) Approximate Weight 13.3 kg (29.2 lbs) 455 kg (1000 lbs) 566 kg (1245 lbs) 566 kg (1245 lbs) Maximum Operating 80 °C (176 °F) 80 °C (176 °F) 80 °C (176 °F) 80 °C (176 °F) Temperature(2, 3) Maximum Operating 6 bar (87 psi) 6 bar (87 psi) 6 bar (87 psi) 6 bar (87 psi) Pressure
(1) Cassette blocks (2 m2 [21.6 ft2] or 2.5 m2 [26.9 ft2]) are recommended. If 0.5 m2 [5.3 ft2] cassettes are used, stabilizer plates must be used between every 5 cassettes (fine/medium screen) or 3 cassettes (suspended screen). (2) Maximum operating temperature may be restricted by cassette operating temperature limit. (3) Holder may be steamed with compatible cassettes, or without cassettes at up to 142 °C (287.6 °F).
Materials of Construction for Wetted Parts Centramate PE Centramate LV Centramate/Maximate Centrasette P Centrasette/Maxisette Plates UHMW polyethylene 316L Stainless Steel 316L Stainless Steel Polypropylene 316L Stainless Steel Flow Distribution UHMW polyethylene 316L Stainless Steel 316L Stainless Steel Polypropylene 316L Stainless Steel Manifold Other Components EPDM O-ring on SS EPDM sanitary threaded Luer connector gaskets
Ordering Information The following table lists individual cassette holders as well as holders sold in combination with fittings packages. Additional combinations and a variety of other accessories are available. For complete descriptions and additional offerings, contact your local Pall representative.
Description Part Number Centramate Centramate PE Holder, Including torque wrench and socket FS002K10 Centramate PE Holder, Including fittings package with 3 pressure gauges FS013K10 Centramate LV Holder, Including torque wrench and socket FS003K10 Centramate SS Holder, Including torque wrench and socket FS001K10 Centramate SS Holder, Including torque wrench,fittings package with 3 pressure gauges, 2 diaphragm valves FS011K10 Centrasette 5 manual torque Including torque wrench and socket FS001K05 Centrasette Centrasette P Holder Including torque wrench and socket FS039K05 Centrasette LV Holder Including torque wrench and socket FS044K05 Centrasette LV holder,Including torque wrench and socket,fittings package with 3 pressure gauges,2 diaphragm valves FS046K05 Centrasette 5 Including torque wrench and socket FS001K05 Centrasette 5 holder,Including torque wrench and socket,fittings package with 3 pressure gauges,2 diaphragm valves FS014K05 Centrasette 5AT Holder FS020K05 Centrasette 5AT holder,Including torque wrench and socket,fittings package with 3 pressure gauges,2 diaphragm valves FS022K05 Centrastak Centrastak 100 AT FS050K05 Centrastak 200 AT FS034K05 Centrastak 300 AT FS036K05 Centrastak 400 AT FS038K05 Maximate Maximate holder,including torque wrench and socket FS001G01 Maximate fitting package, Including torque wrench and socket,fittings package with 3 pressure gauges and 2 diaphragm valves FS003G01 Maxisette Maxisette 25 AT FS009K50 Maxisette 50 AT FS013K50 Maxisette 100 AT FS016K50 193 Pilot and Process Development Capabilities
Pall offers a range of tangential flow filtration systems from small scale and process development to full-scale process systems. These include standard systems such as the Minimate, Centramate Pilot, and Centrasette 5AT Systems as well as standard and custom engineered process systems that meet the most stringent control and validation requirements. Various levels of automation from simple manual systems to full automation control and data acquisition are available or can be custom-developed to meet specific requirements. Contact Pall for further details. • Scalable design • Multiple membrane formats • Ease of use Maxim benchtop TFF System for process development and Microza* Benchtop System pilot scale applications Pall Engineering
• Mechanical Design ASME BPE Clean In Place (CIP) Sterilize In Place (SIP) • Electrical Design Explosion-proof (XP)design UL508 Panel fabrication National Electric Code (NEC) UL CSA and cUL standards.
Controls
• GAMP-compliant • PLC /PC based • SCADA Packages • DCS
• Standard Package modifications Centrastak Workstation
Project Support
• Process Development • Project Management • System Fabrication • Documentation
Service
• Factory Acceptance Test • Site Acceptance Test • Installation Qualification • Operation Qualification • Start-up/Commissioning • Operator Training Large Process system with automated valves and process control for up to 800 ft2 • Maintenance of membrane. • Troubleshooting and Support
* Microza is a trademark of Asahi Kasei Corporation 194 Tangential Flow Filtration Systems Pre-Designed Systems for Scalable Processing
Pall offers scalable, pre-designed systems Process Automation to suit your specific process needs. Pall Puts Control in the Hands of your Standard systems are ready-to-use, Process Engineers engineered systems with integrated recipe management tools to expedite your User-friendly recipe management tools approval processes and reduce your time include a suite of default recipes for to market. pre-production, production, and post-production operations. Your process The pilot system includes the flexibility of experts can make applications work both semi and full automation, a UV without waiting for programmers to sift detector, a pH monitor, an Integrity through cryptic proprietary software code. Analyzer, and an integrated tank. The system expedites the development and The flexible software design enables users scale-up of filtration processes in to build recipes and develop processes accordance with FDA cGMP regulations without PLC programming expertise. Our and guidelines. software is ideal for use in a variety of environments, including process: Pall Pre-designed Pilot Systems • Development Pall offers a range of pre-designed systems • Optimization to meet your process goals. • Production These include: Streamlined Validation • Centramate 0.1 – 0.5 m2 (1 – 5 ft2) Our recipes are configured from modules • Maximate 0.2 – 0.9 m2 (2 – 10 ft2) which are tested configuration-based sequences that reduce the number of • Centrasette(1) 0.5 – 7.0 m2 (5 – 75 ft2) validation steps. • Centrastak(1) 0.9 – 18.6 m2 Operations (10 – 200 ft2) From a touch screen,any authorized user (1) Autotorque hardware included and optional can create and store recipes so an Instrumentation for UV, pH, Conductivity, Integrity, and Auxiliary Pump. Tanks also available. operator can run process tasks simply, easily, and accurately. Features Pall’s pre-programmed recipes can be • Intuitive Automated Control System used to automatically sanitize, concentrate, Top and Middle: Centramate Pilot Automated recover product, and clean in place. Development and Optimization Systems • Fully scalable design and components Bottom: System Overview Display Data Storage • Complete validation package with comprehensive IQ/OQ documentation • 21 CFR Part 11 compliant data-handling • Compact sanitary ergonomic design for enhanced cleanability, portability, and • Convenient data storage and retrieval accessibility • Outputs to electronic or printed formats • Optional AutoTorque™ (AT) hardware Reports provides uniform cassette sealing • Real-time trend analysis • Comprehensive Recipe Management • Historic Trend Overlays • Adheres to ASME BPE, ANSI ISA, and • Comprehensive Batch Reports cGMP standards • Exports common text and table formats • Time-saving 195 Tangential Flow Filtration Systems Pre-Designed Systems for Scalable Processing
Left: Centrasette System Middle: Maxisette System Right: Centrastak System
Engineered Solutions Process Design
Pall engineers are available to help you design and build systems to Making your process work reliably and repeatably is our goal. Pall accommodate your specific process needs. Decades of experience in Process engineers are available to work with you throughout the the BioProcess Industry has proven our ability to provide innovative, entire development phase. Some of the typical activities our process cost-effective solutions. experts can help you with are: Our team of process engineers and design specialists work with you • Membrane screening trials every step of the way to ensure that systems meet your application • Initial scale-up work needs and delivery requirements. • Process optimization Design • Cleaning
Our patented designs provide higher process efficiency, enhanced • Scale-down studies process control, lower pressure drops, and minimized holdup • Process Audits volumes to ensure: • Maximum yield Project Execution
• Cleanability and Recovery To ensure that our entire project team understands your needs, our • Compact cost-effective systems – more membrane area per Process Engineers will manage your project throughout the entire square-foot of floor space design, build, and commissioning cycle. Our process engineers will direct the project team to meet your process requirements on time • Autotorque device offers consistent pressure for a reliable seal on every time. cassettes to ensure batch process repeatability with minimal labor overhead
Pre-Engineered Systems Centramate Pilot Maximate Pilot Centrasette 5 SAT Centrastak 100 SAT Feed Flow Range 7 7 65 120 (L/Min) @ 60 psig
Membrane Area 0.1 –0.5 m2 (1 – 5 ft2) 0.2 – 0.9 m2 (2 – 10 ft2) 0.5 – 7.0 m2 (5 – 75 ft2) 0.9 – 18.6 m2 (10 – 200 ft2)
1 1 1 1 Connections ⁄2 in. Sanitary Flange ⁄2 in. Sanitary Flange 1 ⁄2 in. Sanitary Flange 1 ⁄2 in. Sanitary Flange
Membrane Holder Manual Torque Manual Torque Auto Torque Auto Torque
Optional Instrumentation UV, pH, UV, pH, UV, pH, UV, pH, Conductivity, Integrity, Conductivity, Integrity, Conductivity, Integrity, Conductivity, Integrity, Auxiliary Pump, Tanks Auxiliary Pump, Tanks
Hold-up Volume 275 mL 275 mL < 2.5 L < 3.5 L
196 TFF Polymeric Hollow Fiber Membranes and Ceramic Modules For Demanding Duties in Ultrafiltration and Microfiltration
Polymeric Membranes All membranes are available in modules ranging in size from a few square Pall’s polymeric hollow fiber membranes centimeters of surface area through and modules comprise the Microza* range. multiple square meters in a single module Microza membranes are durable, industry- to cover every scale of operation from the leading fibers available in a wide variety of laboratory to the largest manufacturing ratings and polymers for applications as plant with consistent fiber geometry. diverse as clarification, concentration and purification of bulk enzyme solutions,to Membrane modules can be cleaned for optimized designs for long-term sterility multiple re-use, the simple design maintenance and performance in critical facilitating such cleaning or, because of the mammalian cell culture perfusion. convenience of the stand-alone modular design, may be treated as single-use items Available ratings span the range from low for many critical applications, such as the molecular weight ultrafiltration through to production of recombinant proteins in microfiltration. All Microza membranes are perfusion cell culture. supplied as self-contained modules, with no additional requirement for housings, Systems enabling simplicity of system design. Modules are available that can be Pall’s experience with systems built to autoclaved, and many can be utilize Microza membranes, is second to live-steamed, facilitating aseptic operation none, and includes construction of some through the use of SIP. of the largest and most complex process unit operations in the bioprocessing industry.
* Microza is a trademark of Asahi Kasei Corporation
197 Microza Membranes Technical Specifications
Polymeric Membrane Morphology Microza Module Types
Microza* ultrafiltration membranes are unique in their construction. Microza hollow fiber modules are available with housings made from Every membrane has an asymmetric structure,with a membrane layer polysulfone (native, clear), filled polysulfone (white, opaque), and both on the inside, and on the outside of the fiber, overlaying a core polyvinylchloride (PVC). Polysulfone modules will withstand comprising a very open support for excellent flow characteristics, and autoclaving and in some cases steaming. Clear polysulfone modules a central strengthening layer for outstanding fiber durability in are recommended for more critical pharmaceutical applications. Filled long-term service. Microza ultrafiltration membranes are resistant to polysulfone and PVC modules are ideally suited to long term flow in both directions, so there is no risk of delamination or installations where light might cause biofilm to form, or for bulk membrane rupture during accidental back-pressure. In fact, in many processes involving light sensitive materials. PVC modules are ideal installations, backpulsing can be used to maintain flux during for use in feed water systems and bulk processes. extended run times. Microza modules are available with industry standard clamp fittings Microza micofiltration membranes have smooth inner and outer on the feed and retentate side, and some with quick connects. All membrane skins with a highly porous symmetrical support structure steamable modules designed for long term use in critical applications giving high-flow rates. These modules can also be backflushed. such as perfusion have sanitary clamp connections on the feed/retentate and filtrate sides, or filtrate hose barbs on laboratory All Microza membranes have surfaces that minimize entrapment and scale modules. facilitate cleaning. All Microza membranes are manufactured in a single step, and are not composed of laminates. Membranes and modules are subjected to rigorous quality control to ensure Retrofitting Existing Applications consistency of performance, durability in service, and module integrity To retrofit an existing application,membrane rating should be chosen for the most demanding applications. to be equivalent or superior in performance. For ultrafiltration membranes, this may require testing more than a single cut-off. Membrane Types Differences in membrane area and lumen diameter can typically be accommodated by adjustments to operating conditions to ensure Polysulfone (PS) that trans-membrane pressure and fluid velocity conditions at the Polysulfone membranes exhibit excellent resistance to pressure, membrane surface are similar. Hollow fiber modules can be joined temperature and aggressive cleaning regimes. Very low affinity and end-to-end as required to create similar path length systems. Small adsorption characteristics results in high product recoveries, and long adjustments to physical dimensions, and differences in connection service life. type are accomplished using adapters. Please contact Pall for Polyacylonitrile (PAN) assistance with selecting the right modules to retrofit an existing PAN membranes are ideally suited to bulk process applications, such installation. as the purification of enzymes. They exhibit high-strength, coupled The following pages list modules firstly by membrane material, and with high flux rates, minimizing installation size. PAN has a low fouling then within each material by rating, available sizes and available characteristic for these applications, simplifying cleaning. connection types. Polyvinylidene Fluoride (PVDF) PVDF membranes are widely used for the filtration of biological solutions. In hollow fiber format, these membranes show excellent retention characteristics, allowing use in critical applications where absolute removal over long periods is required. Lower non-specific binding than many PS membranes used in protein recovery applications ensures excellent results in leading-edge biotechnology processes. PVDF membranes are steamable in situ for additional process security. PVDF exhibits superior chemical resistance to many other polymers used in microfiltration processes. Polyolefin (P) Polyolefin membranes are a good choice for bulk clarification processes where sterility is not essential. Nevertheless, P-membranes have good retention characteristics coupled with high flux rates. Availability in fine microfiltration retention ratings ensures protection of downstream processing equipment.
* Microza is a trademark of Asahi Kasei Corporation
198 Microza Membranes Polysulfone Membranes – Technical Specifications
Microza SP, SV and VP series hollow fiber ultrafiltration modules have Key Features a unique double-skinned proprietary polysulfone (PS) membrane with • Combination of high-strength and high-flow due to unique dense internal layer. Currently available in 3000, 4000, 6000, and membrane construction 10000 molecular weight cut-offs, the modules are used in a range of • Double-skin provides assurance of removal rating pharmaceutical applications including pyrogen removal from water, buffer solutions active ingredients such as antibiotics, and • High-strength fiber allows reverse filtration to assist cleaning in concentration of protein solutions. SV modules are used for clarifying difficult applications antibiotic and other broths used for small molecule API production. • Available in a range of sizes from 0.015 m2 (0.16 ft2) to more than 12 m2 (125 ft2) Materials of Construction • All SP and VP modules may be hot water sanitized: up to 95 °C (203 °F) – SIP and SLP, or 90 °C (194 °F) – SEP and SAP; and all Membrane Polysulfone (with silicone coating on ends in VIP–3017S) may run continuously at 80 °C (176 °F) Housing Native clear polysulfone (P) or PVC (V) • SP Modules may be autoclaved in single use applications Potting Material Epoxy resin • VIP 6000 MWCO version steam-sterilizable up to 50 cycles at Gasket Silicone (P) or butyl rubber (NBR) (V) 125 °C (257 °F) at a differential pressure of 100 mBar Bacteriostat Glycerin 65%, ethanol 2%, • SV modules are designed for maximized recovery in bulk water balance fermentation, limited to 50 °C (122 °F) Connectors and Adapters Contact Pall for wide range of fittings for • Compatible with a wide range of cleaning agents, up to 5000 ppm these modules sodium hypochlorite or 4% sodium hydroxide
Connectors and Adapters • Meets the specification for biological tests listed in the current revision of USP for class VI plastics at 121 °C (249 °F) For available connections, please refer to table on p202. • pH range 1 – 14
Part Number(1) Rating Fiber Nominal Membrane Clean Crossflow Maximum Volume Volume Feed/ Permeate (MWCO, ID Length(2) Area Water Flux Rate for Pressure Feed Permeate Retentate Connection Daltons) Lh -1 bar 1ms-1 fluid (barg) at Side(3) Side(3) Connection velocity 50 °C (mL) (122 °F) SEP-0013 3000 0.8 mm 130 0.017 2.5 181 1/1/1 9 9 A2 A1 SEP-1013 3000 0.8 mm 347 0.2 25 724 3/3/2 90 120 B1 B1 SEP-2013 3000 0.8 mm 552 1.0 130 1629 5/3/2 300 500 C4 C3 SEP-3013 3000 0.8 mm 1129 4.7 650 3655 5/3/3 1200 3700 C5 C4 SAP-0013 4000 0.8 mm 130 0.017 3.6 181 1/1/1 9 9 A2 A1 SAP-1013 4000 0.8 mm 347 0.2 36 724 3/3/2 90 120 B1 B1 SAP-3013 4000 0.8 mm 1129 4.7 900 3655 5/3/3 1200 3700 C5 C4 SAV-3013 4000 0.8 mm 1126 5.6 1100 4343 5/3/3 1200 3700 C7 D2 SAV-5013 4000 0.8 mm 1126 12.1 2400 9950 5/3/3 3800 5300 C8 D3 SIP-0013 6000 0.8 mm 130 0.017 4.0 181 1/1/1 9 9 A2 A1 SIP-1013 6000 0.8 mm 347 0.2 40 724 3/3/2 90 120 B1 B1 SIP-1023 6000 0.8 mm 347 0.2 44 724 3/3/2 90 130 B1 B1 SIP-2013 6000 0.8 mm 552 1.0 200 1629 5/3/2 300 500 C4 C3 SIP-3013 6000 0.8 mm 1129 4.7 1000 3655 5/3/3 1200 3700 C5 C4 SIP-3023 6000 0.8 mm 1129 7.2 1700 5610 5/3/3 700 3700 C5 C4 VIP-3017S 6000 0.8 mm 1129 4.7 1000 3655 5/3/3 1200 3700 C5 C4 SLP-0053 10000 1.4 mm 130 0.015 5.7 277 1/1/1 11 9 A2 A1 SLP-1053 10000 1.4 mm 347 0.1 40 776 3/3/2 85 120 B1 B1 SLP-2053 10000 1.4 mm 552 0.6 150 1773 5/3/2 310 500 C4 C3 SLP-3053 10000 1.4 mm 1129 4.5 1500 5819 5/3/3 1850 3700 C5 C4
(1) Third letter represents housing material: P – Clear native Polysulfone with silicone gasket, V – white PVC with butyl rubber gasket. (2) Nominal length is flange to flange, or to ends of connectors on quick-connect modules. Detailed drawings available upon request. (3) Guideline module filling volume to allow calculation of minimum system working volumes when added to volumes of attached piping and other components. Drained residual volumes are considerably less. (4) VIP-3017S – Maximum Inlet pressure for steam at 121 °C is 1.1 barg, max TMP 0.1 barg, filtrate pressure 0 (open steaming, no back pressure). 199 Microza Membranes Polyacrylonitrile Membranes – Technical Specifications
The AP and AV series of Microza hollow fiber ultrafiltration modules Key Features feature unique double-skinned proprietary polyacrylonitrile (PAN) • Hydrophilic polyacrylonitrile membrane provides low fouling and membranes with dense internal layer. Available in 6,000, 13,000, excellent flux recovery 50,000 and 80,000 molecular weight cut-offs, the modules are used in a range of pharmaceutical applications especially in purification and • Combination of high-strength and high-capacity due to unique processing of aqueous enzymes and protein solutions. 80,000 membrane construction MWCO modules are especially useful for raw water pretreatment to • High-strength fiber allows reverse filtration to assist cleaning in pharmaceutical water purification plant. difficult applications
• Available in a range of sizes from 0.012 m2 (0.13 ft2) to more than Materials of Construction 40 m2 (425 ft2) Membrane Polyacrylonitile • Compatible for continuous operation up to 50 °C (122 °F) Housing Native clear polysulfone (P) or PVC (V) • Easily cleanable in most biological applications using minimum Potting Material Epoxy Resin chemicals or detergents Gasket Silicone (P) or butyl rubber (NBR) (V) • Meets the specifications for biological tests listed in the current Bacteriostat Glycerin 65%, Ethanol 2%, revision of USP for class VI plastics at 121 °C (249 °F) water balance • LGV and LOV modules especially optimized for raw water duty
Connectors and Adapters • pH 2 -10 For available connections, please refer to table on p202.
Part Number(1) Rating Fiber Nominal Membrane Clean Crossflow Maximum Volume Volume Feed/ Permeate (MWCO, ID Length(2) Area Water Flux Rate for Pressure Feed Permeate Retentate Connection Daltons) Lh -1 bar 1ms-1 fluid (barg) at Side(3) Side(3) Connection velocity 50 °C (mL) (122 °F) AIP-0013 6000 0.8 mm 130 0.017 1.0 181 1/1/1 9 9 A2 A1 AIP-1010 6000 0.8 mm 347 0.2 10 724 3/3/2 90 120 B1 B1 AIP-2013 6000 0.8 mm 552 1.0 50 1629 5/3/3 300 500 C4 C3 AIP-3013 6000 0.8 mm 1129 4.7 160 3655 5/3/3 1200 2700 C5 C4 AIV-3010 6000 0.8 mm 1126 4.7 170 3655 3/3/3 1200 2700 C7 D2 AIV-5010 6000 0.8 mm 1126 12.3 700 10134 3/3/3 3800 5300 C8 D3 ACP-0013 13000 0.8 mm 130 0.017 3.4 181 1/1/1 9 9 A2 A1 ACP-0053 13000 1.4 mm 130 0.012 1.9 222 1/1/1 10 9 A2 A1 ACP-1010 13000 0.8 mm 347 0.2 10 724 3/3/2 90 120 B1 B1 ACP-1050 13000 1.4 mm 347 0.12 19 776 3/3/2 90 120 B1 B1 ACP-2013 13000 0.8 mm 552 1.0 160 1629 5/3/3 300 500 C4 C3 ACP-2053 13000 1.4 mm 552 0.6 90 1773 5/3/3 310 500 C4 C3 ACP-3013 13000 0.8 mm 1129 4.7 750 3655 5/3/3 1200 2700 C5 C4 ACP-3053 13000 1.4 mm 1129 3.1 360 3990 5/3/3 1200 2850 C5 C4 ACV-3010 13000 0.8 mm 1126 4.7 830 3655 3/3/3 1200 2700 C7 D2 ACV-3050 13000 1.4 mm 1126 3.1 420 3990 3/3/3 1200 2700 C7 D2 ACV-5010 13000 0.8 mm 1126 12.3 2200 10134 3/3/3 3800 5300 C8 D3 ACV-5050 13000 1.4 mm 1126 7.8 1100 11084 3/3/3 3800 5300 C8 D3 LGV-3010 13000 0.8 mm 1126 7.6 500 3257 3/3/3 ––C7/D2 C7 LGV-5210 13000 0.8 mm 2227 41 4000 8686 3/3/3 ––C8/D3 C8 AHP-0013 50000 0.8 mm 130 0.017 8.3 181 1/1/1 9 9 A2 A1 AHP-1010 50000 0.8 mm 347 0.2 82 724 3/2/2 90 120 B1 B1 AHP-2013 50000 0.8 mm 552 1.0 460 1629 4/2/2 300 500 C4 C3 AHP-3013 50000 0.8 mm 1129 4.7 2250 3655 4/2/2 1200 2700 C5 C4 AHV-3010 50000 0.8 mm 1126 4.7 2500 3655 3/3/3 1200 2700 C7 D2 LOV-3010 80000 0.8 mm 1126 7.6 1500 3257 3/3/3 ––C7/D2 C7 LOV-5210 80000 0.8 mm 2227 41 7000 8686 3/3/3 ––C8/D3 C8
(1) Third letter represents housing material: P – Clear native Polysulfone with silicone gasket, V – white (gray – LGV, LOV) PVC with butyl rubber gasket (2) Nominal length is flange to flange, or to ends of connectors on quick-connect modules. Detailed drawings available upon request. (3) Guideline module filling volume to allow calculation of minimum system working volumes when added to volumes of attached piping and other components. 200 Drained residual volumes are considerably less. Microza Membranes Polyvinylidenedifluoride Membranes – Technical Specifications
The U series of Microza hollow fiber microfiltration modules feature Key Features unique proprietary membranes in specially resistant PVDF for • Low non-specific protein binding for long term flux maintenance in microfiltration applications. Available in 0.2 µm (UM series) and cell culture applications 0.65 µm (UJ series) rating, the modules are used in a range of pharmaceutical applications especially in cell harvesting, perfusion cell • Available different fiber diameters allows optimization to different culture, viral vector production, and clarification of microbial extracts. particulate or colloidal loadings • Superior chemical resistance of Microza PVDF ensures Materials of Construction compatibility in a broad range of processing and cleaning Membrane Polyvinyldenedifluoride applications Housing Native clear polysulfone (P) • Highly characterized,optimized void structure ensures reproducible or filled polysulfone (W) separation efficiency and high throughput Potting Material Epoxy Resin • High-strength fiber allows reverse filtration to optimize yield and Gasket Silicone (P) performance in difficult applications Bacteriostat Glycerin 65%, Ethanol 2%, 2 2 2 2 water balance • Available in a range of sizes from 0.02 m (0.21 ft ) to 5 m (54 ft ) • U series can operate continuously in processes up to 80 °C Connectors and Adapters (176 °F) and may be steamed in situ at 125 °C (257 °F) for 20 cycles For available connections, please refer to table on p202. • Meets the specification for biological tests listed in the current revision of USP for Class VI plastics at 121 °C (249 °F) • pH 2 – 10
Part Number(1) Rating Fiber Nominal Membrane Clean Crossflow Maximum Volume Volume Feed/ Permeate (MWCO, ID Length(2) Area Water Flux Rate for Pressure Feed Permeate Retentate Connection Daltons) Lh -1 bar 1ms-1 fluid (barg) at Side(3) Side(3) Connection velocity 50 °C (mL) (122 °F) UMP-053 0.2 2.6 mm 130 0.015 1.5 287 1/1/1 1/1/1 12 9 A2/A1 UMP-153 0.2 2.6 mm 347 0.08 8 956 3/3/3 3/3/3 90 120 B1/B1 UMP-353 0.2 2.6 mm 1129 2.2 200 5161 3/3/3 3/3/3 1700 2700 C5/C4 UMW-553 0.2 2.6 mm 1172 5.0 500 12424 3/3/3 3/3/3 3800 5400 C6/C5 UMP-0047R 0.2 1.4 mm 314 0.02 19 116 3/3/1.5 2/2/1 23 30 C1/A2 UMP-1047R 0.2 1.4 mm 316 0.09 80 554 3/3/1.5 2/2/1 202 – C2/C1 UMP-1147R 0.2 1.4 mm 546 0.19 180 554 3/3/1.5 2/2/1 360 – C2/C1 UMP-1147M 0.2 1.4 mm 546 0.33 330 953 3/3/1.5 2/2/1 297 – C2/C1 UMP-2147R 0.2 1.4 mm 546 0.77 750 2216 3/3/1.5 2/2/1 ––C4/C2 UMP-3147R 0.2 1.4 mm 630 2.0 2000 – 3/3/1.5 2/2/1 ––C4/C3 UMP-3247R 0.2 1.4 mm 1129 4.0 4000 – 3/3/1.5 2/2/1 ––C4/C3 UJP-0047R 0.65 1.1 mm 314 0.02 24 92 3/3/1.5 2/2/1 23 33 C1/A2 UJP-1047R 0.65 1.1 mm 316 0.10 120 462 3/3/1.5 2/2/1 204 – C2/C1 UJP-1147R 0.65 1.1 mm 546 0.19 230 428 3/3/1.5 2/2/1 370 – C2/C1 UJP-1147M 0.65 1.1 mm 546 0.32 380 708 3/3/1.5 2/2/1 310 – C2/C1 UJP-2147R 0.65 1.1 mm 546 0.73 850 1625 3/3/1.5 2/2/1 ––C4/C2 UJP-3147R 0.65 1.1 mm 630 1.9 2300 – 3/3/1.5 2/2/1 ––C4/C3 UJP-3247R 0.65 1.1 mm 1129 3.8 4600 – 3/3/1.5 2/2/1 ––C4/C3 (1) Third letter represents housing material: P – Clear native Polysulfone with silicone gasket, V – white (gray – LGV, LOV) PVC with butyl rubber gasket (2) Nominal length is flange to flange, or to ends of connectors on quick-connect modules. Detailed drawings available upon request. (3) Guideline module filling volume to allow calculation of minimum system working volumes when added to volumes of attached piping and other components. Drained residual volumes are considerably less.
201 Microza Membranes Polyolefin Membranes – Technical Specifications
The P series of Microza hollow fiber microfiltration modules feature Key Features unique proprietary membranes in polyolefin for general microfiltration • Available different internal fiber diameters provides suitability for applications. Available in 0.1 µm rating, the modules are used in a processes with varying particulate or colloidal loading range of pharmaceutical applications especially in clarification of microbial cultures for enzyme production, clarification of natural • Broad chemical resistance ensures compatibility in a wide range of product extracts, and nutraceutical production. processing and cleaning conditions • Highly characterized,optimized void structure ensures reproducible Materials of Construction separation efficiency and high throughput Membrane Polyolefin • High-strength fiber allows reverse filtration to optimize yield and Housing Native clear polysulfone (P)or PVC (V) performance in difficult applications Potting Material Epoxy resin • Available in a range of sizes from 0.09 m2 (1 ft2) to over 8 m2 Gasket Silicone (P) (85 ft2) Bacteriostat Glycerin 65%, ethanol 2%, • P series compatible for continuous operation up to 50 °C (122 °F) water balance • Meets the specification for biological tests listed in the current revision of USP for Class VI plastics at 121 °C (249 °F) Connectors and Adapters
3 A – A1 Small hose barb 4.5 mm ( ⁄16 in.),
1 A2 Small hose barb 6 mm ( ⁄4 in.) B – B1 Quick-connect. 1 To convert feed/retentate to 1 ⁄2 in. sanitary clamp order 1 part no. 0450163 (fits in body of module), to ⁄4 in. sanitary clamp order part no. 2055675 (fits in body of module), 1 to ⁄4 in. hose barb (fits on quick-connect), 1 order part 2055999 no. (polypropylene), and to ⁄4 in. FNPT (fits on quick-connect), order part no. 2089150 (316L stainless steel).
C – C3 1 in. sanitary flange (ferrule face 34 mm, [1.34 in.])
1 C4 1 ⁄2 in. sanitary flange (ferrule face 50 mm [1.98 in.])
C5 2 in. sanitary flange (ferrule face 64 mm [2.52 in.])
C7 4 in. sanitary flange (ferrule face 117 mm [4.61 in.])
C8 6 in. sanitary flange (ferrule face 157 mm [6.18 in.]) D – D2 Cap Nut, 38.5 mm diameter D3 Cap Nut, 48.5 mm diameter
Part Number(1) Rating Fiber Nominal Membrane Clean Crossflow Maximum Volume Volume Feed/ Permeate (MWCO, ID Length(2) Area Water Flux Rate for Pressure Feed Permeate Retentate Connection Daltons) Lh -1 bar 1ms-1 fluid (barg) at Side(3) Side(3) Connection velocity 50 °C (mL) (122 °F) PSP-103 0.1 0.7 mm 347 0.2 25 554 3/2.2/2 90 120 B1 B1 PSP-113 0.1 1.9 mm 347 0.1 7 714 3/2.5/2 110 110 B1 B1 WSP-143 0.1 1.4 mm 347 0.09 13 554 3/2.5/2 90 120 B1 B1 PSP-303 0.1 0.7 mm 1129 6.0 700 3879 5/2.2/3 1200 2700 C5 C4 PSV-303 0.1 0.7 mm 1126 6.0 700 3879 5/2.2/3 1200 2700 C7 D3 PSV-313 0.1 1.9 mm 1126 2.9 240 4900 5/2.5/3 1500 2600 C7 D3 WSP-543 0.1 1.4 mm 1172 8.2 930 11083 4/2.5/4 3800 5300 C7 C6 (1) Third letter represents housing material: P – Clear native Polysulfone with silicone gasket, V – white (gray – LGV, LOV) PVC with butyl rubber gasket (2) Nominal length is flange to flange, or to ends of connectors on quick-connect modules. Detailed drawings available upon request. (3) Guideline module filling volume to allow calculation of minimum system working volumes when added to volumes of attached piping and other components. Drained residual volumes are considerably less.
202 Membralox® Ceramic Membrane Products For Long Service Life even under Extreme Conditions
Membralox ceramic membranes comprise • Components are FDA-listed in 21 CFR a highly controlled surface membrane layer Part 11 that is formed on the inner (feed-side) • 100% bubble point integrity-tested surface of a more open support layer. Three different types of materials are Applications available, ultrapure, µalumina, zirconia and Pall’s Membralox® ceramic membrane titania. All of these materials are FDA-listed • Clarification of bulk fermentation broths elements are ideal for applications that for suitability in pharmaceutical processes. • Protein removal from antibiotics involve extreme processes, such as high Ceramic membranes exhibit near zero non- solids bulk processes, the use of high specific adsorption of biological materials. • Processing of alginates and other temperatures or pressures, or aggressive excipients Membralox ceramic elements featuring an solvents, and where significant long-term asymmetric membrane structure combine • Clarification of solvent extracts durability is required. a unique design and manufacturing • Pyrogen and bacteria removal in high Available ratings start at very low molecular process resulting in a product ideally suited purity systems weight ultrafiltration used for duties such as for applications involving chemicals, unwanted protein removal from antibiotic including solvents, extremes of pH, high Membrane Module Versatility solutions, through to open (up to 5 µm) temperatures and pressure processing of microfiltration membranes that can be and fermentation broths. Membralox membrane elements are used to process difficult materials such as assembled in housings containing modules The compact multi-channel geometry and microspheres, or clarify solvent-based with up to 60 elements per module. This high permeability are optimized for bulk plant extracts in transgenic processes. versatility simplifies system designs, processing applications. Multiple modules allowing optimal sizing of membrane area Membralox membrane elements are each comprising a number of membrane for each application. available in 3 different channel diameters to elements can be easily assembled on allow optimization for solids loading. Some manifolds to handle any scale of operation. configurations are available with unique Membralox GP Ceramic Microfiltration Membranes longitudinal permeability gradients, that Features and Benefits facilitates the control of permeate rate The Membralox GP range of ceramic • Reliability along the length of the module. membrane elements have a calibrated Membrane elements are available in sizes • Ease of use longitudinal permeability gradient, that ranging from small laboratory devices • High flux maintains a constant and uniform flux through individual modules of over 20 along all parts of the element. This • Proven long operational life square meters surface area, ensuring the optimizes the microfiltration of complex, ability to evaluate and scale up processes • Wide chemical and pH (0 – 14) transmission sensitive feed streams. to any size. compatibility • Stability of the filtration regime • Excellent thermal stability • Standard modules accommodate these • Sanitizable and sterilizable unidirectional flow directional membranes • Element burst pressure > 50 bar • Uniform transmembrane pressure • Ability to withstand high frequency simplifies system designs backpulsing cycles • A wide range of calibrated permeability gradient options are available to suit different feedstream characteristics Ceramic Membrane Structure; Electron Micrograph showing Membralox membrane layers on top of a more open support layer 203 Membralox Ceramic Membrane Products Technical Specifications
Membralox SD Modules Membrane Element Configurations Element Type P37 – 30 P19 – 40 P19 – 60 The Membralox SD module features a fully sanitary design for stringent pharmaceutical processes. All wetted components are Channel Diameter 3 mm 4 mm 6 mm swept by cleaning solutions ensuring compliance with requirements Number of Channels 37 19 19 of cleaning validation. Module hardware and gaskets are available in Filtration Surface 0.35 m2 0.24 m2 0.36 m2 materials that meet the demands of all cleaning regimes. Area (3.77 ft2) (2.58 ft2) (3.88 ft2) • All wetted parts fully accessible by cleaning chemicals Length 1020 mm 1020 mm 1020 mm Material Ultrapure α alumina (> 99.7%) • Vertical operating position enables total drainage
• High-performance sealing assembly with gasket leak detection, Membrane Pore Sizes eliminates by-pass possibility between retentate and permeate side Microfiltration 5.0, 2.0, 1.4*, 0.8*, 0.5*, 0.2*, 0.1* µm • Modules and membrane components fully traceable, materials (α alumina) certificate available upon request Ultrafiltration 100, 50, 20 nm (zirconia) 5000, 1000 Da MWCO (titania) • Long-life, stable and reliable performance * Available in Membralox GP membrane version. Membralox HCB Modules Operating Limits in Aqueous Liquids The Membralox HCB module range takes advantage of the unique Temperature 95 °C (203 °F) hexagonal shape of the Membralox ceramic membrane elements to Pressure 8 – 10 barg(1) obtain a high membrane packing density up to 240 m2/m3 Differential Back Pressure 8 bard (2583 ft2/ft3), thus significantly reducing filtration system costs. (1) Depending on module selected. Contact Pall for additional information. Features of the HCB module – increased surface area, reduced permeate hold-up volume, PTFE gaskets for a wider chemical Membralox SD Sanitary Modules compatibility – provide economical solutions in bulk fermentation Element Type P19 – 60 P19 – 40/P37 – 30 broth clarification and pharmaceutical effluent treatment. Number of Membranes 1 – 3 – 12 – 22 1 – 3 – 7 – 19 – 37 • Highly compact for cost-effective system design and small Filtration Surface Area up to 7.9 m2 up to 13.0 m2 footprint (85 ft2) (140 ft2)
• Reduced permeate hold-up volume Permeate Connections Sanitary clamps/3A gaskets • Proprietary built-in gasketing solution to ensure perfect sealing Construction of 316L SS, ceramic, EPDM or FPM Wetted Materials • Wide chemical compatibility • Long service life Membralox HCB Industrial Modules Part Number 36P2 60P1 Membralox T1-70 Modules Element Type P19-60 P19-40/P37-30 Potential applications can be conveniently evaluated using this Number of Membranes 36 60 laboratory scale module with integrated ceramic membrane element. Filtration Surface Area 13.0 m2 14.4/21.0 m2 Feasibility testing allows the appropriate membrane pore size to be Retentate Connections Bolt flanges with O-rings selected for pilot scale studies. The module has a low permeate Permeate Connections Bolt flanges with flat gaskets hold–up volume of 7 mL. Construction of 316L SS, ceramic, PTFE Wetted Materials Membralox Pilot Scale Systems Membralox T1-70 Modules(2) Pilot-scale evaluation of Membralox technology with full scale modules can be performed on pilot plant systems. Several options Channel Diameter 7 mm are available on request. Length 250 mm Surface Area Filtration 0.005 m2 (0.054 ft2) Housing Material 316L SS (2) The T1-70 module housing holds individual ceramic tubes; please specify desired membrane pore size at time of order in accordance with membrane pore size selection chart. This module is suitable for use with Pall laboratory and pilot-scale test systems. Contact Pall for additional information.
204 Pallsep™ Vibrating Membrane Filtration Technology
Pallsep filtration technology represents a Applications significant innovation in membrane The technology can be successfully filtration. In the Pallsep system, controlled applied to clarification applications where horizontal oscillation moves the membrane high product transmission through the elements through the feed fluid over 50 membrane is essential and not easily times per second. The oscillation Above: Pallsep PS400 and achieved with conventional TFF systems, generates vibrational energy at the a System and harvesting applications where product membrane surface, giving shear (higher loss with conventional TFF/centrifugation is than that typically generated in unacceptably high. conventional TFF systems) that is limited to a small boundary layer above the • Recovery of therapeutic proteins from membrane surface, and which is not recombinant mycelial cultures applied to the bulk of the fluid. This • Clarification of high suspended solids ensures that even in high solids feed fermentation broths such as Picha streams, the membranes do not cake with pastoris and Saccharomyces the retained species. Fluids are processed in a very gentle manner through an open • Processing of plant and animal extracts flow path with minimal pressure drop and from transgenic or natural sources
even transmembrane pressure distribution. * Wet cell weight – see Postlethwaite et al. Journal of Very high suspended solids levels can be Membrane Science 228 (2004), 89 – 101. achieved (> 60% w/v*) maximizing recovery of the permeate. In some applications it is possible to concentrate solids in a single pass with no recirculation. Both the concentrated solids and the filtrate can be recovered from the system if required by the application. All Pallsep machines consists of a stack of membrane elements, which are mounted on a torsion bar. Kinetic energy from a small motor is efficiently converted to PS10 in use with a Pall System vibrational energy in the stack There are three Pallsep variants: PS10 and PS400 representing nominal installed membrane areas of 1, and 40 m2 respectively per machine.
Features and Benefits
• Very low recirculation rates • Energy efficient • Tolerant of viscous feeds • Processing to high suspended solids • Gentle processing • Small system footpaint
• Low system hold-up volume 205 Pallsep Vibrating Membrane Filtration Technology Technical Specifications
Pallsep Membrane Elements Pallsep PS400 The membrane elements are a composite of 0.45 µm PTFE coated Operating Conditions onto flexible stainless steel plates. Typical Range Limit System Pressure 0.4 – 3 barg 8.3 barg (5.8 – 43.5 psi) (120.3 psi) Materials of Construction(1, 2) Trans-membrane 0.2 – 1.5 barg 4 barg (3) Membrane Emflon PTFE Pressure (2.9 – 21.7 psi) (58 psi) Other Fluid Contact 316L stainless steel Operating 4 – 50 °C 55 °C Materials Polyphenyl sulfide Temperature (39 – 122 °F) (131 °F) Polyethylene Ethylene propylene Fluid Recirculation 60 – 120 L/m Dependent on EPDM for 40 m2 (400 ft2) feed and system Silicone Other Technical Information (1) Full material traceability is available if required. (2) All polymeric contact surfaces have passed USP XXI class VI testing. Process Connections Feed/ 38 mm (1.5 in.) (3) Contact Pall for further information. Retentate: Sanitary Clamp Permeate: 25 mm (1 in.) Pallsep PS10 Sanitary Clamp The PS10 is an ideal device for process development departments to Electrical Requirement US: 480V 440V, 400V, 60 Hz, 3 phase demonstrate the feasibility of Pallsep technology for larger scale Europe: 380V, 50 Hz 3 phase processes. The unit can work with an installed area of between 0.1 Nominal Dimensions Membrane Element: and 1 m2. This range makes the device suitable for use with the Diameter 610 mm (24 in.) QuattroFlow pump and several Pall systems. Base Machine, Stack and Pipework: Height 3338 mm (119 in.) Width 1600 mm (63 in.) Operating Conditions Depth 1177 mm (46 in.) Typical Range Limit Weight Base Machine Only: 1452 kg (3200 lbs) System Pressure 0.4 – 3 barg 4 barg (5.8 – 43.5 psi) (58 psi) Assembled Membrane Stack: 544 kg (1200 lbs) Trans-membrane 0.2 – 1.5 barg 4 barg Pressure (2.9 – 21.7 psi) (58 psi)
Operating 4 – 50 °C 55 °C Temperature (39 – 122 °F) (131 °F)
Fluid Recirculation 0.5 – 10 L/m Dependent on dependent on feed and system installed area
Other Technical Information
Process Connections Feed, Retentate and Permeate: 1 13 mm ( ⁄2 in.) Sanitary Clamp Electrical Requirement Base Machine: Single phase, 240/110 volts, 50/60 Hz, 20 A Nominal Dimensions Membrane Element: Diameter 300 mm (12 in.) Machine, Stack and Pipework: Height 2108 mm (83 in.) Width 870 mm (35 in.) Depth 870 mm (35 in.) Weight Base Machine: 180 kg (397 lbs) Membrane Housing: 25 kg (55 lbs)
206 Sheet TFF Membranes For Bulk Pharmaceutical and Bio-Industrial Processes
A significant number of established large Longer membrane life therefore results in volume processes use ultrafiltration and significant savings in labor costs, and microfiltration membranes in a variety of allows equipment to be operational for a sheet formats. These sheets are fitted into longer period of time – improving process specialized suppliers’ holding devices, economics. typically called “plate and frame” systems Proprietary Membranes (i.e., DDS/DOW, DSS). Polyethersulfone membranes available from Pall are the low protein binding, high flux Range of Membranes Omega (OM) with the largest range of Pall offers three basic types of membrane Molecular Weight Cut-off ratings in the for flat sheet applications with ultrafiltration industry; Alpha (AM) — specifically membranes rated from 650 Da to designed to offer resistance to fouling by 1000 kDa and microfiltration membranes. antifoams and Supor TFF (PM) for Both the ultrafiltration and microfiltration microfiltration. Above: M38 membranes can be supplied to fit most existing equipment. Standard part numbers are listed overleaf. If the retrofit is not listed, please contact Pall. Superior Performance Evaluation work carried out with customers has shown that Pall membranes may exhibit superior flux and provide superior resistance to commonly used cleaning agents, allowing maximum re-use and a longer working life than other membranes. Such systems, with their large number of individual membranes, are time-consuming to re-sheet.
Left: M39
207 Sheet TFF Membranes Ordering Information
Table 1 – Ultrafiltration Membranes Code D65 001 003 005 010 030 050 070 100 200 300 500 990 MWCO 0.65 1 3 5 10 30 50 70 100 200 300 500 1000 (kDa) Alpha AM –––– ––––– –– Omega OM
Table 2 – Microfiltration Membranes Code M10 M20 M45 M65 M80 M12 994 Pore size 0.1 0.2 0.45 0.65 0.8 1.2 0.16 (µm) abr. Supor PM – Omega OM ––––––
Table 3 – Flat Sheet Format Code Format Comments M38 DDS/DOW or DSS hardware Oval M39 DDS/DOW or DSS hardware Rectangle To Order, choose: 1. Membrane type from Tables 1 and 2 above (e.g. OM, AM or PM) Table 4 – Membrane Backing(1) 2. Choose MWCO or µm rating code from Tables 1 or 2 as appropriate (e.g. 010 = 10 kD, M20 = 0.2 µm) Code Membrane Backing 3. Choose format code from Table 3 left (e.g. M38) P Polypropylene 4. Add substrate code from Table 4 left (always P for AM and PM T Polyolefin T membrane, T for OM) (1) P backing for AM and PM membrane, T backing for OM membrane. 5. Add pack size required from Table 5
Table 5 – Pack Size Code Number of Sheets Typical Examples: 010 10 AM010M38P100 PMM20M39P050 050 50 100 100 Membrane Alpha Membrane Supor MWCO/Rating 10 kD MWCO/Rating 0.2 µm Format M38 Format M39 Substrate Polypropylene Substrate Polypropylene Pack Quantity 100 Pack Quantity 50
208 Chromatography Chromatography
Column chromatography is a well-established Mustang ion-exchange chromatography capsules bioprocessing purification method. Ion-exchange are prepacked, single-use systems specifically resin columns have been especially effective and designed to provide high throughputs. Therefore, no reliable parts of successful purification. Affinity, column packing or cleaning is required, resulting in hydrophobic interaction and other media effect high significantly shorter processes cycles. Because of the resolution purifications of specific target molecules. high dynamic binding capacities of Mustang But column-packing and packing validation can be capsules, they are particularly well-suited for use in time-consuming and expensive. The high cost of the initial purification of the target molecule, or for process columns, along with the cost of associated removing contaminating molecules, such as DNA or equipment, cleaning, and storage validation can viruses, in the final polishing steps. Mustang E is impact process economics. Pall’s ideally placed to used to remove endotoxin from water, saline, and give guidance on the most effective purification buffer solutions. strategy for your product. Mustang starter kits, coins, and modules can be Processing biomolecules for initial capture of target used to determine the suitability of Mustang product, purification of the target molecule, and the technology and the determination of optimal removal of potentially harmful contaminants from process conditions, including binding and elution. the purified product, all place different demands on the chromatography process. A single technology Column Chromatography will not address all of these issues. Therefore, Pall Pall offers a complete range of chromatography offers chromatography users a variety of columns and packing stations. Resolute® columns chromatography process options to optimize are available with acrylic or stainless steel tubes, separation efficiency and your economics. with fixed or variable bed heights, with manual or Membrane Chromatography pneumatically actuated packing nozzle, and are buttressed by range of support equipment including Mustang® membranes are an innovative integral column hydraulic systems for simple yet ion-exchange support containing functional safe column maintenance or column packing. quaternary amine (Q) or sulfonic acid (S) groups. The large pores of Mustang membranes allow Pall can offer expertise in packing most biomolecules to access all the binding sites by commercially available sorbents. For availability of direct fluid convection, rather than being dependent chromatography media in a wide range of types and on the restrictions imposed by diffusive flow, the chemistries, please contact Pall, or visit method of operation of chromatography resins. This www.pall.com. results in high dynamic flow, very steep break- Whatever your requirement for a chromatography through curves, equivalent or higher capacity than system, Pall has the products, the support, and the resins for most target species, and process flow experience to help you optimize your process and rates that can be as high as 25 to 50 column your budget. volumes per minute.
210 Mustang® Membrane Chromatography Starter Kits Disposable Membrane Chromatography Units
Features and Benefits • Mustang E membrane features propriety membrane surface Disposable Membrane Chromatography modifications to effectively remove units are designed for the rapid selection of endotoxin from water, saline and buffer appropriate chemistry and method solutions. development. Typical binding capacities for The Mustang membrane chromatography Mustang E membranes are: starter kit includes both strong anion and Approximately 500,000 EU/Acrodisc or cation exchange membrane approximately 4 x 106 EU/mL chromatography Acrodisc® units, as well as membrane volume specific endotoxin removal Acrodisc units. These allow both the rapid selection of the Under the following conditions: 0.9% appropriate chemistry for your application, sodium chloride and the opportunity to quickly screen for Minimum challenge level: optimal process parameters to enhance 10,000 EU/ml and simplify your process method Minimum challenge volume: 60 mL development. Endotoxin source: Escherichia coli Starter Kit Contents strain 055:B5 (no dispersing agents).
• Mustang Q membrane is a strong Applications anion exchanger that effectively binds plasmid DNA, negatively-charged • The rapid identification of the correct proteins, and viral particles. membrane chemistry for a specific application Typical binding capacities for Acrodisc units with Mustang Q • Rapid screening of key process membranes are: parameters DNA: 3.6 – 4.5 mg/Acrodisc or 20 – 25 mg/mL membrane volume BSA: 9 – 11 mg/Acrodisc or 50 – 60 mg/mL membrane volume • Mustang S membrane is a strong cation exchanger that effectively binds positively-charged proteins and viral particles. Typical binding capacities for Acrodisc units with Mustang S membranes are: Lysozyme 8 – 9 mg/Acrodisc or 45 – 50 mg/mL membrane volume
211 Mustang Membrane Chromatography Starter Kits Technical Specifications
Materials of Construction
Media Mustang membrane of appropriate chemistry Housing Polypropylene
Membrane Bed Volume Mustang S and Q 0.18 mL Mustang E 0.12 mL
Inlet and Outlet Connections Female Luer-Lok* inlet, male slip luer outlet * Luer-Lok is trademark of Becton-Dickenson & Co.
Operating Pressures
Typical Differential Pressure < 0.07 bard @ 1 mL/min (< 1.0 psid @ 1 mL/min)
Maximum Operating 5.5 bar (80 psi) Pressure and Temperature at 21 – 24 ºC (70 – 75 ºF) 2.1 bar (30 psi) at 60 °C (140 °F)
The following Charts and Graphs Demonstrate the High Resolution and High Dynamic Binding Capacities of Mustang Membrane Chromatography Units
Mustang S Membrane
25 mm (1 in.) Acrodisc Unit with Mustang S Membrane 25 mm (1 in.) Acrodisc Unit with Mustang S Membrane Resolution with Cytochrome C and Lysozyme Dynamic Binding with Lysozyme 250 450 Absorbance Lysozyme Elution Peak Conductivity 400
200 350
300 150 250
200 100 Protein (µg/mL) Protein 150
Cytochrome C 100
Absorbance 280 mm (11 in.) (in AU) 50 52 mg/mL at 0 breakthrough 50
0 0 01 23 4 5 6 0 5 10 15 20 25 Time (min) Time (min)
The conditions used to generate data for the graph above include buffer: A solution of 0.512 mg/mL Lysozyme was pumped through the Acrodisc unit at 10 mM MES pH 5.5; salt: 1M NaCl in 10 mM MES pH 5.5; gradient: 0 to 1M NaCl in 2.3 mL/min. Breakthrough occurred at 8.0 minutes and was calculated as 52 mg/mL 50 column volume (cv); flow rate: 2.3 mL/min (13 cv/min). using: (flow rate [2.3 mL/min] X initial protein Lysozyme concentration [0.512 mg/mL] X time [8.0 min]) membrane bed volume of Mustang S in 25 mm (1 in.) Acrodisc unit (0.18 mL)
212 Mustang Membrane Chromatography Starter Kits Technical Specifications
Mustang Q Membrane
25 mm (1 in.) Acrodisc Unit with Mustang Q Membrane 25 mm (1 in.) Acrodisc Unit with Mustang Q Membrane Resolution with BSA and Goat IgC Dynamic Binding with BSA 30 1800 Elution Peak Absorbance Conductivity Goat IgG 1600 25 1400
BSA 20 1200
1000 15 800 unbound protein from Goat IgG 600 10
Absorbance (280 mm (11 in.)) 400
5 54 mg/mL at 0 200 breakthrough
0 0 0 5 10 15 20 25 0 1 2 3 4 5 6 Time (min) Time (min)
The conditions used to generate data for the resolution graph above include buffer: A solution of 0.524 mg/mL BSA was pumped through the Acrodisc unit at 2.3 mL/min. 25 mM Tris pH 8.0; salt: 1M NaCl in 25 mM Tris pH 8.0; gradient: 0 to 0.5M NaCl in Breakthrough occured at 8.1 minutes and was calculated as 54 mg/mL using: 50 column volume (cv); flow rate: 2.3 mL/min (13 cv/min); sample loading: 4% of total binding capacity. (flow rate [2.3 mL/min] X initial protein BSA concentration [0.524 mg/mL] X time [8.1 min]) membrane bed volume of Mustang Q in 25 mm (1 in.) Acrodisc unit (0.18 mL)
Mustang E Membrane
Effect of [NaCl] in 25 mM Tris (pH 8) on Endotoxin Dynamic Effect of pH on Endotoxin Dynamic Binding Capacity to Binding Capacity to Acrodisc Unit with Mustang E Membrane Acrodisc Unit with Mustang E Membrane
>7.03E+07 >6.98E+07 6.6E+07 1.0E+08 1.0E+08 4.04E+07 4.1E+07 4.1E+07 1.87E+07 1.86E+07 1.12E+07 +07 +07
1.72E+06 +06 +06
+05 +05
+04 +04
+03 +03 Endotoxin Binding (EU/mL MV) Endotoxin Binding (EU/mL MV)
+02 +02
+01 +01 0 0.15 0.5 1 2 5 6 789 NaCl (M) pH
213 Mustang Membrane Chromatography Starter Kits Technical Specifications
Ordering Information Product No. Description Packaging MSTG25KIT Mustang Starter Kit 4 per package Acrodisc 25 mm (1 in.) with Mustang Q membrane (MSTG25Q6) 4 per package Acrodisc 25 mm (1 in.) with Mustang S membrane (MSTG25S6) 2 per package Acrodisc 25 mm (1 in.) with Mustang E membrane (MSTG25E3)
Complementary Products Product No. Description Packaging MSTG25Q6 Acrodisc 25 mm (1 in.) with Mustang Q membrane 10 per package MSTG25S6 Acrodisc 25 mm (1 in.) with Mustang S membrane 10 per package MSTG25E3 Acrodisc 25 mm (1 in.) with Mustang E membrane 10 per package MSTG18H16 Mustang Coin Holder 1 per package MSTG18Q16 Mustang Q Coin, 0.35 mL bed volume 10 per package MSTG18S16 Mustang S Coin, 0.35 mL bed volume 10 per package CLM05MSTGQP1 Mustang Q Capsule, 10 mL bed volume 1 per package CLM05MSTGSP1 Mustang S Capsule, 10 mL bed volume 1 per package CLM05MSTGEP1 Mustang E Capsule, 10 mL bed volume 1 per package CL3MSTGQP1 Mustang Q Capsule, 60 mL bed volume 1 per package CL3MSTGSP1 Mustang S Capsule, 60 mL bed volume 1 per package CL3MSTGEP1 Mustang E Capsule, 40 mL bed volume 1 per package NP6MSTGQP1 Mustang Q Capsule, 260 mL bed volume 1 per package NP6MSTGSP1 Mustang S Capsule, 260 mL bed volume 1 per package NP6MSTGEP1 Mustang E Capsule, 160 mL bed volume 1 per package NP7MSTGQP1 Mustang Q Capsule, 520 mL bed volume 1 per package NP7MSTGSP1 Mustang S Capsule, 520 mL bed volume 1 per package NP8MSTGQP1 Mustang Q Capsule, 780 mL bed volume 1 per package NP8MSTGSP1 Mustang S Capsule, 780 mL bed volume 1 per package
214 Mustang® Coin Unit Ideal for Method Development for Mustang Q and S Membrane Units
The disposable Mustang Coin Unit is the Features and Benefits companion product to Mustang capsules Disposable — No cleaning or cleaning and cartridges. validation. Mustang membranes are an innovative Binding Efficiency — Biomolecules are new ion exchange support with pendant bound in a single pass. quaternary amine groups or sulfonic functional groups in a cross-linked Speed — High-flow rates allow fast polymeric coating. The pores in Mustang processing of large volumes. membranes are large enough to allow Scalability — Linear scale-up from molecules as large as DNA access to all laboratory to process scale. the binding sites by direct fluid convection. This produces a very high dynamic binding Cost — Lower operating costs and capital capacity in comparison to chromatography investment compared to conventional beads with diffusive pores. columns that need validated packing. Combining this high-capacity membrane High Quality Standards with a unique pleated design resulted in the highly efficient Mustang product line. Manufactured to high quality assurance Each coin unit contains 16 layers of standards in accordance with ISO 9000. membrane. Mustang capsules and • Membrane lots tested for dynamic cartridges are specifically designed to be protein binding capacities; peak disposable to eliminate cleaning, cleaning positions are verified with standard validation, and cross-contamination. proteins
Designed for Scale-Up • Certificate of conformance is supplied Capabilities with each unit • Extensive validation ensures consistent The Mustang Coin Unit uses the same and reliable performance 16-layer construction as the larger capacity elements. It has been designed to allow • Comprehensive validation guide is direct scale-up or scale-down studies to available for process scale units the larger capsules. The coin is placed directly into a specially designed stainless Applications steel housing, where the flow is uniformly • Scale-up and scale-down studies distributed across the membrane coin. The Mustang Coin Unit is the ideal tool for • Determination of optimal binding and modeling scale-up of DNA clearance. elution conditions Mustang coins and capsules will eliminate • Determination of breakthrough curves requalification since there is no need to • Identification of process operating change membrane materials during the parameters transition from lab to production scale.
215 Mustang Coin Unit Technical Specifications
Materials of Construction DNA Breakthrough Curve on Mustang Q Coin Unit Membrane Modified hydrophilic polyethersulfone 100 Housing 316 L stainless steel
Support Frit 316 B stainless steel 80 Housing Clamp 300 series stainless steel housing Herring Sperm DNA 25 nM Tris-HCI, pH 8.0 O-rings Silicone elastomer 60
Operating Characteristics(1) Maximum Temperature 38 °C (100 °F) 40 Maximum Sanitization 1 N NaOH for 30 minutes Conditions (one cycle only) sUV Absorbance (260 nm) 20 (1) With fully compatible fluids that do not soften, swell, or adversely affect the membrane or its materials of construction.
0 Size and Capacity 0 30 60 90 120 mL Membrane Bed Volume 0.35 mL DNA breakthrough curves such as the one above, demonstrate the high Typical Herring Sperm DNA 20 – 25 mg/mL of bed volume dynamic capacity of Mustang Q coin for DNA. Dynanic Binding Capacity A sonicated solution of herring sperm DNA at a concentration of 129 µg/mL in Mustang Q 25 mM Tris HCI, pH 8.0 was passed through a coin at a flow rate of 3.5 mL/min, and the A260 absorbance measured downstream. Typical BSA Binding Capacity 50 – 60 mg/mL of bed volume Mustang Q
Typical Lysozyme Binding 45 – 50 mg/mL of bed volume Capacity Mustang S
Typical IgG Binding Capacity 60 mg/mL of bed volume Nominal Dimensions Nominal Flow Rate 3.2 mL/min at 0.5 bar(2) Coin Unit 18 mm (0.7 in.) outer diameter (2) For liquid of 1 cP. For other liquids divide the flow rate by the viscosity expressed in cP. Housing 51 mm (2 in.) height Fittings M6 male to 15 mm (0.625 in.) OD tubing and M6 male to luer lock female fittings
Ordering Information
Part Number Description Membrane Accessible Flow @ 10 psi Typical Coin Pack Size Volume Capacity
MSTG18S16 Mustang S coins for 0.35 mL > 3.5 mL/min 16 – 18 mg for Lyzozyme 10 method development
MSTG18Q16 Mustang Q coins for 0.35 mL > 3.5 mL/min 7 – 9 mg for DNA 10 method development 17.5 – 21 mg for BSA MSTG18H16 Mustang Coin Housing 1
216 Mustang® Chromatography Capsules and Cartridges High Throughput Pleated Units for Process Scale Ion-exchange Chromatography
Mustang Q Membrane Convenience — Ready to use, Mustang Q membrane is an anion autoclavable and disposable to eliminate exchange support with pendant quaternary potential packing, cleaning, validation and amine functional groups in a cross-linked cross-contamination issues. polymeric coating on a 0.8 µm pore size Flexible — Available in capsule or membrane. This gives high dynamic cartridge format. capacities for high molecular weight Combining high-capacity ion-exchange Cost — Lower operating costs and capital products such as DNA, plasmids or even Mustang membranes, with a unique investment compared to conventional particles as large as viruses. 16-layer open pleat design, results in columns that need validated packing and high-flow rate, high-capacity, single-use, Mustang S Membrane cleaning. versatile, range of pleated products that Mustang S membrane is a cation can be used for a wide range of exchange support with pendant sulfonic High Quality Standards applications. This 16-layer construction is functional groups in a cross-linked held constant from the laboratory scale • Manufactured to high quality assurance polymeric coating on a 0.8 µm pore size Mustang coin unit to the largest industrial standards in accordance with ISO 9000 membrane. This gives high dynamic process scale capsule, ensuring constant capacities for high molecular weight • Membrane lots tested for dynamic chromatography bed depth in all formats. products such as IgG, Factor VIII and protein binding capacity, and peak Mustang E capsules use 3 layers of a some viruses. position using standard proteins standard pleat format membrane to remove endotoxin from process Mustang E Membrane • Identified by lot number and a unique feedstreams. The 3-layer construction is Mustang E membrane is a highly serial number for complete traceability held constant from the Mustang E cross-linked quaternized amine charge of manufacturing history, satisfying Acrodisc format to the largest industrial polymer coating based on stringent QC/QA requirements process scale capsule. polyethyleneimine on a 0.2 µm pore size • Supplied with Certificate of Analysis to The ease of linear scale up ensures a membrane. This gives very high dynamic confirm the quality and quality control of shortened process development time by capacities, under selected conditions for Pall the removal of endotoxin from process significantly reducing the re-optimization • Meets USP Biological reactivity tests in feedstreams, buffers and water required between scale up steps. These vivo in accordance with USP Class VI units are specifically designed to be 50 ºC and all materials listed in Drug single-use. This eliminates cleaning and the Features and Benefits Master File submitted to the FDA costs associated with cleaning validation. Binding Efficiency — Charged Mustang capsules are fully self contained biomolecules are readily bound in a single Comprehensive Validation units that connect directly into a system pass. using 18 mm (1.5 in.) sanitary flange • Extensive validation to ensure connectors. Mustang cartridges require Speed — High-flow rates enable the consistent and reliable performance processing of large volumes in less than a the use of a Code 7 housing which • A comprehensive validation guide is single working shift. Mustang units requires cleaning and reassembly after available for each of the membrane typically operate at flow rates between 10 each use. chemistries, Q, S and E on request. to 40 membrane volumes per minute, making them much faster than conventional columns which typically operate at 0.5 column volumes per minute. Scalability — A full range of sizes accommodates the different volumes and capacities required in BioPharmaceutical processing.
217 Mustang Chromatography Capsules Technical Specifications
Materials of Construction Capsules Operating Characteristics(2)
CLxMSTG*P1 NPxMSTG*P1 Maximum Operating 4.1 bar (59.5 psi) at 38 °C (100 °F) Membrane Modified hydrophilic Modified hydrophilic Pressure polyethersulfone polyethersulfone Maximum Differential 4.1 bar (59.5 psi) at 38 °C (100 °F) Membrane Support Polypropylene Polypropylene Pressure and Drainage Layer Maximum Sanitization 1 N NaOH for 30 minutes for Assembly Conditions one cycle only Core and Cage Polypropylene Polypropylene Maximum Autoclave 121 °C (250 °F) for 30 minutes Endcaps and Adapters Polyester Polyester Conditions for one cycle only
Housing Bowl Polyetherimide Polypropylene (2) With fully compatible fluids that do not soften, swell or adversely affect the capsule or its materials of construction. Housing Head Polyetherimide Polypropylene with TiO2 with TiO2 O-rings Silicone elastomer Silicone elastomer Note: For CLxMST*P1, x = M05 for a Q, S or E unit with a bed volume of 10 mL 3 for a Q or S unit with a bed volume of 60 mL or an E unit with a bed volume of 40 mL
For NpxMSTG*P1, x = 6 for a Q or S unit with a bed volume of 260 mL or an E unit with a bed volume of 160 mL 7 for a Q or S unit with a bed volume of 520 mL or an E unit with a bed volume of 320 mL 8 for a Q or S unit with a bed volume of 780 mL or an E unit with a bed volume of 480 mL
* = Q for a unit with Q (quaternary amine) chemistry membrane S for a unit with S (sulfonic acid) chemistry membrane E for a unit with E (polyethyleneimine) chemistry membrane
Nominal Dimensions for Capsules Capsule Type CLM05MSTG*P1 CL3MSTG*P1 NP6MPSTG*P1 NP7MSTG*P1 NP8MSTG*P1 Maximum Diameter 123 mm 123 mm 154 mm 154 mm 154 mm (Including Valves) (4.8 in.) (4.8 in.) (6.1 in.) (6.1 in.) (6.1 in.)
Length with Sanitary 84 mm 157 mm 335 mm 581 mm 831 mm Flange Fittings (3.3 in.) (6.2 in.) (13.2 in.) (22.9 in.) (32.7 in.)
Bed Volume 10 mL Q and S = 60 mL Q and S = 260 mL Q and S = 520 mL Q and S = 780 mL E = 40 mL E = 160 mL E = 320 mL E = 480 mL
* Q for a unit with Q (quaternary amine) chemistry membrane S for a unit with S (sulfonic acid) chemistry membrane E for a unit with E (polyethyleneimine) chemistry membrane.
Typical Capsule Binding Characteristics
Chemistry Molecule MW or Size Typical Mustang Membrane Capacity for CLM05 CL3 NP6 NP7 NP8 Q BSA 65 kD 0.5 – 0.6 g 3.0 – 3.6 g 13 – 16 g 26 – 31 g 39 – 47 g Q Thyroglobulin 650 kD 0.3 g 1.8 g 7.8 g 15.6 g 23.4 g Q DNA 0.20 – 0.25 g 1.2 – 1.5 g 5.2 – 6.5 g 10.4 – 13.0 g 15.6 – 19.5 g Q Plasmid DNA 4.5 kb plasmid 0.15 g 0.9 g 3.9 g 7.8 g 11.7 g Q Plasmid DNA 12 kb plasmid 0.15g 0.9 g 3.9 g 7.8 g 11.7 g Q Adenovirus 70 – 90 nm 5 x 1013 3 x 1014 1.3 x 1015 2.6 x 1015 3.9 x 1015 viral particles viral particles viral particles viral particles viral particles
S Lysozyme 14.3 kD 0.45 – 0.50 g 2.7 – 3.0 g 11.7 – 13.0 g 23.4 – 26.0 g 35.1 – 39.0 g S Human IgG 160 kD 0.2 g 1.2 g 5.2 g 10.4 g 15.6 g E Endotoxin Units 4 x 107 1.6 x 108 6.4 x 108 1.28 x 109 1.92 x 109 EU/capsule EU/capsule EU/capsule EU/capsule EU/capsule
218 Mustang Chromatography Cartridges Technical Specifications
Nominal Dimensions for Cartridges Materials of Construction Cartridge Type Diameter Length Bed Volume ABxMSTG*7PH4 AB1MSTG*7PH4 70mm 254 mm 260 mL (2.75 in.) (10 in.) Membrane Modified hydrophilic polyethersulfone Membrane Support and Polypropylene AB2MSTG*7PH4 70 mm 508 mm 520 mL Drainage Layer Assembly (2.75 in.) (20 in.) Core and Cage Polypropylene AB3MSTG*7PH4 70 mm 762 mm 780 mL (2.75 in.) (30 in.) Endcaps, Adapters and Polyester Bomb Fins * = Q for a cartridge with Q (quaternary amine) chemistry membrane S for a cartridge with S (sulfonic acid) chemistry membrane. O-rings Silicone elastomer x = 1 for a 10 in. (254 mm) Q or S unit with a bed volume of 260 mL 2 for a 20 in. (508 mm) Q or S unit with a bed volume of 520 mL 3 for a 30 in. (762 mm) Q or S unit with a bed volume of 780 mL
* = Q for a unit with Q (quaternary amine) chemistry membrane S for a unit with S (sulfonic acid) chemistry membrane
Cartridge Operating Characteristics(3)
Maximum Operating 3 bar (43.5 psi) at 38 °C (100 °F) Pressure
Maximum Differential 3 bar (43.5 psi) at 38 °C (100 °F) Pressure
Maximum Sanitization 1 N NaOH for 30 minutes for Conditions one cycle only
Maximum Autoclave 121 °C (250°F) for 30 minutes Conditions for one cycle only
(3) With fully compatible fluids that do not soften, swell or adversely affect the cartridge or its materials of construction.
Typical Cartridge Binding Characteristics
Chemistry Molecule MW or Size Typical Mustang Membrane Capacity for AB1 AB2 AB3 Q BSA 65 kD 13 – 16 g 26 – 31 g 39 – 47 g Q Thyroglobulin 650 kD 7.8 g 15.6 g 23.4 g Q DNA 5.2 – 6.5 g 10.4 – 13.0 g 15.6 – 19.5 g Q Plasmid DNA 4.5 kb plasmid 3.9 g 7.8 g 11.7 g Q Plasmid DNA 12 kb plasmid 3.9 g 7.8 g 11.7 g Q Adenovirus 70 – 90 nm 1.3 x 1015 2.6 x 1015 3.9 x 1015 viral particles viral particles viral particles S Lysozyme 14.3 kD 11.7 – 13.0 g 23.4 – 26.0 g 35.1 – 39.0 g S Human IgG 160 kD 5.2 g 10.4 g 15.6 g
219 Mustang Chromatography Capsules and Cartridges Ordering Information
Capsules Ordering Information
Chemistry Bed Volume Pack Quantity Part Number Description Q 10 mL 1 CLM05MSTGQP1 38 mm (1.5 in.) sanitary connectors, in-line capsule Q 60 mL 1 CL3MSTGQP1 38 mm (1.5 in.) sanitary connectors, in-line capsule Q 260 mL 1 NP6MSTGQP1 38 mm (1.5 in.) sanitary connectors, in-line capsule Q 260 mL 1 NT6MSTGQP1 38 mm (1.5 in.) sanitary connectors, T-style capsule Q 520 mL 1 NP7MSTGQP1 38 mm (1.5 in.) sanitary connectors, in-line capsule Q 520 mL 1 NT7MSTGQP1 38 mm (1.5 in.) sanitary connectors, T-style capsule Q 780 mL 1 NP8MSTGQP1 38 mm (1.5 in.) sanitary connectors, in-line capsule S 10 mL 1 CLM05MSTGSP1 38 mm (1.5 in.) sanitary connectors, in-line capsule S 60 mL 1 CL3MSTGSP1 38 mm (1.5 in.) sanitary connectors, in-line capsule S 260 mL 1 NP6MSTGSP1 38 mm (1.5 in.) sanitary connectors, in-line capsule S 520 mL 1 NP7MSTGSP1 38 mm (1.5 in.) sanitary connectors, in-line capsule S 780 mL 1 NP8MSTGSP1 38 mm (1.5 in.) sanitary connectors, in-line capsule E 10 mL 1 CLM05MSTGEP1 38 mm (1.5 in.) sanitary connectors, in-line capsule E 40 mL 1 CL3MSTGEP1 38 mm (1.5 in.) sanitary connectors, in-line capsule E 160 mL 1 NP6MSTGEP1 38 mm (1.5 in.) sanitary connectors, in-line capsule E 320 mL 1 NP7MSTGEP1 38 mm (1.5 in.) sanitary connectors, in-line capsule E 480 mL 1 NP8MSTGEP1 38 mm (1.5 in.) sanitary connectors, in-line capsule
Cartridge Ordering Information
Chemistry Bed Volume Pack Quantity Part Number Description Q 260 mL 1 AB1MSTGQ7PH4 10 in. (254 mm) cartridge element with Code 7 adapter Q 520 mL 1 AB2MSTGQ7PH4 20 in. (508 mm) cartridge element with Code 7 adapter Q 780 mL 1 AB3MSTGQ7PH4 30 in. (762 mm) cartridge element with Code 7 adapter S 260 mL 1 AB1MSTGS7PH4 10 in. (254 mm) cartridge element with Code 7 adapter S 520 mL 1 AB2MSTGS7PH4 20 in. (508 mm) cartridge element with Code 7 adapter S 780 mL 1 AB3MSTGS7PH4 30 in. (762 mm) cartridge element with Code 7 adapter
220 Resolute* Chromatography Columns Process Columns for Fast, Contained and Reproducible Operation
Resolute columns are ideally suited for Sanitary Design process purification in the • Fully flushed flow path and adjuster seal BioPharmaceutical industry. A patented for clean-in-place (CIP) nozzle valve provides all column functions required for packing, unpacking and • Minimum dead space fixed cell seal running of the column in a closed system. arrangement Based on established and well proven • Reduced risk of corrosion designs, the Resolute column provides non metallic nozzle flow path for high improved column performance and true salt and low pH conditions linear scalability combined with forged stainless steel tube eliminates reproducible column packing methods for weld seams on tube wall and flanges today’s high performance media. Euroflow, inventor of the pack in place sanitary • Visible valve flow path aids detection of nozzle valve in 1994, continues to work entrapped air closely with the BioPharmaceutical • Sanitary clamp terminations manufacturing industry to advance the • Leachate free acrylic tube — no state of the art for both chromatographic phthalates performance and productivity. The packing process is controlled by a slurry packing • Peroxide cured seals — no sulphur system which, combined with a Resolute containing leachate column, offers a complete solution for • Process wetted materials meet process chromatography from regulatory requirements development to manufacturing scale. Column Options Features and Benefits Standard Columns • Standard column diameters from • Actuated nozzle valve; fits 400 to 280 mm to 1200 mm – all with 1200 mm diameter columns selectable bed heights from 100 mm up • Bed supports: Below: 800M Hydraulic Column to 600 mm Polyethylene 10/20/60 µm • Bed Height: fixed or adjustable Stainless steel 10/20/50 µm (200 mm adjustment) • Lockable castors and adjustable feet • Nozzle Valve: choice of manually supplied as standard* operated Resolute DM, or * Up to 1000 mm diameter only. pneumatically actuated Resolute DP columns Engineered Columns • Operating pressure up to 10 bar • Choice of bed supports in polyethylene or stainless steel • Columns from 400 mm to 2000 mm diameter • Piston seal and precision bore tube • Certification to ASME Div VIII sec 1 or eliminates need for additional PD5500.CE where applicable mechanical compression or pneumatic activation of adjuster seals • Service frames for piston end cell maintenance • Compatible with a wide range of Chromatographic Media • Alternative materials: Hastalloy C22, Stainless Steel 1.4435, 1.4439 • Hydraulic Actuators — see technical * Resolute is a trademark of Euroflow (UK) Limited. specifications for operating modes 221 Resolute Chromatography Columns Technical Specifications – Resolute Fixed and Adjustable Columns (280 – 1200 mm diameter)
Material Specifications Column Specifications
Process Wetted Components Resolute Fixed and Adjustable Columns Column Tube Acrylic (cast PMMA) 180 – 1200 mm (7 – 47 in.) diameter or Stainless Steel 316L (1.4404) Operating Pressure 180 – 280 mm (7 – 11 in.): Distribution Cell Polypropylene 5 bar (73) psi Nozzle Body PVDF/Acrylic(1) 400 – 1200 mm (15.7 – 47 in.): 3 bar (44) psi Process Terminations and PEEK Slurry Nozzle Tip Operating Temperature 2 – 30 ºC (35 – 86 °F) Slurry Inlet Port 180 and 280 mm columns:(2) PEEK Bed Support, Type Stainless Steel Mesh: and Rating 10, 20, 50 µm 400 to 1200 mm columns:(2) Stainless Steel 316L Polyethylene Sinter: 10, 20, 60 µm Bed Support Polyethylene sinter or Stainless Steel mesh Product Flow Path Stainless Steel surface finish < 0.6 µm Ra, Electropolished Seals EPDM (Peroxide cured) FEP encapsulated silicone Exterior Components Stainless Steel surface finish < 0.9 µm Ra, Electropolished Wiper Blade PTFE Pressure Retaining Plates Stainless Steel surface finish External Components < 1.5 µm Ra, 240 (UK) Grit Sateen Stand, Adjustable Feet Stainless Steel 316L Column Frame Stainless Steel surface finish Castor Stainless Steel 304L Bright polished Castor Tyre Polyurethane Media Transfer Nozzle DM: (1) PVDF/PVDF version available for increased chemical resistance. Manual actuation (2) Components not in mobile phase flow path. DP: Manual control with pneumatic actuation
Hydraulic Actuators (Optional) Type Mode of Operation Application HEP Hydraulic linear actuator when column is empty or Set up prior to Pack in Place and Maintenance Hydraulic Endcell Positioning primed and has an open flow path with < 1 bar column pressure
DAP Hydraulic linear actuator when column is empty or Flow Packing at optimal linear velocity Dynamic Axial Packing filled with slurry and has an open flow path with < 3.0 bar column pressure
/M Option Actuators and integral support and safety devices Access to top and bottom bed supports and seals Hoist-free Maintenance move and secure Top Adjuster and Column Tube for changeout (/M option available for either HEP or DAP model)
Column Capacity and Ordering Information Description Diameter CSA Adjustable Height Adjustable Capacity Operating Pressure Resolute 280 280 mm (11.in.) 620 cm2 100 – 300 mm 6.2 – 18.5 L 5 bar (73 psi)
Resolute 400 400 mm (15.7 in.) 1260 cm2 100 – 300 mm 12.6 – 37.7 L 3 bar (44 psi)
Resolute 600 600 mm (23.6 in.) 2830 cm2 100 – 300 mm 28.3 – 84.8 L 3 bar (44 psi)
Resolute 800 800 mm (2.6 ft) 5030 cm2 100 – 300 mm 50.3 – 150 L 3 bar (44 psi)
Resolute 1000 1000 mm (3.2 ft) 7850 cm2 100 – 300 mm 79 – 235 L 3 bar (44 psi)
Resolute 1200 1200 mm (3.9 ft) 11310 cm2 100 – 300 mm 113 – 339 L 3 bar (44 psi)
Resolute 1400 1400 mm (4.6 ft) 15390 cm2 100 – 300 mm 154 – 461 L 3 bar (44 psi)
Resolute 1600 1600 mm (5.2 ft) 20110 cm2 100 – 300 mm 201 – 603 L 3 bar (44 psi)
Resolute 1800 1800 mm (5.9 ft) 25450 cm2 100 – 300 mm 255 – 763 L 3 bar (44 psi)
Resolute 2000 2000 mm (6.6 ft) 31420 cm2 100 – 300 mm 314 – 942 L 3 bar (44 psi)
For alternative column capacities and complete product ordering information please contact your local representative. (1) Variable bed heights are also available in the ranges: 200 – 400 mm, 300 – 500 mm and 400 – 600 mm, as well as fixed capacity columns from 180 mm diameter.
222 Resolute* Slurry Packing Systems Integrated systems for Scalable Packing and Unpacking of Process Chromatography Columns
Resolute slurry packing systems (SPS) are Compatible with a wide range of optimized for use with Resolute columns. Chromatographic Media With the flexibility of 4 systems in the Increasingly, new types of chromatographic series, column packing and unpacking can media with specific packing methods are be optimized for one or multiple columns specified for purification processes now in up to 2000 mm diameter. The Resolute development. Packing an efficient column SPS provides simple control of the column requires a comprehensive understanding of packing and unpacking process within a the media characteristics as well as a cGMP environment. The proven design packing system with adequate flow provides scalable packing performance capacity and flow control. Resolute for column diameters from 400 mm to systems deliver excellent performance with 2000 mm with most commonly used a wide range of media types and column media types. A range of ancillary configurations including axial compression equipment integrates all aspects of the techniques. packing and unpacking process.
Features and Benefits Optimized for Pilot and Manufacturing Operation Efficient User-friendly Control Interface To reduce the burden of transferring The simple control panel provides: packing methods during scale-up, each • Operating controls and parameters in system in the series has an output capacity one place matched to both packing and unpacking • User-friendly calibration flow rates as column diameter is increased. Effective removal of all media from the • Motive air supply regulator for effective column during the unpacking process pump flow control requires increased flow rates compared • Panel mounted valve selector switch for with packing flow rates. To meet the fluid circuit configuration requirements for all commonly used media types the Resolute SPS series offers • Valve status indicators packing flow rates from as low as 4 L/min • Emergency stop button and up to 500 L/min at 0.5 bar with a • Convenient packing and effective maximum pressure limit of 5 bar. unpacking Selecting a suitable model for your process • Integrated pulse dampener improves depends upon the column linear velocity, bed homogeneity column diameter and media characteristics. An integrated pulse • Compact footprint with multi-column dampener further enhances homogeneity operation capability of the packed bed by providing a steady • Validated for most media types flow of media into the column towards the end of the packing cycle. This, together • Vessel and hose sets maximize with the selection of proven system performance and media recovery components at all scales, assures reproducible packing conditions at all column diameters and significantly reduces the validation effort during commissioning. * Resolute is a trademark of Euroflow (UK) Limited.
223 Resolute Slurry Packing Systems Technical Specifications
Operating Conditions Model SPS-M1 SPSM2/2E SPS M3 Dimensions 1300 x 875 x 1300 x 875 x 1400 x 875 x (L x W x H) 1259 mm 1259 mm 1292 mm (51 x 34 x 49 in.) (51 x 34 x 49 in.) (55 x 34 x 50 in.)
Weight 175 Kg 200 Kg 290 Kg (385 lbs) (440 lbs) (639 lbs)
System Capacity 4 – 107 10 – 270 (M2) 18 – 500 L/min @ 4 – 270 (M2E) 3 bar (44 psi)
System Pressure 10 bar 10 bar 10 bar Rating (146 psi) (146 psi) (146 psi)
Materials 316L SS, 316L SS, 316L SS, Process Wetted PTFE, EPDM PTFE, EPDM PTFE, EPDM
Maximum Air(1) 20 scfm 30 scfm 40 scfm Consumption @ 6 bar (90 psi)
(1) Instrument air filtered to 20 micron, -20 ºC (68 °F) dew point, oil free.
Ordering Information Packing Accessories
Slurry Packing System(2) Transfer Adapter Kit High performance PTFE lined tube with stainless steel braid and external EDA13A123A99 TAK-1 Component i.d. suitable for use with EPDM rubber cover. 400 mm ø column Part Number Model Description EDA13A137A99 TAK-2 Component i.d. suitable for use with 600, 800 and 1000 mm ø columns(3) EBA12A125A99 SPS-M1 Minimum and maximum capacity (L/min): 3 @ 3 bar/107 @ 0.5 bar) EDA13A138A99 TAK-3 Component i.d. suitable for use with 1000 and 1200 mm ø columns(4) EBA12A126A99 SPS-M2 Minimum and maximum capacity (L/min): Pressure Gauge and Flow Meter Kit 10 @ 3 bar/270 @ 0.5 bar) EKA14A123A99 PFK-1 Component i.d. suitable for use with EBA12A127A99 SPS-M2E Minimum and maximum capacity (L/min): 400 mm ø column 3 @ 3 bar/270 @ 0.5 bar) EKA14A130A99 PFK-2 Component i.d. suitable for use with EBA12A128A99 SPS-M3 Minimum and maximum capacity (L/min): 600 mm ø column 18 @ 3 bar/500 @ 0.5 bar) EKA14A124A99 PFK-3 Component i.d. suitable for use with 800 mm ø column Transfer Hose Set EKA14A131A99 PFK-4 Component i.d. suitable for use with EKA12A126A12 TH-1 Hose Kit with 3 meter (9.8 ft) length 1000 mm ø column hoses (6) and sanitary TC connectors. Connects SPS-1 to 400 and 600 mm ø EKA14A125A99 PFK-5 Component i.d. suitable for use with column and SPS-2 to 400, 600, and 1200 mm ø column 800 mm ø column Media Slurry Tanks TH-1C As TH-1 except with Heavy wall wire EDA11A123A99 SV-1 500 litre (132 gal) nominal capacity reinforced PVC hose EKA12A126A15 EDA11A124A99 SV-2 1000 litre (264 gal) nominal capacity EKA12A127A12 TH-2 Hose Kit with 4 meter (13 ft) length EDA11A125A99 SV-3 2000 litre (528 gal) nominal capacity hoses (6) and sanitary TC connectors. (2) Requires Transfer Host Set and Transfer Adapter Kit matched to column size. Connects SPS-2 to 600, 800 and (3) Select TAK-2 for use with 1000 mm column and SPS 2. 1000 mm ø column and SPS-2E to 400, (4) Select TAK-3 for use with 1000 mm column and SPS 3. 600, 800 and 1000 mm ø column
TH-2C As TH-2 except with Heavy wall wire reinforced PVC hose EKA12A126A15
EKA12A128A12 TH-2 Hose Kit with 4 meter (13 ft) length hoses (6) and sanitary TC connectors. Connects SPS-3 to 1000 and 1200 mm ø column
TH-3C As TH-3 except with Heavy wall wire reinforced PVC hose EKA12A126A15
224 PK Chromatography Skids Improving Choice, Flexibility and Operating Costs for Purification Processes
Pall’s standard PK chromatography • Designed for full CFR 21 part 11 systems are based on consistent design compliance GAMP Compliance principles and quality components that • System design is in recognition of the assure: GAMP guide, to ensure that all process • Adherence to process requirements application and regulatory requirements are met and documented to GMP • Conformance to regulatory demands criteria • A reduction in downtime • Documentation and protocols include • Increased process efficiency DQ, IQ/OQ and FAT are used to verify To complement the standard PK systems compliance to user requirements Pall offers fully customized • Customized solutions based on chromatography equipment and services, industry-standard PK system ranging from Process Development scale platform.Pall provides a complete family to manufacturing scale. of control systems for chromatography- Each Pall chromatography system is supporting ion exchange, affinity, supplied in accordance with specific hydrophobic and gel permeation process requirements. Our automation, applications. engineering and process packages are PK systems are based on a consistent designed with efficiency, flexibility and easy layout for true linear scale-up of scale-up in mind. With the ever-increasing chromatography processes. Available in trend of manufacturing processes being four sizes: PK10 (10 – 100 LPH), sited around the world, Pall can provide PK25 (25 – 400 LPH), technical support and advice as necessary PK50 (50 – 1000 LPH) and on a global basis, assuring reliable system PK300 (300 – 4000 LPH), the broad flow and process performance regardless of range for each system(1), coupled with location. optimized design and components, Each Pall system is designed to provide: enables a range of applications from pilot/small scale to production scale with • Conformance to critical industry excellent chromatography results for a standards range of column diameters. • Reduction in time spent in process [1] Customized versions of this design extend the development and manufacturing capability to larger flow ranges where needed. applications • Optimum flexibility for changing process demands • Efficient installation and ease of use • Segmented system and operator control structure facilitates remote operation
225 PK Chromatography Skids Technical Specifications
Hardware Features and Benefits System Ratings (Applicable to all)
Sanitary Multi-port Reduces dead-legs to a minimum Working Pressure 6 barg (87 psig) Valve Technology Compacts flow path Working Temperature 2 – 60 °C (36 – 140 °F) 316L Stainless Steel Robust, chemically-resistant flow path Surface Finish Internal: Wetted Flow Path In-line valve fabrication minimizes clamp 0.4 µm (16 µ-in.) Ra + Electro-polish connections Operating Environment Temperature and Humidity: Two-pump Gradient and Precise in-line mixing 30 °C (86 °F) maximum, 95% humidity In-line Dilution Fast accurate step and gradient formation Electrical Ratings IP54/NEMA 13 Electrical and Safety CE and UL Designed for CIP Turbulent Flow velocities achievable in Approvals pipe work Extended temperatures possible Quality Systems ISO 9000
Flow through Instrumentation Instrumentation flow cell in-line, Design Standards ASME BPE, GAMP eliminating dead-legs and minimizing CFR 21 Part 11 Compliance Yes hold-up volume
Industry Standard Reliable monitoring and control of Instrumentation process conditions
Conformance to ASME, BPE Major components designed for conformance to BPE for inherent sanitary design
FDA Conforming Validation and compatibility with Non Metallic Parts pharmaceutical manufacturing requirements
System Drain Post-pump system fully drainable for storage
Diaphragm Pump (4-piston) Pump head design gives virtually pulsation-free flow
No Manual Pump-stroke Fully automated control – repeatable Adjustment setting with reduced operator intervention
System Validation Testing protocols, including DQ, IQ/OQ and FAT support, for fast track validation and system start-up
Documentation Comprehensive support documentation in accordance with GAMP guidelines Easily Accessible Parts Easy maintenance and replacement. Standard Skid Range uses Consistent scale-up Consistent Layout Philosophy and Components
System Sizes System PK10 PK25 PK50 PK300 Flow Range (L/H) 10 – 100 25 – 400 50 – 1000 300 – 4000 Piping id 4.6 mm (0.18 in.) 12.5 mm (0.5 in.) 15.7 mm (0.62 in.) 34.8 mm (1.4 in.)
Pipe Connections 6 mm (0.25 in.) 12.5 mm (0.5 in.) 18 mm (0.75 in.) 38 mm (1.5 in.) Sanitary Clamp Sanitary Clamp Sanitary Clamp Sanitary Clamp
Dimensions 900 mm x 1300 mm 950 mm x 1300 mm 950 mm x 1300 mm – x 1400 mm x 1400 mm x 1400 mm (35 in. x 51 in. (37 in. x 51 in. (37 in. x 51 in. x 55 in.) x 55 in.) x 55 in.)
Uncrated Weight 250 kg (550 lbs) 275 kg (606 lbs) 300 kg (660 lbs) –
226 Palltronic® Instruments Palltronic® Instruments
Palltronic Instruments are designed to provide precise, accurate and reliable results in the most demanding production and laboratory environments.
These compact, splash-proof instruments are designed for ease of use and convenient service. And most important, each instrument comes with extensive validation documentation, including hardware and software qualification, that can help ensure compliance with industry and regulatory standards.
228 Palltronic® Flowstar XC Filter Integrity Test Instruments
Palltronic Flowstar XC instruments Features and Benefits perform accurate and precise • Direct-flow measurement eliminates measurement of the upstream Forward errors and time associated with Flow, Bubble Point, Water Intrusion and traditional pressure hold test technology combined Forward Flow/Bubble Point tests. • Extensive validation documentation and qualification of hardware and software The Palltronic Flowstar XC instrument is a ensures compliance with industry and unitized, compact and splash-proof filter regulatory requirements integrity test instrument especially designed for use in the most demanding • Easy-to-follow commands for production environments. user-friendly operation Featuring the latest in touch-screen • Data security and electronic signature technology, the Palltronic Flowstar XC features compliant with CFR 21 part 11 system is extremely user-friendly, with • Unitized, durable construction with simple menu-driven data input. The new splash-proof design allows testing in Palltronic XC system can store up to 500 any environment test programs and up to 10,000 test results, which makes it ideal for • Large, graphic LCD display enables large-volume manufacturing and easy reading of real time test multi-product processes in the measurements pharmaceutical industry. Its increased • Unique external vent valve prevents memory capacity provides maximum liquid back flow into the unit for data-handling flexibility and security. increased service reliability In addition, an ethernet port is available in • Hard copy printout, with date and time the Palltronic Flowstar XC unit that allows displayed, facilitate documentation a high-speed PC link for a rapid data requirements backup. • Password-protected for added security The Palltronic Flowstar XC instrument • Self-Test verifies proper functioning of incorporates direct flow measurement software and internal components to technology, which can reduce testing times streamline maintenance and labor by 50% or more, without compromising requirements the validity of test results. The Palltronic High-flow Flowstar XC instrument is expressly designed for filter systems requiring high-flows, is capable of providing flow rates up to 2000 mL/min without any reduction in flow measurement accuracy.
See Also: Palltronic Flow Check Device p. 233 229 Palltronic Training Program p. 234 Palltronic Flowstar XC Filter Integrity Test Instruments Technical Specifications
Physical Dimensions Electrical Requirements Weight 9.8 kg (21.5 lbs) Input Voltage Adjustable between 100 – 240 VAC Size 160 x 365 x 370 mm Input Frequency 50/60 Hz (6.3 x 14.4 x 14.6 in.) Power Input 50 watts (typically)
Filter Tests Fuse 1.6A (inert)
Forward Flow, Bubble Point, Water Intrusion and Combined Forward Flow Touch Screen and Bubble Point Size Diagonal 239 mm (9.4 in.) 640 x 480 Pixel Software Function Tests Display Black and White Self-Test and Flow Check Test Background Illuminated Contrast Adjustable Additional Software Functions
Air Clean Program, Auto-Test Mode, Storage, 500 Test Programs, Printer 10,000 Test Results and 250 User IDs Type Thermal Resolution 832 Dots/Line Language Options Printout Lifetime 10 Years English (US), English (UK), French, German, Italian, Spanish and Japanese Speed 25 – 50 mm/sec (Katakana with English) Paper Width 112 mm (4.4 in.) Electronic Interface Paper Roll Diameter 50 mm (1.9 in.) Ports COM Two (2) Serial RS232C Pneumatic Specifications (V24)/Asynchronous/DB9 Auxiliary Test Gas Clean Dry Air or Nitrogen For Remote Operation Maximum Inlet Pressure 8000 mbar (116 psi) Data One (1) RSJ45 for high-speed data Minimum Pressure Above Testing Pressure transfer Standard Flow Range: 0.01 – 60 mL/min 1000 mbar (14.5 psi) Test Measuring Ranges 61 – 120 mL/min 1500 mbar (22.8 psi) Palltronic Flowstar XC 121 – 200 mL/min 2000 mbar (29.0 psi) Forward Flow 0.1 – 200 cc/min High-flow Flow Range: 0.01 – 200 mL/min 1000 mbar (12.5 psi) Water Intrusion 0.05 – 50 mL/min 200 – 1000 mL/min 2000 mbar (29.0 psi) Bubble Point 700 – 6000 mbar (10 – 87 psi) 1000 – 1500 mL/min 3000 mbar (43.5 psi) 1500 – 2000 mL/min 4000 mbar (58 psi) Palltronic Flowstar High-flow XC Test Pressure Range 50 – 6000 mbar (0.7 – 87 psi) Forward Flow 0.1 – 2,000 mL/min Water Intrusion 0.05 – 50 mL/min Connections Bubble Point 700 – 6000 mbar (10 – 87 psi) Inlet Stäubli* Nipple Accuracy Outlet Stäubli* Coupling
Forward Flow ± 3% or ± 0.05 mL/min Vent Hose Connection 8 mm (0.31 in.) Outer Diameter (whichever is greater)
Water Intrusion Test ± 3% or 0.02 mL/min Environmental Options (whichever is greater) Splashproof IP54 Regulation (DIN 40050 Standard) Operating Temperature 5 °C – 50 °C (41 °F – 122 °F) Calibration Limits Storage Temperature 20 °C – 70 °C (-4 °F – 158 °F) Flow Measurement ± 3% of measurement Humidity 95% Relative Humidity Pressure Measurement ± 0.33% of full scale (No Condensation)
Resolution Ordering Information Forward Flow Test Standard FFSXC Measured Flow < 10 mL/min, 0.01 mL/min Flowstar HighFlow FFSXCH Measured Flow > 10 mL/min, 0.1 mL/min Standard Flowstar (US) FFSXCAM Standard Flowstar (Japan) FFSXCJ High-flow (US) FFSXCHAM 230 High-flow (Japan) FFSXCHJ *Stäubli is a trademark of Stäubli AG. Palltronic® Aquawit XC System
The Palltronic Aquawit XC system offers Hydraulic Bridge major benefits for integrity-testing of The hydraulic bridge removes all air from hydrophobic gas filters. All stages of the the upstream filter system and tubing. Flow water intrusion test can now be performed measurement is then performed in a more fully automatically on gas filters — and on controlled environment within the line. The operator simply connects the Palltronic Aquawit unit. Stable results can Palltronic Aquawit XC unit to the filter be obtained even when environmental system, inputs test parameters on the easy temperatures are changing by 10 °C to use touchscreen and starts the test (18 °F) or more. Direct flow and real time sequence. The filling, testing, draining and measurement further adds to the accuracy, drying is performed without further speed and reliability of the test result. operator involvement and a detailed test result is saved and printed. Versatility The Palltronic Aquawit XC system has With Pall direct flow measurement been designed to test vent filters in technology and a hydraulic bridge link to positions with difficult access where the test filter, accurate and reproducible environmental temperatures may be results are ensured even during changes in fluctuating. The hydraulic bridge permits environmental temperature. the Water Intrusion test to be performed on: Features and Benefits • Filters in elevated positions, for Accuracy and Reliability example, product storage and WFI In validation studies flow was measured at tanks different environmental temperatures using • Filters which are inside equipment, for a small filter with a typical water intrusion example lyophilizers or sterilizers which flow rate of 0.04 mL/min to represent are difficult to access worst case conditions. Even under conditions where the environmental • Several different filter installations temperature of the filter as 20 °C (36 °F) testing from a fixed point higher than water temperature, an accurate Variable Environmental Temperature test result was obtained.
Palltronic direct flow Air space Validation work has also shown that measurement system replaced by water accurate measurements can be performed using filter installations at a distance of at Air space least 10 m (33 ft) and a height of 2.5 m Measurement chamber (8 ft) or more. Pall can assist in qualifying the Palltronic Aquawit XC system for individual purposes. Water tank Hydraulic bridge
Palltronic Aquawit XC System
See Also: Palltronic Flow Check p. 243 Pall Advanta Gas Housings Pall Advanta AGT p. 165 Single Round Housings Pall Advanta AVL p. 167 Single Round Housings Emflon PFR Filter Cartridges p. 127 231 and Capsules Palltronic Aquawit XC System Technical Specifications
Physical Dimensions Electrical Data Weight Empty 100 kg (220 lbs) Mains Voltage 90 – 230 Volts Height, Width and Depth 1100 mm, 580 mm and 840 mm Mains Frequency 50 – 60 Hz (43 in., 22 in. and 33 in.) Power 200 W Water Tank Volume 14 Liters (3.7 US gallons) Interface 1 x RS232C, serial, asynchronous, DB9 auxiliary Filter Tests External Vent Valve 24 V Water Intrusion Test (fully-automatic), Water Intrusion Test (semi-automatic), Forward Flow Test (semi-automatic), Bubble Point Test Touch Screen Specifications (semi-automatic) and Combined FF and BP Test (semi-automatic) Size 238 mm (9.4 in.) 640 x 480 pixel Function Tests Features Black and white, illuminated background and adjustable contrast Self Test, Flow Check Test and Valve Check Materials Other Functions Stainless Steel – Water Wet DIN 1.4404(1) Air Clean program, Test Program memory capacity of 500 programs, Test Stainless Steel – Frame DIN 1.4301(2) result memory capacity, 10,000 test results and User ID memory capacity of 250 users Seals EPDM
Language Options Connections
English, French, German, Italian, Spanish, US English and Japanese Compressed Air Inlet (Katakana with English) Staübli Nipple RBE03.6150 Compressed Air Outlet Electronic Interface Staübli Coupling RBE03.2904 Ports Water Line to Fill Filter 25 mm (1 in.) Sanitary clamp COM Two (2) Serial RS232C (V24)/Asynchronous/DB9 Auxiliary Water Line to Fill Tank 25 mm (1 in.) Sanitary clamp For Remote Operation Water Drain (Bottom Level) 25 mm (1 in.) Sanitary clamp Data One (1) RSJ45 for high-speed data transfer Environmental Conditions Splash Proof IP54 Measuring Range Operating Temperature +5 °C to +40 °C (+41 °F to +104 °F) Water Intrusion Test 0.05 – 50 mL/min Storage Temperature -20 °C to +70 °C (-4 °F to +158 °F) Forward Flow Test Standard: 0.1 – 200 mL/min Humidity 95% rh (no condensation) High-flow: 0.1 – 2,000 mL/min Printer Bubble Point Test 700 – 6000 mbar (10 – 87 psi) Type Thermal Printout Lifetime 10 Years Accuracy Paper Width 112 mm (4.4 in.) Forward Flow Test +/- 3% or +/- 0.05 mL/min, Paper Roll Diameter 50 mm (1.9 in.) whichever is the greater
Water Intrusion Test +/- 3% or +/- 0.02 mL/min, Pneumatic Specifications whichever is the greater Test Gas Clean Dry Air or Nitrogen Maximum Inlet Pressure 8000 mbar (116 psi) Calibration Limits Minimum Pressure Above Testing Pressure Flow Measurement +/- 3% of measurement Standard Flow Range: Pressure Measurement +/- 0.33% of full scale 0.01 – 60 mL/min 1000 mbar (14.5 psi) 61 – 120 mL/min 1500 mbar (22.8 psi) Resolution 121 – 200 mL/min 2000 mbar (29.0 psi) Water Intrusion Test 0.01 mL/min Test Pressure Range 50 – 6000 mbar (0.7 – 87 psi) Forward Flow Test Measured Flow >10 mL/min: 0.1 mL/min Ordering Information Measured Flow <10 mL/min: 0.01 mL/min Standard High-flow Bubble Point Test 50 mbar (0.72 psi) Part Number AW02XC AW02XCH (1) DIN 1.4404 element composition limits are comparable to 316L. 232 (2) DIN 1.4301 element composition limits are comparable to 304. Palltronic® Flow Check Device
The Palltronic Flow Check device enables Features and Benefits allows a fast and simple check to be • Allows for fast and simple checks of performed on an integrity test instrument integrity test instrument flow to show that it is measuring flow correctly. measurement A Flow Check test can be performed as often as the user requires in order to • Fully portable, lightweight and easy to ensure complete confidence in the integrity use test instrument. The user simply connects • Can be used with all integrity test the device to their integrity test instrument, instruments which give a flow value performs a Flow Check test (available with Palltronic Flowstar and Aquawit • High precision capillary, with calibrated instruments), or a Forward Flow or flow, ensures accurate readings Diffusion Test. The flow measured by the • Internal Pall Gaskleen® filter protects integrity test instrument is then compared components for increased service life with the calibrated flow of the Flow Check • Robust, sanitary stainless steel design device. Each Palltronic Flow Check unit is makes it ideal for the supplied with a Calibration Certificate, with BioPharmaceutical industry the calibrated flow value permanently marked on the device. Full operating • Easy to use Stäubli connections and instructions and Stäubli* fittings are fittings supplied with every device. * Stäubli is a trademark of Stäubli AG.
Nominal Dimensions Weight 1.67 kg (3.68 lbs) Size (H x W x D)(1) 90 x 150 x 180 mm (3 in. x 5 in. x 6 in.) (1) L = maximum length including Staübli* connection)
Environmental Conditions Operating Temperature 20 °C ± 2 °C (68 °F ± 35 °F) Storage Conditions Room temperature in dry conditions
Pneumatic Specifications Operating Pressure 2 barg (29 psig) Maximum Inlet Pressure 3.0 barg @ 40 °C (44 psig @ 104 °F) Test Gas Clean, dry, compressed air or nitrogen Flow Range 1 – 10 mL/min
Connections Inlet Stäubli* nipple RBE03.6150 Outlet Hose Connection: 8 mm (0.25 in.) outer diameter
* Stäubli is a registered trademark of Stäubli AG.
Ordering Information Part Number FC01 233 Palltronic® Training Program The Missing Piece from your 21 CFR 11 Compliance Puzzle
Part I. Basics of Integrity Test – Part II. Hands-on Lab Classroom Presentation Operating Instructions and SOP • Why integrity test? • Perform BP, FF and/or WIT • Types of integrity tests: • External Vent Valve Assembly Bubble Point, Forward Flow, Pressure Hold and Water Intrusion • Flow Check device • Factors influencing integrity-testing: Maintenance and Troubleshooting Temperature, Upstream Volume and • Cleaning procedures and practices Wetting Agent • Review error messages and fixes • Automated vs. Manual integrity-testing • Look for filter failure mode • Design features of automated device • Line pressure requirements FDA specifies in its 21 CFR Part 11 regulation that procedures should be employed to ensure: “Determination that persons who develop, maintain, or use electronic record/electronic signature systems have the education, training, and experience to perform their assigned tasks.”
234 Drivers for Palltronic® Filter Integrity Test Instruments Controlled Integrity-testing with a Programmable Logic Controller
Introduction Features and Benefits
Within the pharmaceutical industry there is • Process automization can minimize a growing use of automated manufacturing operator involvement, saving time and techniques, electronic signatures and reducing errors storage of critical batch records. • Integrity test results can easily be In order to help satisfy the industry’s needs incorporated into batch records and for more centralized control, Pall has stored centrally on the PLC or SCADA developed a range of drivers for Palltronic system integrity test devices. • Full integration of the Palltronic device into the normal operation of the plant Description allows control of the test device from Drivers for the Palltronic filter integrity test outside critical or difficult-to-access instruments enable a PLC to remotely areas control the integrity test device. The • The PLC or SCADA system can be Programmable Logic Controller (PLC) can configured to be compliant with initiate a self test or filter test and when 21 CFR 11 Part 11 when storing test completed, the Palltronic device transmits results the test result, the device serial number and other information back to the PLC. This information can then be stored in a Supervisory Control and Data Acquisition (SCADA) system using the data received by the PLC to form part of a comprehensive batch record. A standard package includes: driver software supplied on CD-ROM, full installation instructions and a 2 m (26 ft) communications cable between the PLC and integrity test device. Standard drivers are available for Siemens, Mitsubishi and Allen Bradley PLCs. Drivers for other PLC manufacturers can be developed on request. The software has been developed and tested according to the latest GAMP guidelines.
See Also: Palltronic Flowstar p. 239 235 Aquawit Instruments p. 241 Drivers for Palltronic Filter Integrity Test Instruments Technical Specifications
Schematic
The schematic below shows signals and data transfer between the Palltronic test device, PLC and SCADA systems
SCADA
Serial Number Software Version Last Calibration Date Self Test Result Flowrate or BP Measurement Result
PLC Test Start Command Self Test Start Command
Serial Number Serial Number Test Time Software Version Software Version Test Pressure Flowrate or BP Measurement Last Calibration Date Maximum Flow Rate Result Self Test Result Minimum BP Status Test Mode
Driver Palltronic Device Operation Test Running
Ordering Information(1) Part Number Palltronic Device PLC Other Requirements SDFFS02 Palltronic Flowstar FFS02 Siemens S7-300 RS232 communications module and XC instruments FFS02 device and S7-400
MDFFS02 Palltronic Flowstar FFS02 Mitsubishi A Series Serial communication module and XC instruments FFS02 device
ADFFS02 Palltronic Flowstar FFS02 Allen Bradley Serial communication module and XC instruments FFS02 device SLC500 series
PDFFS02 Palltronic Flowstar FFS02 or Siemens S7-300 or Profibus DP module XC Instrument S7-400
CDFFSXC Palltronic Flowstar XC OPC Server Any PC package which supports OPC Serial communication port (RS232C)
(1) This is a guide to the part number structure only. For availability of specific options, please contact Pall or your local Pall representative. Drivers for other Palltronic models and PLC manufacturer makes and models can be developed on request. Please contact your local Pall company or distributor for further information. A Palltronic Flowstar FFS02 interface description for remote operation and on-line data logging is available. Pall literature reference USTR2148.
236 Palltronic® Filter Manager Automated Filterability Test Unit
The Palltronic Filter Manager is an • Hard copy printout with date and time automated filterability test unit which can displayed helps documentation be used to test direct flow filters either at requirement constant pressure or at constant flow. This • Provides the technological controls to allows to simulate exactly your processes, meet the regulatory requirements of and such a unit can be used for modeling 21 CFR Part 11 of filtration processes either during scale-up or during scaling down for trouble • Automatic Self Test to check proper shooting processes or validation test work. functioning of software and internal components Palltronic Filter Manager, an instrument especially designed for laboratory • Extensive validation documentation and environment is compact, flexible and qualification of hardware and software splash-proof. The latest touch-screen for compliance with industry and technology makes the unit extremely user- regulatory requirements friendly with simple menu-driven data • Designed for easy servicing input.
Features and Benefits
• Designed to perform either constant
flow test or constant pressure test Constant Flow Test Configuration Pressure Pressure • Up to 2 filters can be tested in series Transducer 1 Transducer 2 • Available in 3 different conformations for ease of use Peristaltic Filter Filter Pump • Results displayed in both tabular and Holder 1 Holder 2 Temperature graphical format Transducer
• Output (in L/m2 of membrane area) will be calculated for each filter Fluid Collecting Vessel • Splash proof design allows testing in a Vessel laboratory environment Balance • Storage of up to 50 tests in the hard drive Constant Pressure Test Configuration Pressure Pressure Transducer 1 Transducer 2 Temperature Transducer
Fluid Filter Filter Vessel Holder 1 Holder 2
Collecting Control Air Supply Vessel Panel (Unregulated) Balance
237 Palltronic Filter Manager Technical Specifications
Physical Dimensions (Nominal – Control Panel Only) Electrical Data
Weight 10 kg (22 lbs) Main Voltage Automatically adjusted between Height, Width and Depth 470 x 330 x 195 mm 100 – 240 V AC (18.5 x 13.0 x 7.7 in.) Main Frequency 50 Hz or 60 Hz
Filterability Tests Power Input – Typically 440W Constant Flow Test P cap Fuse 4A Constant Pressure Test V cap Interface RS232C x 2 External Valve 24V DC Function Test
Self-test Screen
Size Language Options Diagonal — 264 mm (10.4 in.), 640 x 480 pixels English (US), English (UK), French, Spanish, Dutch, Italian and German Features Full color display and touch screen functionality Communication Ports RS 232C port for PC Pneumatic Specifications
Maximum Gas 6000 mbar/87 psi Accuracy Supply Pressure Pressure ±1% full scale Temperature Monitoring ±2 °C (35 °F) Internal Printer Mass ±1 g Life Time of Printout Up to 15 years (depending on paper Instrument Measuring Range type and storage conditions) Paper Width 112 mm (4.4 in. approximately) Mass (Including beaker) 0.005 – 6 kg (0.2 oz – 13lb 3 oz) (approx.) Paper Roll Diameter 50 mm (2 in. approximately) Pressure 0 – 6000 mbarg (0 – 87 psig) Environmental Conditions Temperature 0 °C to +100 °C (32 °F to +212 °F) Note: System operating temperature range +5 °C to +40 °C/+41 °F to +104 °F) only. Splash Proof IP54 Operating Temperature +5 °C to 40 °C (+41 °F to +104 °F) Peristaltic Pump Storage Temperature -20 °C to + 60 °C (-4 °F to + 140 °F) Speed Range 10 – 600 rpm Humidity 95% RH (no condensation) Flow Rate 0.6 – 36 mL/min with 0.8 mm (0.03 in.) internal diameter tubing
8 – 480 mL/min with 3.2 mm (0.125 in.) internal diameter tubing
Ordering Information
Manual Palltronic Filter Manager UM01M (Test stand and disc holders)
Automated Palltronic Filter Manager UM01P (Test stand, disc holder, control panel, instruments and load cell: will run Constant Pressure tests only)
Complete Palltronic Filter Manager UM01F (Test stand, disc holders, control panel, instruments, load cell and pump: will run Constant Pressure and Constant Flow tests) Load cell for Palltronic UpScale Manager system to upgrade P to F system UM01B IQ/OQ documents for UM01P PGGUMPD IQ/OQ documents for UM01F GGUMFD Design documentation package documents for Palltronic UpScale Manager (for UM01P and UM01F) GMPUM01 System Acceptance Test documents for Palltronic UpScale Manager (made to order — P or F system to be specified) GSUMD Paper Roll ACS0664BA
238 Pall Technical Services Pall Technical Services
With over 50 years of experience in separation Pall’s Total Fluid Management program technologies, and global reach, Pall provides a provides a full range of products, services and comprehensive range of technical and support to meet your fluid processing needs. consultative services: We maintain thirty five well equipped laboratories worldwide to help solve your • Validation of filtration processes filtration, separation and purification problems and provide access to more than four • Aseptic connector validation hundred trained Pall scientists and engineers, • Disposable systems validation as well as links with many specialists in industry and academia. • Validation of integrity test equipment
• Contamination analysis and control
• Process development and optimization
• Training
• Pre-inspection reviews
• Troubleshooting and consultancy services
• Qualification of integrity test equipment
• Contract technical services
240 Process-Specific Filter Validation
Pall fully appreciates the stringent The Filter Validation Package regulatory demands for filter validation The filter validation package will be tailored documentation in the BioPharmaceutical to meet your specific needs and may industry and maintains a comprehensive include some or all of the following: global filter validation service to help meet these demands. • Compatibility assessment Many of Pall’s Validation Laboratories are • Challenge viability study stand-alone facilities where specialists • Bacterial, mycoplasma, or working to GLP principles perform specific bacteriophage retention study customer tests. To date, in excess of 2000 customer validation studies have been • Extractables analysis completed in these facilities. • Evaluation of adsorptive effects First-time regulatory approval of the • Generation of product wet integrity filtration validation package is our mission. test data Pall’s close links with industry and We can also develop customized regulatory agencies ensure we can adhere microbiological procedures using your to current good manufacturing processes specific process isolates. and respond to the most recent regulatory guidelines. Prior to the start of any test, a protocol detailing the test methodology and Validation Objectives acceptance criteria will be issued for approval. To prove the suitability of the filter for a At the conclusion of testing, a process, the following questions must be comprehensive report including all answered: experimental data is provided. • Does the product affect the filter? • Does the filter affect the product? • Does the product affect microbial retention by the filter? To achieve these objectives, Pall uses a Parametric Approach to ensure that filter validation is performed taking into account all critical product attributes and process parameters. This is in line with regulatory expectations and the recommendations of PDA Technical Report 26.
241 Process-Specific Filter Validation Technical Specifications
Ordering Information Test Summary Test Requirements Part Numbers Compatibility Assessment To be suitable for use in the manufacture of a pharmaceutical drug product, a – Full process information PTS01CA filter cartridge must be both chemically and physically resistant to the process – Full product composition stream and operating conditions. Laboratory tests can be used to establish – Approximately 2000 mL of product chemical compatibility. Product Viability Study Many pharmaceutical products are bactericidal. This test verifies the survival – Full process information PTS01VA (Basic) capacity of the organism selected for microbial challenge testing, in the whole – Full product composition PTS01VB (Mid) product or a suitable product simulant, for the process time. – Approximately 200 mL of product PTS01VC (Complex) Microbial Retention Study This is to qualify the ability of the filter media to produce sterile filtrate in the – Full process information PTS01BA (Basic) process. A solution of the product or simulant will be inoculated with the – Full product composition PTS01BB (Mid) challenge organism at a concentration > 1 x 107 viable organisms/m2 of filter – Approximately 1000 mL of product PTS01BC (Complex) membrane area. The challenge is carried out on three filter membranes from different production batches, with at least one being at minimum specification. Extractables Analysis Both quantitative and qualitative information on extracted materials must be – Full process information PTS01EA (Generic) generated. Commonly, extractables cannot be evaluated directly in the actual – Full product composition PTS01EB (Laboratory tests) product, but a “Model Solvent” approach must be developed. The Pall Validation Laboratories use a filter cartridge tested with the appropriate “Model Solvent” to reproduce a worst case situation. Evaluation of Adsorptive Effects It is critical that filters are selected to minimize adsorption and loss of product – Full process information PTS01AA components. Laboratory scale tests can be used to generate adsorption – Full product composition profiles to help with filter selections and process qualification. – Approximately 1000 mL of product – Analytical test methods Generation of Product Wet Integrity Test Parameters Integrity tests performed on critical filters immediately before and after batch – Full product composition PTS01PA filtration confirm performance to specification. In order to optimize processing – Approximately 1000 mL of product it may be more convenient to integrity test the filter cartridge wet with the product. Pall Validation Services Groups can provide users with the integrity test data for these specific products.
Charges What’s the Next Step?
Wherever possible, we provide a fixed price in advance for the Contact your local Pall representative. They will discuss project. Where this is not possible, we will give an estimate to assist your specific requirements with you and forward your enquiry to you in budgeting and cost control. The final invoice gives details on Pall Validation Services Teams. We recommend you do this well in items such as labor, and materials. advance of a regulatory audit to ensure there is adequate time to generate appropriate test data.
242 Kleenpak™ Connector Validation
The Kleenpak aseptic connector Validation Objectives represents the latest in connection The objective is to prove the suitability of technology, allowing for the dry connection the Kleenpak connector for the selected of two separate fluid pathways while fluid transfer process by answering the maintaining the sterile integrity of both. following questions: Much of the validation of the Kleenpak connector can be applied generically and • Does the product affect the Kleenpak is provided in the product Validation Guide. connector? Users often supplement this data with • Does the Kleenpak connector affect application and product-specific validation the product? studies and training. Pall’s Aseptic Connector Validation Services aim to • Does the product affect the aseptic ensure a smooth implementation connection connector? without delay. Pall leverages its design knowledge of the The Kleenpak Connector Validation Kleenpak connector to ensure that these Services are an extension of the validation objectives are met by taking into established Pall Validation Services and are account all critical product attributes and an integral part of the user’s validation of process parameters. Pall disposable systems. The services are always backed by Pall’s expertise and The Validation Package scientific resources. The validation package will be tailored to Pall’s close links with the industry and the meet your specific needs and will include regulatory agencies ensure that your some or all of the following: protocols and documentation can adhere • Compatibility Assessment to current good manufacturing processes and respond to the most recent regulatory • Extractables Analysis guidelines. • Soiling Test Prior to the start of any test, a protocol detailing the test methodology and acceptance criteria will be submitted for approval. Upon completion of testing, a comprehensive report including all experimental data will be provided.
Male and Female Connector Assemblies prior to Connection
Collection Bag
Female Connector
Tubing
Supply Bag
Clamp Male Connector 243 Kleenpak Connector Validation Technical Specifications
Ordering Information Test Summary Part Numbers Compatibility Assessment The Kleenpak connector is considered compatible with a product if exposure under process conditions does not PTS01CG alter its ability to perform intended functions. Tests that evaluate the physical integrity of the Kleenpak connector, such as the pressure exposure test can be used to establish compatibility with specific product or process conditions. During the pressure exposure test, the connector is exposed to process pressure conditions for a suitable duration at process temperature. Dimensions are measured to verify conformance to specifications under process conditions. Soiling Test The soiling test was developed to evaluate the ability of the Kleenpak connector to produce a sterile fluid path after the protective peel-away strips of the male and female connectors have been intentionally contaminated with a Geobacillus stearothermophilius spore suspension. After the deliberate contamination, the connection is made and sterile trypticase soy broth (TSB) is passed through the connector to a collection container. The container is incubated and analyzed for contamination. The results of this soiling test are reported in the Validation Guide of the Kleenpak connector. Process-specific soiling tests can be developed and performed as below: Fluid specific: standard organism (Geobacillus stearothermophilius), specific product fluid PTS01SA Organism specific: process specific organism, standard fluid (TSB) PTS01SB Full process specific: process specific organism and fluid PTS01SC Extractables Analysis Extractables analysis can be performed on the Kleenpak connector by choosing suitable model solvents as the PTS01EJ extracting agent to represent a range of buffers, media and process fluids. Quantitative and qualitative analysis can be performed. TOC, pH value and conductivity can be determined as well.
Note: To ensure timely and accurate analytical work, Pall laboratories require complete information on product specification and process conditions such as pressure, temperature and duration before commencing analysis. Each of the validation projects also requires approximately 2000 – 3000 mL of product. Charges What’s the Next Step?
Wherever possible, we provide a fixed price in advance for the Contact your local Pall representative. They will discuss project. Where this is not possible, we will give an estimate to assist your specific requirements with you and forward your enquiry to you in budgeting and cost control. The final invoice gives details on Pall Validation Services Teams. We recommend you do this well in items such as labor, and materials. advance of a regulatory audit to ensure there is adequate time to generate appropriate test data.
244 Disposable Filtration System Validation
Disposable filtration systems typically Validation Services Available to a consist of disposable components such as Disposable System capsule filters, aseptic connectors, bags • Capsules and piping or tubing. As an integrator of disposable systems, Pall can provide Bacterial Challenge reliable validation assistance to the users of Compatibility disposable systems. Pall has the product knowledge and laboratory analytical Product Viability expertise to complete validation projects Product Wet Integrity Testing for disposable systems of a wide range of • System sizes and materials of construction. Pall's close link with industry and regulatory Extractables agencies ensures an up-to-date validation • Bags approach reflecting the latest thinking, thus achieving an effective and successful Extractables validation. Compatibility • Kleenpak Connector Approaches Extractables Analytical work can be performed for Compatibility individual components or to the entire disposable system. A model system is Case Study: used for the validation analysis. This model Extractables analysis for system is composed of the same materials disposable bags of construction as those of the user system and is assembled as it is used in process. Pall can perform analyses and provide If the actual system is sterilized by comprehensive reports on the quantification gamma-irradiation before use, then the test and identification of extractable materials is performed on an irradiated system. from a disposable system. The type and the amount of extractable material found In the case of extractables study, a model following storage of filled bags is typically solvent approach is used to select a included in these studies. The tests are suitable extracting solvent for analysis. done for real time storage, with interim tests For example, worst-case solvents can be performed for disposable systems that are selected to represent a range of buffers stored for extended periods of time. with varying pH values. For applications An appropriate storage temperature is used that involve a filter attached to a bag or a throughout the storage period. filter attached to a bag with an aseptic connector, the model solvent is filtered into A number of analytical methods can be the bag according to the specific process used to analyze the fluid after extraction. steps and then stored for the appropriate The selection of methods will depend on period. Typical models for buffer solutions the requirements of the application. include: water for injection (WFI) pH Examples of methods include: adjusted to > 9, < 9, and WFI at neutral pH • GC-MS or LC-MS (5 – 7). A similar approach can be used for • Total Organic Carbon (TOC) media and for product. • Particulate analysis • pH • Conductivity 245 Disposable Filtration System Validation Further Information
The Validation Package Charges
The validation package will be tailored to meet the client’s specific Wherever possible, we provide a fixed price in advance for the needs and will include some or all of the following evaluations project. Where this is not possible, we will give an estimate to assist depending on the disposable components being tested: you in budgeting and cost control. The final invoice gives details on items such as labor, and materials. • Compatibility Assessment
• Extractables Analysis What’s the Next Step? • Soiling Test Contact your local Pall representative. They will discuss • Bacterial Challenge your specific requirements with you and forward your enquiry to • Product wet integrity testing Pall Validation Services Teams. We recommend you do this well in advance of a regulatory audit to ensure there is adequate time to Prior to the start of any test, a protocol detailing the test methodology generate appropriate test data. and acceptance criteria will be submitted for approval. Upon completion of testing, a comprehensive report including all experimental data will be provided.
An Example of the Final Report
1. Introduction: An overview of the project and objectives of the project. 2. Summary: A description of the general experimental approach. 3. Methods: A description of the specific techniques used. 4. Results: Detailed data tables with explanations of data, as needed. 5. Discussion: An analysis of the data with conclusion for each test. 6. Appendices: Detailed explanation of test methods
Ordering Information Test Services Part Numbers Capsules Microbial Retention PTS01BA (Basic) PTS01BB (Mid) PTS01BC (Complex) PTS01BD (Cartridge challenge studies) PTS01BE (Process specific bacteria) PTS01BF (Cytotoxics)
Compatibility PTS01CA (Basic) PTS01CB (Complex)
Product Viability PTS01VA (Basic) PTS01VD (Process specific) PTS01VE (Cytotoxics)
Product-wet Integrity Test Parameters PTS01PA (One pressure source) PTS01PB (Two pressure sources) PTS01PC (Cytotoxics)
Extractables PTS01EA (Generic) PTS01EB (Lab tests) PTS01EC (Complex tests) Disposable Bags Extractables PTS01EH Compatibility PTS01CF Kleenpak Connectors Extractables PTS01EJ Compatibility PTS01CG Soiling tests (for details, see Kleenpak Connector Validation data sheet) PTS01SA (Fluid specific) PTS01SB (Organism specific) PTS01SC (Full process specific) System Extractables PTS01EK
246 Contamination Analysis
The presence of unexpected particulate or Particulate Contaminants microbial contaminants in process fluids Pall Life Sciences have available a wide can lead to system failure, batch range of microscopic and analytical reprocessing, or even batch rejection. equipment for the analysis of particulate It is critical that these contaminants be and/or amorphous contaminants including: quickly isolated and identified, so that • Optical microscopy possible sources can be traced and corrective actions applied to the process. • Scanning electron microscopy • X-Ray emission spectroscopy How Can Pall Help? • Computer-enhanced image analysis Pall has over fifty years experience in contamination analysis and control and Analysis of Process Bioburden offers a range of standard services for analysis of particulate and microbial The full quantification and identification of contaminants. natural process bioburden is of increasing regulatory interest. Some bacteria, when In the simplest form, we can often provide subjected to particular environmental the necessary advice and corrective conditions, are known to produce actions by telephone or via e-mail. particularly diminutive forms capable of Alternatively, samples can be sent to a Pall penetrating 0.2 µm sterilizing grade filter facility for analysis or we can sample on cartridges. site. These investigations will be fully A typical analysis procedure is as follows: documented and a technical report is supplied following conclusion of the test • Filter samples through 47 mm diameter work and process review, to ensure that analysis discs any change control is correctly managed • Place discs on nutrient agar plates and and implemented. incubate • Count colonies to quantify bioburden Microbiological Contaminants Strike out individual colony types The isolation and identification of microbio- • Examine colony morphology logical contaminants from process fluids • Gram stain and examine requires specialist laboratory facilities and microscopically expertise, all of which can be offered by Pall Life Sciences. • Perform biochemical tests to establish identity Typical microbiological studies include: • Document and report results • Total bacterial count • Bioburden analysis • Identification and review of process isolates
247 Contamination Analysis Further Information
Typical Investigation Procedure for SEM showing contamination retained by filter Particulate Contaminants in a Water System membrane Sample Points Set Up
Silt Density Index (SDI) Test Performed
Contaminant Collected
Chemical – Physical Analysis
Optical Microscopy Charges
Wherever possible, we provide a fixed price in advance for the project. Where this is not possible, we will give an estimate to assist Scanning Electron Microscopy with X-ray Emission Spectroscopy you in budgeting and cost control. The final invoice gives details on items such as labor, and materials.
What’s the Next Step? Final Report and Recommendations Simply contact your local Pall representative. They will discuss your specific requirements with you and forward your enquiry to Pall contamination analysis specialists.
Part Number Structure
PTS 04 **
Pall Technical Contamination Type of Services Analysis Analysis
Typical Part Number: PTS04AE Contamination analysis with scanning electron microscopy and XES
248 Process Development and Optimization
Pall has the capability to support our Typical Services Available customers in development of separation Services available as individual or and purification processes. Whether driving combined activities include: to bring new products to market or streamlining and troubleshooting existing • Membrane and module selection tests processes, Pall Life Sciences can provide • System-design optimization tests flexible solutions and high quality documentation to back it up. • Cleaning cycle development Pall specialists operating in the field can • Analytical services quickly access dedicated Pall • Qualification of disposable process technologists, equipment, and laboratories for services ranging from simple advice to • Process modelling pilot investigations or full detailed research • Systems design proposals. • Inspection and report Unit Operations for an Integrated • Engineering services for vessels and Process pipework
Since Pall is the largest provider of separation and purification media, hardware and both automated and disposable systems, we are uniquely positioned to quickly optimize solutions for each customer. The technologies upon which we focus include: • Direct flow depth and membrane filtration • Tangential (cross) flow membrane filtration • Dynamic membrane separations • Membrane chromatography • Coalescing filters • Specialized R&D processes (for example, novel uses of membranes for affinity based separation techniques) • Water treatment and purification equipment In addition to the above, and for the purpose of process integration, we have established links to a wide range of other suppliers who can provide support for implementation of complementary technologies.
249 Process Development and Optimization Further Information
Facilities Charges
Pall's Scientific and Laboratory Services (SLS) is represented by thirty Each project is assessed individually. Wherever possible, we provide a five laboratory facilities at strategic locations world-wide. Many of fixed price in advance. Where this is not possible, we will offer an these laboratories have their own process wet test area where estimate to assist you in budgeting and cost control. customer fluids or simulated products can be tested. Equipment can The final invoice gives details on items such as labor, and materials. also be rented for trials. This laboratory network is backed by specific centers of expertise in What’s the Next Step? downstream processing and has direct access to core R&D centers where more advanced customer liaison. Contact your local Pall representatives. They will discuss your specific requirements with you and forward your enquiry to Pall technical In response to the increasing importance of biotechnology processes specialists. and products, specialized biologics laboratories have been created in Portsmouth (UK) and in Florida and New York (USA). Capabilities include mammalian cell culture and bacterial fermentation with qualification to handle genetically modified organisms to Class 2, equipment for optimization of downstream processes including membrane chromatography, development of disposable systems, and many aspects of bioanalytical support.
Time is Valuable
Pall recognizes customers’ increasing requirement to reduce the time to take products to market. Pall has over 50 years of innovation and development experience with proven solutions, for membrane purification and separation. Whether it is direct flow filtration, tangential flow filtration, chromatography or disposable systems, Pall can deploy a range of scalable and reproducible products for every application. This is backed with the capability to provide complete documentation for every test protocol or complete unit operation. Delegating process development to Pall technologists can substantially reduce process-development time.
Part Number Structure
PTS 07 **
Pall Technical Process Type of Services Development Work
Typical Part Number: PTS07AA Process development involving membrane/module selection tests
250 Training
Effective training of personnel at all levels is Features and Benefits important for maintaining a profitable Benefits of Pall’s training courses: operation and meeting the needs of regulatory authorities. For example, lack of • Courses designed and led by experts qualified training can and has resulted in • Each course customized to ensure manufacturers being issued with warning maximum relevance to your operation letters by the FDA. • Optimum use of training budgets International GMP regulations state that personnel should receive training • Can be held locally or at Pall’s appropriate to the duties assigned to them specialized facilities and continuing training should be given. Training Course Topics
Pall Life Sciences Technical Group Topics most commonly covered are: Training is given by experts in filtration • Introduction to filtration processes who have extensive experience • Filter system operation in applications in pharmaceutical manufacturing operations and awareness • Integrity testing of the latest regulatory expectations. • Filter validation and regulatory They are able to provide a range of training requirements courses to ensure operators and managers attain the optimum level of competence in • Introduction to separation technology all filtration and separation disciplines. • Operation of downstream processing systems Customized Training Courses • Basic or advanced tangential flow To ensure that the training is relevant to filtration your operation and provides value for We can also work with your local training money, courses can be customized to department to develop a course that meet each client's specified needs. meets any requirement you have. Information on theory and application is carefully balanced to keep the content interesting. Courses are designed to ensure maximum participation by the trainees, and, where appropriate, practical exercises can be introduced. Depending on your requirements, courses can be arranged at (or near) the site of operation or at one of Pall’s specialized training facilities.
251 Training Example Training Courses
Introduction to Integrity Testing Filter Validation and Regulatory Requirements
Who should attend Who should attend Operators, supervisors and managers requiring a working knowledge Key personnel from Quality Assurance, Regulatory Compliance, of integrity testing. Technical Support, R&D and Manufacturing Departments. Course Objectives Course Objectives To ensure attendees: Provide those who have a responsibility for ensuring that the sterilizing filtration process meets current regulatory requirements, • Understand the importance of testing critical filters with the knowledge they require to review and improve existing • Understand how the theory and practice of the range of available procedures. integrity tests differ Course Content • Have practical experience of operating manual and automatic • Core validation, continuous validation and process specific integrity test devices validation — how they differ Course Content • Recent changes in regulatory requirements • Destructive versus non-destructive tests • Current regulatory requirements • Different non-destructive methods: Forward Flow, Bubble Point, • Documentation requirements and Water Intrusion Tests • Practical approaches to process validation • Regulatory requirements Course Duration • Correlation of integrity tests to filter performance 1 Typically ⁄2 day • Operating manual and automated test devices Location Course Duration On site or at Pall's local training facility Typically 1 day
Location Charges On-site or at Pall’s local training facility Wherever possible, we provide a fixed price in advance based on course requirements. Where this is not possible, we will an estimate to assist you in budgeting and cost control. The final invoice gives details on items such as labor and materials. For more information and to discuss your training requirements, please contact your local Pall Life Sciences representative.
Part Number Structure
PTS 03 **
Pall Technical Training Type of Services Services Training
Typical Part Number: PTS03AA Training on the basic principles of filtration for a half day at customer site
252 Pre-Inspection Reviews
Filtration is often seen as a critical process Features and Benefits in the manufacture of pharmaceutical • Reviews are carried out by experts in products, especially if the filter is used filtration processes to: towards the end of the production process. Therefore regulatory authorities Ensure that users are employing the often review and inspect the equipment, most suitable filtration system and procedures, and documentation optimal procedures are employed associated with users’ filtration processes. Reduce risk of adverse reports from regulatory inspections Pre-Inspection Reviews Give personnel more time to focus on Pall Life Sciences can assist you in being other critical activities fully prepared for inspections by both • The Pre-inspection review is internal and external auditors by offering accompanied by a report containing pre-inspection reviews. This includes a recommendations of corrective actions review of the process, procedures, and documentation. Where appropriate, we Ensures that the pharmaceutical provide recommendations of additional manufacturer has time to implement work required. suggested changes prior to regulatory inspection Pall Life Sciences Technical • Support for implementing corrective Services actions and process improvements
Pre-inspection reviews* are carried out by Vital help where resources are short experts in filtration applications who have or required elsewhere extensive experience with of applications in • Review ensures all filters are optimal for pharmaceutical manufacturing operations each specific application and are familiar with the key regulatory expectations. The reviewers spend time Minimizes operating costs and risk of on-site with operators and managers to process failures assess key areas such as: * The review of filtration processes is a comprehensive technical assessment of these areas. It is the user’s • Technical data responsibility to ensure that all aspects critical to regulatory compliance are assessed in preparation for • Validation data inspection. • Filter selection • Product certification • System design • Operating procedures • Sterilization procedures • Integrity testing practice
253 Pre-Inspection Reviews Technical Data and Filter Selection
Regulatory authorities will expect BioPharmaceutical manufacturers to Operating and Sterilization Procedures understand the technical specifications of the filters that they use and Processing limits for critical filters (temperature and pressure, for to be able to justify that each filter is appropriate for the process. example) are provided by Pall in its technical documentation. It is Pall specialists will: necessary to understand how these limits relate to the process in • Document all the filters you use, by part number and application which the filter is being used. This is important to avoid damage to the filter and possible adverse effects on the product being • Assess whether the filters are suitable for the operation in which processed. This therefore can form part of a regulatory authority they are being used audit. • Ensure you have key technical data and filter qualification reports Our experts will review the types of filters being used, review the available in a form ready for audit processes being operated, and review the documentation supporting the processes. We will then detail any improvements recommended Validation Data and, if requested, will help with the rewriting of documents such as Regulatory authorities expect that the users of sterilizing-grade filters Standard Operating Procedures. have assessed and confirmed that: Integrity Testing Procedures • The filter does not alter the product adversely • The product does not affect the filter adversely Integrity testing is a mandatory requirement for critical production filters. Regulatory audits would normally include a review of: • The process conditions do not affect the filter adversely • Integrity test method employed This usually involves a range of process simulation tests involving techniques such as bacterial retention, extractables analysis, active • Test parameters ingredient adsorption etc. • Temperature range We will advise you of the current filter validation requirements as part • Integrity test equipment used of the review, assess your current documentation, and recommend • Documentation available to support test instruments any additional testing. We review all these areas and can recommend possible Product Certification improvements.
Where Pall filters are supplied for critical processes they are Charges supported by a manufacturer's certificate of test. Regulatory authorities expect this certificate to be checked before the filter is Wherever possible, we provide a fixed price in advance for the used and referenced in batch documentation. As part of the pre- project. Where this is not possible, we will give an estimate to assist inspection review, we will ensure the user understands the data you in budgeting and cost control. supplied and discuss how it should best be used. The final invoice gives details on items such as labor, and materials
What’s the Next Step?
Simply contact your local Pall representatives. They will then discuss Part Number Structure your specific requirements with you and forward your enquiry to Pall technical specialists. We recommend you do this well in advance of a regulatory audit to ensure there is adequate time to review all the key PTS 05 ** areas and put into place any corrective actions.
Pall Technical Pre-inspection Type of Services Review Review
Typical Part Number: PTS05AA Pre-inspection review for one day
254 Filter Integrity Test Equipment Validation
Filter integrity testing can be one of the 2. Alternatively, all OQ tests in the form of most critical procedures in a filtration a standard system acceptance test process and may be an essential (SAT) can be performed on your requirement for batch release of a product. specific instrument. A customized SAT The increasing requirement for accuracy protocol can also be prepared for you if and documentation has resulted in a wider required. use of automated integrity test equipment. Performance Qualification PQ Use of such equipment must be validated We can also assist in generating to ensure that it satisfies both process and customized PQ protocols and, if required, regulatory requirements. perform the tests.
How Can Pall Assist? Features and Benefits
Expertise • Pall’s expertise ensures instrument We have over twenty years experience in validation of your integrity test the design, manufacture and qualification instruments will meet the latest industry of Palltronic integrity test equipment. and regulatory requirements Time and cost saving • All materials, measuring equipment and Our approach to instrument validation labor supplied by Pall for trouble-free minimizes time and costs. testing Quite simply, we make instrument • Completed GAMP OQ1 document on validation, IQ, OQ and PQ easier for reference instruments saves time and you. costs • Tests can be performed on-site or Validation Tests off-site for maximum flexibility Installation Qualification IQ • The ultimate benefit to you is a faster We check all the equipment components and more secure validation process to and documentation. The suitability of the meet regulatory requirements testing environment and services are also * Good Automated Manufacturing Practice guidelines checked if the instrument is qualified on issued by the GAMP Forum and ISPE. your site. Operational Qualification OQ We offer two options. 1. GAMP* guidelines state that the OQ of standard instruments such as integrity test units can be divided into two parts. A completed OQ1 containing extensive qualification studies on a reference instrument. A shorter OQ2 protocol on your specific instrument is then performed, saving both time and cost.
255 Filter Integrity Test Equipment Validation Further Information
Where are Tests Performed? Documentation
At a Pall site Standard Qualification and Validation Documents We perform the tests in our purpose-designed laboratories. Standard protocols for IQ/OQ2 or SAT can be purchased from Pall. If required, you can view the testing. Completed OQ1 documents are also available together with validation support documentation based on GAMP guidelines. On your site We set up and perform the tests at your location. Customized Protocols We work closely with your personnel to ensure that the format and Equipment and Materials content of customized protocols meet your requirements.
We have all the necessary equipment to ensure that qualification tests Reports are performed accurately and reliably. We also supply materials such On completion of the tests, the final reports are reviewed, approved as filters. This capability means that we can offer a fast, professional and signed by a competent Pall specialist. The full documentation is and cost-effective service. then submitted to you for approval.
Range of Qualification Service Charges
The service covers the Palltronic Flowstar and Palltronic AquaWIT In most cases, we can provide a fixed price in advance for the instruments. Specialized versions of these instruments can also be service. qualified as appropriate. For some special requirements, we provide an estimate to assist you in budgeting and cost control. The final invoice will itemize actual costs including labor and materials.
Part Number Structure
PTS 02 **
Pall Technical Qualification of Test Type of Services Equipment Qualification
Typical Part Number: PTS02AB IQ/OQ2 Qualification at Pall Site
256 Troubleshooting and Consultancy Services
Filtration, separation, and purification We can develop with you intranet/internet systems, when correctly designed and systems to assist troubleshooting and installed, should operate successfully information exchange without problems. Even the best systems, however, may be Features and Benefits affected by unpredictable events such as • An approach to troubleshooting that is variations in the quality of process fluid or quick and cost effective environmental factors — and often at the most critical time. Such events can result • A unique consultancy service that can in costly down-time or even loss of a achieve improved process efficiency product batch. and cost savings In addition, continuous improvement is a • A global capability that ensures local necessary requirement today, with support when and where you need it increasing pressure on process efficiency and costs. Whether your needs are for Typical Projects troubleshooting or process improvements, • Plant filtration surveys Pall Life Sciences’ specialized advice and expect troubleshooting experts can bring • Improved life of filtration system significant benefits and cost savings. • Investigating non-sterility in a sterile filtration process What Can Pall Offer? • Evaluation of integrity test methodology A unique and cost-effective • Variable product activity after troubleshooting and consultancy service purification based on: • Poor separation of protein components • More than fifty years experience in • Reduction of endotoxin contamination process separation systems in final product • A capability and response unparalleled • Malfunction of control sensor in process in the filtration and separations field • Improved steam-in-place procedures How Can Pall Solve Your • Filter steaming process validation Problems? • Scale-up of processes Our specialists provide the best available professional advice to ensure a rapid and effective investigation. We have state-of-the art equipment to assist in problem solving and process monitoring. Our worldwide laboratories offer analytical services for the widest range of fluids. Our specialists can visit your site to review the process in more detail and to perform studies locally.
257 Troubleshooting and Consultancy Services Further Information
Facilities In all cases, the report will be reviewed, approved and signed by the Pall specialist. You may choose to countersign the document as Laboratories confirmation of receipt and acceptability of content. We maintain thirty five laboratories well equipped worldwide to help Our aim is to ensure not only that your problems are resolved or solve your filtration, separation, and purification problems processes improved, but that the investigations are fully documented People and comply with appropriate manufacturing practices. We are a network of more than four hundred trained scientists within If required, we will present the basis of the report in a formal meeting Pall as well as links with many specialists in industry and academia. with you. Equipment Our equipment includes scanning electron microscopy, HPLC, mass Charges spectrometry, TOC analysis, FTIR spectroscopy, GC, filterability kits, The variable nature of troubleshooting and consultancy work means integrity test units…and many more. that we have to assess projects individually. Wherever possible, we Databases provide a fixed price in advance. Where this is not possible, we will We maintain a comprehensive range of internal databases for give an estimate to assist you in budgeting and cost control. troubleshooting. We also subscribe to external databases to ensure The final invoice gives details on items such as labor, and materials. the broadest capability and fastest response. Communications What’s the Next Step? We operate a Lotus Notes and Intranet system to ensure fast and Contact your local Pall representatives. They will discuss your specific efficient communications worldwide twenty four hours a day. requirements with you and forward your enquiry to Pall technical Documentation specialists. Our investigations are fully documented in the form of a technical report. This report can be of special importance in regulatory audits and in management of change control. The report can be prepared to your specific format, if required, to maintain consistency within your documentation.
Part Number Structure
PTS 06 **
Pall Technical Consultancy and Type of Services Troubleshooting Service
Typical Part Number: PTS06AB Consultancy work for two days
258 Systems Systems
Pall’s capabilities include a variety of system solutions using the full range of technologies described in this catalog.
From manual to fully automated, from stand-alone packages to fully integrated total processes and from single-use plastic to long life fully validated cleanable stainless steel hardware fit for biopharmaceutical, biological, and chemical pharmaceutical demands.
Details on standard TFF systems can be found in the Tangential Flow Filtration section and details on chromatography systems can be found in the Chromatography section. Other systems are described in the Systems section.
Additional information on fully integrated or customized processes to meet any demand are available on request.
260 Pall Process Engineered Systems Automated Separation and Purification Systems
The requirements for a new process are Expert Application Knowledge for seldom the same. Therefore, we begin Our Customers each enquiry with a project review based Pall has a large multi-disciplinary team of on the individual requirements. engineers and scientists with in-depth Our product portfolio and technology knowledge of applications and operating platform is comprehensive and allows us to parameters for separation systems in always offer the best technical approach biological, BioPharmaceutical and chemical for each application. We use proven processes. Operating within the PASS (Pall features, proven designs and proven Advanced separations Systems) group for packages wherever appropriate. projects and within the SLS (Scientific and Laboratory Services) and R&D Short Timescales — Best Results organizations for longer term development and analysis, they enhance the total The time-span from drug development to package for process development and market introduction is crucial for advanced solutions. commercial success. with our extensive experience and production capabilities, pall can help to keep this time to a minimum. GMP and GAMP Approach our project teams focus on your We manage our projects and design our requirements and directly interlink with your systems in accordance with industry team over the whole project from guidelines to ensure customer and specification to commissioning. This regulatory requirements are met. approach helps to build each system to The GMP requirements on validation and your user documentation in the shortest documentation for automated systems in possible time. BioPharmaceutical production are defined in Annex 15 of the EC Guide to Good Process Automation for Cost Manufacturing Practice of Drug Products Savings and in other international regulatory With GMP and documentation guidelines. For the US market, 21 CFR requirements increasing, process Part 11 further influences the design of automation is a good investment to electronic recording systems. In addition, optimize overall production costs: the ISPE Forum has published its Less operator interference makes comprehensive GAMP Guide to create a processes run smoothly, validation easier common project design approach for and with minimum downtime. industry users and vendors, from a formal user requirement Pall’s automation solutions are designed for specification to system commissioning and process integration and interfacing, in ongoing maintenance of a validated compliance with 21 CFR 11, from simple system. The ASME Bioprocessing and data logging to full batch records with European (EHEDG) guidelines are also electronic signatures. important reference points for specific equipment.
261 Pall Process Engineered Systems
Over and above these general guidelines, Pall brings its long-standing experience in design and manufacture of purification and separation
systems for GMP applications. This unique combination of experience Enquiry or in implementation of sanitary design and regulatory requirements Tender together with process technology know-how provides reassurance of Early Process & Initial System Design In Depth System Engineering Design & Accurate Budget & Process Design our ability to meet quality targets. Technical Review Cost Submittal Review
Process During the whole qualification phase of a new project, Pall is ready Development and willing to provide support services. we routinely provide a clear
Final System Design Regular Project understanding of the scope of responsibilities, develop formal Contract Review & Fixed Price Review & Update Meeting validation plans and are prepared to assist with all stages of Submittal Meetings, Reports qualification from factory acceptance through to site installation. When in operation, your Pall system can be monitored continuously
to predefined parameters and all relevant process data logged in a System FAT Delivery & SAT comprehensive batch record file to assure the consistency of your (Factory Acceptance (Site Acceptance Ongoing Support Test) Test) process in accordance with cGMP criteria.
Customer Support
Pall is organized functionally and geographically to give us the closest link to our customers and fastest response times.
Pall Advanced Separation System Retirement Pall Advanced Separation Systems (PASS) is the applications, engineering and procurement entity for Pall’s global process Operation & Planning Maintenance systems business. To successfully deliver integrated solutions that meet industry and customer requirements this group has Process Performance excellence in: Requirement Qualification • Process system design Verifies • project management Equipment Control Operational URS System URS Qualification • Systems fabrication • Documentation GxP and Installation Safety Review Qualification • Risk analysis • Validation/qualification • Installation support Equipment FS Control Operational System FS Check • Operator training • After-market service Mechanical and Operating Control Installation Electrical Design Interface Design System Design Check • Service contracts
FAT & SAT • Spare parts provision
Module Integration and Design Review and Approval Development Testing
Mechanical and Electrical Build
Operating Interface Build
Control System Programming
GMP and GAMP Approach 262 DGM Plate and Frame Filter Systems
With the Membraplan® DGM filter press Features and Benefits system, a new generation of sheet filters • Totally enclosed sheet filter system was developed, setting new standards for eliminating undesirable product loss modern pharmaceutical and biotechnological production. It can be used • Enclosed design allows for CIP cleaning for a wide range of applications from initial and SIP* sterilization cell harvest to down stream clarification • Mechanical dehydration (DGM) ensures steps. higher yield and reduction of residual The Membraplan DGM is a multiple sheet moisture in the filter cake filter for filtration with depth filter sheets. It • Mechanical dehydration (DGM) allows is the first system of its kind allowing for Above: DGM Filter Plates for a dry compact cake in a short time complete CIP cleaning and sterilization and when compared to typical gas drying thus meeting all requirements for pharmaceutical equipment. • Utilizes standard depth filter sheets for maximum selectivity The key to the success of the Membraplan DGM lies in the unique • Sizes from 300 x 300 mm (11.8 x design of the filter plates. Each filter plate is 11.8 in.) to 1000 x 1000 mm (39.3 x sealed with an O-ring at the outer edge of 39.3 in.) for maximum scalability the plate. This allows for zero leakage from • Cake washing plates available for the filter press during processing and CIP maximum product recovery cleaning and eliminates any product • Can be equipped with automatic plate contact with the surrounding environment. shifters and cleaning portals for The Membraplan DGM is available as a 800 x 800 mm (31.4 x 31.4 in.) and plate and frame (DG) or as a plate and 1000 x 1000 mm (39.3 x 39.3 in.) frame with mechanical dehydration (DGM) designs design. The DGM version allows for • Filter plate and frames materials in USP mechanical squeezing of the filter cake certified polypropylene or 316 stainless with an elastic membrane thus increasing steel yields by reduction of moisture in the solids. This results in a dry and compact * (Stainless steel version only). filter cake, which can be easily removed from the frame.
263 DGM Plate and Frame Filter Systems Technical Specifications
Applications
• Plasma fractionation • Cell harvest • Clarification of therapeutical proteins, vaccines, diagnostics, enzymes, and antibiotics • Removal of activated carbon • Activated carbon filter • Removal of filter aids • Removal of catalysts Due to the enclosed design of the Membraplan DGM, for the first time a complete CIP cleaning can be carried out, which — in combination with manual precleaning-guarantees the reproducibility of the cleaning method by the FDA Inspection Guide on Cleaning Validation. The filer plate design was specially developed for strict requirements on hygiene and cleanliness in the biotechnological and pharmaceutical industry taking the recommendations and regulations of FDA, GMP and 3-A into consideration. Closing of the filter pack is carried out via hydraulic cylinder with mechanical locking. The pneumatically operated hydraulics are installed on the cross member and are explosion proof as standard (no electrical components).
Technical Specifications Membraplan DGM DG Filter Press DGM Plate and Frame Size 300 = 300 x 300 mm 600 = 600 x 600 mm (11.8 x 11.8 in.) (23.6 x 23.6 in.) 400 = 400 x 400 mm 800 = 800 x 800 mm (1.7 x 15.7 in.) (31.4 x 31.4 in.) 1000 = 1000 x 1000 mm (39.3 x 39.3 in.)
Materials K = Polypropylene P = Stainless Steel
Chassis Size 30 60 50 100 150 200
Note: Please contact Pall Corporation for additional technical information for sizing and selection of the correct Membraplan DGM filter press system.
264 ZHF Centrifugal Discharge Filter System
The ZHF centrifugal discharge filter is a • No emissions due to enclosed system totally enclosed filter that is designed for • Cake-washing possible automatic discharge of filter cake by rotation of the filter bundle. • Filter elements can be equipped with different types of septums ZHF filters are used for filtrate and or cake recovery. The filter solids can be treated • Available with lip seals or mechanical (washed, dried, extracted) in place within seals the filter. Solids are then discharged using an integral mechanical discharge aid as a Applications dry cake or as a slurry. The ZHF filter can • Activated carbon recovery be operated with or without filter aids depending on the characteristics of the • Activated carbon filter cake being developed. • Precious metal catalyst recovery Sizes are available from 0.3 m2 – 150 m2 of • Enzyme clarification filter area and are available in 316, 316L • Cell harvest and 904 L stainless steel and Hastelloy C construction. Complete systems are available for automation of the entire ZHF filter plant.
Advantages
• Totally enclosed system for safe operation • Short down time by automatic discharge of filter cake • Even distribution of filter cake by the horizontal filter element arrangement • Easy installation and reduced filter height due to bottom mounted filter drives • Minimal liquid phase loss due to recovery via scavenge filtration system • Easy assembly and low maintenance using wearing sleeves on all dynamic seal areas • Seals and bearing can be changed without removing the filter internals • Filtration possible with or without use of filter aids
265 ZHF Centrifugal Discharge Filter System Technical Specifications
Ordering Information
Filter Type Number of Filter Area of Number of Scavenge Scavenge Total Theoretical Filter Elements Main Elements Filter Elements Filter Area Filter Area Cake Volume ZHF-SR 2.5 13 2.2 m2 (23.6 ft2) 2 0.35 m2 (3.76 ft2) 2.55 m2 (27.4 ft2)70 L ZHF-SR 5.0 10 4.7 m2 (50.5 ft2) 2 0.94 m2 (10.11 ft2) 5.64 m2 (60.7 ft2) 170 L ZHF-SR 10 21 9.87 m2 (106.2 ft2) 2 0.94 m2 (10.11 ft2) 10.81 m2 (116.3 ft2) 300 L ZHF-SR 15 32 15.04 m2 (161.8 ft2) 2 0.94 m2 (10.11 ft2) 15.98 m2 (172.0 ft2) 450 L ZHF-SR 20 28 19.88 m2 ((213.9 ft2) 2 1.42 m2 (15.2 ft2) 21.3 m2 (229.2 ft2) 600 L ZHF-SR 25 35 24.85 m2 (267.4 ft2) 2 1.42 m2 (15.2 ft2) 26.27 m2 (282.7 ft2) 760 L ZHF-SR 30 28 30.1 m2 (323.9 ft2) 3 2.1 m2 (22.6 ft2) 32.2 m2 (346.5 ft2) 900 L ZHF-SR 40 37 39.77 m2 (428.0 ft2) 4 2.8 m2 (30.1 ft2) 42.57 m2 (458.2 ft2) 1200 L ZHF-SR 50 47 50.52 m2 (543.7 ft2) 4 2.8 m2 (30.1 ft2) 53.32 m2 (573.9 ft2) 1500 L ZHF-SR 60 55 59.12 m2 (636.6 ft2) 5 3.5 m2 (37.6 ft2) 62.62 m2 (674.0 ft2) 1800 L ZHF-SR 80 61 64.66 m2 (695.9 ft2) 6 4.2 m2 (45.2 ft2) 68.86 m2 (741.2 ft2) 1900 L ZHF-SR 90 72 76.32 m2 (821.5 ft2) 6 4.2 m2 (45.2 ft2) 80.52 m2 (866.7 ft2) 2300 L ZHF-SR 100 81 85.86 m2 (924.2 ft2) 7 6.36 m2 (68.4 ft2) 92.22 m2 (992.6 ft2) 2600 L ZHF-SR 110 59 97.35 m2 (1047.8 ft2) 6 6.36 m2 (68.4 ft2) 103.71 m2 (1116.3 ft2) 2900 L ZHF-SR 130 69 113.85 m2 (1225.4 ft2) 6 6.36 m2 (68.4 ft2) 120.21 m2 (1293.9 ft2) 3400 L ZHF-SR 150 77 123.2 m2 (1326.1 ft2) 7 7.21 m2 (77.6 ft2) 130.41 m2 (1403.7 ft2) 3700 L Note: Maximum usable volume is 2/3 of theoretical volume.
266 PEF Multi Purpose Processor
Equipment Features and Benefits
The PEF Multiprocessor is unique • Combines multi-processes into one processor that all allows for reaction and piece of equipment (reaction and mixing, crystallization, filtration and mixing, crystallization, filtration and cake-drying all in one piece of equipment. drying) It is essentially a pivoted pressure vessel • Optimized drying due to efficient design suspended in a frame. The vessel can be heated or cooled and is fitted with a filter • Excellent agitation and mixing septum over its base. properties due to special agitator design The vessel is fitted with a reversible and retractable agitator equipped with a • Maximum removal of solids specially designed stirring arm. With the • Low contamination with no product hydro-mechanically operated pivoted transfers between steps system using integral safety brake, the • Filter septum acts as dust filter during vessel can be smoothly and infinitely drying variable swung into the required position. To change the filter media or any worn • Fully automatic process possible parts, the filter base can be hydraulically • IP cleanable (all instruments and valves lowered and swung on its hinge for access included) — turn-key unit) to the filter internals. All operating and control gear is grouped for easy access on the main frame panel. The solid discharge port is positioned to suit different requirements.
267 PEF Multi Purpose Processor Technical Specifications
Possibilities in Filter Position Possibilities in Reactor Position
• Receive slurries • Receive slurries • Filter • Receive solutions • Smooth/dewater cake • Discharge slurries • Wash cake • Discharge solutions • Plough cake • Prepare solutions • Re-slurry cake • Crystallize or precipitate slurries • Dissolve cake • Reactions • Evaporations Basic Chemical Methodology • Dry solids 1. Reaction (including dissolutions) • Discharge solids 2. Crystallization (including precipitations) 3. Transfers Comparison between a Multi-purpose Processor and Filter Dryer 4. Filtration 1. Enlarged heat exchange area — reduction of drying time of up to 5. Slurry 80 % 6. Drying 2. More complete discharge 7. Sieving, grinding and blending 3. All process steps can be carried out in one unit A Multi-purpose processor is the only single piece of equipment that 4. No dust filter necessary — filter medium acts as dust filter can perform steps 1 to 6 and is excellent at all 7. 5. Drying is not done on the filter media — no blocking 6. Special designed agitator with helix — excellent mixing and blending properties
Technical Specifications Materials Stainless steel, Hastelloy, Titanium Pressure Rating Up to 6 bar (higher pressures upon request)
Sizes and Materials
Type Filter Area Effective Filter Cake Filter Cake Stirrer Est. Con. Weight Dimensions Volume Volume Height (rpm) Load (KW) Empty (t) (L x W x H)
450 0.15 m2 120 L 30 L 200 mm 5 – 26 2.2 1.1 1800 x 1420 x 2800 mm (1.61 ft2) (7.87 in.) (71 x 56 x 110 in.)
600 0.26 m2 250 L 65 L 250 mm 5 – 28 8.0 1.9 2860 x 1720 x 2760 mm (2.80 ft2) (9.84in.) (112 x 68 x 109 in.)
800 0.48 m2 550 L 120 L 250 mm 5 – 28 9.5 2.9 3260 x 1920 x 3500 mm (5.17 ft2) (9.84 in.) (128 x 76 x 138 in.)
1000 0.78 m2 850 L 234 L 300 mm 2.5 – 22 15.5 3.4 4160 x 2200 x 3580 mm (8.40 ft2) (11.8 in.) (164 x 87 x 141 in.)
1250 1.2 m2 1300 L 420 L 350 mm 2 – 15 15.5 6.5 4215 x 2000 x 3700 mm (12.9 ft2) (13.8 in.) (166 x 79 x 146 in.)
1600 2.0 m2 2300 L 840 L 420 mm 2 – 15 23.0 9.6 4110 x 2500 x 4380 mm (21.5 ft2) (16.5 in.) (162 x 98 x 172 in.)
2000 3.0 m2 3800 L 1260 L 420 mm 2 – 12 36.0 12.7 4900 x 2820 x 5000 mm (32.3 ft2) (16.5 in.) (193 x 111 x 197 in.)
268 Water Systems
Pall’s high-purity water systems are Microfiltration designed to comply with international Crossflow microfiltration (MF) is a highly codes and regulations governing medicinal efficient way to remove small suspended product manufacture referred to in various solids, large colloids, and micro-organisms regional Pharmacopeia as, for example, from large volumes of water. USP, EP, and JP. These regulations specify standards of purity for a number of waters New generations of membranes in robust including Purified Water, Highly Purified materials and large area format, which are Water, and Water For Injection. These unique to Pall, provide excellent economy waters are used in the preparation of and exceptionally stable performance compendial doseage forms in a variety of independent of variability in feed water. applications from bulk primary processing, Operating pressures are lower than UF media make up, equipment and container (typically 1 to 2 bar) and the systems use rinsing to use in final formulations. Controls backwash and air scrubbing techniques to include microbial and total organic carbon Top: Aria Microfiltration System minimize requirements for chemical (TOC) and in the latter cases, endotoxin. Bottom: USP 24-WFI System regeneration. Non-compendial water used in • Removes turbidity, suspended solids, pharmaceutical processing must also meet bioburden specified criteria. This water may be used applied in early stages of synthesis or • Reduces silt density index (SDI) to cleaning and as the feedwater to high protect RO/NF and ion exchange purity water treatment systems. Typically • Compatible with chlorine and other this water must meet at least potable chemicals which may be present in (drinking water) standards and usually has feed additional limits specified (for example • Minimal waste stream hardness, silica, total bacteria count). • Low operating cost Pretreatment • Stable filtrate and low chemical compared to multimedia filters Raw water supply varies in quality. Typical impurities which need to be reduced or controlled include Ultrafiltration • Particulates Ultrafiltration membranes, when incorporated in our systems, retain • Inorganics particles, bacteria, viruses, pyrogens • Micro organisms (endotoxins), colloids and large organic • Dissolved gases molecules. Dissolved salts and smaller organic molecules pass freely through • Organic compounds these systems. A wide variety of Pretreatment reduces the effect of potential proprietary membranes are available to variations in feedwater quality, minimizing Pall, but the two most common the operating and maintenance applications for pharmaceutical water requirements in the final treatment stages. processing are in pretreatment (eg colloid Typically it has little effect on some removal) and for pyrogen control in both parameters indicative of final water quality low and high temperature distribution using such as anions, total bacteria count, TOC both hollow fiber and ceramic and volatile components but pretreatment technologies. must be effective to minimize plant operating costs. 269 Water Systems
Full process review and skilled design optimization mean that Pall can Other important features of Pall’s high purity water systems include, apply UF in its systems with considerable advantages to end-users. according to process requirements, ozone dosing, ultraviolet (UV) treatment, carbon filters, ion exchange (softeners) and chemical Benefits include dosing. Pall’s own cartridge filters are also employed to protect tank • Excellent protection when used in prefiltration vents, and as highly effective prefiltration or point-of-use guard filters. • Steam in place options available for pyrogen applications Storage and Distribution • Sanitary and cleanable designs where required in final processing Total system design ensures that water is purified, stored and Reverse Osmosis distributed with quality maintained to specification all the way. Tank designs take into account sizing, choice of material and microbiogical Reverse osmosis (RO) is the finest level of membrane separation in considerations. Additional components such as heat exchangers, liquids. The RO membranes used in Pall systems act as an efficient filters, UV, ozone and point-of-use valves are selected on technical barrier to all dissolved salts and inorganic molecules as well as most merit, simplicity, efficiency and cost effective maintenance. Loop organic compounds (organics typically greater than 100 Daltons in pressure and flow rates are carefully designed and controlled to meet molecular weight). microbiological and safety considerations. Water passes freely through, while salts are rejected typically from 98% to over 99%. Microbiological Protection
Pall has optimized the pretreatment, design and staging of RO High quality water has to be properly handled and protected from systems in single or multipass arrangements for stable and low contamination right up to point-of-use. fouling performance and for extremely high recovery (water conversion) rates without the use of chemicals. The hydrophobic vent filters in Pall systems provide high sterility assurance and generous air flow rates with minimum risk of blockage Benefits include by wetting. Integrity testing of the filters is achieved with minimum • Compact and modular design fuss and maximum confidence. • No added chemicals Final water quality at point-of-use is ensured by high flow rate, long life sterilizing grade filters capable of absolute removal of even the • Very high rejection rates producing high purity filtrate smallest organisms which may be encountered in practice. • Maximum efficiency in throughput • Recovery rates as high as 95% Pall Advanced Separations Systems Pall Advanced Separations Systems (PASS) is an independent Nanofiltration engineering and procurement entity for Pall’s global separations Pall also uses nanofiltration (NF) water technology with similar but systems business. To successfully deliver high purity water systems slightly more open membranes than RO. The modules have higher that meet stringent customer requirements we have excellence in: unit capacity and lower operating pressures for greater economy • Process System Design where higher passage of monovalent ions and some small organics is • Documentation not an important factor. • Systems Fabrication These systems are used typically to produce softened process water and for removal of high levels of common organic compounds found • Project Management in some waters. PASS will provide the following:
Other Technologies • Installation Support • Systems Design Membrane systems listed above can meet most requirements for process water, purified water and highly purified water or water for • Document Preparation injection (WFI) quality. • Validation/Qualification Some regulations still demand that WFI must be prepared using • Risk Analysis distillation. Pall systems can be used in parallel or in series with • Operator Training distillation and are often employed to take load off existing distillation installations. Distillation can be incorporated into systems when • Spare Parts required. • Service Contracts • After-Market Service
270 Appendix Filter Configurations and Dimensions
AB Series – Dimensions (Length) mm mm Adapter Code 2 Adapter Code 3 AB02 87 AB1 254 AB04 102 AB2 508 AB05 147 AB3 762 ØØ AB1 254 AB4 1016 Length Length
Adapter Code 7 Diameters of Adapters Code 2 56.4 mm (2.22 in.) Ø Code 3 44.2 mm (1.74 in.) Code 7 56.4 mm (2.22 in.) Length
1000 Series – Dimensions (Length) mm mm RF, RMF, PFY MBS, and MCS MCY1001 R05 F 127 MCY 1003 762 R1 F 254 MCY 1004 1016 R2 F 510 MCS 1001 254 Ø 63.5 Ø 70 R3 F 768 MBS 1001 254 R4 F 1022 MBS 1002 508 Length Length RM1 F 254 MBS 1003 762 RM2 F 508 MBS 1004 1016 RM3 F 762 PFY1 254 RM4 F 1016 PFY2 508 MCY 1001 254 PFY3 762 MCY 1002 508 PFY4 1016
Sealkleen – Dimensions (Length) mm mm Sealkleen SLK SLK7001 66 SLK7002 133
Length
Junior – Dimensions (Length) mm mm MCY2230, MCY4463, and MCS4463 MCY1110, 2220, and 4440 MCY2230 76 MCS4463 133 MCY4463 136 SBF 62 MCY1110 48 AVF021 66 MCY2220 57 AVF022 133 MCY4440 120 Length Length
SBF1 AVF
Length Length
272 Filter Configurations and Dimensions (Continued)
Kleenpak – Dimensions (Height) mm mm Kleenpak Nova – In-Line with Nova – In-Line with Nova – T-Style KA1 107 KA3 175 Sanitary Flange Hose Barb KA2 158 KA4 286
Nova – Dimensions (Height) mm mm NP6 332 NT6 349 NP7 581 NT7 598
NP8 831 NT8 848 Height Height Height Height
Nova – Typical Configurations Nova Nova Nova 10 in. with 20 in. with 30 in. with Sanitary Flange Sanitary Flange Sanitary Flange
Height Height Height
Novasip – Dimensions (Height) mm mm PCF Novasip – CM5 Novasip – C3 CM5 84 C3 157
PCF – Dimensions (Height) mm PCF 170
Height Height
Note Height In this catalog, any reference to sanitary flanges for housings or disposable filters pertains to ferrules designed for use in connection with mating Tri-Clamp* fittings of the same dimension, unless otherwise specified.
* Tri-Clamp is a registered trademark of Alfa Laval, Inc.
273 O-ring and Gasket Reference Guide
Cartridge O-rings and Gaskets Code Materials Cartridge Styles H FKM(1) O-rings: AB codes 7, 8, 2 and 3, Juniors Gaskets: 1001 style, 1201 style, Uni Loc
H1 FEP-encapsulated FKM(1), (2) O-rings: AB codes 7, 8, 2 and 3, Juniors
H2 PTFE(3) Gaskets: 1001 style and Uni Loc
H4 Silicone O-rings: AB codes 7, 8, 2 and 3, Juniors Gaskets: 1001 style, 1201 style, Uni Loc
H13 Buna-N O-rings: Juniors Gaskets: 1001 style, 1201 style, Uni Loc
H15 FEP-encapsulated Silicone(2) O-ring: AB codes 7, 8, 2 and 3, Juniors
J Ethylene Propylene O-rings: AB codes 7, 8, 2 and 3, Juniors Gaskets: 1001 style, Uni Loc
J7 Ethylene Propylene for Steam Gaskets: 1001 style
Housing O-rings and Gaskets Code Material Temperature Limits H FKM(1) -29 °C to +232 °C (-20 °F to +450 °F)
H1 FEP-encapsulated FKM(2),(1) -29 °C to +204 °C (-20 °F to +400 °F)
H2 PTFE(3) -29 °C to +232 °C (-20 °F to +450 °F) H4 Silicone -29 °C to +232 °C (-20 °F to +450 °F) H13 Buna-N -29 °C to +121 °C (-20 °F to +250 °F)
H15 FEP-encapsulated Silicone(2) -29 °C to +204 °C (-20 °F to +400 °F) J Ethylene Propylene -29 °C to +149 °C (-20 °F to +300 °F) J7 Ethylene Propylene for Steam -29 °C to +191 °C (-20 °F to +375 °F) Note: Temperature ratings apply for compatible fluids at steady state process conditions. Maximum temperature limit for housing seal material may exceed maximum temperature limit for selected filter cartridge(s). See cartridge data sheet for maximum assembly operating and steaming temperatures.
(1) FKM = Fluorocarbon Elastomer. (2) FEP = Fluoronated Ethylene Propylene. (3) PTFE = Polytetrafluoroethylene.
274 Index Acids – Capsules
A Acids – filtration of Auxiliaries and Water Purification 10 Bubble Point Test Sterilizing-grade Capsules Integrity Test Instruments ® ® Kleenpak™ Capsules with Supor EKV B Palltronic Aquawit XC System 231 Membrane Assemblies 79 Palltronic® Flowstar XC Filter Integrity Kleenpak™ Nova Sterilizing-grade and Bacterial Challenge Tests Test Instruments 229 Virus Removal Capsule Filters 101 Disposable Filtration System Validation 245 Test Parameters Novasip™ Liquid Sterilizing-grade Process-Specific Filter Validation 241 Process-Specific Filter Validation 241 Capsule Filters 99 Bacterial Contamination Analysis Buffer Exchange Sterilizing-grade Cartridges Contamination Analysis 247 Tangential Flow Filtration Membrane Cassettes 185 Fluorodyne® II Hydrophilic PVDF Filter Cartridges 87 Supor® EBV Sterilizing-grade Filter Cartridges 83 Bacterial Removal – air and gas applications Buffer Filtration Supor® EKV Sterilizing-grade Filter Cartridges 81 Capsules Capsules Kleenpak™ Capsules with Emflon® II Kleenpak™ Capsules with Supor® EKV Activated Carbon Removal and Recovery Membrane Assemblies 115 Membrane Assemblies 79 DGM Plate and Frame Filter Systems ® 263 Kleenpak™ Capsules with Emflon PFR Kleenpak™ Nova Sterilizing-grade and 101 Rigimesh® Sintered Metal Mesh Membrane Assemblies 117 Virus Removal Capsule Filters Filter Cartridges ® 137 Novasip™ Capsules with Emflon PFR Mini Kleenpak™ Sterilizing-grade Supracap™ 200 Encapsulated Membrane Assembles 113 Capsule Filters 77 Depth Filter Modules 33 Cartridges Cartridges Supracap™ 60 Depth Filter Capsules ® 31 Emflon CPFR High-temperature Supor® EBV Sterilizing-grade Filter Cartridges 83 Supradisc™ Depth Filter Modules 27 Sterilizing-grade Filter Cartridges 125 Supor® EKV Sterilizing-grade Filter Cartridges 81 Supradisc™ II Modules 29 ® Emflon PFR Junior Style Filter Cartridges 121 Bulk Chemical for Filtration for APIs ZHF Centrifugal Discharge Filter Systems 265 Emflon® PFR Sterilizing-grade Filter Cartridges 123 Emflon® FM Filter Cartridges 73 Activated Carbon Trap Filter Bacterial Removal – liquid applications ® ® Marksman™ Elements with Nexis A Emflon FM Filter Cartridges 73 Capsules ® Series Filters 67 Marksman™ Elements with Nexis A ® Kleenpak™ Capsules with Fluorodyne II Marksman™ Elements with Poly-fine® II Series Filters 67 Membrane Assemblies 85 ® Series Filters 71 Marksman™ Elements with Poly-fine II ® Kleenpak™ Capsules with Posidyne Marksman™ Elements with Poly-fine® XLD Series Filters 71 Membrane Assemblies 95 ® Series Filters 69 Marksman™ Elements with Poly-fine XLD Kleenpak™ Capsules with Supor® EKV Series Filters 69 Membrane Assemblies 79 ® ® C Profile Filter Cartridges with Ultipleat Kleenpak™ Capsules with Ultipor® N66 Construction 59 Membrane Assemblies 89 Cake-drying ® Profile Star Filter Cartridges 55 Kleenpak™ Nova Sterilizing-grade and 101 PEF Multi Purpose Processor 267 Activated Carbon – depth filters with Virus Removal Capsule Filters Calibration Supracap™ 200 Encapsulated Mini Kleenpak™ Sterilizing-grade Capsule Filters 77 Palltronic® Flow Check Device 233 Depth Filter Modules 33 Novasip™ Liquid Sterilizing-grade Supracap™ 60 Depth Filter Capsules 31 Capsule Filters 99 Capsules – chromotography ® Supradisc™ Depth Filter Modules 27 Cartridges Mustang Chromatography Capsules Fluorodyne® II Hydrophilic PVDF Filter Cartridges 87 and Cartridges 217 – 220 After-market Service ® Posidyne® Filter Cartridges 97 Mustang Membrane Pall Process Engineered Systems 261 Sealkleen™ Membrane Filter Cartridges 91 Chromatography Starter Kits 211 – 214 Air-Gas Filtration 111 – 142 Supor® EBV Sterilizing-grade Filter Cartridges 83 Capsules – depth filter Amine Charged Polymer Supor® EKV Sterilizing-grade Filter Cartridges 81 Supracap™ 200 Encapsulated ® Mustang® Chromatography Capsules Ultipor N66 Sterilizing-grade Filter Cartridges 93 Depth Filter Modules 33 and Cartridges 217 – 220 Bacterial Retention Studies Supracap™ 60 Depth Filter Capsules 31 Analytical Services Process-Specific Filter Validation 241 Capsules – direct-flow filtration Contamination Analysis 247 Bacteriophage retention studies Prefilters – air and gas Disposable Filtration System Validation 245 Process-Specific Filter Validation 241 Kleenpak™ Capsules with HDC® II Filter Integrity Test Equipment Validation 255 Gas Filter Assemblies 119 Bases – filtration of Kleenpak™ Connector Validation 243 Prefilters – liquid Sterilizing-grade Capsules Process Development and Optimization 249 Kleenpak™ Capsules with HDC® II Kleenpak™ Capsules with Supor® EKV Process-Specific Filter Validation 241 Filter Assemblies 47 Membrane Assemblies 79 Anion Exchange Kleenpak™ Nova Particulate and Prefilter Kleenpak™ Nova Sterilizing-grade and 101 Capsule Filters 41 Mustang® Chromatography Capsules Virus Removal Capsule Filters Mini Profile® Capsule Filters 45 and Cartridges 217 – 220 ® Kleenpak™ Ultipor N66 Sterilizing-grade PreFlow™ Capsule Filters 43 Mustang® Membrane Capsule Filters 89 Sterile Filters – air, gas, and vent Chromatography Starter Kits 211 – 214 Novasip™ Liquid Sterilizing-grade Kleenpak™ Capsules with Emflon® II Antibiotics Capsule Filters 99 Membrane Assemblies 115 Sterilizing-grade Cartridges Air and Gas Filtration 111 – 142 Kleenpak™ Capsules with Emflon® PFR ® Depth Sheet Filters and Modules 13 – 34 Supor EBV Sterilizing-grade Filter Cartridges 83 Membrane Assemblies 117 ® Systems 259 – 270 Supor EKV Sterilizing-grade Filter Cartridges 81 Novasip™ Capsules with Emflon® PFR ® Tangential Flow Filtration 175 – 208 Ultipor N66 Sterilizing-grade Filter Cartridges 93 Membrane Assembles 113 Antifoam Resistance Binding and Elution Sterile Filters – liquid ® Alpha Membranes 178 Mustang Chromatography Capsules Kleenpak™ Capsules with Fluorodyne® II Regen™ Membrane 179 and Cartridges 217 – 220 Membrane Assemblies 85 Kleenpak™ Capsules with Posidyne® API (Active Pharmaceutical Ingredients) 6 Bioburden Analysis Contamination Analysis 247 Membrane Assemblies 95 Appendix 271 – 284 Kleenpak™ Capsules with Supor® EKV Bioburden Reduction Membrane Assemblies 79 Aqueous Enzymes Processing Ultipor® N66 Particulate and Bioreduction Microza Membranes 198 – 202 Kleenpak™ Nova Sterilizing-grade and 101 Filter Cartridges 75 Virus Removal Capsule Filters Aseptic Connections BioSeries Depth Filter Sheets 15 Kleenpak™ Ultipor® N66 Sterilizing-grade Kleenpak™ Connectors 39 Capsule Filters 89 Biotechology and Cell Culture 2 Aseptic Connector Validation Mini Kleenpak™ Sterilizing-grade Capsule Filters 77 Kleenpak™ Connector Validation 243 Blood Products and Fractionation 4 Novasip™ Liquid Sterilizing-grade Bonded Glass Fiber – Positive Zeta Capsule Filters 99 Aseptic Packaging Validation Formulation and Filling 8 Capsules Kleenpak™ Nova Particulate and Prefilter Disposable Filtration System Validation 245 Autoclave Vacuum Break Capsule Filters 41 Process-Specific Filter Validation 241 ® Emflon PFA Filter Cartridges 127 PreFlow™ Capsule Filters 43 Virus Removal Filters ® Emflon PFR Sterilizing-grade Filter Cartridges 123 Cartridges Kleenpak™ Nova Sterilizing-grade and 101 Autoclaves – sterile venting PreFlow™ Filter Cartridges 65 Virus Removal Capsule Filters Emflon® PFR Sterilizing-grade Filter Cartridges 123 Ultipor® GF Plus Filter Cartridges 63 Novasip™ DV20 and V50 Virus Removal Filter Capsules 103 Automated systems Breakthrough Curves See Systems Chromatography 209 – 226 Capsules – tangential flow filtration Minimate™ Tangential Flow Filtration Capsules 181 275 Index Carbon Removal – Emflon® FM Filter Cartridges
Carbon Removal Cassettes Compatibility Assessment See Activated Carbon Removal and Recovery Centramate™ 185 Disposable Filtration System Validation 245 Carbon-containing Depth Filters Centrasette™ 185 Kleenpak™ Connector Validation 243 Maximate™ Process-Specific Filter Validation See Activated Carbon – depth filters with 186 241 Maxisette™ 186 Cartridges Concentration Chromatography Cassettes – tangential flow filtration Depth Sheet Filters and Modules 13 – 34 Tangential Flow Filtration DGM Plate and Frame Filter Systems Mustang® Chromatography Capsules 263 Membrane Cassettes Tangential Flow Filtration and Cartridges 217 – 220 185 – 187 175 – 208 High-temperature Gas Service Catalyst Fines – removal Connector for Disposable Systems Emflon® CPFR High-temperature Emflon® FM Filter Cartridges 73 Kleenpak™ Connectors 39 Sterilizing-grade Filter Cartridges 125 Catalyst Recovery and Removal Contamination Analysis 247 ® PMM Metal Membrane Filter Cartridges 141 DGM Plate and Frame Filter Systems 263 Cross-flow Filtration ® PSS Porous Metal Filter Cartridges 139 Rigimesh® Sintered Metal Mesh See Tangential Flow Filtration ® Rigimesh Sintered Metal Mesh Filter Cartridges 137 Filter Cartridges 137 Metal Cryogenic Fluid Supracap™ 200 Encapsulated ® ® PSS Porous Metal Filter Cartridges 139 PMM Metal Membrane Filter Cartridges 141 Depth Filter Modules 33 ® PSS Porous Metal Filter Cartridges 139 Supracap™ 60 Depth Filter Capsules 31 Crystal Recovery ® Rigimesh Sintered Metal Mesh Filter Cartridges 137 Supradisc™ Depth Filter Modules 27 Membralox® Ceramic Membrane Products 203 Prefilters – air, gas, and vent Supradisc™ II Modules 29 Crystallization HDC® II Gas Filter Cartridges 131 ZHF Centrifugal Discharge Filter Systems 265 PEF Multi Purpose Processor 267 LG Liquid and Gas Coalescing Filter Cartridges 135 Pallcell® Air and Gas Filter Cartridges 133 Cation Exchange ® Ultipor® GF Plus Air and Gas Filter Cartridges 129 Mustang Chromatography Capsules D Prefilters – liquid and Cartridges 217 – 220 ® Deionized Water – filtration of Emflon™ FM Filter Cartridges 73 Mustang Membrane Water Systems 269 HDC® II Filter Cartridges 61 Chromatography Starter Kits 211 – 214 HDC® II Junior Style Filter Cartridges 49 Cell Culture Perfusion Depth Sheet Filters and Modules Marksman™ Elements with Nexis® A Microza Membranes 198 – 202 Capsules Series Filters 67 Supracap™ 200 Encapsulated Cell Harvest and Product Separation Marksman™ Elements with Poly-fine® II Depth Filter Modules 33 BioSeries Depth Filter Sheets 15 Series Filters 71 Supracap™ 60 Depth Filter Capsules 31 DGM Plate and Frame Filter Systems 263 Marksman™ Elements with Poly-fine® XLD Disposables E-Series Depth Filter Sheets 25 Series Filters 69 Supracap™ 200 Encapsulated Matching Membrane Cassettes to Applications 180 PreFlow™ Filter Cartridges 65 Depth Filter Modules 33 Membralox® Ceramic Membrane Products 203 Profile® Filter Cartridges with Ultipleat® Supracap™ 60 Depth Filter Capsules 31 Minimate™ Tangential Flow Filtration Capsules 181 Construction 59 Modules Pallsep™ Vibrating Membrane Filtration Profile® II Filter Cartridges 51 Supracap™ 200 Encapsulated Technology 205 Profile® II Plus Filter Cartridges 53 Depth Filter Modules 33 P-Series Depth Filter Sheets 17 Profile® Star Filter Cartridges 55 Supradisc™ Depth Filter Modules 27 Supradisc™ Depth Filter Modules 27 Starclear™ Filter Cartridges 57 Supradisc™ II Modules 29 Tangential Flow Filtration Ultipor® GF Plus Filter Cartridges 63 Sheets Membrane Cassette Holders 189 – 193 Ultipor® N66 Particulate and Bioreduction BioSeries Depth Filter Sheets 15 Tangential Flow Filtration Filter Cartridges 75 E-Series Depth Filter Sheets 25 Membrane Cassettes Sterile Filters – air, gas, and vent 185 – 187 K-Series Depth Filter Sheets 19 Tangential Flow Filtration Systems 195 Aerosol challenge P-Series Depth Filter Sheets 17 Ultrafiltration and Microfiltration Emflon® PFA Filter Cartridges 127 T-Series Depth Filter Sheets 21 Membranes for Cassettes Sterile Filters – air, gas, and vent 178 Z-Series Depth Filter Sheets 23 ZHF Centrifugal Discharge Filter Systems 265 Liquid Challenge Systems Emflon® CPFR High-temperature Ceramic Modules DGM Plate and Frame Filter Systems 263 ® Sterilizing-grade Filter Cartridges 125 Membralox Ceramic Membrane Products 203 Depyrogenation ® Emflon PFR Junior Style Filter Cartridges 121 Ceramic – tubular See Endotoxin Removal ® Emflon PFR Sterilizing-grade Filter Cartridges 123 Membralox® Ceramic Membrane Products 203 Sterile Filters – liquid DGM Plate and Frame Filter Systems 263 Fluorodyne® II Hydrophilic PVDF Filter Cartridges 87 Challenge Viability Studies Diafiltration Posidyne® Filter Cartridges 97 Disposable Filtration System Validation 245 See Tangential Flow Filtration Sealkleen™ Membrane Filter Cartridges 91 Process-Specific Filter Validation 241 Direct Flow Liquid Filtration 35 – 110 Supor® EBV Sterilizing-grade Filter Cartridges 83 Chromatography Supor® EKV Sterilizing-grade Filter Cartridges 81 Capsules Direct Flow Measurement ® Ultipor® N66 Sterilizing-grade Filter Cartridges 93 Mustang® Chromatography Capsules Palltronic Aquawit XC System 231 ® Virus Removal Filters and Cartridges 217 – 220 Palltronic Flowstar XC Filter Integrity Ultipor® VF Grade DV20 Virus Removal Cartridges Test Instruments 229 Filter Cartridges 107 Mustang® Chromatography Capsules Disposable Filtration System Validation 245 Ultipor® VF Grade DV50 Virus and Cartridges 217 – 220 Disposable Systems Filter Cartridges – SBF Junior Style 105 Coin devices ® Disposable Systems 37 Ultipor VF Grade DV50 Virus Removal Mustang® Coin Units 215 Kleenpak™ Connectors 39 Filter Cartridges 109 Columns Cassette Capsules Resolute™ Chromatography Columns 221 Disposables Minimate™ Tangential Flow Filtration Capsules 181 Packing Systems See Capsules Resolute™ Slurry Packing Systems 223 Downstream Processing Systems Cassette Holders Skids Polypropylene PK Chromatography Skids 225 PK Chromatography Skids 225 Systems 195, 261 Centrasette™ P 189 Starter Kits ® Polyethylene Mustang® Membrane Drivers for Palltronic Filter Integrity Centramate™ PE 189 Chromatography Starter Kits 211 – 214 Test Instruments 235 Stainless Steel Systems Centramate™ 189 PK Chromatography Skids 225 E Centramate™ LV 189 Centrasette™ 189 Clarification E-Series Depth Filter Sheets 25 Maximate™ 189 See Depth Sheet Filters and Modules Emflon® CPFR High-temperature Maxisette™ 189 See Prefiltration Sterilizing-grade Filter Cartridges 125 Cassette Membranes Cleaning Cycle Development Emflon® II Filters 115 Tangential Flow Filtration Process Development and Optimization 249 ® Membrane Cassettes 185 – 187 Columns – standard and engineered Emflon PFA Filter Cartridges 127 Ultrafiltration and Microfiltration Resolute Chromatography Columns 221 Emflon® PFR Junior Style Filter Cartridges 121 Membranes for Cassettes 178 Combined Forward Flow and Bubble Point Test Emflon® PFR Sterilizing-grade Filter Cartridges 123 Palltronic® Flowstar XC Filter Integrity Emflon® FM Filter Cartridges 73 276 Test Instruments 229 Index Endotoxin Contamination – Gamma-irradiatable
Endotoxin Contamination Supracap™ 60 Depth Filter Capsules 31 Polyvinylidenedifluoride (PVDF) Troubleshooting and Consultancy Services 257 Supradisc™ Depth Filter Modules 27 Fluorodyne® II Hydrophilic PVDF Filter Cartridges 87 ® Endotoxin Removal Supradisc™ II Modules 29 Kleenpak™ Capsules with Emflon II Kleenpak™ Capsules with Posidyne® T-Series Depth Filter Sheets 21 Membrane Assemblies 115 ® Membrane Assemblies 95 Ultrafiltration and Microfiltration Kleenpak™ Capsules with Fluorodyne II Minimate™ Tangential Flow Filtration System 183 Membranes for Cassettes 178 Membrane Assemblies 85 Mustang® Chromatography Capsules Z-Series Depth Filter Sheets 23 Microza Membranes 198 – 202 Glass Fiber and Cartridges 217 – 220 Mini Kleenpak™ Sterilizing-grade Mustang® Membrane LG Liquid and Gas Coalescing Capsule Filters 77 Chromatography Starter Kits 211 Filter Cartridges 135 Novasip™ Liquid Sterilizing-grade Posidyne® Filter Cartridges 97 PreFlow™ Capsule Filters 43 Capsule Filters 99 Profile® II Plus Filter Cartridges 53 PreFlow™ Filter Cartridges 65 Sealkleen™ Membrane Filter Cartridges 91 ® P-Series Depth Filter Sheets 17 Starclear™ Filter Cartridges 57 Ultipor VF Grade DV20 Virus Removal ® Starclear™ Filter Cartridges 57 Ultipor GF Plus Air and Gas Filter Cartridges 107 ® Ultipor® GF Plus Filter Cartridges 63 Filter Cartridges 129 Ultipor VF Grade DV50 Virus Nylon 6,6 Z-Series Depth Filter Sheets 23 Filter Cartridges – SBF Junior Style 105 Kleenpak™ Ultipor® N66 Sterilizing-grade Ultipor® VF Grade DV50 Virus Removal Engineering Services Capsule Filters 89 Filter Cartridges 109 Process Development and Optimization 249 Novasip™ Liquid Sterilizing-grade Stainless Steel – 304L Ethanol Filtration Capsule Filters 99 Rigimesh® Sintered Metal Mesh Filter Cartridges 137 Emflon® PFR Sterilizing-grade Filter Cartridges 123 Sealkleen™ Membrane Filter Cartridges 91 Stainless Steel – 316L Emflon® PFR Junior Style Filter Cartridges 121 Ultipor® N66 Particulate and Bioreduction PMM® Metal Membrane Filter Cartridges 141 Kleenpak™ Capsules with Emflon® PFR Filter Cartridges 75 PSS® Porous Metal Filter Cartridges 139 Membrane Assemblies 117 Ultipor® N66 Sterilizing-grade Filter Cartridges 93 Titania Nylon – positively charged Membralox® Ceramic Membrane Products 203 Evaluation of Adsorptive Effects Kleenpak™ Capsules with Posidyne® Zirconia Process-Specific Filter Validation 241 Membrane Assemblies 95 Membralox® Ceramic Membrane Products 203 Exhaust Venting ® Posidyne Filter Cartridges 97 Filter Selection See Capsules – gas Polyacrylonitrile Filter Selection 12 See Cartridges – gas Microza Membranes 198 – 202 Pre-Inspection Reviews 253 Extractables Analysis Polyethersulfone – chromatography ® Filter System Operation Disposable Filtration System Validation 245 Mustang Chromatography Capsules Training 251 Kleenpak™ Connector Validation 243 and Cartridges 217 – 220 ® Process-Specific Filter Validation 241 Mustang Coin Units 215 Filter Validation Polyethersulfone – filtration Disposable Filtration System Validation 245 Kleenpak™ Capsules with Supor® EKV Filter Integrity Test Equipment Validation 255 F Membrane Assemblies 79 Process-Specific Filter Validation 241 Fermentation Mini Kleenpak™ Sterilizing-grade Training 251 Capsule Filters 77 See Cell Culture Filterability Test Instruments Sheet TFF Membranes 207 Palltronic® Filter Manager 237 Filter Aid Removal Supor® EBV Sterilizing-grade Filter Cartridges 83 Depth Sheet Filters and Modules 13 – 34 Supor® EKV Sterilizing-grade Filter Cartridges 81 Filtration Principles DGM Plate and Frame Filter Systems 263 Ultrafiltration and Microfiltration Training 251 Filter Configurations and Dimensions 273 Membranes for Cassettes 178 Filtration System Enhancements Polyethylene Filter Housings 143 Troubleshooting and Consultancy Services 257 Marksman™ Elements with Nexis® A Filter Integrity Test Equipment Validation 255 Series Filters 67 Flat Sheet Tangential Flow Filtration Membranes Filter Integrity Test Instruments Polyolefin Sheet Tangential Flow Filtration Membranes 207 Flow Measurement Microza Membranes 198 – 202 Palltronic® Flow Check Device 233 Polypropylene Flow Measurement ® Palltronic® Aquawit XC System 231 HDC II Filter Cartridges 61 Palltronic® Flow Check Device 233 ® ® HDC II Gas Filter Cartridges 131 Palltronic Flowstar XC Filter Integrity 229 Fluorodyne® II Capsules HDC® II Junior Style Filter Cartridges 49 Test Instruments Kleenpak™ Capsules with Fluorodyne® II Kleenpak™ Capsules with HDC® II Process Automization Membrane Assemblies 85 ® Filter Assemblies 47 Drivers for Palltronic Filter Integrity Mini Kleenpak™ Sterilizing-grade Kleenpak™ Capsules with HDC® II Test Instruments 235 Capsule Filters 77 Remote Control Gas Filter Assemblies 119 ® ® Fluorodyne II Hydrophilic PVDF ® Marksman™ Elements with Nexis A Drivers for Palltronic Filter Integrity Filter Cartridges 87 Test Instruments 235 Series Filters 67 ® Validation Marksman™ Elements with Polyfine II Formulation and Filling 8 Filter Integrity Test Equipment Validation 255 Series Filters 71 Forward Flow Test ® Marksman™ Elements with Polyfine XLD ® Filter Integrity Test Methodology Palltronic Aquawit XC System 231 Series Filters 69 Palltronic® Flowstar XC Filter Integrity Troubleshooting and Consultancy Services 257 ® Mini Profile Capsule Filters 45 Test Instruments 229 Filter Integrity Tests Profile® Filter Cartridges with Ultipleat® Disposable Filtration System Validation 245 Construction 59 Fractionation Palltronic® Training Program 234 Profile® II Filter Cartridges 51 Blood Products and Fractionation 4 Pre-Inspection Reviews 253 Profile® II Plus Filter Cartridges 53 Freeze-dryer Vacuum Break Filters Process-Specific Filter Validation 241 Profile® Star Filter Cartridges 55 Air and Gas Filtration 111 – 142 Training 251 Polypropylene and Polyethylene Marksman™ Elements with Nexis® A Filter Media Series Filters 67 G Activated Carbon Polypropylene and Positively-charged Gamma-irradiatable Supracap™ 200 Encapsulated Glass Fiber Disposable Systems Depth Filter Modules 33 37 Starclear™ Filter Cartridges 57 Kleenpak™ Capsules with Emflon® II Supracap™ 60 Depth Filter Capsules 31 Polysulfone Membrane Assemblies Supradisc™ Depth Filter Modules 27 115 Microza Membranes 198 – 202 ® Alumina Kleenpak™ Capsules with Fluorodyne II Polytetrafluoroethylene (PTFE) Membrane Assemblies Membralox® Ceramic Membrane Products 203 85 Emflon® CPFR High-temperature ® Bonded Glass Fiber – positive Zeta Kleenpak™ Capsules with Posidyne Sterilizing-grade Filter Cartridges 125 Membrane Assemblies Ultipor® GF Plus Filter Cartridges 63 95 Emflon® PFA Filter Cartridges 127 ® Cellulose Kleenpak™ Capsules with Supor EKV Emflon® PFR Junior Style Filter Cartridges 121 Membrane Assemblies BioSeries Depth Filter Sheets 15 79 Emflon® PFR Sterilizing-grade Filter Cartridges 123 E-Series Depth Filter Sheets 25 Kleenpak™ Connectors 39 Emflon® FM Filter Cartridges 73 K-Series Depth Filter Sheets 19 Kleenpak™ Nova Particulate and Prefilter Kleenpak™ Capsules with Emflon® PFR Pallcell® Air and Gas Filter Cartridges 133 Capsule Filters 41 Membrane Assemblies 117 P-Series Depth Filter Sheets 17 Kleenpak™ Nova Sterilizing-grade and 101 Novasip™ Capsules with Emflon® PFR Supracap™ 200 Encapsulated Virus Removal Capsule Filters Membrane Assembles 113 ® Depth Filter Modules 33 Kleenpak™ Ultipor N66 Sterilizing-grade 277 Pallsep™ Vibrating Membrane Capsule Filters 89 Filtration Technology 205 Index Gamma-irradiatable – Low-volume Parenterals
Mini Kleenpak™ Sterilizing-grade Perfluoroalkoxy (PFA) Installation Qualification Capsule Filters 77 Megaplast™ Plastic Filter Housings 173 Integrity Test Instruments Novasip™ DV20 and V50 Virus Removal Plastic Housings Filter Integrity Test Equipment Validation 255 Filter Capsules 103 Megaplast™ Plastic Filter Housings 173 Systems Gas and Liquid Filtration – housings PCY Polypropylene Filter Housings 171 Pall Process Engineered Systems 261 Junior B series Filter Housings Polypropylene 145 Instrument Air – filtration of Pall Advanta™ In-Line Liquid and Gas Megaplast™ Plastic Filter Housings 173 Polyvinylidine Emflon® PFA Filter Cartridges 127 Filter Housings 155 Pall Advanta™ Jacketed Housings 157 Megaplast™ Plastic Filter Housings 173 Integrity Test Data Sanitary Depth Filter Module Housing Pall Advanta™ Junior F Gas Filter Housings 152 Process-Specific Filter Validation 241 Veladisc™ Module Housings 165 Pall Advanta™ Junior Gas Filter Housings 150 Integrity Test Equipment Validation Sanitary Housings Sealkleen™ Filter Housings 147 Filter Integrity Test Equipment Validation 255 Junior B Series Filter Housings 145 Gas Filtration Pall Advanta™ AGT Gas Filter Housings 159 Integrity Test Instruments 227 – 236 See Air, Gas, and Vent Filtration Pall Advanta™ ALT Liquid Filter Housings 153 See also Filter Integrity Test Instruments Gene Therapy Pall Advanta™ ALT4 Multi-round Housings 163 and Filter Integrity Tests See Cell Culture Pall Advanta™ AVL Liquid and Integrity Test Methodology Gas Filter Housings 161 GMP Requirements Troubleshooting and Consultancy Services 257 Pall Advanta™ In-Line Liquid and Pall Process Engineered Systems 261 Gas Filter Housings 155 IOL and IDL Single-round Industrial Housings 169 Pall Advanta™ Jacketed Housings 157 Ion Exchange H Pall Advanta™ Junior F Liquid Filter Housings 151 Mustang® Chromatography Capsules Pall Advanta™ Junior Filter Housings 149 Hastelloy* and Cartridges 217 – 220 Sealkleen™ Filter Housings 147 ® PEF Multi Purpose Processor 267 Mustang Coin Units 215 Sanitary Housings – accessories ® ZHF Centrifugal Discharge Filter Systems 265 Mustang Membrane Pall Advanta™ Electrical Trace Heaters 167 Chromatography Starter Kits 211 – 214 Haze and Colloid Particle Removal Small-scale Production Resolute Chromatography Columns 225 ® Profile II Plus Filter Cartridges 53 Junior B Series Filter Housings 145 Resolute Slurry Packing Systems 223 Starclear™ Filter Cartridges 57 Pall Advanta™ Junior F Gas Filter Housings 152 IQ Ultipor® GF Plus Filter Cartridges 63 Pall Advanta™ Junior Filter Housings 149 See Installation Qualification HDC® II Filter Cartridges 61 Pall Advanta™ Junior Gas Filter Housings 150 Sealkleen™ Filter Housings 147 ® HDC II Filters Stainless Steel J ® Kleenpak™ Capsules with HDC II IOL and IDL Single-round Industrial Housings 169 Junior B Series Filter Housings 145 Filter Assemblies 47 Junior B Series Filter Housings 145 ® Kleenpak™ Capsules with HDC II MDS Junior Style Industrial Housings 168 Junior Style Gas Filter Assemblies 119 Pall Advanta™ AGT Gas Filter Housings 159 Cartridges ® HDC® II Gas Filter Cartridges 131 Pall Advanta™ ALT Liquid Filter Housings 153 Emflon PFR Junior Style Filter Cartridges 121 Pall Advanta™ ALT4 Multi-round Housings 163 HDC® II Junior Style Filter Cartridges 49 HDC® II Junior Style Filter Cartridges 49 Pall Advanta™ AVL Liquid and Sealkleen™ Membrane Filter Cartridges 91 HEPA-quality Air and Gas Filtration Gas Filter Housings 161 Ultipor® VF Grade DV50 Kleenpak™ Capsules with HDC® II Pall Advanta™ In-Line Liquid and Virus Filter Cartridges – SBF Junior Style 105 Filter Assemblies 47 Gas Filter Housings 155 Housings High Cell Concentration Pall Advanta™ Jacketed Housings 157 See Housings – junior style Pallsep™ Vibrating Membrane Filtration Pall Advanta™ Junior F Gas Filter Housings 151 Technology 205 Pall Advanta™ Junior Filter Housings 149 K Sealkleen™ Filter Housings 147 High-temperature Use Veladisc™ Module Housings 165 Kleenpak™ Capsules with Emflon® II See Cartridges – high-temperature T-flow Membrane Assemblies 115 Holders IOL and IDL Single-round Industrial Housings 169 Kleenpak™ Capsules with Emflon® PFR See Cassette Holders MDS Junior Style Industrial Housings 168 Membrane Assemblies 117 Megaplast™ Plastic Filter Housings 173 Hollow Fiber ® Pall Advanta™ AGT Gas Filter Housings 159 Kleenpak™ Capsules with Fluorodyne II Microza Membranes 198 – 202 Pall Advanta™ ALT Liquid Filter Housings 153 Membrane Assemblies 85 TFF Polymeric Hollow Fiber Membranes Pall Advanta™ ALT4 Multi-round Housings 163 Kleenpak™ Capsules with HDC® II Gas Filter and Ceramic Modules 197 Pall Advanta™ Junior F Gas Filter Housings 151 Assemblies 119 Hot Water Tank Vent Trace Heaters Pall Advanta™ Junior Filter Housings 149 Kleenpak™ Capsules with Posidyne® Pall Advanta™ Electrical Trace Heaters 167 PCY Polypropylene Filter Housings 171 Membrane Assemblies 95 Hot WFI Vents Veladisc™ Module Housings 165 Kleenpak™ Capsules with Supor® EKV Emflon® CPFR High-temperature Hydrophobic Filters Membrane Assemblies 79 Sterilizing-grade Filter Cartridges 125 Emflon® CPFR High-temperature Kleenpak™ Connector Validation Housings Sterilizing-grade Filter Cartridges 125 243 ® Industrial Housings Emflon PFA Filter Cartridges 127 Kleenpak™ Connectors 39 ® IOL and IDL Single-round Industrial Housings 169 Emflon PFR Junior Style Filter Cartridges 121 ® Kleenpak™ Nova Particulate and Prefilter MDS Junior Style Industrial Housings 168 Emflon PFR Sterilizing-grade Filter Cartridges 123 ® Capsule Filters 41 In-line Emflon FM Filter Cartridges 73 ® Junior B series Filter Housings 145 HDC II Gas Filter Cartridges 131 Kleenpak™ Nova Sterilizing-grade and 101 ® Pall Advanta™ In-Line Liquid and Kleenpak™ Capsules with Emflon II Virus Removal Capsule Filters Membrane Assemblies Gas Filter Housings 155 115 Kleenpak™ Ultipor® N66 Sterilizing-grade ® Pall Advanta™ Jacketed Housings 157 Kleenpak™ Capsules with Emflon PFR Capsule Filters 89 Pall Advanta™ Junior Filter Housings 149 Membrane Assemblies 117 ® K-Series Depth Filter Sheets 19 Sealkleen™ Filter Housings 147 Novasip™ Capsules with Emflon PFR Jacketed Membrane Assembles 113 Pall Advanta™ Jacketed Housings 157 Hydrophobic Filters – integrity testing L Junior Style ® Palltronic Aquawit XC System 231 Large Process Volumes Junior B Series Filter Housings 145 ® Palltronic Flowstar XC Filter Integrity Tangential Flow Filtration MDS Junior Style Industrial Housings 168 Test Instruments 229 Membrane Cassettes 185 – 187 Pall Advanta™ Junior Filter Housings 149 Sealkleen™ Filter Housings 147 L-flow Housings L-flow I See Housings – L-flow Junior B Series Filter Housings 145 In-line Housings LG Liquid and Gas Coalescing Filter Cartridges 135 Pall Advanta™ AVL Liquid and See Housings – in-line Gas Filter Housings 161 Liquid Direct Flow Filtration Inoculum Transfer See Direct Flow Liquid Filtration Kleenpak™ Connectors 39 Low-volume Parenterals Inspections Ultipor® N66 Sterilizing-grade Filter Cartridges 93 Pre-Inspection Reviews 253 278 Process Development and Optimization 249 Index Lyophilizers – Pre-reverse Osmosis Filtration
Lyophilizers – sterile venting Mycoplasma Removal Pallsep™ Vibrating Membrane Emflon® CPFR High-temperature Fluorodyne® II Hydrophilic PVDF Filtration Technology 205 Sterilizing-grade Filter Cartridges Filter Cartridges 125 87 Palltronic® Aquawit XC System 231 Emflon® PFR Filters and Sealkleen Ultipor® N66 Sterilizing-grade Filter Cartridges 93 ® Palltronic® Flow Check Device 233 Cartridges with Emflon PFR Membrane Mycoplasma Retention Studies Emflon® PFR Junior Style Filter Cartridges ® 121 Process-Specific Filter Validation 241 Palltronic Flowstar XC Filter Integrity Emflon® PFR Sterilizing-grade Filter Cartridges 123 Test Instruments 229 Kleenpak™ Capsules with Emflon® PFR Palltronic® Instruments 227 – 238 Membrane Assemblies 117 N Palltronic® Training Program Lysates Nanofiltration 234 Profile® II Filter Cartridges 51 Water Systems 269 PAN ® Profile Star Filter Cartridges 55 Novasip™ DV20 and V50 Virus See Filter Media – polyacrylonitrile Tangential Flow Filtration 175 – 208 Removal Filter Capsules 103 Parenterals – filtration of Novasip™ Capsules with Emflon® PFR Formulation and Filling 8 M Membrane Assembles 113 Particle Removal Mammalian Cell Culture Perfusion Novasip™ Liquid Sterilizing-grade See Capsules and Cartridges – prefiltration Microza Membranes 198 – 202 Capsule Filters 99 Particulate Analysis Marksman™ Elements with Nexis® A Contamination Analysis 247 Series Filters 67 O PCY Polypropylene Filter Housings 171 ® Marksman™ Elements with Poly-fine II Oil Droplet Removal PEF Multi Purpose Processor 267 Series Filters 71 LG Liquid and Gas Coalescing Filter Cartridges 135 Perfluoroalkoxy (PFA) ® Marksman™ Elements with Poly-fine XLD Oleophobic Filters Megaplast™ Plastic Filter Housings 173 Series Filters 69 LG Liquid and Gas Coalescing Filter Cartridges 135 Performance Qualification MDS Junior Style Industrial Housings 168 Operating Procedures Filter Integrity Test Equipment Validation 255 Media and Buffer Sterile Filtration Pre-Inspection Reviews 253 PES ® Fluorodyne II Hydrophilic PVDF Filter Cartridges 87 Operational Qualification See Filter Media – polyethersulfone Kleenpak™ Capsules with Fluorodyne® II Filter Integrity Test Equipment Validation 255 PFA Membrane Assemblies 85 Kleenpak™ Capsules with Supor® EKV Operator Training See Filter Media – perfluoroalkoxy (PFA) Membrane Assemblies 79 Pall Process Engineered Systems 261 Pilot and Process Development Capabilities 194 Training 251 Kleenpak™ Nova Sterilizing-grade and 101 PK Chromatography Skids 225 Virus Removal Capsule Filters Ophthalmics Supor® EKV Sterilizing-grade Filter Cartridges 81 Fluorodyne® II Hydrophilic PVDF Plant Filtration Surveys Troubleshooting and Consultancy Services 257 Megaplast™ Plastic Filter Housings 173 Filter Cartridges 87 Kleenpak™ Capsules with Fluorodyne® II Plasma Derivatives – virus filtration Melt-blown Depth Filter Elements Membrane Assemblies 85 Ultipor® VF Grade DV20 ® Marksman™ Elements with Nexis A Kleenpak™ Capsules with Supor® EKV Virus Removal Filter Cartridges 107 Series Filters 67 Membrane Assemblies 79 Ultipor® VF Grade DV50 Membralox® Ceramic Membrane Products 203 Kleenpak™ Nova Sterilizing-grade and 101 Virus Filter Cartridges – SBF Junior Style 105 Virus Removal Capsule Filters ® Membrane Selection Ultipor VF Grade DV50 Mini Kleenpak™ Sterilizing-grade Virus Removal Filter Cartridges Process Development and Optimization 249 109 Capsule Filters 77 Plasma Fractionation Matching Membrane Cassettes Profile® II Filter Cartridges 51 Blood Products and Fractionation 4 to Applications 180 Profile® Star Filter Cartridges 55 ® PLC Membranes – ceramic Supor EBV Sterilizing-grade Filter Cartridges 83 ® Drivers for Palltronic® Filter Integrity Membralox® Ceramic Membrane Products 203 Supor EKV Sterilizing-grade Filter Cartridges 81 Test Instruments 235 Membranes vibrating Optimization – ® Pallsep™ Vibrating Membrane Filtration Process Development and Optimization 249 PMM Metal Membrane Filter Cartridges 141 Technology 205 OQ Posidyne® Capsules ® Microbial Retention Studies See Operational Qualification Kleenpak™ Capsules with Posidyne Membrane Assemblies 95 Process-Specific Filter Validation 241 Ordering Information Posidyne® Filter Cartridges 97 Microbiological Studies Organic Solvents – filtration of Contamination Analysis 247 Emflon® FM Filter Cartridges 73 Positive Zeta Potential Kleenpak™ Capsules with Posidyne® Microza Membranes 198 – 202 O-rings Membrane Assemblies 95 O-ring and Gasket Reference Guide 275 Mini Kleenpak™ Sterilizing-grade Posidyne® Filter Cartridges 97 Capsule Filters 77 Profile® II Plus Filter Cartridges 53 Mini Profile® Capsule Filters 45 P Starclear™ Filter Cartridges 57 Ultipor® GF Plus Filter Cartridges 63 Minimate™ Tangential Flow Filtration Capsules Packing Systems – chromatography 181 Z-Series Depth Filter Sheets 23 Resolute Slurry Packing Systems 223 Minimate™ Tangential Flow Filtration System 183 PQ Pall Advanta™ AGT Gas Filter Housings 159 Mixing See Performance Qualification PEF Multi Purpose Processor Pall Advanta™ ALT Liquid Filter Housings 153 267 Prefilters – liquid Modules Pall Advanta™ ALT4 Multi-round Housings 163 See Capsules – prefilters, liquid Depth Filter Pall Advanta™ AVL Liquid and See Cartridges – prefilters, liquid Supracap™ 60 Depth Filter Capsules 31 Gas Filter Housings 161 See Depth Sheet Filters and Modules Supradisc™ Depth Filter Modules 27 Pall Advanta™ Electrical Trace Heaters 167 Prefilters – air, gas, and vent Supradisc™ II Modules 29 See Capsules – prefilters, air, gas and vent Selection Pall Advanta™ In-Line Liquid and Gas See Cartridges – prefilters, air, gas and vent Process Development and Optimization 249 Filter Housings 155 PreFlow™ Capsule Filters 43 Mustang® Chromatography Pall Advanta™ Jacketed Housings 157 Capsules and Cartridges 217 – 220 PreFlow™ Filter Cartridges 65 Pall Advanta™ Junior F Gas Filter Housings 152 Mustang® Coin Units 215 Pre-Inspection Reviews 253 Pall Advanta™ Junior F Liquid Filter Housings 151 Mustang® Membrane Pre-reverse Osmosis Filtration Pall Advanta™ Junior Filter Housings 149 ® Chromatography Starter Kits 211 – 214 Marksman™ Elements with Nexis A Pall Advanta™ Junior Gas Filter Housings 150 Series Filters 67 Mycel Separation Marksman™ Elements with Poly-fine® II Membralox® Ceramic Membrane Products Pall Process Engineered Systems 261 203 Series Filters 71 Pall Technical Services 239 – 258 Pallcell® Air and Gas Filter Cartridges 133 279 Index Pre-reverse Osmosis Filtration – Tangential Flow Filtration
R Marksman™ Elements with Poly-fine® XLD Reaction Spare Parts Provision Series Filters 69 PEF Multi Purpose Processor 267 Pall Process Engineered Systems 261 Press System Regulatory Approval Starclear™ Filter Cartridges 57 DGM Plate and Frame Filter Systems 263 See Validation Steam Service Pretreatment for Water Regulatory Inspections PMM® Metal Membrane Filter Cartridges 141 Water Systems 269 Pre-Inspection Reviews 253 PSS® Porous Metal Filter Cartridges 139 ® Prion Removal Regulatory Requirements Rigimesh Sintered Metal Mesh Filter Cartridges Mustang® Chromatography Capsules Training 251 137 and Cartridges 217 – 220 Removal of Activated Carbon Steaming Process Validation Virus Filters Troubleshooting and Consultancy Services 103 – 110 See Activated Carbon Removal and Recovery 257 P-Series Depth Filter Sheets 17 Removal of Catalysts Steam-in-place Procedures Troubleshooting and Consultancy Services Process Automation See Catalyst Fines – removal 257 ® Drivers for Palltronic Filter Integrity Removal of Filter Aids Sterile Filtration – air, gas, and vent Test Instruments Liquid Challenge 235 See Filter Aid Removal ® Pall Process Engineered Systems 261 Emflon CPFR High-temperature Removal of Mammalian Cells Sterilizing-grade Filter Cartridges 125 Process Chromatography 209 – 226 See Cell Culture Emflon® PFR Junior Style Filter Cartridges 121 Process Development and Optimization 249 Resolute Chromatography Columns 221 Kleenpak™ Capsules with Emflon® II Membrane Assemblies 115 Process Modeling Resolute Slurry Packing Systems 223 Kleenpak™ Capsules with Emflon® PFR Process Development and Optimization 249 Retention Studies Membrane Assemblies 117 Process Purification Process-Specific Filter Validation 241 Novasip™ Capsules with Emflon® PFR Chromatography 209 – 226 Reverse Osmosis Membrane Assembles 113 Process Scale-up Water Systems 269 Sterile Filtration – liquid Troubleshooting and Consultancy Services ® 257 Rigimesh® Sintered Metal Mesh Fluorodyne II Hydrophilic PVDF Filter Cartridges 87 ® Process Simulation Filter Cartridges 137 Kleenpak™ Capsules with Fluorodyne II Palltronic® Filter Manager 237 Membrane Assemblies 85 Risk Analysis Kleenpak™ Capsules with Posidyne® Process System Design Pall Process Engineered Systems 261 Membrane Assemblies 95 Pall Process Engineered Systems 261 Kleenpak™ Capsules with Supor® EKV Process Troubleshooting S Membrane Assemblies 79 Process Development and Optimization 249 Kleenpak™ Nova Sterilizing-grade and 101 Sampling Virus Removal Capsule Filters Process-Specific Filter Validation 241 Kleenpak™ Connectors 39 Kleenpak™ Ultipor® N66 Sterilizing-grade Product Activity after Purification Sanitizing Agents Capsule Filters 89 Troubleshooting and Consultancy Services 257 See Acids – filtration of Mini Kleenpak™ Sterilizing-grade Product Certification See Bases – filtration of Capsule Filters 77 Novasip™ Liquid Sterilizing-grade Pre-Inspection Reviews 253 Scale-up Capsule Filters 99 Troubleshooting and Consultancy Services 257 Product Vessel Venting Posidyne® Filter Cartridges 97 Air and Gas Filtration 111 – 142 Scientific and Laboratory Services Sealkleen™ Membrane Filter Cartridges 91 Product Viability Studies Process Development and Optimization 249 Supor® EBV Sterilizing-grade Filter Cartridges 83 ® Disposable Filtration System Validation 245 Screening Supor EKV Sterilizing-grade Filter Cartridges 81 ® Process-Specific Filter Validation 241 Mustang® Membrane Ultipor N66 Sterilizing-grade Filter Cartridges 93 Production Temperature Control Chromatography Starter Kits 211 – 214 Sterilization Procedures ® Pall Advanta™ Electrical Trace Heaters 167 Palltronic Filter Manager 237 Pre-Inspection Reviews 253 Profile® Filter Cartridges with Ultipleat® Sealkleen™ Filter Housings 147 Supor® EBV Sterilizing-grade Filter Cartridges 83 Construction 59 Sealkleen™ Membrane Filter Cartridges 91 Supor® EKV Sterilizing-grade Filter Cartridges 81 ® Profile II Filter Cartridges 51 Service Contracts Supracap™ 200 Encapsulated Profile® II Plus Filter Cartridges 53 Pall Process Engineered Systems 261 Depth Filter Modules 33 Profile® Star Filter Cartridges 55 Service Lines – air and gas Supracap™ 60 Depth Filter Capsules 31 Emflon® PFA Filter Cartridges 127 Programmable Logic Controller Supradisc™ Depth Filter Modules 27 ® Sheet Tangential Flow Filtration Membranes 207 Drivers for Palltronic Filter Integrity Supradisc™ II Modules 29 Test Instruments 235 Sheets – depth filters Systems BioSeries Depth Filter Sheets 15 Project Management Automated Systems E-Series Depth Filter Sheets 25 Pall Process Engineered Systems 261 Pall Process Engineered Systems 261 K-Series Depth Filter Sheets 19 Centrifugal Discharge Filter Systems Protection for Sterile Filter Membranes P-Series Depth Filter Sheets 17 PEF Multi Purpose Processor 267 See Prefiltration T-Series Depth Filter Sheets 21 Chromatography Protein Recovery Z-Series Depth Filter Sheets 23 PK Chromatography Skids 225 Tangential Flow Filtration 175 – 208 Single-use Systems Design PS Disposable Systems 37 Process Development and Optimization 249 See Filter Media – polysulfone Skids – Chromatography Disposable Systems 37 P-Series Depth Filter Sheets 17 PK Chromatography Skids 225 Fabrication Pall Process Engineered Systems 261 ® PSS Porous Metal Filter Cartridges 139 SLS PEF Multi Purpose Processor 267 PTFE See Scientific and Laboratory Services Plate and Frame Filter Systems See Filter Media – polytetrafluoroethylene (PTFE) Soiling Tests DGM Plate and Frame Filter Systems 263 Sheet Filters Purification of Bulk Enzyme Solutions Disposable Filtration System Validation 245 DGM Plate and Frame Filter Systems 263 TFF Polymeric Hollow Fiber Membranes Kleenpak™ Connector Validation 243 Tangential Flow Filtration Systems 195 and Ceramic Modules 197 Solvent Filtration for APIs Validation Emflon® FM Filter Cartridges 73 PVDF Disposable Filtration System Validation 245 Marksman™ Elements with Nexis® A See Filter Media – polyvinylidenedifluoride (PVDF) Water Systems 269 Series Filters 67 Pyrogen Removal Marksman™ Elements with Poly-fine® II See Endotoxin Removal Series Filters 71 T Marksman™ Elements with Poly-fine® XLD Tangential Flow Filtration 175 – 208 Series Filters 69 Q Capsules Profile® Filter Cartridges with Ultipleat® Minimate™ Tangential Flow Filtration Capsules 181 Qualification Construction 59 See Validation Profile® Star Filter Cartridges 55 280 Index Tangential Flow Filtration – Z-Series Depth Filter Sheets
Cassettes and Holders TFF Polymeric Hollow Fiber Membranes and Validation Data Tangential Flow Filtration Membrane Cassettes 185 Ceramic Modules 197 Pre-Inspection Reviews 253 T-flow Housings Tangential Flow Filtration Veladisc™ Module Housings 165 Membrane Cassette Holders 188 See Housings – T-flow Cell Harvest and Product Separation Virus Concentration Tissue Culture Media Capsules Tangential Flow Filtration Membrane Cassettes 185 Kleenpak™ Capsules with Supor® EKV Ceramic Modules Minimate™ Tangential Flow Filtration Capsules 181 Membrane Assemblies 79 ® Cassettes Membralox Ceramic Membrane Products 203 Kleenpak™ Nova Sterilizing-grade and 101 Pall Tangential Flow Filtration Cassettes 185 – 187 High Cell Concentration Virus Removal Capsule Filters Pallsep™ Vibrating Membrane Filtration Mini Kleenpak™ Sterilizing-grade Virus Removal Technology 205 Capsule Filters 77 Capsules Hollow Fibers PreFlow™ Filter Cartridges 65 Novasip™ DV20 and DV50 Virus Removal Microza Membranes 198 – 202 Supor® EBV Sterilizing-grade Filter Cartridges 83 Filter Capsules 103 Lab-scale Systems Supor® EKV Sterilizing-grade Filter Cartridges 81 Cartridges Minimate™ Tangential Flow Filtration System 183 Ultipor® VF Grade DV50 Virus Removal Ultipor® VF Grade DV20 Virus Removal Tangential Flow Filtration Technology 194 Filter Cartridges 109 Filter Cartridges 107 Large Process Volumes Ultipor® VF Grade DV50 Trademarks Tangential Flow Filtration Membrane Cassettes 185 Virus Filter Cartridges – SBF Junior Style 105 Legal Warranty and Trademarks Membranes – ceramic 282 Ultipor® VF Grade DV50 Virus Removal Membralox® Ceramic Membrane Products 203 Troubleshooting and Consultancy Services 257 Filter Cartridges 109 Membranes – hollow fiber Troubleshooting Processes Microza Membranes 198 – 202 Process Development and Optimization Membranes – sheet 249 W Sheet Tangential Flow Filtration Membranes 207 T-Series Depth Filter Sheets 21 Water Droplet Removal Membranes – vibrating LG Liquid and Gas Coalescing Filter Cartridges 135 Pallsep™ Vibrating Membrane Filtration U Water for Injection Technology 205 Water Systems 269 Mycel Separation Ultipor® GF Plus Air and Gas Filter Cartridges 129 ® Water Intrusion Test Membralox Ceramic Membrane Products 203 Ultipor® GF Plus Filter Cartridges 63 Pilot Scale Palltronic® Aquawit XC System 231 ® Centramate™ Cassettes and Holders 185 Ultipor N66 Particulate and Palltronic® Flowstar XC Filter Integrity Research and Pilot Studies Bioreduction Filter Cartridges 75 Test Instruments 229 Centramate™ Cassettes and Holders 189 – 193 Ultipor® N66 Sterilizing-grade Filter Cartridges 93 Water Purification Minimate™ Tangential Flow Filtration Capsules 181 Ultipor® VF Grade DV20 Water Systems 269 Systems Virus Removal Filter Cartridges 107 Pilot and Process Development Capabilities 194 Water Storage and Distribution Tangential Flow Filtration Systems 195 Ultipor® VF Grade DV50 Water Systems 269 Virus Filter Cartridges – SBF Junior Style 105 Water Systems 269 Training 251 ® Ultipor VF Grade DV50 WFI Tangential Flow Filtration Membrane Virus Removal Filter Cartridges 109 See Water for Injection Cassette Holders 189 – 193 Tangential Flow Filtration Systems 195 Ultrafiltration WIT Matching Membrane Cassettes to Applications 180 See Water Intrusion Test Tanks – sterile venting Membralox® Ceramic Membrane Products 203 ® Emflon CPFR High-temperature Minimate™ Tangential Flow Filtration Capsules 181 Sterilizing-grade Filter Cartridges 125 Sheet Tangential Flow Filtration Membranes 207 Z ® Emflon PFR Junior Style Filter Cartridges 121 Tangential Flow Filtration Membrane ® ZHF Centrifugal Discharge Filter Systems 265 Emflon PFR Sterilizing-grade Filter Cartridges 123 Cassette Holders 189 – 193 ® Z-Series Depth Filter Sheets 23 Kleenpak™ Capsules with Emflon PFR Tangential Flow Filtration Systems 195 Membrane Assemblies 117 TFF Polymeric Hollow Fiber Membranes Technical Data and Ceramic Modules 197 Pre-Inspection Reviews 253 Water Systems 269 Technical Training and Services Ultrafiltration and Microfiltration Analysis and Review Membranes for Cassettes 178 Contamination Analysis 247 UpScale™ Products Pre-Inspection Reviews 253 Disposable Systems 37 Process Development Kleenpak™ Capsules with Emflon® II Process Development and Optimization 249 Membrane Assemblies 115 Test Instruments Kleenpak™ Capsules with Fluorodyne® II ® Palltronic Training Program 234 Membrane Assemblies 85 Training Kleenpak™ Capsules with Posidyne® ® Palltronic Training Program 234 Membrane Assemblies 95 Troubleshooting Kleenpak™ Capsules with Supor® EKV Troubleshooting and Consultancy Services 257 Membrane Assemblies 79 Validation Kleenpak™ Ultipor® N66 Sterilizing-grade Disposable Filtration System Validation 245 Capsule Filters 89 Filter Integrity Test Equipment Validation 255 Mini Kleenpak™ Sterilizing-grade Kleenpak™ Connector Validation 243 Capsule Filters 77 Process-Specific Filter Validation 241 Mini Profile® Capsule Filters 45 Temperature Control for Hot Water or Steam Mustang® Coin Units 215 Pall Advanta™ Jacketed Housings 157 Mustang® Membrane Chromatography Starter Kits 211 – 214 Test Instruments PreFlow™ Capsule Filters 43 Filter Integrity Test Instruments Supracap™ 60 Depth Filter Capsules 31 Palltronic® Aquawit XC System 231 Palltronic® Flowstar XC Filter Integrity Test Instruments 229 V Filterability Test Instruments Vaccines Palltronic® Filter Manager 237 Tangential Flow Filtration Membrane Process Automization Cassette Holders 189 Drivers for Palltronic® Filter Integrity Tangential Flow Filtration Test Instruments 235 Membrane Cassettes 185 – 187 Remote Control Tangential Flow Filtration Systems 195 Drivers for Palltronic® Filter Integrity Test Instruments 235 Validation Verification of Flow for Integrity Test Instruments Aseptic Connectors 243 Palltronic® Flow Check Device 233 Disposable Filtration System Validation 245 Filter Integrity Test Equipment Palltronic® Instruments 227 – 236 281 Trademarks
Trademarks The Following trademarks, also used in this publication, are the property of the Pall and are registered trademarks companies listed below. of Pall Corporation. ATTC: American Type Culture Collection The following trademarks or service marks used in this publication are the property of C-Flex: Consolidated Polymer Pall Corporation. Technologies, Inc. The following are registered trademarks of Easy-Load Cole-Palmer Instrument Co. Pall Corporation: Flaretek: Entegris, Inc. Acro Acrodisc Hastelloy: Haynes International, Inc. Emflon Fluorodyne L/S Cole-Palmer Instrument Co. Gaskleen HDC Membralox Membraplan Luer-Lok: Becton, Dickenson & Company Mustang Nexis Masterflex: Cole-Palmer Instrument Co. Nova Pallcell Palltronic PMM Microza: Asahi Kasei Poly-Fine Posidyne Nitronic: Armco, Inc. Profile PSS Pharmed Saint-Gobain Performance Rigimesh Supor Plastics Corp. Supradur Suporlife Ultipleat Ultipor Resolute: Euroflow (UK) Ltd. The following are trademarks of Pall Santoprene: Advanced Elastomer Corporation: Systems, LP, an ExxonMobil Chemical Affiliate. AcroPak Alpha Centramate Centrasette Stäubli: Stäubli AG Centrastak Kleenpak Swagelok: Cranford Fitting Company Marksman Maxim Maximate Maxisette Tri-Clamp, Tri-Clover: Alfa Laval, Inc. Megaplast Omega Viton: DuPont Dow Elastomers L.L.C. Novasip Pall Advanta Pallsep PreFlow Pall Corporation’s North American Regen Sealkleen Manufacturing, Engineering, Sales and Starclear Supracap Marketing Operations have received Supradisc ISO 9001 Certification from Lloyd's The following are service marks of Pall Register Quality Assurance Limited. Corporation: ISO 9001 is the most comprehensive Pall Advanced Separations System standard since only it includes the design Upscale and development functions as well as Filtration. Separation. Solution production and installation, the latter covered in ISO 9002. This complements © 2005 Pall Corporation extensive ISO 9000 Certifications by the same registrar for several Pall groups in Europe. This is independent recognition that Pall’s quality systems are designed to meet customer requirements.
282 International Offices
Argentina Pall Corporation-Argentina Riobamba 1236. Piso 8 of “C” 1116 Buenos Aires Tel: 54.1.814.4730, Fax: 54.1.814.4724 Australia Pall Corporation-Australia Melbourne Office: 1-2 Wandarri Court, Cheltenham VIC 3192 Tel: 61.39.5848100, Fax: 61.39.5846647 E-mail: [email protected] Sydney Office: Unit 2, 11-13 Orion Road, Lane Cove, Sydney, NSW 2066 Tel: 61 02 9424 3000, Fax: 61 02 9420 3388 Austria Pall Austria Filter GmbH Seeböckgasse 59, 1160 Wien Tel: 43.1.49192.0, Fax: 43.2.49192.400, E-mail: [email protected] Belgium Pall Belgium Leuvensesteenweg 633-unit C, B-1930 Zaventem, Belgium Tel: 32.2.755.91.74, Fax: 32.2.755.91.70 Canada Pall (Canada) Ltd. Ontario Office 7205 Millcreek Drive, Mississauga, Ontario L5N 3R3 Tel: 905.542.0330, 800.263.5910 (Canada only) Fax: 905.542.0331, 800.943.4455 (Canada only) Quebec Office 2535 De Miniac, Ville St.Laurent, Quebec, H4S 1E5 Tel: 514.332.7255, Alternate Tel: 800-435-6268 (Canada only) Fax: 514.332.0996, Alternate Fax: 800-808-6268 (Canada only) China Pall Filter (Beijing) Co., Ltd. B706-709 Pengrun Building No.26, Xiaoyun Road, Chaoyang District, Beijing 100016, PR China Tel: 86.10.8458.4010, Fax: 86.10.8458.4001 3/F Bailing Bldg. No.1 Zuojiazhuang Qianjie, Chaoyang Dist., Beijing 100028 Tel: 86.10.6464.9156/9157, Fax: 86.10.6464.9139 Changchun Regional Office: Rm.1508, Tonghui Building, No.60, Tongzhi Street, Changchun 130021 Tel: 86.431.566.8333, Fax: 86.431.563.2856 Guangzhou Regional Office: Rm.C, 8/F, Haiyun Building, No.308, Binjiang Zhonglu, Haizhu District, Guangzhou 510220 Tel: 86.20.8410.2211, Fax: 86.20.8410.2033 Hong Kong Office: Rm 1407 and 1409,14/F, Tung Ying, Building 100, Nathan Road, Tsim Sha Tsui, Kowloon, Hong Kong Tel: 852.2583.9610, Fax: 852.2511.5773 Shanghai Regional Office of Pall China Room 1008-1014, 10/F, Tower A, City Center of Shanghai, No.100 Zunyi Road, Changning District, Shanghai 200030 Tel: 86.21.6237.1988. Fax: 86.21.6237.2088 France Pall France 3 rue des Gaudines, BP 5253, 78175 Saint-Germain-en-Laye Cedex, France Tel: 33.1.30.61.38.00, Fax: 331.30.61.57.08, E-mail: [email protected] Germany Pall GmbH, Geschaftsbereich BioPharmaceuticals Phillipp-Reis Strasse 6, D-63303 Dreieich Tel: 49.6103.3070, Fax: 49.6103.34037, E-mail: [email protected] India Pall India Pvt. Ltd. Sahney Kirkwood Compound, 1st Floor 27, Kirol Vidyavihar (West), Mumbai 400086 Tel: 91.22.55995555, Fax: 91.22.55995556 Indonesia Pall Filtration Pte Ltd Indonesia Rep. Office Menara Imperium 1t, 20, Suite C & D Metropolitan Kuningan, Superblok Kav 1, J1 H R Rasuna Said, Jakarta 12980 Tel: 62.21.8379.5442/43, Fax: 62.21.8379.2549 Italy Pall Italia s.r.l. Via G., Bruzzesi 38/40, 20146 Milano, Italia Tel: 39.0247.7961, Fax: 39.0241.22985, E-mail: [email protected] Japan Nihon Pall Ltd. 6-8-1, Nishishinjuku, Shinjuku-ku, Tokyo, 163-6017, Japan Tel: 81.3.6901.5800, Fax: 81.3.5322.2134
283 International Offices
Korea Pall Korea Limited Il-dong Building – 4th Floor, 968-5, Daechi-3dong, Gangnamgu, Seoul, 135-736 Korea Tel: 82.2.560.7833, Fax: 82.2.569.9092 Malaysia Pall (Malaysia) Sdn Bhd, (Penang Branch Office) B-4-16, Krystal Point, 303, Jalan Sultan Azlan Shah, 11900 Bayan Baru, Penang Tel: 60.4.642.2648, Fax: 60.4.642.2869 Pall (Malaysia) Sdn Bhd (Johor Bahru Branch Office) 38, Jalan Teratai 8, Taman Johor Jaya, 81100 Johor Bahru Tel: 60.7.353.8477, Fax: 60.7.355.2095 Pall Malaysia Sdn Bhd 23, Jalan Pengacara U1/48, Temasya Industrial Park, Glenmarie 40150 Shah Alam, Selangar Darul Ehsan Tel: 60.3.5569.4892, Fax: 60.3.5569.4896 New Zealand 27 Kaimiro Street, PO Box 10 492, Hamilton Tel: 64.7.957.9510, Fax: 64.7.957.9513 Norway Pall Norge AS Barbroveien 6, N-3511 Hoenfoss Tel: 47.32.18.1470, Fax: 47.32.18.1487, E-mail: [email protected] Philippines Pall Filtration Pte Ltd, Philippine Representative Office Unit 509, 5th Floor, Prestige Tower Cond., Emerald Avenue, Ortigas Center Pasig City, Tel: 63.2.6353620, Alternate Tel: 63.916.571.9258, Fax: 63.2.6353560 Poland Pall Poland, Ltd. ul.Kasprowicza 151 pok.315, 01-949 Warszawa Tel: 48.22.834.81.86, Fax: 48.22.835.83.83, E-mail: [email protected] Russia Pall GmbH, Moscow Representative Office Vyatskaya Street 27, Building 13-14, 127015 Moscow Tel: 7.095.787.76.14, Fax: 7.095.787.76.15 Singapore Pall Filtration Pte Ltd 17 Changi Business Park Central 1, #06-01/04, Honeywell Building Singapore, 486073 Email: [email protected] Customer Service Hotline: +65 6388 8688, Tel: +65 6389 6500 Alternate Tel: +65 6388 8688, Fax: +65 6389 6501 South Africa Pall South Africa Pty, Ltd. 33 New Road, Grand Central, Midrand 1685, Johannesburg Tel: 27.11.266.2300, Fax: 27.11.315.3243 Spain Pall España Edificio Mendez, C/Isla de Corcega, No.2 Alcobendas, 28100, Madrid, Spain Tel: 34.91.657.9800, Fax: 34.91.657.9837, E-mail: [email protected] Switzerland Pall (Schweiz) AG Schaeferweg 16, CH-4057 Basel, Switzerland Tel: 41.61.638.3900, Fax: 41.61.638.3940, E-mail: [email protected] Taiwan Taipei Liaison Office Customer Service Center, 18, Lane 607, Kuang-Fu Rd.Sec 1, Hsin Chu City, Taiwan Tel: 03.579.8326, Fax: 03.577.9187 Thailand Pall Thailand Unit 2501 Rasa Tower 25th Floor, Phaholyothin Road, Kwang/Khet Chatuchak, Bangkok 10900 Thailand Tel: 66.2.937.1055, Fax: 66.2.937.1066 United Arab Emirates Pall Middle East PO Box 38124 Dubai, Tel: 971.4.340.6204, Fax: 971.4.340.6205 United Kingdom Pall Life Science Europa House, Havant Street, Portsmouth, Hampshire, PO1 3PD Tel: 44.23.9230.3303, Fax: 44.23.9230.2506, E-mail: [email protected] United States Pall Corporation 2200 Northern Boulevard, East Hills, NY 11548 Tel: 516-484-5400, Fax: 516-801-9548, E-mail: [email protected]
284
Pall has the most comprehensive family of scalable separation products. 2200 Northern Boulevard East Hills, New York 11548-1289 Visit us on the web at www.pall.com/biopharmaceutical +1 800.717.7255 toll free Pall Corporation has offices and plants throughout the world in locations including: +1 516.484.5400 phone Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, +1 516.801.9548 fax New Zealand, Norway, Poland, Puerto Rico, Russia, Singapore, Spain, South Africa, [email protected] e-mail Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. Distributors are located in all major industrial areas of the world.
Europa House, Havant Street Portsmouth PO1 3PD, United Kingdom +44 (0)23 9230 3303 phone +44 (0)23 9230 2506 fax [email protected] e-mail USD 2293
Supor® UEAV Filter Cartridges For Extended Service Life and High Flow Rates Supor UEAV Filter Cartridges For Extended Service Life and High Flow Rates
High area 0.2 µm filter with bioburden and particle removal capability for extended service life and high flow rates in biologic fluids, cell culture media and buffers
New and advanced best-process technology, Quality and Bio-Safety (P Grades) such as the Pall Supor UEAV range of filters, Supor UEAV high flow, long life cartridges is more and more important to meet have been specially designed and qualified expectations. for use in applications with buffers, as well as biologic and biotech fluids. The “P” Certificate Pall Supor UEAV filter cartridges incorporate meets and confirms pharmaceutical a new hydrophilic and asymmetric machV requirements on the effluent regarding: technology polyethersulfone membrane for superior dirt load capacity for even finest Effluent Quality Tests particles combined with a broad pH • Cleanliness per USP Particulates in compatibility. injectables on Fiber-Releasing per 21 CFR Moreover, the patented Ultipleat® technology, • Non-Pyrogenic per USP Bacterial with a narrow core and mechanically robust Endotoxins (< 0.25 EU/mL) filter configuration, offers maximum membrane • Meets total organic carbon (TOC) and area and extended service life with the most conductivity per USP Purified Water, pH complex biologic fluids, as well as very short per USP Sterile Purified Water processing times in case of high-volume • Meets pH-shift per USP Sterile Purified buffers, cell culture media or supernatants. Water Biological Tests The amalgamation of new and advanced design and construction concepts contribute • Meets USP biological reactivity, in vivo, to significantly higher service life and lower for Class VI 121°C plastics pressure drops in all kinds of biologic process The quality management system for applications. manufacturing of Supor UEAV filter cartridges occurs in an controlled environment and in In biotech, blood product, vaccine and buffer conformance with Certified Quality System applications, these membrane and design ISO 9001. benefits mean higher yield, higher process safety, less time, less handling and less cost. Each filter is 100% integrity tested and fully traceable by individual marked lot and serial number. Supor UEAV Filter Cartridges Technical Specifications
Features Typical Liquid Flow Rates at 20°C (68°F)* • Ultipleat filter cartridge configuration with crescent-shaped pleat gpm structure and narrow diameter polypropylene core results in a 0oo 5 10 15 300 higher membrane area within a compact membrane package 4 Supor • machV technology incorporates hydrophilic asymmetric 250 polyethersulfone membrane 3 • Filters that pass the appropriate Forward Flow test have been 200 shown in laboratory tests to typically provide titer reductions in 6 excess of 1 x 10 when challenged with aqueous suspensions of 150 2 Brevundimonas diminuta (ATCC 19146) • Cartridge integrity testable by Forward Flow test 100
1 (psi) Pressure Differential Differential Pressure (mbar) Pressure Differential Benefits 50 • Smaller housings and fewer filter cartridges to be changed out for given flow and pressure drop requirements 0 0 0oo 10 20 30 40 50 60 • Fewer cartridges or capsules needed to maintain required flow L/min per 254 mm (10 in.) module • Additional service life combined with minimum pressure drop when * For fluids at 1 cP viscosity. For other viscosities, divide flow rate by using the maximum number of filter cartridges per housing viscosity in cP. Determined on unused filters in laboratory testing. • Exceptionally high flow rates and superior service life for processing large fluid volumes • Excellent retention of microorganisms, for superior protection of final filters and downstream equipment such as tangential flow or chromatographic systems • Polyethersulfone filter medium minimizes unspecific adsorption effects or unwanted enzyme activation as known from certain filter or fiber materials • Broad pH compatibility allows the use of polyethersulfone membrane in a full range of biological fluids and buffers • Bioburden reduction efficiency for processes with variable bioburden and critical applications with high flow requirements • The Forward Flow test allows safe, easy and fast confirmation of filter integrity after steaming and filtration Supor UEAV Filter Cartridges Technical Specifications
Materials of Construction Typical Cumulative Steam Life(1)
Membrane Hydrophilic, asymmetric polyethersulfone 10 hours (1 hour cycles) at 125°C (257°F) (0.2 µm particulate rating) (1) The steam life and service life data were determined by testing under controlled laboratory Drainage Layers Polypropylene conditions up to the time indicated. Actual operating conditions may affect the filter’s long term resistance to steam sterilization and hot air service. Filters should be qualified for End Cap and Cage Polypropylene each process application.
Core Polypropylene Maximum Forward Steaming Conditions Adapter Polypropylene with internal stainless steel reinforcing ring 300 mbard ∆p at 125°C (4.4 psid at 257°F)
Effective Surface Area Maximum Temperature and Differential Pressure(2)
AB1UEAV7PH4 Typically 1.06 m2 (11.4 ft2) Maximum forward differential pressures in compatible fluids are:
2 2 AB2UEAV7PH4 Typically 2.12 m (22.8 ft ) 5.5 bard at 40°C (80 psid at 104°F)
2 2 AB3UEAV7PH4 Typically 3.18 m (34.2 ft ) 3.0 bard at 80°C (43 psid at 176°F) AB4UEAV7PH4 Typically 4.24 m2 (45.6 ft2) (2) In compatible fluids which do not soften, swell, or adversely affect the filter or its materials of construction.
Typical Extractables per 254 mm (10 inch) module Forward Flow Integrity Test Values(3) ≤ 50 mg in water at 20°C (68°F) after a 1 hour autoclave cycle and 4 hours ≤ extraction time With water wet cartridges and air as test gas 50 mL/min at 2060 mbar (30 psi). Preflush at 5 L/min per module for 10 minutes prior to Forward Flow testing.
(3) Please contact Pall for multi-element integrity test values. Values are for one 254 mm (10 inch) filter at 20°C (68°F).
Ordering Information(4)
Pall Part Number: AB UEAV P
Code Nominal Length Code Cartridge Style Code O-ring Material
1 254 mm (10 inch) 2 Double O-ring with bayonet lock and flat end H4 Silicone
2 508 mm (20 inch) 7 Double O-ring with bayonet lock and finned end J EPR
3 762 mm (30 inch)
4 1016 mm (40 inch)
(4) This is a guide to the part number structure only. For availability of specific options, please contact Pall or your local Pall distributor.
Pall has the most comprehensive family of scaleable separation products. New York - USA +1 516 484 5400 phone Visit us on the web at www.pall.com/biopharmaceutical +1 516 801 9548 fax pharmafi[email protected] e-mail Pall Corporation has offices and plants throughout the world in locations including: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth - Europe Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, +44 (0)23 9230 3303 phone Sweden, Switzerland, Taiwan, Thailand, United Kingdom, the United States and Venezuela. +44 (0)23 9230 2506 fax Distributors are located in all major industrial areas of the world. [email protected] e-mail Because of developments in technology these data or procedures may be subject to change. Consequently we advise users to review their continuing validity annually. , Pall, Ultipleat and Supor are trade marks of Pall Corporation. Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. Part Numbers quoted above are protected by the Copyright of Pall Europe Limited. ® indicates a trademark registered in the USA. © 2004, Pall Europe Limited. 09.2004 BIOSEPRA® Q & CM HYPERZ™ in industrialoperations. Proteinbinding typi- not beendesignedforoptimal productivity Existing ionexchangesorbents forEBAhave Reducestotalcapture-step costsby20-40%. • Improvesproduct qualityandyield, • eliminating post-fermentation clarification, Significantlyreducesprocesscycletime by • considerable operationalbenefits: proteins byexpandedbedadsorptionoffers proteins. Rapid,directcaptureoftarget plasmids, IgGandvariousrecombinant ical feedstocksandforthepurificationof processing oflargevolumescrudebiolog- raphy isatechnologyideallysuitedforrapid Expanded bedadsorption(EBA)chromatog- *)Breakthroughcapacityat10%using5mghuIgG/mlin50mMsodiumacetatebuffer, pH4.7,150mMNaCl. (**) Breakthroughcapacityat10%using5mgBSA/mlin50mMTris-HCl buffer, pH8.6,150mMNaCl. (*) • Outstandingchemicalresistance. • Highdensityallowsoperationwithhigherflowratesandbiomassloads. • Smallbeadproducesmorerapidbindingandhighercapacity. • Limiteddilutionrequiredforefficientbinding. • Directcapturefromcrude,unclarifiedfeedstock. High ProductivityExpandedBedAdsorptionChromatography. Q &CMHyperZ laigp -41-14 4.13 Glycerol form(2g~1ml) Dry 1-14 form(2g~1ml) Dry 3.2g/ml 40-105 ~50(huIgGs)** 4-13 100-180 75 Glycerol Stabilizer containedinthesorbent Packaging 3.2g/ml Cleaning pH 80(BSA)* Carboxymethyl(CM) Working pHrange 40-105 100-180 Degree ofexpansion(H/H 75 Binding capacity(mg/ml) amine(Q) Quaternary Mean particledensity Particle sizedistribution Ionic capacity(µeq/ml) Nature ofionicgroups Average particlesize(µm) Table 1:HyperZ Chemical stability Stable in all commonly used aqueous buffers and also 2M NaOH, Stableinallcommonlyusedaqueousbuffersandalso2M Chemical stability ™ Sorbents MainProperties. 0 t30c/ 2at300cm/h 2at300cm/h ) ™ Ion ExchangeSorbents yeZCMHyperZ Q HyperZ 1 MHCl,20%ethanol,6guanidine-HCl 1 from Pall of anewfamilyhigh-density sorbents BioSepra process cycleduration. ing flowrates,substantiallyincreasing only beachievedbyareductioninoperat- (>10% ww/v);exceedingtheselevelscan are incompatiblewithhighbiomassloads and loadtimes.Inaddition,thesesorbents unacceptably increasingprocessvolumes cally requiressignificantfeedstockdilution, single passoperation. ly fromcrude,unclarifiedfeedstocks ina and efficientcaptureofbiomolecules direct- productivity expandedbed chromatography ® ® , specificallydesignedforhigh Q andCMHyperZ PRODUCT NOTE ™ are members BIOSEPRA® Q & CM HYPERZ™ CM HyperZ charge densityinitshydrogelmoiety, the expanded bedsorbents.Duetoahigh flow rangepossibleofanycommercial designed todeliverthebroadestusefullinear are obtainedwithHyperZ elutriation. Typically, bedexpansionsof2-3 with CMHyperZ higher linearflowvelocitiescanbeused dard profileforanSPEBAsorbent:~2times sonable (2-3)bedexpansionrates(see high biomassloadswhilemaintainingrea- of QandCMHyperZ Figure 2showsthehydrodynamicbehavior • Highdensityparticles:Fasterflowrates. of largevolumesfeedstream. scale, likeavoidingorlimitingthedilution This providessignificantbenefitsatprocess binding propertiesinthepresenceofsalt. The HyperZ sacrificing capacity. Higher biomassandflowratewithout h rsneo %gyeo.Figure 3.Bedexpansionasafunctionofbiomass. the presenceof9%glycerol. Figure 2.Comparisonofhydrodynamicbehaviorin CM HyperZ • Higherbiomassloads. packed bedmode. as resolutionwhenthesorbentisusedin cle sizealsoimprovesmasstransferaswell or upperfritclogging.75µmaverageparti- expansion, leadingtoaparticleelutriation cle sizes,showmuchhigherdegreesofbed which havelowerdensitiesandlargerparti- conditions, conventionalEBAsorbents, ear velocitiesof300cm/h.Undersimilar Bed expansion SP EBAsorbent Conventional ™ ™ ™ can operateinthepresenceof sorbent hasuniqueprotein product rangehasbeen ™ without riskofparticle ™ sorbents, andastan- Linear velocity(cm/h) ™ sorbents atlin- CM HyperZ Q HyperZ 2 • Scaleup:Useanycommercially avail- available columns. cy, from5cmto30I.D.commercially example oftheexcellentpackingconsisten- benefits ofbedstability. Figure5showsan type ofEBAcolumnandoffersubstantial HyperZ sorbentscanbeeasilypackedinany prior tointroductionofthehydrogel. Scanning electronmicrographimageofHyperZbeadandsurface Figure 1.StructureofHyperZsorbents. Bed Expansion culture (12x10 highdensitycell sions of2-3,evenwithvery ing 300cm/hareobtainedatbedexpan- Figure 4showsthatlinearvelocitiesexceed- processed directly. highly concentratedfeedstocksneedtobe Figure 3).Thisisofcriticalimportancewhen tivity. able EBAcolumnandimproveproduc- Conventional PRODUCT NOTE EBA sorbent 6 cells/ml). Biomass (%wetweight) HyperZ sorbent Figure 4. CM HyperZ expansion in the presence of different Figure 6. Efficient separation of a mixture of proteins in mammalian cell concentrations. packed bed mode using CM HyperZ sorbent.
6 12 x 10 cells/ml 3 x 106 cells/ml 280 A Bed expansion
No cells, acetate buffer
Time (min) Linear velocity (cm/h) Column: 1.1 cm I.D., 8 cm packed bed height. Sample: 1 ml load (15 Column:1 cm I.D., 10 cm settled bed height CM HyperZ sorbent. Sample: mg/ml ovalbumin (A), 3 mg/ml cytochrome c (B) and 5 mg/ml lysozyme crude high density hybridoma cell culture diluted with equilibration buffer (C)). Conditions: Linear gradient 50 mM acetate, pH 4.5, 0-120 mM NaCl. (50 mM acetate / 5 mM citrate, 75 mM NaCl, pH 4.7).
Figure 5. Scale-up with Q and CM HyperZ sorbents. Short residence times, high dynamic bind- ing capacity: Increase throughput. HyperZ™ are composite sorbents which represent an extension of the well-known HyperD® family of enhanced diffusion sorbents. These unique sor- Bed Expansion bents are composed of a high-capacity hydrogel polymerized within the pores of a rigid inert bead. The hydrogel moiety has a very high number of ionic binding sites. Proteins diffuse quickly within the hydrogel, and are rapidly "captured" by these 5 cm I.D. 20 cm I.D. Linear velocity (cm/h) 10 cm I.D. 30 cm I.D. highly accessible charges.
20 cm settled bed height. Conditions: 50 mM acetate / 5 mM citrate, Residence time gives a broad measure of produc- pH 4.5 or 50 mM Tris-HCl, pH 8.6. tivity and sorbent performance, independently of column geometry. Figure 7 illustrates that short residence times are needed for protein capture on Maximum flexibility: Packed bed or CM HyperZ™. Only a modest reduction of the Expanded Bed, in any commercially avail- dynamic binding capacity (DBC) is observed if res- able column. idence time is decreased from 10 min. to 5 min., Establishing and maintaining a basic purification in contrast to conventional EBA sorbent. process and choice of chromatography sorbents throughout development, pilot studies and pro- Figure 7. Dynamic capacity vs. residence time. duction can significantly reduce process re-opti- mization time and effort during scale-up. CM HyperZ HyperZ™ sorbents provide the ultimate in process flexibility. With clarified feedstocks, HyperZ™ can be used in conventional packed bed mode for process optimization, scale-up and even in very Conventional DBC 10% (mg/ml) EBA sorbent large-scale production settings. The relatively small particle size of HyperZ® (75 µm, to be compared to 200 µm for conventional EBA sorbents) increas- es efficiency and resolution of the separation when the sorbent is used in a regular packed bed col- Residence time (min) umn (Figure 6), while still operating at low back- pressure. Sample: 5 mg/ml hu IgG in 50 mM acetate / 5 mM citrate, 150 mM NaCl, pH 4.5. Studied performed in packed bed columns.
3 BIOSEPRA® Q & CM HYPERZ™ of CMHyperZ Figure 9showstheadsorptionperformance cycle timeandlowercost. mally dilutedfeedstock,resultinginshorter ofproteinsfromundilutedormini- harvest exchange EBA. Q HyperZ ty. CMHyperZ to processingtime,costandproductquali- These dilutionstepssignificantlycontribute achieve reasonableproteinbindingcapacity. water orlow-saltbufferisrequiredto significant feedstockdilution(2-5fold)with With conventionalcationexchangesorbents, CM HyperZ With QHyperZ to 19mS/cm). salt (150mMNaCl,orconductivityfrom14 obtained, eveninthepresenceofmoderate ties from25to60mg/mlofIgGare ture fromcrudefeedstock:routinely, capaci- is particularlywellsuitedtodirectIgGcap- With QHyperZ sources, including binant proteinsandenzymesfromvarious has beenusedtopurifynaturalandrecom- Expanded bedanionexchangeadsorption As illustratedinFigures8and9,CMHyperZ the operationcapacityofsorbent. times of2-5min.arealsosufficienttoreach buffer at300cm/h. mg/ml ofBSAareobtainedinaTris pH8.6 150 mMNaCl). high saltconcentration(>60mg/mlwith atrelatively high capacitiesareobserved 4.5 invarioussaltconditions.Remarkably results. cell disruption methodscouldimprove the meeting) suggeststhatspecial caregivento of sorbentcapacity. Recentwork(EBA2002 al groups,resultinginfouling anddecrease tend tobeadsorbedbyQ orDEAEfunction- as celldebrisofyeasthomogenates orDNA limited bythefactthatanimalcellsaswell broad useofEBAanionexchangehasbeen ma andmilkfromtransgenicanimals.The unclarified crudeyeasthomogenates,plas- with minimalfeedstockdilution. ™ : Anewtoolforanion ™ : AnIgGCapturetool, ™ ™ ™ ™ for huIgGmeasuredatpH , averagecapacitiesof80 can beusedforthedirect (data notshown),residence E.coli fermentation, ™ 4 CM HyperZ maximal sorbentfoulingcanoccur. Qand use inexpandedbedoperationswhere HyperZ demonstrated thatcontinuous storageof Other experiments(datanotshown)have CM HyperZ place treatments.Longtermstoragedataof harshclean-in- neered towithstandvery also beused for regenerationandcleaning. ethanol/1 M NaOH) oracidicmixtures can ethanol, 30%isopropanol or mixtures(20% Agentssuchas20% bent performance. 55°C) forseveraldaysdoes notimpactsor- using CMHyperZsorbent. Figure 9.DirectcaptureofhuIgGinthepresencesalt - QHyperZ:50mMTris-HCl, pH8.6.Sample:5mg/ml BSA. 4.5. Sample:5mg/mlhuIgG. - CMHyperZ:50mMacetate/5citrate,150NaCl,pH 300 cm/h(2Xbedexpansion).Equilibrationbuffer: 1 cmI.D.EBAcolumn,11settledbedheight.Linearvelocity: Figure 8.HyperZsorbentdynamiccapacity. The HyperZ standing chemicalresistance. Increased sorbentlifetimeduetoout- bration buffer. recorded at10%breakthrough.Sample:5mg/mlhuIgGinequili- cated. Linearflowrates:100cm/h.Dynamicbindingcapacities 50 mMacetate/5citrate,pH4.5.AdjustedinNaClasindi- 1.1 cmI.D.column,8packedbedheight.Equilibrationbuffer: DBC hu IgG (mg/ml) DBC hu IgG (mg/ml) ™ ratruh%breakthrough % breakthrough MHpr QHyperZ CM HyperZ in hotsolutionsofNaOH(1 Mat ™ ™ ™ PRODUCT NOTE are showninFigure10. sorbents havebeenengi- product rangeisdesignedfor NaCl concentration(mM)
DBC BSA (mg/ml) Figure 10. CM HyperZ sorbent long-term stability to NaOH. • Application 2. Purification of recombinant endostatin on CM HyperZ™ after method optimization on CM ProteinChip® Arrays. Courtesy of Dr. Joseph Shiloach, NIDDK, NIH, Bethesda, MD (USA) Figure 11 (upper part) shows a chromatographic
DBC hu IgG (mg/ml) purification of recombinant endostatin from a crude P. pastoris fermentation extract. The binding and elution conditions were first optimized on a CM ProteinChip® Array (data not shown). The "on-
Days of storage in 2 M NaOH chip" optimized conditions were transferred on a CM HyperZ™ sorbent : adsorption of endostatin Capacity at 10% breakthrough hu IgG determined at 100 cm/h in packed bed columns. Sample: 5 mg/ml hu IgG in 50 mM acetate / 5 mM citrate, was done at pH 5.0, and desorption achieved by a 150 mM NaCl, pH 4.5. two-step gradient of NaCl (200 and 800 mM). Linear flow rate was 300 cm/h. Collected fractions
Applications. Figure 11. Capture of endostatin from P. pastoris fermentation broth on CM HyperZ sorbent and fraction analysis using the ProteinChip® technology. Typical applications for CM and Q HyperZ™ sorbents include : - Direct capture of IgG and IgG fragments from a variety of 280 feedstocks. A - Purification of intracellular and extracellular enzymes. - Purification of recombinant proteins from E. coli or yeast fer- mentation. RC-MS analysis on NP20 ProteinChip® arrays - Recombinant proteins from transgenic milk or plant extracts. - Potential alternative to packed bed ion exchange sorbents.
• Application 1. Protein cap- ture in the presence of high E. coli biomass. Table 2 shows comparative cap- ture of lysozyme from E. coli lysate at 2.5% and up to 11.5% ww/v concentrations. In con- Table 2: Purification of lysozyme from E. coli lysate. trast to the conventional EBA CM HyperZ CM HyperZ SP Agarose SP Agarose sorbent (SP agarose), CM HyperZ™ 11.5% 2.5% 11.5% 2.5% biomass biomass biomass biomass tolerates biomass loads up to 11.5%, without significant Loading time (28 CV) 180 min at 83 min at 350 min at 228 min at decrease of the linear flow. 120 cm/h 260 cm/h 65 cm/h 100 cm/h Acceptable bed expansion can Estimated lysozyme binding capacity (mg/ml) 19 25 11 23 be maintained and process time decreased. Recovery >80% and Estimated recovery (%) 68 89 62 84 purity of >65% were achieved in 1 cm I.D. column, 13 cm settled bed height. Equilibration: 50 mM acetate/5mM citrate, 50 mM a single pass. NaCl, pH 4.5; Elution: same buffer + 1 M NaCl.
5 BIOSEPRA® Q & CM HYPERZ™ • Application4.Purificationfromunclari- >85% (GPC)and95%recovery. centrated 30Xinasinglestep,withpurity tion. TheMousemonoclonalIgG body purification,withoutfeedstockdilu- showsatypicalmonoclonalanti- Figure 12 ent andthefeedstockrespectively). the cytochromecconcentrationinefflu- total proteinpresentinsample. Figure 13.Effectoflinearflowrateondynamicbindingcapacity CMHyperZsorbentinpresenceof20%biomass. HyperZ Dynamic BindingCapacitypermlofCM The upperpartofthefigureshows suspended inbuffer. yeast preparedbywet-millingofcellpaste chrome cfromunclarifiedlysatesofbaker Figure 13showsthepurificationofcyto- Group,UniversityofBirmingham(U.K.) Recovery Biochemical Courtesy ofM.Jahanshahi&A.Lyddiatt, ProteinChip usingthe of-Flight MassSpectrometry), Desorption-Ionization, combinedtoTime- EnhancedLaser SELDI-TOF-MS (Surface were analyzed(lowerpartoffigure)by original undisruptedcells,relativetothe suspensionvolume(ww/v).Cytochromecwasquantifiedbyspectrophotometric assay. bound cytochromeCinallstudies.Typical elution volumes:1.3-1.5CV. Concentrations oflysatesareexpressedasthefrozenw 1 cmI.D.column,20bedheight. Application3.DirectCaptureofMurine • one step. protein, with strated afastandefficientcaptureofthe loads. fied yeastlysateat20%ww/vbiomass IgG
C/C0 1 from HybridomaCellCulture ™ Cytochrome Cchallenge(mg/mlsettledadsorbent) at C/C ® reader. CMHyperZ a 10Xconcentrationfactorin 0 =0.1 (CandC Binding: 10mMTris-HCl, of pH7.5.Elution:60mMNaCl,50cm/hinpackedbed.>90%recovery Sample: Unclarifiedyeastlysate.20%(wet weight)biomass. 250 cm/h,DBC6.0mg/ml 300 cm/h,DBC5.3mg/ml 400 cm/h,DBC3.9mg/ml 0 represent ™ 1 demon- was con- 6 biomass. bed mode. 18 mS/cm.Elution:50mMacetate,pH4.5,1MNaClinexpanded serum-free mediumsupernatantonCMHyperZsorbent. Figure 12.PurificationofmuIgG CM HyperZ of umes demonstrateexcellentperformance Capacities, flowratesandlowelutionvol- supernatant. (1x10 in presenceofcells). pH 4.5,120mMNaCl;Flowrate:300cm/h(2.5Xbedexpansion Equilibration:50mMacetate, 1 cmI.D.x15heightcolumn.
Cytochrome C (mg/ml) A280nm ™ 6 PRODUCT NOTE cells/ml) adjustedtopH4.5.Conductivity: in the presence of very high in thepresenceofvery Sample: 3L,undiluted,hybridomacellculture Cytochrome Crepresentsonly1-2%of Volume (ml) 1 Volume (ml) from hybridoma et weightof
Conductivity (mS/cm) • Application 5. Purification of a lipase from reduction of the ionic strength below 6 mS/cm. Y. lipolytica on Q HyperZ™. Elution was peformed by use of an NaCl linear Courtesy of Prof. R.M. Willemot, INSA Toulouse, France. gradient from 0 to 1 M in one hour. Flow rate was Figure 14 shows direct capture of a recombinant 300 cm/h. Collected fractions analyzed both by lipase from a crude clarified fermentation broth of SDS-PAGE and RC-MS (Ciphergen Biosystems) Yarrowia lipolytica. Adsortion of the enzyme was indicate that lipase (# 36kDa) was efficiently cap- ™ performed at pH 9.0 with diluted sample for tured on Q HyperZ sorbent.
Figure 14. Capture of lipase from Y. lipolytica fermentation broth on Q HyperZ sorbent.
® Flowthrough Elution RC-MS Analysis on ProteinChip Arrays SDS-PAGE Analysis
Lipase
A280 nm Load
FT Regeneration Lipase Wash
Elution
20000 40000 60000 80000
04080 120 160 Time (min) MM Load FT W EL
0.7 ml Q HyperZ packed bed column; Equilibration: 50 mM Tris-HCl , pH 9.0 ; Sample (2 ml) is diluted 3 times; Linear flow rate 300 cm/h; Elution in 50 mM Tris-HCl, 1 M NaCl, pH 9.0 at 150 cm/h; Regeneration: 1 M NaOH.
Large-scale manufacturing, Regulatory and References Validation support HyperZ™ sorbents are manufactured at large-scale 1. Trinh, L., et al., Bioseparation 9 (2000) 223. 2. Voute, N., et al., IJBC Vol. 5/1 (2000) 49. under ISO 9001 at the BioSepra Process Division 3. Voute, N. and Boschetti, E., Bioseparation 8 (1999) 115. of Pall. Regulatory support documents and plant 4. BioSepra Process Proteomics Product Note LPN PN702-001: audits are available on request. "Q, S, DEAE, CM Ceramic HyperD® ion exchange sorbents" (01/2002).
Ordering Information
Product Cat. No. Size
Q HyperZ™ 21012-010 50 g (~25 ml ) 21012-020 250 g (~125 ml) 21012-030 1 kg (~500 ml) 21012-040 4 kg (~2 L) 21012-050 10 kg (~5 L) CM HyperZ™ 21011-010 50 g (~25 ml ) 21011-020 250 g (~125 ml) 21011-030 1 kg (~500 ml) 21011-040 4 kg (~2 L) 21011-050 10 kg (~5 L)
2 grams are approximately equivalent to 1 ml. Custom packaging available on request.
7 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, HyperZ, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN PN702-003 - 12/2004
8 BIOSEPRA® Ceramic HYPERD® ceramic bead.CeramicH absolute dimensionalstabilityofarigid soft, high-capacityhydrogelwiththe combines thedesirablecharacteristicsofa bead. AsshowninFigure1,thisdesign ized withinthegigaporesofarigidceramic employ ahigh-capacityhydrogelpolymer- tional macroporousionexchange sorbents. straints typicallyencountered withconven- sorbent tooperatefreeof operational con- known asenhanceddiffusion –allowsthe uct. Thismechanismofmass-transfer – hydrogel, facilitatingrapiduptakeofprod- molecules. Proteinsdiffuserapidlywithinthe the hydrogelarehighlyaccessibletoprotein conductivity. Abundantionexchangesitesin not shrinkorswellwithchangesinpH Q, S,DEAE,CMCeramicH sorbents. High productivityfromrigid,composite Improve throughputwithCeramicH • • • • • Ion ExchangeSorbents Q, S,DEAE,CMCeramicH chromatography sorbents. B • The"GelinaShell"designprovides ty orproductivitylimitations. ventional sorbentsdisplaysignificantcapaci- capacity (DBC)underconditionswherecon- designed tomaintainhighdynamicbinding scale application,thesesorbentsare feedstocks. Ofparticularvalueinprocess- purification ofbiomoleculesfromavariety cially designedfortheefficientandscaleable exchangers arehighcapacitysorbentsspe- IO ing. rapid masstransferandeffectivebind- Regulatory SupportFiles(RSF)available. Regulatory Easy cleaningwithsodiumhydroxide. Rigid, non-compressiblesorbent–easytopack. High-efficiency capturefromdilutefeedstock. High DynamicBindingCapacityathighflowrates. S EPRA Ceramic H YPER ionexchangers D YPER YPER sorbentsdo D ion D 1 passed productivity. Thistranslatesintounsur- and exceptionaldimensionalstability. Figure 1.The“Gel-in-a-Shell”Design. Ceramic H ciently. Dynamicbindingcapacitywith Feedstock canbeprocessedrapidlyandeffi- Captureproductathighlinearvelocity. • Ceramic H traditional ionexchangers is notobserved. flow-dependent behaviorassociated with process scaleseparations.The pronounced or cally used–orsoughtin laboratory independent oflinearvelocity atvaluestypi- binding sites are drawnintothebead YPER YPER backbone Ceramic Protein opposite YPER enhanceddiffusion D Molecules with sorbentsdeliver outstanding dynamiccapacity D D YPER charge PRODUCT NOTE ® ion exchangersisvirtually D as beadareexcluded same Molecules with Hydrogel charge BIOSEPRA® Ceramic HYPERD® Using CeramicH fromdilutefeedstock. Efficientharvest • *** Sample:5mg/mlhuIgGin50mMsodiumacetate,100NaCl,pH4.7. ** Sample:5mg/mllysozymein50mMsodiumacetate,pH4.5. Sample:5mg/mlBSAin50mMTris-HCl buffer, pH8.6. * or flowrate.Indeed, thesorbentsarestable response tochanges inpH,ionicstrength stable beds.Theydonotswell orshrinkin Ceramic H Absolutedimensional stability, excellent • diafiltrationordilution. nary feedstock canbeappliedwithoutprelimi- 180 mMsalt.Thus,inmanyapplications 19 mSconductivity–equivalentto fromfeedstock of body hasbeenharvested strength. Forexample,monoclonalanti- present infeedstockofmoderateionic effective bindingevenwhenproductis H ent withinthehydrogelofCMCeramic The extraordinarilyhighliganddensitypres- Recoverproductfromfeedstockof • purification scheme. enhancing theproductivityofoverall concentration,thereby need forpreliminary fromdilutefeedstockwithout harvested bents. Inmanyapplications,productcanbe associated withclassicalmacroporoussor- that isfundamentallydistinctfrom novel materialsoperatebyamechanism traditional sorbents–illustratesthatthese with tothatobserved behavior –contrary concentrated feedstock(seeFigure6).This obtained withdilutefeedstockthan bents, higherdynamicbindingcapacityis YPER pack. pressure/flow characteristics, easyto moderate ionicstrength. okn H2-12 Working pH yai idn aaiy(gm)BAlszm S yoyeBAIgG BSA lysozyme BSA lysozyme BSA 10% breakthroughat200cm/h Dynamic bindingcapacity(mg/ml) rsuerssac 0gae Fgrade: 1-14 20grade: Pressure resistance Volumes changesduetopHandionicstrength Cleaning pH Amount ofionicgroups(µeq/ml) Average particlesize(µm) TABLE 1:CeramicH Fionexchangesorbentallows for D YPER Type ofCeramicH ionexchangers formvery D YPER YPER ionexchangesor- D IonExchangersMainProperties. D rd 02 F F F F 20 20 Grade YPER DEAE CM S Q QS D 0 a 300pi >70bar(1,000psi) 200 bar(3,000psi) ≥ ≥ ~ 250 85* 20 2 H owing tothe dense natureoftheCeramic ing isaccomplishedquickly andeasily than 2bar. Equallyimportant,columnpack- pressure generatedbythe sorbentisless 16 cm)operatedat500cm/h, operating example, inapilot-scalecolumn (9cmIDx ment (seeFigure2andTable 2).For tion usinglow-pressurecolumnsandequip- and hascharacteristicswellsuitedtoopera- bent provideslinearpressure/flowbehavior, does notdeformunderfluidflow, thesor- at pressuresupto70bar. Sincethebead pH 8.6. Column: 9cmIDx16cm;Buffer:50mMTris-HCl, 0.5MNaCl, H onQCeramic Figure 2.Pressurevs.FlowrateCurve ≥ ≥ YPER YPER o.Ø10c/ 0 mh500cm/h 300cm/h 100cm/h Col. Ø 5c ,5 ,5 13,250 5,880 2,120 533 7,950 3,530 1,270 320 2,650 1,180 420 45 cm 110 30 cm 18 cm 9 cm ~ AL . ExamplesofVolumetric Flowvs. TABLE 2. 85** 150 Pressure 20 DF. beads. D psi 10 20 30 0.4 0.8 1.2 1.6 2.0 bar Non compressible ≥ ≥ 0 ~ Linear FlowRate. 250 85* 50 PRODUCT NOTE 100 200 ≥ ≥ ~ Flow rate(ml/min) 75** 150 50 300 400 Flow rate(cm/h) ≥ ≥ ~ 0 5-400 250- 200 85* 50 500 600 ≥ ~ 60*** 50 TABLE 3. Lot-to-lot Consistency of Q Ceramic HYPERD F Sorbents. Lot No. 1 2 3 4 5 6 7 8 9 10 11 Ionizable groups (µeq/ml) 375 329 314 317 322 342 349 349 329 318 338 Dynamic binding capacity for BSA (mg/ml), 10% breakthrough: - at 200 cm/h 105 102 97 118 94 103 102 104 97 115 107 - at 600 cm/h 109 93 89 111 89 92 91 89 89 109 96
• Robust, safe and documented for vali- Figure 3. Structure of Ceramic HYPERD Ion Exchange dation. Sorbents. Ceramic HYPERD sorbents are manufactured in BIOSEPRA S.A. ISO 9001 registered manu- facturing facility. Extensive experience on batch-to-batch reproducibility (see Table 3) guarantees the reliable performance and supply you need for your process. The sor- bents can be treated with NaOH for effi- cient cleaning and sanitization. Ceramic HYPERD sorbents are used in a num- ber of registered products, as well as in many clinical and preclinical trials, in columns larger than 500 liters. All grades of BIOSEPRA ion exchange Ceramic HYPERD have Drug Master Files (DMF) :
- Q/S Ceramic HYPERD 20, F: DMF No. 13241 Ceramic backbone Gold-labeled albumin High rigidity - DEAE Ceramic HYPERD F: DMF No. 13242 Derivatized hydrogel - CM Ceramic HYPERD F: DMF No. 11856 High capacity and for numerous chromatography sorbents, and provides full documentation to support regulatory validation. Figure 3. A cross section through the bead Ceramic HyperD is supplied in 1 M NaCl shows binding of gold-labeled albumin. containing 20% ethanol / 1.2 mM EDTA. It Notice that the hydrogel completely fills the is available in a range of package sizes. pores within the ceramic shell, and that Custom packaging to meet specific manu- gold-labeled albumin – visible as dense facturing requirements is available on request. black dots – is distributed homogeneously throughout the hydrogel. The enhanced diffusion concept. The hydrogel carries an extraordinarily high concentration of ion-exchange functional Traditional macroporous ion exchangers groups : 150-400 µeq/ml. The average dis- operate on the basis of classical pore diffu- tance between charged sites on the hydro- sion. Pore diffusion is characterized by rap- gel is ~20 Å. Thus, a protein molecule with- idly decreasing binding capacity with in the gel is simultaneously in contact with increased flow rate. In contrast, the unique a large number of ion exchange sites. It structure of Ceramic HYPERD supports a remains in contact with a similar number of more rapid mechanism of mass transfer, sites no matter where it moves within the known as enhanced diffusion. Rapid mass three-dimensional structure of the hydrogel. transfer overcomes classical flow rate As a result, the protein is energetically dependence. Since product is bound unconstrained and may migrate freely. throughout the gel-filled pore – not merely Protein diffuses rapidly within the hydrogel at the interior surface of the pore – total to give a homogeneous distribution, facili- binding capacity is enhanced. tating uptake of additional material from Binding of protein within the hydrogel is solution. Under binding conditions, strong illustrated by the electron micrograph in attractive electrostatic forces between the
3 BIOSEPRA® Ceramic HYPERD® pH 4.6. Column: 0.2cmID x 15cm;Sample:HuIgGin50mMacetate, Figure 6.BindingCapacityofSCeramicH Dynamic bindingcapacityat10%( Ceramic H Figure 5.BindingCapacityvs.ResidenceTime ofQ pH 8.6;Dynamicbindingcapacityat10%breakthrough. Column: 6.6cmIDx16cm;BSA(5mg/ml)in50mMTris-HCl, Q CeramicH Figure 4.DynamicBindingCapacityvs.Flowrateon Sample Concentration. Dynamic Binding Capacity for BSA(0.5mg/ml)in50mMTris-HCl, pH8.6. Dynamic Binding Capacity Dynamic Binding Capacity (mg/ml) (mg/ml) (mg/ml) 100 100 100 125 25 50 75 50 25 50 75 200 0 ,0 ,0 3,000 2,000 1,000 0 . . . . . 3.0 2.5 2.0 1.5 1.0 0.5 0 YPER YPER 0 0 0 0 0 700 600 500 400 300 100 DF. DF. 10 mg/ml • ) and50%( 0.5 mg/ml Linear velocity(cm/h) Linear velocity(cm/h)
) breakthrough Time (min) YPER F vs. D 4 Ceramic H higher loads,betterthroughput. Go fastwithoutsacrificingcapacity: mechanism providesareillustratedbelow. characteristics thatthisnovelstructureand The productivity-enhancingoperational ofproteinintothegel. drive entry highly substitutedhydrogelandtheprotein at 10%breakthroughforQCeramicH only 0.4min,DBCforBSAisover85mg/ml of columngeometry. Ataresidencetimeof characteristics withoutreferencetodetails This approachallowsassessmentofsorbent the influenceofresidencetimeonDBC. many process-developersprefertoexamine For abroad-basedmeasureofproductivity, 600 cm/h. ing DBCvaluesdeterminedat200and demonstrated bydatainTable 1,compar- than 650cm/h.Thisbehaviorisfurther velocity isincreasedfrom50cm/htomore a modestdeclineinDBCforBSAaslinear velocity. AsshowninFigure4,thereisonly dynamic bindingcapacityathighlinear In contrast,CeramicH concentration inthefeedstock isreduced. dynamic bindingcapacitydeclinesifprotein With traditionalmacroporoussorbents, feedstock. concentrationofdilute preliminary Simplify theprocessbyeliminating ductivity andenhancedprocesseconomics. ume –allofthesefactorssupporthighpro- reduced bedvolume,buffervol- High flowvelocity, shortresidencetime, volume requirementsmayalsobereduced. reducing bedvolumerequirements,buffer using columnsofmoderatevolume.By tration inthe feedstock. sorbent isindependent ofproteinconcen- because theabsoluterate of uptakeintothe tion ofenhanceddiffusion, andarises feedstock. Thisuniquebehavior isafunc- vide higherbindingcapacity withdilute Ceramic H ied. Theinherentlyhighbindingcapacityof achieved overtherangeofconditionsstud- ranging from~85to120mgBSA/mlwere reduced from3minto0.4min.DBCvalues est reductioninDBCasresidencetimeis F. AsshowninFigure5,thereisonlymod- YPER YPER PRODUCT NOTE ionexchangersdeliverhigh D sorbentspermitsoperation D YPER sorbents pro- D YPER D This useful behavior is illustrated in Figure 6. Figure 7. One-step Capture of Mouse IgG1 from CCS Over a broad range of linear velocity values, on CM Ceramic HYPERDF.
higher DBC is observed for feedstock con- 1 taining 0.5 mg hu IgG/ml than for that con- IgG taining 10 mg hu IgG/ml. With Ceramic NaOH
HYPERD used for product capture, it is possi- Elution ble to reduce or eliminate the need for pre- O.D. liminary concentration of feedstock. Indeed, a column of Ceramic HYPERD can serve as a U.V. device for both concentration and initial I.S. purification of the target protein.
Simplify the process by eliminating pre- Time (min) liminary diafiltration or dilution of feed- stock containing moderate concentra- IgG1 purity: 90%; Column: 9 cm ID x 5.2 cm (330 ml); Load: 31 L CCS 100-150 µg/ml adjusted to pH 4.7; Equilibration and post- tions of salt. load wash: 50 mM sodium acetate, 0.1 M NaCl, pH 4.7; Elution: same buffer + 1.5 M NaCl; Duration: 164 min; Residence time: With its highly substituted hydrogel, the 1 min; Linear velocity: 260 cm/h. CM Ceramic HYPERD F ion exchange sorbent binds effectively even in the presence of moderate concentrations of salt. As shown Stability and Cleaning. in Figure 7, IgG1 was harvested from 31 L of clarified cell culture supernatant (CCS) using • Chemical stability. a 330 ml column of CM Ceramic HYPERDF. Ceramic HYPERD F ion exchangers can be Prior to loading, the pH of the CCS was easily sanitized using NaOH (i.e. 5 column adjusted to pH 4.7. Conductivity of the volumes of 0.5 M NaOH for 1 hour contact feedstock was 19 mS/cm, equivalent to time at room temperature). Data from about 180 mM sodium chloride. The con- Regulatory Support Files demonstrate long centration of IgG in the feedstock was term resistance (over 200 cycles) and no modest : 150 µg/ml. At a linear velocity of significant modification of the sorbent per- 260 cm/h, loading was accomplished in formance of Ceramic HYPERDF. 112 min, and chromatography was com- Other chemical agents such as 20% plete in 164 min. Residence time was only ethanol/1 M acetic acid mixtures can also 1 min. Isolated IgG was >90% pure. be used for cleaning in place (for other Eliminating the need for preliminary diafil- chemical agents, contact our Technical tration or dilution will simplify the process Service). and enhance productivity of the scheme. • Thermal stability. Achieve high flow velocities using The cation exchange Ceramic HYPERD sor- standard chromatography equipment. bents are stable over a wide range of tem- The rigid ceramic skeleton of Ceramic peratures. They can be autoclaved (121°C for 20 min). Caution needs to be taken with HYPERD F allows work at high linear veloci- ties (typically over 300 cm/h) with low or the anion exchangers however, due to the moderate backpressures (typically less than progressive degradation of the tertiary and 3 bar) without compression or shrinkage. quaternary amine groups. Standard low pressure chromatography pumps and columns can be used, contribut- Regulatory and Validation Support. ing to overall process economy. Figure 2 Ceramic HYPERD ion exchange sorbents are shows pressure vs. flow rates curves for manufactured under ISO 9001. They are Q Ceramic HYPERD F, and Table 2 gives available in a 20µm grade (“20”) for pilot examples of volumetric flow rates of scale and polishing applications and a 50µm different column diameters. grade (“F”) for full scale production. Regulatory support can be provided to customers to help qualify the material and
5 PRODUCT NOTE
the chromatographic purification in Applications. regulated processes. Ceramic HYPERD F sorbents are ideally suited Ceramic HYPERD F sorbents are fully validat- for purification of biomolecules in research, ed products, presently used in the clinical scale-up and full-scale pharmaceutical man- production of several biopharmaceuticals, ufacturing. including full scale manufacturing of FDA- The Ceramic HYPERD 20 particle size is registered products. more adapted for polishing steps or rapid An example of the typical batch-to-batch separations when a higher resolution is
® consistency of Ceramic HYPERD sorbents is required. shown in Table 3. The data are part of the - Direct capture of biomolecules from a Regulatory Support File for Q Ceramic variety of feedstocks. D HYPERDF. - Polypeptides, IgG, albumin purification. - Large-scale purifications. - Purification of monoclonal antibodies from Figure 8. Purification of Hexokinase and 3-phospho- ascites or cell culture. glycerate-Phosphokinase on Q Ceramic HYPERD 20. - Plasmid purification. YPER 0.27 - Process polishing steps. - Rapid high resolution purification (20µm 3-Phosphoglycerate-Phosphokinase O.D. 0.23 grade).
0.19 • Direct one-step Capture of an IgG1 from diluted cell culture supernatant 0.16 (CCS) on CM Ceramic HYPERDF. 0.12 CM Ceramic HYPERD F can be applied for a
0.08 direct, one-step capture of monoclonal anti- Hexokinase body from cell culture supernatant (see 0.04 Figure 7).
0 4.6 9.2 13.8 16.4 • Rapid purification of yeast proteins on Q Ceramic HYPERD 20. Time (min) The 20µm grade allows rapid method Column: 0.5 cm ID x 10 cm (1.7 ml); Adsorption, washing, equili- development for enzyme separation using a
Ceramic H bration in 50 mM Tris-HCl / Tris base, pH 7.2; Elution by 0 to 1 M NaCl gradient; Protein concentration: 1 mg/ml; Linear velocity: salt gradient (see Figure 8). 1,223 cm/h (4 ml/min). ®
Figure 9. Two-step Purification of IgG1 from Ascites Fluid on MEP HYPERCEL followed by DEAE Ceramic HYPERDF.
IgG1 IgG1 (purity 80%) (purity 98%) adsorbed EPRA
O.D. impurities WASH WASH 12 S 3 IO B
Time (min)
Capture on MEP HYPERCEL Polishing on DEAE Ceramic HYPERD F
MEP HYPERCEL column: First wash with 50 mM Tris-HCl buffer, pH 8, second wash with 25 mM sodium caprylate in same buffer
(arrow 1), followed by a water wash (arrow 2), to remove albumin. Elution with 50 mM sodium acetate, pH 4.0. The IgG1 enriched fraction is added with Tris base up to pH 8.8 and ionic strength of 7.4 mS/cm, and injected onto the DEAE Ceramic HYPERD F column. Wash with same buffer to collect the antibody. DEAE Ceramic HYPERD column: 0.6 cm ID x 10 cm; Equilibration: 50 mM Tris-HCl, pH 8.8; Linear velocity: 160 cm/h. IgG do not bind, adsorbed impurities are eluted by 1 M NaCl (arrow 3).
6 • Polishing step on DEAE Ceramic HYPERD F after monoclonal antibody capture on • More Regulatory Support information. MEP HYPERCEL. Regulatory Support Files are updated DEAE Ceramic HYPERD F has been used in a periodically. Please contact your local represen- two-step process for a polishing step to tative. purify a mouse IgG1 from ascites fluid (see Figure 9). The first step is a capture of the • Information from Regulatory Support
IgG1 on a MEP HYPERCEL column (Hydro- Files. phobic Charge Induction Chromatography - Long term storage data, – HCIC –), which results in a good initial - Material Safety Data Sheets, capture of the IgG1 (93%). - Lot-to-lot consistency information,
A purity of 98% for the IgG1 is achieved in - Detailed Quality Control procedures, two steps. - Chemical stability in various media, - Cleaning in place (CIP) studies, - Extractives and leachables quantification.
References Ordering Information
1. Duval, M., et al., Job Life Sciences 316 (1993) 1463. Product Cat. No. Size 2. Boschetti, E., et al., J. Biochem. Biophys. Meth. 32 (1996) 15. Q Ceramic HYPERD 20 20040-051 5 ml 3. Coffman, J.L., Boschetti, E., Bioseparation & Biopro- 20040-044 25 ml cessing, Wiley-VCH Verlag Press, Vol. 1 (1998) 157. 20040-036 100 ml 4. Necina, R., Amatschek, K., Jungbauer, A., Biotech- 20040-028 500 ml nology and Bioengineering Vol. 60/6 (1998) 689. 20040-010 1 L 5. Hanser, E., Mollerup, I., J. Chromatogr. A827 (1998), 259. S Ceramic HYPERD 20 20038-055 5 ml 6. Hahn, R., et al., J. Chromatogr. A795 (1998) 277. 20038-048 25 ml 7. Moure, F., Rendueles, M., Diaz, M., ECCE2 (Second 20038-030 100 ml European Congres of Chemical Engineering) (1999) 20038-022 500 ml Montpellier. 20038-014 1 L 8. Fernandez, A., et al., J. Chrom. A 746 (1996) 169. 9. Boschetti, E. & Jungbauer, A., Separation Science & Q Ceramic HYPERD F 20066-098 5 ml 20066-031 25 ml Technology, Academic Press Vol. 2 (2000) 535. 20066-023 100 ml 10. Riedel, K.-U., et al., Eur. J. Biochem. 231 (1995) 742. 20066-015 1 L 11. Jouanneau, Y., et al., Eur. J. Biochem. 267 (2000) 780. 20066-064 5 L 12. Sookkheo, B., et al., Protein Expression and 20066-056 10 L Purification 20 (2000) 142. 13. Couriol, C., et al., Chromatographia 52/7-8 (2000) S Ceramic HYPERD F 20062-089 5 ml 465. 20062-030 25 ml 20062-022 100 ml 20062-014 1 L 20062-048 5 L 20062-055 10 L
DEAE Ceramic HYPERD F 20067-070 5 ml 20067-039 25 ml 20067-021 100 ml 20067-013 1 L 20067-054 5 L 20067-047 10 L
CM Ceramic HYPERD F 20050-084 5 ml 20050-035 25 ml 20050-027 100 ml 20050-019 1 L 20050-050 5 L 20050-043 10 L
7 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, HyperD, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN PN702-001 - 12/2004
8 BioSepra® Trisacryl® point. Variations inpHmodifytheionizationof the proteinsuchasmolecular weightandisoelectric nature ofthecounter-ion,and thecharacteristicsof factors, includingbufferpHand ionicstrength,the mechanism. Thecapacitydependsonanumberof is affectedbygeneralrulesfortheionexchange Each Trisacryl structure (SeeFigure1). three dimensional are foundwithinits the polymerstructure are anintegralpartof exchange groupswhich strongly boundion copolymers. The microbeads ofacrylic spherical semi-rigid ion exchangersare Trisacryl BioSepra DEAE,CM,SP Ion ExchangeChromatographySorbents DEAE, CMandSPTrisacryl The proteinadsorptioncapacityofTrisacryl Capacity large scale.Trisacryl range ofapplicationsat dedicated toabroad ion exchangesorbents bents arehighcapacity and preventnon-specificadsorption.Trisacryl hydrophilic groupswhichensurebiocompatibility sub-unit possesses molecular sieving. easy accesstoionizablegroupsandtheabsenceof of macromoleculesduetothehighmasstransfer, the provides severaladvantagessuchasarapiddiffusion exchangers aremacroporous.Theiropenstructure Longlifetime • Wide stabilityrange • Fastreequilibrationandregeneration • Superiordynamiccapacity • Excellentresolution • ® M, LSsor- ® polymer ® Figure 1:ChemicalstructureofavailableionizablegroupsTrisacryl ionexchangers. – CH CH CH CH 2 2 2 DEAE Trisacryl CH CH CH CH – – – – CONH CONH CONH CONH ® – – (CH (CH sorbents ® 2 2 ® ) ion ) 2 2 – M, LS – N N CH CH CH C C CH CH CH CH CH – – – 2 2 2 2 2 2 2 2 CH CH (CH OH OH OH OH – – – – CH CH CH CH 2 2 OH OH 2 ) 3 3 3 3 2 – 1 N CH CH 2 2 ionizable groups. which providesagreateravailability oftheproteinto uted tothemacroporousnature ofthesupport, the flowrateincreases.Thisphenomenon isattrib- decrease. Theadsorption since aflowrateincreaseoftenresultsinca taken inconsiderationwhendiscussingproductivity, tivity levelofthesupport.Thesetwofactorsareboth exchange supportsincetheydeterminetheproduc- ofanion are indicativefeaturesintheperformance given protein.Theadsorptioncapacityandflowrate ionic strengthwillresultinacapacitydecreasefor net chargeoftheprotein.Usually, anincrease of and thepHofbuffer, whichinturnmodifiesthe capacity isparticularlyaffectedbytheionicstrength ber ofgroupsforproteinadsorption.Theadsorption support groupsandthusmodifytheavailablenum- – – CH CH 3 3 ® – CH CH CH M/LS CM Trisacryl 2 2 CH CH CH CH--COOH – – – CONH COOH CONH PRODUCT NOTE ® – – C C CH CH CH CH ,L SPTrisacryl M, LS – – CH 2 2 CH 2 2 OH OH OH OH 2 2 OH OH capacity remainshighas – CH CH CH 2 2 2 CH CH CH CH – – – – CONH CONH CONH CONH – – – – ® C C C C CH CH CH CH CH CH CH CH M, LS – – – – pacity 2 3 3 CH CH 2 2 CH CH 2 3 3 OH OH OH OH 2 2 2 2 OH OH – – SO SO 3 3 H H BioSepra® Trisacryl® degradation. completely resistant toenzymaticandmicrobial Trisacryl Thermal Stability Trisacryl Chemical Stability Trisacryl Mechanical Stability Trisacryl Biological Stability properties. claved during20min)without modificationoftheir from -20°Cto+121°C(thesorbentsmaybeauto- sanitization anddepyrogenationofthesorbent. large scaleapplicationssincetheypermitefficient All thesepropertiesareparticularlyimportantin thetic origin. supports –andtoenzymaticattackduetheirsyn- tomost synthetic highly alkalinesolutions–contrary topolysaccharide-based supports–to contrary – These sorbentsareresistanttohighlyacidicsolutions as organicacids,e.g.fortheseparationofpeptides. be usedwithinorganicacids(i.e.1MHCl),aswell Trisacryl as tritonX-100, chaotropic (8 Murea,6guanidinehypochlorideandother denaturing agentscommonlyusedinbiochemistry solutions. Additionally, thematrixisresistantto matography, andhaveagoodresistancetoalkaline used solventsinlowandmediumpressurechro- lem ofdenaturation. thus avoidingpossibleprob- sorbent canbeminimized, labile biochemicalwiththe ciently. Thecontacttimeof rapidlyandeffi- performed tion andregenerationmaybe column equilibration,separa- Under highflowrates,the in largecolumns. tures providehighflowrates physical andchemicalfea- merization conditions.Their obtained underspecificpoly- three-dimensional structure support collapseduetothe rigid andhighlyresistantto ® ® ® ® ® is atotallysyntheticsorbentand istherefore sorbents toleratehighthermalvariations ion exchangersareacid-resistant,theycan sorbents areinsolubleinallcommonly sorbents aresemi- agents) andtonon-ionicdetergentssuch octylglucoside, andTween 80. xlso ii d) >10 40-80(Mgrade);80-160(LS Exclusion limit(dt)* Particle size(µm) Amount ofionicgroups(µEq/ml) Nature ofionizablegroups Table 1.MainPropertiesofTrisacryl M,LSionexchangers. hra tblt -20°Cto+121°C 1.5-1.8 1-11 1 Excellent Stabletoallsolventscommonlyusedinliquid 4.7 Reequilibration volume(cv) Thermal stability >80(lysozyme)*** 6.2;10.7 >135(lysozyme)*** Chemical stability >75(BSA)** Microbial stability Working pH Binding capacity(mg/ml) pK ofionicgroups **Very shortperiodoftime **** * Sodiumacetate,pH5containing300mMNaCl;Sample:2.5mg/ml lysozymesolution *** o lblrpoen **10mMTris-HCl, pH8.6,sample:10mg/mlBSAsolution Forglobularproteins * 2 for stepwiseelutions. tion conditionsandselectionofpHionicstrength These experimentswillallowoptimizationoftheelu- dient aration profiles,asshownon Figure 2. other counter-ionscanbeused, givingdifferentsep- cation exchangers(CMandSP Trisacryl NaCI in the NaCI in buffer andcollectthenon-adsorbedproteinfraction. sorbent. of 1 ml for CMandSPTrisacryl low ionicstrengthbuffer(0.01-0.05M),e.g.acetate for theanionexchangers(DEAE Trisacryl elution dependsonthecompetition withNa increase oftheNaCIconcentration.Inthiscase, byan Salt elutiongradientsareusuallyperformed Choice oftheCounter-lons ■ ■ ■ ■ lowing procedureisrecommended: For thefractionationofanunknownsample,fol- Choice ofInitialSeparationConditions Trisacryl - pH2-6forSPTrisacryl eeaea oi teghgain ih0t M Generate anionicstrengthgradientwith0to1 Wash thecolumnwithatleast1cvofsame Inject thesample,startingwith2mgofproteinfor - pH7-9forDEAETrisacryl - pH4-6forCMTrisacryl Equilibrate asmallcolumn(5to20cmheight)in hoaorpy( undn yohoie Murea) Mguanidinehypochloride,8 chromatography (6 diethylaminoethyl slope 2-7 9-3 190-250 190-230 320-370 ® . RecommendedpHrangesareasfollows: EEC SP CM DEAE should rangefrom5to10mM/cm. same lowionicstrengthbuffer. The PRODUCT NOTE abxmty sulfopropyl carboxymethyl ® and Tris-HCl forDEAE ® ® ® 7 ® ), andCl ® ). However, + for the gra- - Figure 2. Separation on DEAE Trisacryl M of a mixture of cytochrome c (A), human hemoglobin Figure 3. Separation of oligomers of 5'(d)-TMP (B), ovalbumin (C) and β-lactoglobulin (D) according to the counter-ion. on DEAE Trisacryl M.
NaCl [E] A B DI [E] [E] 0.5 b b a d Conc. TRI a d 0.5 0.5 0.4 c c Conc. Conc. TETRA 0.3 PENTA 0.2 0.1
0 20 100 150 (ml) 0 50 100 Vr 0 50 100 Vr
C D Column: 1.6 x 18.4 cm; Sample: 4 mg of oligonu- [E] [E] a b cletides in 1 ml buffer; 0.025 M sodium acetate, a b 0.5 0.5 c d c 0.2 M NaCl, pH 5.3; Elution gradient: NaCl from Conc. Conc. d 0.2 to 0.5 M; Flow rate: 30 cm/h.
0 50 100 Vr 0 50 100 Vr
--- E= concentration in Eq./L; Vr = retention volume; Column dimensions: 1.6 cm I.D. x 10 cm; Buffers: Tris-PO4 -- - - (A), Tris-SO4 (B),Tris-Cl (C), Tris-CH3COO (D), pH 8.6; Gradient slope: 10 mE/cm; Flow rate: 32.5 cm/h.
The affinity order of different counter- 5. Calculate the column cross-sectional References ions is as follows: area and diameter. 1. Lebart, M.C., et al., J. of Biol. Chem. Vol. 268, No. 8 ■ For cation exchangers: (1993) 5642. ++ ++ + + + Applications 2. Tousch, D., et al., Biochrom. 5 (1990) 30. Ca > Mg > Na > NH4 > K 3. Séné, C., et al., ChimicaOggi (03/1990), 15. Trisacryl® ion exchangers have proven ■ For anion exchangers: 4. Corthier, G., et al., J. Immunol. Meth. 66 (1984) 75. to be very efficient on the laboratory 5. Girot, P., Boschetti, E., J. Chrom. 213 (1981) 389. Citrate > PO --- > SO -- > Br - > Cl- 4 4 level due to their excellent resolution, 6. Veau, B., et al., Biochim. Biophys. Acta 1428 (1999) > CH COO- 39. 3 and also on industrial scale due to their high productivity performance. Scaling Up a Process DEAE, CM, and SP Trisacryl® sorbents The choice of the equipment size and are commonly used for the fractionation operating parameters for a pilot- or pro- of proteins from various origins and at Ordering Information duction-scale chromatography step is different scales. DEAE Trisacryl® is cur- not an easy task. To help determine the rently used in 500 L columns for the Product Cat. No. Size sorbent volume requirements for a production of insulin. given process, BioSepra’s basic guide- An example of separation obtained on DEAE Trisacryl M 25079-013 300 ml lines are as follows: 25079-054 1 L different Trisacryl® ion exchangers is 1. Determine, by experiments, the opti- 25079-039 10 L shown in Figure 3. mal dynamic capacity and linear velocity. CM Trisacryl M 26708-016 300 ml 26708-032 1 L 2. Determine, by experiments, the opti- Validation 26708-024 10 L mal column height. Drug Master Files are available for dif- SP Trisacryl M 25910-019 300 ml 25910-027 1 L 3. Based on the linear velocity and the ® ferent types of Trisacryl ion exchangers: 25910-035 10 L column height, determine the duration ® - DMF No. 7830 for DEAE Trisacryl DEAE Trisacryl LS 26710-012 1 L of one cycle, and the number of cycles - DMF No. 8039 for SP Trisacryl®. 26710-020 10 L to be run per day. Trisacryl® ion exchangers are currently CM Trisacryl LS 20030-011 1 L 4. Knowing the number of cycles per used by pharmaceutical companies for 20030-037 10 L day, calculate the volume of sorbent the production of injectables. SP Trisacryl LS 26711-010 1 L needed. 26711-028 10 L
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Trisacryl, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN BT203112 - 12/2004
4 PRODUCT NOTE
DEAE & SP Spherodex® LS Silica/dextran composite ion exchangers for liquid chromatography of biologicals.
DEAE and SP Spherodex® LS ion Figure 1. Structure of Spherodex ion exchangers. exchangers are stable composites comprised of two polymers: an inor-
® O ganic silica matrix which provides a HO DEAE CH2 high degree of rigidity to support O high flow rates, and an organic dex- O OH tran component that provides (CH2)2 O hydrophilicity and biocompatible R--N--R + functional groups. The resulting interpenetrated poly- mer network has several advantages O HO SP such as good chemical stability and CH2 O bed stability in both aqueous and O OH organic solvents. The sorbent does SO3 not shrink or swell with pH or ionic O strength, and withstands pressure generated even when exceeding 600 cm/h. The unique network also elimi- The porous silica matrix is coated with a continuous layer of ionizable dextran nates non-specific sorption of proteins. to yield high exchange capacity and improved stability. Spherodex These sorbents were developed
® specifically for large scale process chromatography of therapeutic pro- Table 1. Properties of Spherodex LS Ion Exchangers. teins and industrial enzymes. DEAE (dry) SP (wet) Spherodex® ion exchange sorbents are presently used in column sizes Particle size (µm) 100-300 100-300 from 20 to 3,000 L. Exclusion limit (dt)(1) 106 - 107 106 - 107 EPRA SP Spherodex LS is supplied in wet Ionized groups/volume (µeq/ml)(2) 100 150
S form, in an aqueous suspension con- pK of ionic group 6.5 ; 10 1 taining 1 M NaCl and 20% EtOH. Operating pH range 1-12 1-12 DEAE Spherodex LS is supplied in dry Stability to detergents and excellent excellent IO form. denaturing agents Heat stability good excellent
B The most important properties of these ion exchange sorbents are: Microbial stability excellent excellent Volume changes due to pH and none none ■ Stable bed at very high flow rate. ionic strength ■ Stable to pressure (> 50 bar). Capacity for BSA(3) ≥ 75 mg/ml - ■ Stable in acidic solutions. Capacity for lysozyme(4) - ≥ 60 mg/ml ■ Highly porous and hydrophilic. ■ Low non-specific adsorption. (1) For globular macromolecules. (2) Average. ■ No swelling or shrinking, due to (3) Determined using 10 mg/ml BSA solution in 10 mM Tris-HCl buffer, pH 8.6. (4) aqueous or organic solvents. Determined using 5 mg/ml lysozyme solution in 50 mM acetate buffer, pH 5.
1 BIOSEPRA® Spherodex® heat DEAESpherodex autoclaved at121ºC.However, itisnotadvisableto range oftemperatures.Theycanbesafelyfrozen,or the ionexchangepropertiesofSpherodex pyrogen removalcanbeeffectedwithoutmodifying Classical chemicaltreatmentforsanitizationand agents, andotherorganicproducts. to strongdenaturingmedia,detergents,chaotropic They arealsostabletoacidicandalkalinesolutions, patentedtechnology.prietary chemical cross-linkingofthepolysaccharideviapro- Additionally, theentirestructureisstabilizedby SP(sulfate). - DEAE(diethylaminoethyl). - groups tightlyanchoredontothepolymer: The dextranpolymercarriestheclassicalionizable non-specific adsorptiononsilanolsiseliminated. towards extremesofpH.Additionally, anypossible silanol groups.Thisresultsinimprovedstability covered bydextran,eliminatingtheactivityofactive istotally silica skeleton(Figure1).Thesurface formly distributedwithintheporestructureof 100 and300µm.Thederivatizeddextranisuni- and ionizabledextran.Theparticlesizerangesfrom exchange matricescomprisedofanetworksilica exchangers. advantages: technology. Thisopenstructureoffersthefollowing orous, asaresultofspecificsilicapolymerization ■ The structureoftheSpherodex Porosity. Spherodex Chemical compositionandstructure. Spherodex Thermal stability. Spherodex Chemical stability. ■ tiary amine. tiary of theprogressivedegradation ofthesubstitutedter- (high masstransfer). Rapid diffusionofmacromoleculesintothebeads Absence ofmolecularsievingphenomena. ® ® ® LS ionexchangersarestableoverawide LS sorbentsareinsolubleinallsolvents. sorbents arerigidsphericalion ® repeatedly at121ºCbecause ® network ismacrop- ® ion 2 sodiumchloride;Throughputat1bar:2.3cv/h. M 1 Column: 30cmI.D.x78containing55Lofsorbent;Eluent: Spherodex LScolumn. generatedwithaDEAE Figure 2.Pressurevs.FlowRatecurve The proteinsorptioncapacityofSpherodex Protein sorptioncapacity. ■ ■ Spherodex Mechanical stability. group aswell. and theionization oftheionexchangefunctional Changes inpHmodifythenet chargeoftheprotein provide optionstoimproveresolution. Differences incounterionbinding constantscan exchange andhaspotentialto improveresolution. molecule. Temperature increasestherateof strength leadstoadecreasedcapacityforgiven exchange equilibrium.Typically, anincreaseinionic ionic strengthofthebufferwhichcontrolsion The sorptioncapacityisprimarilyaffectedbythe tein (isoelectricpointandmolecularweight). counter ionandintrinsiccharacteristicsofthepro- buffer, ionic strength,temperature,natureofthe depends onaseriesoffactorsincludingpHthe exchange mechanism.Thissorptioncapacity exchangers followsthegeneralrulesofion mechanical stabilityoffersadditionaladvantages: the linearcolumnflowrate(Figure2).Thisexcellent Pressure thuspresentsaneasymethodforincreasing and maybesubmittedtopressuresover50bar. the chromatographiccycle. rate andchangingitduringthedifferentphasesof Greater flexibilityinselectingtheworkingflow strength, pH,orflowratesvaluesarechanged. No variationofthecolumnvolumeasionic Pressure (bar) 2 1 ® 50 ion exchangersarenon-compressible 100 PRODUCT NOTE 0 300 200 150 250 Flow rate ® L/h cm/h ion Applications. Separation of a protein mixture on SP Spherodex®. Spherodex® LS sorbents have proven to be very efficient in The strong anionic character of this sorbent permits the the laboratory as well as in production scale fractionation of separation of a mixture of three well-known proteins. proteins. DEAE Spherodex® has been used for many years at Impurities are found in the flowthrough (they do not inter- production scale in the fractionation of human plasma pro- act with the sorbent). The three other sample proteins teins and placenta extracts. It has been used at column scale adsorbed to the column are eluted using a linear sodium of 1,500 L in the purification of albumin. It was also suc- chloride gradient in the starting buffer (Figure 4). cessfully used in production scale for the purification of IgG and transferrin from human plasma. Figure 4. Separation of a mixture of (a) β-lactoglobulin, (b) Ovalbumin, ® In other fields of protein fractionation, Spherodex ion (c) Cytochrome c, and (i) impurity on an SP Spherodex column. exchangers were described as being very efficient when used as such or when chemically modified. DEAE Spherodex® has been used for the separation of gangliosides and lipid-like c molecules. It was also used as a matrix for affinity chro- Conc. [NaCl] matography at laboratory scale as well as at large scale for 1 the separation of tetanus toxin after immobilization of gan- ® glioside GM-1 on partially modified DEAE Spherodex and b for the isolation of antitetanus toxin antibodies. a
Albumin separation from human plasma. i In this example (Figure 3), the prepurified albumin is eluted in an acetate buffer, pH 4.7. The albumin fraction thus obtained displays an electrophoretic purity of 90 to 93%. 0 This prepurified albumin is then chromatographed on two 20 40 60 ml other additional columns to obtain pure albumin. Column: 1.1 cm I.D. x 9 cm; Buffer: 0.05 M acetate, pH 4.5; Elution gradi- ent: sodium chloride from 0 to 1 M; Flow rate: 30 ml/h. Figure 3: Example of large scale application of DEAE Spherodex LS, purification of albumin from human plasma.
2 1 3 Liters/h
4 5 Ordering Information
50 100 150 Liters Product Cat. No. Size
DEAE Spherodex LS 26455-023 100 g 26455-031 1 kg 26455-049 10 kg 26455-056 25 kg SP Spherodex LS 20080-024 100 ml 20080-016 1 L 20080-032 10 L 20080-040 25 L
Column dimensions: 100 cm I.D. x 1400 cm (1050 L); Sample volume: 10,000 L/day; Equilibration buffer: 0.01 M phosphate, pH 5.25; Albumin elution buffer: 0.025 M acetate, pH 4.7; Washing with 1 M NaCl (peak 3), with 0.1 M HCl (peak 4) with a mixture of 60% ethanol in 0.5 M acetic acid; Flow rate: 1250 L/h (150 cm/h). Courtesy of Pasteur Merieux Connaught, Lyon, France.
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Spherodex, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN BT205102 - 12/2004
4 BioSepra® Spherosil® gers are available in dry form. gers areavailableindry QMA SpherosilM,LSionexchan- sorbents. teins difficulttoisolateonclassical phy allowsthepurificationofpro- unique mixmodechromatogra- properties tothesorbent.This ionic andslightlyhydrophobic cal use.Thepolymerprovides specifically designedforbiochemi- beads graftedwithpolymer sorbents arecomposedofsilica ion exchangechromatography adsorption andelution,butmay hydrophobic character. Thisallows additionally demonstratessome polyanionic orpolycationic,it Regardless ofwhetherthegel is the proteintobepurified. the cationicpolymeristoadsorb high porosity, whereastheroleof combination ofhighrigidityand Figure 1).Silicaallowsforthe amine(seestructurein ternary ties tothesorbent. and slightlyhydrophobicproper- The polymerprovidestheionic (this occursbycovalentbinding). linked tofunctionalizedpolymers are covering theporesurface available onrequest).Thesilanols with particlesizeof40-100µmis 300 µmforLSgrade(Mgrade, cle sizerangesbetween100and based onporoussilica.Theparti- QMA Spherosil and structure Chemical composition BioSepra QMASpherosil Introduction Silica-based hydrophobicionexchangersforliquidchromatography QMA Spherosil ® are rigidbeads QMA ® is aqua- M, LS Figure 1.Structure(left)andinternalporousstructure(right)ofQMASpherosil. - Rapiddiffusionofmolecules insidethenetwork(highmasstransfer). - Absenceofmolecularsieving phenomenon, silicate polymerizationused(Figure 1).Itoffersfollowingadvantages: The sorbentstructureismacroporous,duetothespecifictechnology of Porosity been previouslydifficultorimpossibletoisolateonclassical gels. chromatography makespossiblethepurificationofproteins whichhave ion exchange.Theabilitytomanipulatetwophysicalproperties during require themodificationofparameterstypicallyselectedin hydrophilic (2)Determinedin0.025Mphosphate buffer, pH6. (1) Forglobularmacromolecules. Average specific area(m surface Average porousvolume(cm Exclusion limit(dt) 40-100 . Mgrade Particle size(µm): Table 1.MainPropertiesofQMASpherosilsorbents. Capacity forBSA(µeq/g) None . Volume changesduetopHandionicstrength Excellent . Microbial stability Good . . Heat stability Excellent . Stability todetergentsanddenaturingagents 1-12 . Working pHrange 11 . pk ofionizablegroup 300 . Average ionizedgroups(µeq/g) amine Quaternary . Nature ofionizablegroup ® M &LS Silica 1 (1) Sgae 100-300 . LS grade Polymer layer ...... 10 . (2) + CH CH ...... 30 . NCH 3 g 1 . /g) 3 3 2 g ...... 25 . /g) 3 PRODUCT NOTE 6 - 10 7 PRODUCT NOTE
Stability this offers the following advan- Protein sorption capacity tages: The sorption capacity of QMA - No variation of the column vol- Chemical stability Spherosil® sorbents varies accord- ume as the ionic strength, pH or ® QMA Spherosil sorbents are flow-rate values are changed. ing to several parameters. The insoluble in all solvents. They are - Greater flexibility in selecting the most important one is the work- resistant to denaturing agents, working flow rates. ing pH. Table II and Figure 5 detergents, chaotropic agents show the results from experi- and other organic solvents. Biological stability ments to determine the amount Their stability in acidic and alka- Since QMA Spherosil® sorbents of proteins adsorbed per ml of line solutions is determined by have a mineral and synthetic com- hydrated support. The test was maintaining the sorbent in 1 M position, they are not sensitive to performed with three acidic pro- HCI or NaOH at room tempera- bacterial and enzymatic attack. teins (albumin, ovalbumin and ture for one hour. QMA Sphero- ® thyroglobulin). The capacity sil® sorbents are not sensitive to increases when the pH of the acids but are sensitive to extreme Figure 4. Titration curve. alkaline pH. When alkaline buffers buffer decreases. However, thy- are required, the sorbents should pH roglobulin does not adsorb on Uncoated sorbent ® be washed rapidly using diluted 11 S1O2 QMA Spherosil .
bases only (e.g. 0.1 M). 9
Thermal stability 7 Applications Since they are based on silica and 5 ® synthetic polymers, QMA 3 QMA Spherosil sorbents are Spherosil® sorbents are stable QMA Spherosil designed for the separations of 1 proteins on the laboratory and over a wide range of tempera- 5 15253545ml industrial scale. They represent a tures. They can be frozen and tol- Titration solutions: 0.1 M HCl or 0.1 M significant step in the resolution
Spherosil erate temperatures of 80-90°C. NaOH. of flow rates problems still Autoclaving is not recommended. encountered today with soft
® material. For example, these sor- Mechanical stability Figure 5. Adsorption capacity as a bents allow the chromatography ® function of pH. QMA Spherosil sorbents are non of proteins on a very large scale compressible and therefore with- (Figure 7), making use of stand pressures of several dozen columns with capacities of several bar. The pressure is an easy way 50 hundreds liters under acceptable of increasing the column linear hygienic conditions for the pro- flow rate (Figure 3). Additionally, duction of injectables. Capacity (mg/ml) 25 Purification of human placenta albumin has already been realized Figure 3. Inlet pressure as a functlon of in installations that are capable of the flow rate in a QMA Spherosil® col- 6789pH separating 180 kilos of albumin umn. per cycle. Capacity determined for bovine albumin in BioSepra Flow rate 0.025 M phosphate buffer using 5 mg/ml L/h cm/h protein solution. 30
300
20 Table II. Adsorption capacity of QMA Spherosil LS for acidic proteins.
150 10 Protein Adsorption capacity (mg/ml of sorbent)* pH 6 pH 7 pH 8 pH 9 Bovine albumin 53 27 10 11
0 0.2 0.4 0.6 Ovalbumin 86 66 39 34 Pressure (bar) Thyroglobulin 0.8 0.9 ND 0.9 Column dimensions: 10.5 cm I.D. x 101 cm length. Particle size: 100-300 µm. * Determined in 0.025 M phosphate buffer by frontal analysis.
2 Other applications in fluidized beds Beyond the described applications, The following examples are illustrative have been reported. Fluidized beds there is a great potential both on the of some of the numerous applications constitute an excellent means for the laboratory and industrial level. of Spherosil®. separation of specific proteins from turbid solutions.
Example I. Separation of sweet whey Example II. Continuous adsorption For continuous sorption operation, a proteins on QMA Spherosil®. of bovine serum albumin in fluidized counter-current fluid bed column Courtesy of S. Stefanos & J. Wietzerbin, Mary bed columns of QMA Spherosil® LS. (100x3 cm) is equipped with a num- Ann Liebert Inc. Publications, NY. Courtesy of Dr. J.P. Van der Wiel, Delft ber of perforated plates to suppress sil- University of Technology, The Netherlands. ica beads mixing. The QMA Spherosil® ab LS sorbent used here is transported downward by temporarily reversing β-lactoglobulin 6 2 the liquid flow as detailed in Figure 7. 9 Figure 8 shows that the pH has an O.D. 280 nm O.D. 280 nm 10 effect on the continuous adsorption 3 process. At pH 6, the adsorption phe- 1 α-lactalbumin nomenon is quicker and makes the continuous separation of albumin pos- sible, even from unfiltered cloudy solu- 5 tion. This represents a significant 7 8 advantage over packed bed chro- 4 matography.
Time Time Figure 7. Experimental set-up for fluidized bed continuous adsorption. Figure 6. HPLC analysis of sweet whey proteins 1: column; 2: sorbent loading vessel; 3: sorbent separated on QMA Spherosil® LS sorbent. container; 4: sorbent collector; 5: pulsation unit; (a) Chromatographic profile before separation. 6: sorbent inlet; 7: sorbent outlet; 8: liquid inlet; (b) Protein profile after separation. 9: liquid outlet; 10: sorbent transport water. Column: TSK-G-3000 SW; Buffer: 0,05 M phos- phate, pH 7.5 containing 0.15 M sodium chloride; Flow rate 1 ml/min. References N mg C (g/L) ab(m2 S ( This example shows a simple and effi- 1. Grandgeorge, N., Tayot, J.L., Proceedings 1.5 1.5 "Colloque technologie sur la purification des cient method for the separation of pH 6 protéines", Paris (1984) 303. α-lactalbumin and β-lactoglobulin pH 7 2. Tayot, J.L., et al., Proceeding IABS Congress, from crude sweet whey: Melbourne (1986). 1 1 - Equilibrate a column (6 mm I.D.) 3. Van der Wiel, Engineering Foundation confer- containing 5 g of QMA Spherosil® in a ence, Uppsala, May 1986. 4. Cueille, G., Tayot, J.L., Proceeding Biotech'85, solution of 0.05% sodium chloride 0.5 0.5 Geneva (1986). (about 0.01 M). 5. Veron, J.L., et al., Biotechnology of Blood - Inject 120 ml of sweet whey (80 g/L) Proteins 227 (1993) 183. into the column. 159Tray No. 159Tray No. - Wash the column with 0.05 M NaCI, elute with 0.1 M HCI. This should be Figure 8. Continuous adsorption of bovine serum performed at a flow rate of 80 ml/h. albumin on QMA Spherosil® LS in counter-current column. Ordering Information - Reequilibrate the column with 0.05 M Buffer: 1 mM Tris-HCI, pH 8 or 7; Liquid flow: NaCI. 49.8 ml/min; Sorbent flow: 1.54 ml/min. Product Cat. No. HPLC analysis shows that the HCI elut- (a) Steady-state concentration profile at different pH. (b) Amount of protein adsorbed per plate. ® ed fraction includes mainly α-lactalbu- QMA Spherosil M 26165 ® min and β-lactoglobulin. QMA Spherosil LS 26099
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Spherosil, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN BT205101- 12/2004
4 BIOSEPRA® HA ULTROGEL® request. manufacturing requirements isavailableon age sizes.Specialpackaging to meetspecific 20% ethanolandisavailable inarangeofpack- The sorbentisshippedin1M NaClcontaining the separation(seefigure1). ity avoidsanymoleculearsievingeffectduring proteins of5,000,000daltons.Thismacroporos- agarose gel,withanexclusionlimitforglobular HA Ultrogelporosityiscomparabletoan perature. ionic strengthchanges,aswelltohightem- an excellentrigidityandstabilitytopH saccharide chainsandgivesthesorbentbeads This createsglycerolbridgesbetweenthepoly- 1.0 MNaOHforregenerationandsanitization. HA Ultrogelcanberegularlytreatedwith0.1- hydrin understronglyalkalineconditions.Thus Ultrogel ischemicallystabilizedwithepichloro- 60 and180µm.TheagarosemoietyinHA agarose mesh.Theparticlesizerangesbetween ofhydroxyapatiteentrappedinthe crystals posed ofcross-linkedagarosebeadswithmicro- HA Ultrogelhydroxyapatitesorbentiscom- applications. used inresearch scaletomulti-litercolumn HA Ultrogeliseasyscaleableandcurrently exchange orhydrophobicinteractiontechniques. tomoretraditionalion ity complementary ety ofprocesses,providingbiomoleculeselectiv- be aneffectivepurificationmechanisminavari- “mixed-mode” ionexchange.Ithasprovento to bea“pseudo-affinity”chromatography, or Hydroxyapatite chromatographyisconsidered and developmentscaletomanufacturing. for theseparationofbiomoleculesfromresearch is ahydroxyapatiteagarosecompositesorbent Biosepra HAUltrogelsorbentavailablefromPall Hydroxyapatite ChromatographySorbent HA Ultrogel • • • • Used inlargescalestep Easy cleaning High porosity Effective purificationmechanisminavarietyofprocesses ® 1 Flow rate:14.4cm/h. ent: 5mMto500potassium phosphate, pH6.8; 1 mlof5mMpotassiumphophate, pH6.8;Elutiongradi- hemagglutinin) (MW128,000)fromPhaseolusvulgaris,in andlymphostimulatingPhyto- (Erythroagglutinating composed ofribonuclease(MW14,700)andPHA-ELs Column: 1.6x6.5cm;Sample:1mgofproteinmixture PHA-ELs. Figure 1.Separationofamixtureribonucleaseand phosphate buffer, pH6.8at 12.5cm/h. ** Determinedusing1mg/mlBSAdiluted50/50inmM phosphatebuffer, pH6.8at30cm/h. in 1 mM Determined using5mg/mlcytochrome cdiluted50/50 * %T (282nm) Table 1.HAUltrogelMainProperties. aaiyfrBA*<7mg/ml 5-14 4-121°C 5-13 >5,000,000dt >7mg/ml Capacity forBSA** Capacity forcytochromec* 60-180µm Thermal stability Cleaning pH 4% Working pH 40% Exclusion limit Agarose (weight/volume) Hydroxyapatite content Particle size 50 04 010ml 100 80 40 10 PRODUCT NOTE Ribonuclease PHA-ELs PO 4 --- [M] 0.1 0.3 0.5 PRODUCT NOTE
Stability Applications The recommended flow rates to be used with Hydroxyapatite adsorption chromatography HA Ultrogel sorbent depend on the column can be used in a variety of applications, includ- geometry and on the separation phase (cap- ing the separation of proteins, peptides and ture, elution or washing steps). At process scale, nucleic acids,from pilot to production scale (see typical flow rates from 30 to 200 cm/h are cur- figures 2, 3, 4). rently applied with multi-liter column sizes. For proteins, the most well-known application Hydroxyapatite crystals are naturally resistant to of hydroxyapatite is the separation of basic pro- most chemical agents, except solutions with a teins (cytochrome c, lysozyme, etc.) and phos- pH less than 4 and complexing agents. phoproteins. HA Ultrogel sorbent can be used ® Hydroxyapatite is dissolved by acidic solutions, for the separation of human serum proteins while EDTA, citrate and other complexing and plant proteins such as lectins, glycopro- agents decrease the adsorption capacity of the teins, glycosidases, phospholipidases, sulfohy- resin. Complexing agents may be used in drolases, sphingomyelinases, transferases, treha- extreme cases, e.g. when the desorption of cer- lases and kinases. tain compounds irreversibly bound to the As a phosphate-containing sorbent, HA Ultrogel matrix is required. can be used for the separation of phosphate-
LTROGEL HA Ultrogel sorbent is resistant to denaturing dependent proteins and enzymes as well as agents: it can be treated with 8 M urea, 6 M DNA-dependent enzymes. guanidine-HCl, 1% SDS and chaotropic agents HA Ultrogel sorbent provides an efficient tool such as 3 M KSCN. for IgG purification in a one step chromato- The agarose moiety of HA Ultrogel sorbent is graphic purification by separation with phos- chemically stabilized by cross-linking with phate buffer. This approach is very mild (neutral
HA U epichlorohydrin in a strong alkaline medium. pH, physiological conditions) compared to tra- HA Ultrogel sorbent is stable in alkaline condi- ditional elution in acidic solutions, and pre- ® tions, and can be regularly treated with 0.1 to serves the biological activity of the antibody. 1M sodium hydroxide for regeneration and HA Ultrogel has been used for the separation depyrogenation. The chromatographic behav- of: ior of the sorbent was not significantly modified
EPRA - Synthetic polypeptides (acidic polypeptides of after 5 weeks of incubation in 1M NaOH, such as poly-L-glutamate, poly-L-aspartate). S pH 13. - Basic polypeptides such as poly-L-lysine, poly- HA Ultrogel sorbent should not be treated with L-ornithine. IO solutions at pH <4 due to the nature of the - Neutral polypeptides such as poly-L-proline.
B hydroxyapatite crystals. It can be used for the separation of various HA Ultrogel sorbent is stable a high tempera- types of nucleic acids, including transfer RNA ture (up to 121°C). It can be sterilized by auto- and low molecular weight glyoxylated deriva- claving without undergoing any changes to its tives of DNA, with reproducibility, stability and chromatographic properties. However, the reliability (see figure 2 and 3). operation should be performed in buffered con- ditions at pH 7 to avoid the presence of phos- phate which may precipitate. HA Ultrogel sorbent should never be frozen.
2 Figure 2. Separation of glycohydrolases from a crude enzyme Figure 4. Separation of trypsin and chymotrypsin from a porcine extract of buckwheat. pancreatic enzyme extract.
A282 nm --- PO4 [M] Spec. Ac. %T (282 nm) 0.8 70 tr.
0.15 ch.
20 200 0.5 90
1 2 3 4 5 10 100 0.05
0.2
e 30 60 ml
a b c d Column: 1.6 x 5 cm; Sample: 30 mg protein in 1 ml of 5 mM phosphate 100 200 300 ml buffer, pH 6.8; Gradient: 5 to 200 mM sodium phosphate, pH 6.8; Flow Column: 2 x 6 cm; Sample: 40 mg of lyophilized extract in 1 ml of rate: 10 cm/h; Temperature: 10°C; Histogram with broken line: trypsin 1 mM phosphate buffer, pH 6.8; Discontinuous elution gradient of phos- activity; Histogram with solid line: chymotrypsin activity. phate buffer; Flow rate: 7.1 cm/h; Temperature: 4°C. Peak a: proteins Spec. Ac.: specific activity in U/mg. tr: trypsin, ch: chymostrypsin. with no glycohydrolase activity; peak b: β-glucosidase. Trypsin activity was primarily found in the peak eluted by 50 mM phos- Courtesy of R. Rourbouze & F. Percheron, Biochemistry Lab., Faculty of phate where the chymotrypsin was eluted by 100 mM phosphate. The Pharmacy, Paris. final yield was approximately 50%.
Figure 3. Purification of damage-specific DNA binding protein from References human placenta. 1. Séné, C. et al., ChimicaOggi 8 (1990) 30. Units/ml Kphos (M) (103) 2. Galand, G., Biochim. Biophys. Acta 789 (1984) 10. 3. Huitorel, P. et al., Eur. J. Biochem. 144 (1984) 233. 0.15 M 0.5 M A280 Kphos Kphos 4. Fournier, N. et al., Biochem. Biophys. Res. Commun. 111 (1983) 326. 5. Ek, K. et al., J. Biochem. Biophys. Meth. 8 (1983). 0.3 12 6. Rousson, R. et al., Biochimie 65 (1983) 115. 7. Nari, J. et al., Plant Sci. Lett. 28 (1983) 307. 0.5 8. Gegenheimer, P. et al., J. Biol. Chem. 258 (1983) 8365. 9. Ait, N. et al., J. Gen. Microbiol. 128 (1982) 569. 0.2 6 10. Nelson, W.J. and Traub, P., J. Biol. Chem. 257 (1982) 5544. 11. Verger, R. et al., Biochemistry 21 (1982) 6883. 0.3 12. Feldberg, R.S. et al., J. Biol. Chem. 257 (1982) 6394. 13. Leblanc, J.P. et al., J. Biol. Chem. 257 (1982) 3477. 0.1 2 14. Sim, R.B. and Discipio, R.G., J. Biochem. 205 (1982) 285. 15. Ryan, D.E. et al., Arch. Biochem. Biophys. 216 (1982) 272. 0.1 16. Degranges, C. et al., Biochim. Biophys. Acta 654 (1981) 211. 17. Rowe, T.C. et al., J.Biol, Chem. 256 (1981) 10354. 18. Akiki, C. et al., J. Chrom. 188 (1980) 435. 20 40 60 80 100 Frac. 19. Monsigny, M. et al., Eur. J. Biochem. 98 (1979) 39. 20. Monsigny, M. et al., Biochimie 60 (1978) 1315. The sample was previously prepurified from human placenta by ammo- nium sulfate precipitation, ion exchange chromatography and gel filtra- tion. Column: 2.5 x 6 cm; Initial buffer: 10 mM potassium phosphate, Ordering Information pH 8 containing 5% glycerol and 13 mM 2-mercapto-ethanol; 1st elution (arrow): 0.15 M potassium phophate buffer; Product Cat. No. Size 2nd (arrow): 0.5 M potassium phosphate buffer; Fraction volume: 1.8 HA Ultrogel 24775-025 100 ml ml. ●—● A280 nm ■—■ DNA binding activity o—o conductivity. Courtesy of R.S. Feldberg, et al., J. Biol. Chem. 257 (1982) 6394-401. 24775-017 500 ml 24775-041 1 L 24775-058 10 L 24775-066 20 L
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They greatly simplify protein purification development and significantly improve biopharmaceutical manufacturing productivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technolo- gy to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New +44 (0)23 9230 3303 phone Zealand, Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, +44 (0)23 9230 2506 fax Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Ultrogel, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN BT200909 - 12/2004 Filtration. Separation. Solution. SM
4 BioSepra® Trisacryl® GF05 Trisacryl matography. for mediumpressuregelfiltrationchro- highly hydrophiliccopolymerdesigned ■ ■ ■ ■ ■ Trisacryl Size ExclusionChromatographySorbents Trisacryl Trisacryl structure. Chemical compositionand the matrix. of anynon-specificinteractionswith sterile conditions,andintheabsence great selectivityundermediumpressure, graphic separationsquicklyandwith chromato- GF05 sorbentstoperform These characteristicsallowTrisacryl ■ ■ ■ al scale. with lowpressure,designedforindustri- grade) forfractionationathighflow use. tion forlaboratory grade) withnarrowbeadsizedistribu- of thegelvolume. per repeatingunit. hydroxymethylgroups of threeprimary amidegroup, andbythepresence ary hydrophilicity contributedby asecond- The moleculefeaturesahigh degree of See chemicalstructureinFigure 1. bifunctionalmonomer.ylated acrylic ymethyl-1,3-propanediol, andahydrox- tion ofN-acryloyl-2-amino-2-hydrox- copolymer formedbythecopolymeriza- advantages overexistinggels: Trisacryl and fortheseparationofsmallmolecules. Highly stableinacidicmedia. Non biodegradable. High flowrates. Ready andeasytouse. Large particlesize(80-160µmforLS Small particlesize(40-80µmforM Large desaltingcapacity, upto33% High separationefficiency. ® ® ® ® GF05 sorbentiscomposedofa GF05 isahighlyhydrophilic GF05 providesawiderangeof GF05 isdesignedfordesalting ® GF05 M,LS ® The exclusionlimitofTrisacryl porosity. Figure 1:ChemicalstructureofTrisacryl GF05sorbents. the cross-linkingagentallowprecisecontrolofTrisacryl The modificationofrelativeconcentrationsthemonomer and Porosity. * Calculatedonthebasisofastandardexperimentalcurve. ducibility fromlottolot. only aregularporosityinside each bead,butalsoexcellentrepro- Close controloverthepolymerizationreactionguarantees not cleotides) is3,000dt. Particle size Table 1.MainpropertiesofTrisacryl GF05sorbents. pH stability Thermal stability Stability todetergentsanddissociatingagents Pressure resistance Desalting capacity Resolution power Linear fractionationrange Exclusion limit – NH CH CO CH I I 1 – – C . CH CH I I . – . 2 CH 2 OH 2 OH .
– . . . CH 2 O CH CO NH I OH I – – CH C CH II I . – 2 2 CH 2
® HCH OH OH – PRODUCT NOTE GF05 (determinedusingoligonu- CH NH CO CH I I 2 OH – – C CH CH I I – 2 2 CH 2 OH OH
– NH . CH CO CH CO I 2 I OH 11 1 - Up to121°C Excellent up to3bar(44psi) 33 %gelvolume 2,500 plates/m dt -2,500 200 dt* 3,000 -160µm LS grade:80 80µm - M grade:40 – – C I CH – 2 CH 2 2 OH OH
– ® 2 GF05 OH PRODUCT NOTE
Chemical stability. Figure 2. Flow rate variation of a Trisacryl GF05 M column as a function of pressure. Trisacryl® GF05 is insoluble in chromatographic sol- vents commonly used in biochemistry (8 M urea, 6 M guanidine), as well as in detergents (Triton X-100, SDS, lubrol, ...). 200 Trisacryl® GF05 is resistant to acid treatments, mak- ing it an ideal matrix for peptide separations which 100
require the use of acetic or hydrochloric acids. The Flow rate (cm/h) matrix is not modified by incubation in the presence of 1 M HCl for several hours. However, Trisacryl® GF05 is sensitive to strong alkaline agents such as 1 2 3 (bar) sodium hydroxide. Sensitivity to alkaline medium is 10 20 30 40 (psi) Pressure minimal in 0.1 M NaOH at +4ºC for a maximum of one hour. If the NaOH concentration or the temper- Column dimensions : 1.4 cm I.D. x 10 cm. The column was packed ature are increased, the sorbent undergoes progres- under pressure from 0 to 2 bar; Flow rates were measured under pres- sures from 2 to 0 bar. GF05 sive hydrolysis of amide groups to give carboxyl groups. This will introduce some ion exchange
® properties.
Thermal stability. column for a molecule eluted in the total available Trisacryl® GF05 is stable at high temperature (up to gel volume). +121ºC). It can be sterilized by autoclaving without The resolution power of Trisacryl® GF05 depends on undergoing any change in its chromatographic the flow rate and varies with the molecular size of properties. However, the operation must be per- the product used. The flow rate needed to obtain formed in buffered conditions, pH 7 in the absence optimal separation ranges from 2 to 3 cm/h. of oxidizing agents. Because the height equivalent of a theoretical plate (HETP) increases very slowly as a function of flow Mechanical stability. rate (2-3 times less rapidly than with soft sorbents), Trisacryl® GF05 provides excellent resolution power Trisacryl Due to its chemical composition which imparts rigidity, Trisacryl® GF05 is resistant to pressures up to for proteins (see Figure 3).
® 2-3 bar. This exclusive property permits elevated flow rates.
Resistance to micro-organisms. Figure 3. HETP variation of Trisacryl GF05 M (height equiv- alent to a theoretical plate) as a function of the flow rate. Due to its synthetic matrix, Trisacryl® GF05 is resist- ant to microbial and enzymatic degradation. 1.0 Fractionation range. 0.8 ®
The effective fractionation range for Trisacryl GF05 HETP (mm) is between 200 and 2,500 dt. This was determined 0.6 with globular proteins below 1000 Kd and extrapo- 0.4 lates up to the exclusion limit.
BioSepra 0.2 Resolution power. The resolution power of the M grade of Trisacryl® 0 5 10 15 GF05 (expressed by the number of theoretical plates Flow rate (cm/h) per meter of column under normal running condi- Column: 1.6 cm I.D. x 36 cm. Sample : 5 mg NAD (nicotinamide ade- tions) is relatively high — about 2,500 plates per nine dinucleotide, MW 700) in 1 ml buffer; Buffer: 0.1 M phosphate meter or HETP (height equivalent to a theoretical buffer, pH 7.4 containing 0.5 M NaCl; Temperature: +20ºC. plate) = 0.4 mm (value obtained using a 40 cm
2 Applications Figure 4. Steps from an automatic desalting of Fractionation and purification of bio- human plasma on a Trisacryl GF05 LS column. logical molecules on Trisacryl® GF05. ® Desalting on Trisacryl GF05. Trisacryl® GF05 permits the separation Trisacryl® GF05 is particularly suitable to of a variety of complex mixtures (see rapid desalting of large solution volumes. Figure 6) such as :
■ Pressure resistance allows high flow D.Pl. D.Pl. D.Pl. D.Pl. D.Pl. D.Pl. D.Pl. D.Pl. D.Pl. D.Pl. - Polypeptides rates. - Oligonucleotides 1 2 3 4 5 6 7 8 9 10 Cycles ■ Provides a low dilution factor (about - Oligosaccharides 1.05-1.1). Column dimensions: 44 cm I.D. x 40 cm (60 L of gel); - Small proteins Buffer: 0.05 M Tris-HCl, pH 8.4; Flow rate: 80 L/h; - Polynucleotides ■ Provides large desalting capacity (up Sample volume: 12.5 L; Desalting time per cycle: 75 - Small water-soluble polymers to 33% gel volume). min (including equilibration time). Volume/h: 1.3. Pressure: 0.7 bar (average). D.Pl. = desalting plasma The best resolution is obtained with a These desalting properties are illustrated fraction. (Courtesy of Mr. J. Saint-Blancard, CTSA sample volume between 0.5 and 4% of by the results obtained in the use of Clamart, France). gel volume. Trisacryl® GF05 for human plasma frac- tionation: 17 L of human plasma were FIgure 6 : Fractionation of peptides obtained run through a 60 L Trisacryl® GF05 col- from trypsin hydrolysis of bovine thyroglobulin. umn (44 cm I.D. x 40 cm) and desalted Determination of the molecular within 1.5 hour. Linear flow rate was weight of an unknown molecule. 35 cm/h, corresponding to a volumetric The measurement of molecular weight Conc. flow rate of 36 L/h. The volume of can be performed by comparing the desalted plasma was 18 L, correspon- Kav of the studied molecule to the Kav ding to a dilution factor of 1.059. relative to standard molecular markers Similar results are illustrated in Figure 4. obtained on Trisacryl® GF05 selectivity Trisacryl® GF05 can be applied to sever- curve (see Figure 5). In this case, it is al other "desalting" operations such as important to notice that the selectivity 0 20 40 60 80 ml removal of small aromatic molecules, curve must be determined using mole- Buffer: 0.1 M KH2PO4, 0.15 M KCl, pH 7.4; Sample: separation of fluorochromes after pro- cules from the same species as the stud- 1 ml. U.V; Detection: 280 nm; Flow rate: 11.5 cm/h; tein labelling, elimination of detergents ied molecule. For example, the stan- Column: 1.6 x 45 cm; Experiment time: 8 hours. in protein solutions, separations of sug- dard molecules must be performed with ars, elimination of peptides. known oligosaccharides if the studied Trisacryl® GF05 has an appreciable time molecule is a sugar. References advantage over dialysis for desalting. 1. Brown, E., et al., Proc. Int. Symp. Aff. Chromatogr., Desalting by gel chromatography is Strasbourg (1979) 37. presently the only available method for Figure 5. Selectivity curve determined using a 2. BoschettI, E., et al., Sci. Tools 30 (1983) 27. removing salts from very labile biologi- mixture of 5'-TMP oligomers on Trisacryl GF05. 3. Girot, P., et al., J. Chromatogr. 213 (1981) 389. 4. Pasero, L., et al., Biochim. Biophys. Acta 869 cal substances. Vo 2 (1986) 147. 3 1 5. De Caro, A., et al., Biochem. J. 222 (1984) 669. Specially designed for preparative chro- 4 6. Eloy, C., et al., J. Chromatogr. 321 (1985) 235. ® Kav 5 matography, Trisacryl GF05 LS offers 1 6 7. Iberg, N., et al., J. Biol. Chem. 261 (1986) 13542. increased flow rate, while retaining the .8 8. Viallard, J.L., et al., Clin. Chim. Acta 161 (1986) 1. properties of Trisacryl® GF05 M. 2 Ve 9. Saint-Blancard, J., et al., Proc. Int. Symp. Aff. .6 Chromatogr., Veldhoven (1981) 305. Flow rates over 80 cm/h are commonly 3 4 used for this type of gel in installations .4 5 using columns of 50 to 200 L, with 6 Ordering Information .2 backpressures less than 1 bar (see Product Cat. No. Size Figure 4). 3 4 5 6 7 8 9 10 20 MW 103 Trisacryl GF 05 M 25914-060 100 ml The range of molecular weight exploited ranges 25914-037 1 L between 306 (monomer) and 1836 (hexamer). 25914-045 10 L Column: 1.6 cm I.D. x 40 cm; Sample volume: 1 ml; Trisacryl GF 05 LS 25916-040 100 ml Buffer: 0.05 M Tris-HCl, pH 7.4 containing 0.17 M 25916-016 1 L sodium chloride; Linear flow rate: 5 cm/h. The insert 25916-032 10 L represents the complete chromatogram obtained.
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Trisacryl, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN BT202915 - 12/2004
4 BIOSEPRA® ULTROGEL® AcA BioSepra UltrogelAcAsorbentsfromPall Size ExclusionChromatographySorbents Ultrogel sorbent designation.Forinstance, UltrogelAcA withthe agarose intheUltrogelAcAbeads vary and The concentrationofpolyacrylamide tion. tion, purificationandmolecular weightpurifica- The sorbentismainlydedicatedforfractiona- weights rangingfrom1,000and1,200,000. the fractionationofmoleculeswithmolecular ent typesofUltrogelAcAareavailableallowing rates withminimallossofresolution.Fivediffer- flow ratesorrapidseparationsathigher between maximumresolutionatrecommended packed. UltrogelAcAsorbentsofferachoice Ultrogel sorbentscanbesimplyandrapidly resolution athighflowrates.Inaddition, These characteristicscombinetoprovidehigh tribution. Theparticlesaresemi-rigid. ticle sizedistributionandanarrowporedis- characteristics ofUltrogelAcAareanarrowpar- um andlargescaleapplications.Theprincipal exclusion sorbents.Theyaresuitableformedi- properties whencomparedtoclassicalsize sess goodmechanicalandchromatographic andagarosegelmatrixpos- polyacrylamide of biologicalmacromolecules.Theyconsist range ofcompositesorbentsforsizeexclusion • • • • eatn aaiy----45%gelvol. 2 3-10 20 - 3-10 4 5 - 3-10 3,000 4 22,000 60-140 4 1,500 3-10 - 90,000 60-140 4 1,500 3 200,000 3-10 60-140 - 1,500 750,000 60-140 2 2 3,000,000 1,000-15,000 1,500 5,000-70,000 60-140 10,000-130,000 Working pH 20,000-350,000 Desalting capacity 100,000-1,200,000 Resolution power(plates/m) Linear fractionationrange(dt) Exclusion limit(dt)* Agarose (%) (%) Acrylamide Particle size(µm) Table 1.MainPropertiesofUltrogelAcASorbents. Narrow poresizedistribution Narrow particlesizedistribution Semi-rigid particles High resolution ® AcA c 2AA3 c 4AA5 AcA202 AcA54 AcA44 AcA34 AcA 22 ® are a 1 ride, 20%ethanoland5mMEDTA. * UltrogelAcA202issuppliedin 1Msodiumchlo- available onrequest. to meetspecificmanufacturing requirementsis in arangeofpackagesizes.Special packaging ride containing20%ethanol* andareavailable The sorbentsareshippedin1Msodiumchlo- be determinedonananalyticalscaleempirically. are unknown,theoptimumsorbenttypecan fractionation range.Ifthemolecularweights of allsamplesolutestobepurifiedfallwithinits should bechosensothatthemolecularweights sample components,UltrogelAcAsorbent In ordertoobtainoptimumseparationofthe tions asafunctionofflowrate. meter). ThereareonlymoderateHETPvaria- the HETPis0.3mm(eq.3,000platesper plates permeter;exceptedforUltrogelAcA202 0.15 mmcorrespondstoover1,500theoretical Theoretical Plate).TheHETPofapproximately the lowHETP(HeightEquivalenttoa excellent separationefficiency, demonstratedby properties ofUltrogelAcA,thissorbentprovides In additiontothesuperiorphysicochemical prised between60and140µm. and 4%agarose(A).Thepar (Ac) 34 sorbentcontains3%polyacrylamide PRODUCT NOTE ticle sizeiscom- PRODUCT NOTE
Stability Figure 1. Determination of a selectivity curve for Ultrogel AcA 54 using a mixture of known proteins. Ultrogel AcA sorbents are semi-rigid particle
sorbents, which possess good mechanical prop- a b d e
erties. They can be used at high flow rate while Conc. Kav c maintaining a good resolution. 0.6 a Ultrogel AcA sorbents are chemically stable in
buffer solutions between pH 3 and 10. Any d 20 40 60 conventional buffer for biochemical separation 0.4
purposes can be used. A high concentration of c denaturing agents such as urea or guanidine 0.2 hydrochloride, or detergents such as SDS, should be avoided. As with all gel fractionation b sorbent, the disruptive influence of such addi- tives should be checked in each case. The 1 2 3 48567 MW (x104) buffers used should have an ionic strength of at
AcA least 0.05 M to minimize non-specific adsorp- Column: 1.6 x 40 cm; Buffer: 0.05 M Tris-HCl, pH 7.4 containing 0.17 M sodium chloride: sample constituted of tion or ion exchange effects between the sam-
® Blue-Dextran 2000 (a) for the determination of the void ple proteins and the sorbent matrix. volume; Bovine serum albumin (b) (MW 68,000); ß-lacto- Detergents and denaturing agents may be used globulin (c) (MW 35,000); Myoglobin (d) (MW 17,800); And cytochrome c (e) (MW 12,400) ; Sample volume: as eluants only in restricted conditions: guani- 0.6 ml; Flow rate: 4.8 cm/h. The insert represents the elu- dine hydrochloride should be used at a maxi- tion curve. mum concentration of 2 M. Urea is a denatur- ing agent comparable to guanidine. It can be currently used at 2 M. SDS, Triton X-100, DOC, Rennex and other detergents can be used with- range. The first step in the process consists in
LTROGEL out significant modifications of the sorbent the determination of a selectivity curve with properties. known standard proteins. The second step con-
U Ultrogel AcA sorbent should be used between sists in the size exclusion of the studied protein 2ºC and 36ºC; a temperature below 0°C is not and the comparison of its elution volume or its ® advised. Ultrogel AcA sorbent cannot be auto- Kav with the selectivity curve (see figure 1). claved, as this may decompose the agarose. ● Desalting The term is used to describe the separation of Applications
EPRA substances present in a solution into 2 groups : The main applications of Ultrogel AcA are: one consisting of the macromolecules which S - Fractionation and purification of biological are totally excluded from the sorbent, and the molecules by size exclusion, other consisting of the low molecular weight
IO - Determination of molecular weights, components which diffuse into the sorbent net- - Desalting. work. Ultrogel AcA 202 sorbent is dedicated to B Ultrogel AcA sorbents allow the separation of this application (see figure 2). components of a complex mixture by size 1. Separation of salts exclusion. The fractionation range is comprised between 1,000 and 12,000,000 daltons. Each If the separation of proteins from salts is opti- type of sorbent has a specific molecular mized, very large volumes may be processed. weight/fractionation range. The sample volume must theoretically corre- spond to the difference between the total sor- ● Determination of molecular weights bent volume and the void volume (generally 60% of the sorbent volume). For sorbents tra- Molecular weights of proteins may be reliably ditionally used for desalting, the recommend- determined by choosing an Ultrogel AcA sor- ed sample volume is only 30% of the sorbent bent which has the required fractionation
2 Figure 2. Example of desalting using Ultrogel AcA 202. Since it is a mild process, size exclusion desalting is some- times the only technique which can be employed for the UV detection total removal of salts from highly unstable biological macro- Salt concentration detection molecules. It should also be noted that desalting is the only
Conc. A technique which can be used for rapid buffer exchange of a protein solution. This is done simply by passing the protein solution through an Ultrogel AcA 202 column reequilibrated with the new buffer. 300 600 ● Affinity
Conc. B Ultrogel AcA also provide excellent supports for the prepara- tion of derivatives for use in affinity chromatography. The quality of the agarose used in the manufacture of these sor- bents results in an almost total absence of the non-specific 300 600 adsorption's which are frequently encountered with compet- itive sorbents of this type. The regular size distribution of Conc. C Ultrogel AcA particles, coupled with their mechanical rigidi- ty, allows their use for extended periods of time with no sig- nificant decrease in flow rate. The large pore sizes also allow high coupling capacities to be achieved. The Ultrogel AcA 0 300 600 sorbent most commonly used in affinity chromatography is Column: 5 x 37 cm; volume: 730 ml; Sample: bovine serum albumin Ultrogel AcA 22. The principal activation methods used for (5 mg/ml) containing NaCl (6.5 mg/ml); Flow rate: 7 cm/h (i.e. 140 attaching a spacer arm or for immobilizing a ligand directly ml/h). Sample volumes: A = 36 ml (5 % of sorbent volume); B = 220 onto the sorbent involve the following reagents: glutaralde- ml (30 % of sorbent volume); C = 327 ml (45 % of sorbent volume); 280 nm U.V. detection. hyde, cyanogen bromide, epichlorohydrin, bis-epoxiranes, benzoquinone, divinylsulfone or periodate. volume. Because the peak broadening is limited with Ultro- gel AcA 202 sorbent, as a result of the regularity of the References particles and the pores, the sample volume on AcA 202 sorbent may be as high as 40% of the sorbent volume, or 1. Gomi, K. and Jajiyama, N., J. Biol. Chem. 276/33 (2001) 36508. even 45% under certain circumstances. Similarly, the con- 2. Sehgal, N. and Goswami, S., Indian J. Biochem. Biophys. 38/4 (2001) 263. 3. Knutson, V.P. et al., J. Immunol. Meth. 145 (1991) 263. centration of each component in the sample may be as 4. Diesterhaft, M., Biochem. Biophys. Res. Commun. 125/3 (1984) 888. high as 40 g/L without affecting the desalting quality. 5. Boschetti, E. et al., Biochimie 54 (1972) 439.
2. Removal of various reagents In addition to the removal of salts, desalting can be extend- Ordering Information ed to : - Removal of low molecular weight sugars (e.g. lactose from Product Cat. No. Size whey). Ultrogel AcA 22 23013-014 1 L - Removal of small aromatic compounds (e.g. phenol during Ultrogel AcA 22 23013-030 10 L the purification of nucleic acids). Ultrogel AcA 34 23015-019 1 L - Removal of fluorescent or radioactive compounds (e.g. flu- Ultrogel AcA 34 23015-035 10 L orescein, rhodamine and I125 during the general labelling Ultrogel AcA 44 23022-015 1 L of proteins). Ultrogel AcA 44 23022-031 10 L - Removal of certain detergents used for the solubilizing Ultrogel AcA 54 23019-011 1 L proteins (SDS, urea, guanidine salts). Ultrogel AcA 54 23019-045 10 L In all cases, desalting with Ultrogel AcA 202 sorbent is supe- Ultrogel AcA 202 24892-010 1 L rior to classical dialysis because of the considerable savings Ultrogel AcA 202 24892-036 10 L in time, the very low degree of dilution, and high recovery.
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Ultrogel, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN BT200912 - 12/2004
4 BIOSEPRA® MEP HYPERCEL® Highpurityinone step.Productpurities - MEP H are wellretained. Large volumesofsamplecanbeprocessed - • Rapidandefficientsampleprocessing. Concentrationofdilutesamplesisnot - Feedstockmaybeappliedwithoutadjust- - Sample preparationisreducedto clarifi- • andprocess-scale: both laboratory binding capacityonMEPH media. IncontrasttoProteinAsorbents,IgG supplemented andserum-supplemented modated, including of cellculture fluid andcellculturesupernatant.Avariety range ofsources, suchasanimalsera,ascites purification ofantibodiesfromabroad MEP H polyclonal antibodies. ture andpurificationofmonoclonal tivity sorbentspeciallydesignedforthecap- "Weakly-binding" variants (e.g.,murineIgG tially independentofsubclassorspecies. MEP H Hydrophobic ChargeInductionChromatography(HCIC)Sorbent MEP H • • • • • achieved. of 70-90%,or greater, aretypically achieved. (at 10%breakthrough)are routinely capacities rapidly andefficiently. Dynamicbinding IgG/ml. even withfeedstocksasdilute~50-100µg necessary. Efficientcaptureisachieved add lyotropicorothersalts. independent ofionicstrength.Noneedto ment. BindingoccursatneutralpH,andis cation. Easy cleaningwithsodiumhydroxide. High IgGcapacity, independentofsubclassorspecies. High purityachievedinasinglestep. Direct sampleloadingwithoutanyadjustmentofpHorionicstrength. Specially designedforpurificationofantibodies. YPER YPER YPER C C C EL EL EL ≥ YPER 30 mgIgGpermlofsorbent provides significantbenefitsat supports efficientcaptureand is ahighcapacity, highselec- formulations arereadilyaccom- protein-free, albumin- C EL ® YPER C EL is essen- 1 ) 1 ments isavailableonrequest. to meetspecificmanufacturing require- range ofpackagesizes.Custom packaging taining 20%ethanolandis availableina Gentleelutionreducestheriskforantibody - Easylongtermcleaningwith1Msodium - • Chemicallystabletobase. MEP H 60 cm/h. Determinedusing5mg/mlhumanIgGinPBS,flowrate: * will elutetheantibody. ing ofthepHto4,atlowionicstrength, desalting ordiafiltration.Asimplelower- aggregation andeliminatestheneedfor advantage overProteinA-basedsorbents. hydroxide givesthismaterialasignificant Dynamic bindingcapacityfor Particle size 80-100 µm 80-100 Particle size TABLE 1:MEPH laigp 3-14 3 <3bar(44psi) -12 3 <1bar(14psi) 70-125µmol/ml Typical workingpressure Pressure resistance Cleaning pH Working pH Ligand density Ligand 4-Mercapto-Ethyl-Pyridine hu IgG*(10%breakthrough) YPER C EL PRODUCT NOTE is suppliedin1MNaClcon- YPER C EL Main Properties. ≥ 20 mg/ml BIOSEPRA® MEP HYPERCEL® B served. tion isreducedandantibodyactivitypre- conditions (pH4.0).Thus,aggregateforma- H Protein Asorbents,elutionfromMEP capture. Comparedtochromatographyon ion exchangechromatographywillfollow extensive diafiltrationinapplicationswhere low ionicstrength,eliminatingtheneedfor tration. Antibodyelutionisconductedat on thebasisofpHratherthansaltconcen- action chromatography, HCICiscontrolled In contrasttotraditionalhydrophobicinter- pH. byreducingthe repulsion. Itisperformed other salts.Desorptionisbasedoncharge achieved withoutadditionoflyotropicor mild hydrophobicinteraction,andis As showninfigure1,adsorptionisbasedon ligand, 4-Mercapto-Ethyl-Pyridine (4-MEP). MEP H behavior ofionizable,dual-modeligands. graphy (HCIC)isbasedonthepH-dependent Hydrophobic ChargeInductionChromato- Chromatography Mechanism Hydrophobic ChargeInduction desorbed. repulsion isinducedandantibody is a positivecharge.Electrostatic also carry Under suchconditions,antibody molecules ligand takesonadistinctpositive charge. values below4.8(typically pH4.0),the When pHofthemobilephase isadjustedto or othersalts. effective bindingintheabsenceoflyotropic ligand densityaredesignedtoprovide thioether group.Bothligandstructureand is furtherenhancedbyinteractionwiththe the aliphaticspacerarm.Antibodybinding contributions tobindingareprovidedby is unchargedandhydrophobic.Additional cal pH,thearomaticpyridinering(figure2) and anionizableheadgroup.Atphysiologi- which is4.8.Itcontainsahydrophobictail and capacityforantibodies,itspKa 4-MEP waschosenforitshighselectivity mise betweencapacityandflowproperty. size is80-100µmtoallowagoodcompro- ty andlownon-specificinteraction.Bead bead confershighporosity, chemicalstabili- Pyridine (4-MEP)islinked.Thecellulose cellulose matrixtowhich4-Mercapto-Ethyl- IO YPER S EPRA C YPER EL MEP H is achievedunderrelativelymild C EL carries anantibody-selective YPER C EL is composedof 2 H Compared toProteinAsorbents,MEP in practicalapplication. feedstock pH, isthusavoided. during adjustmentof sometimes observed tative oftypicalfeedstocks. Precipitation, capacity isachievedatpH values represen- The datademonstratethat highbinding applications. antibody isentirelyunretained inmost on increasingpositivecharge. AtpH4.0, take andantibody– capacity astheligand– 4-MEP, thereisadistinct declineinbinding pH isreducedfurthertowardthepKaof pH 6.5,bindingcapacityis~20mg/ml.As clonal IgGrangesfrom25to33mg/ml.At to 9,thebindingcapacityforhumanpoly- anism describedabove.AtpHvaluesfrom7 consistent withthechromatographicmech- illustrated infigure3.Therelationshipis The influenceofpHonbindingcapacityis • CapacityandpH subclass orspecies. ty forIgGvariantsislargelyindependentof stock composition.Likewise,bindingcapaci- capacity values As shownbelow, however, dynamicbinding Figure 2.MEPH Figure 1.Adsorptionelutionmechanism. H The bindingcapacityspecificationforMEP Capacity (ionic repulsion) YPER YPER ADSORPTION DESORPTION (hydrophobic association) C C EL EL pKa =4.8 (4-MEP) 4-Mercapto-Ethyl-Pyridine is remarkablyindependentoffeed- is ≥ 20 mghumanIgG/mlsorbent. YPER S ≥ C HIC 30 mg/mlaremoretypical EL head group. N During chromatography on Protein A sorbents, elution Preliminary concentration is not required. Indeed, har- of antibody at pH 3 frequently leads to aggregation and vest and concentration of antibody on MEP HYPERCEL loss of activity. Elution from MEP HYPERCEL is achieved can be used to replace traditional concentration proce- under milder conditions. dures. Concentration and initial purification can be achieved in a single step. • Capacity and ionic strength A plot demonstrating the influence of ionic strength on • Capacity for IgG variants binding capacity is shown in figure 3. Dynamic binding The data in table 2 illustrate that binding capacity for capacity was determined in the presence of sodium IgG is little influenced by subclass or species. In contrast chloride, at concentrations ranging from 50 mM to 1 M. with Protein A sorbents, there is no significant difference
Binding capacity is constant over this range. between capacity for murine IgG2a and the IgG1, the Such behavior is typical at pH values where the ligand later being "weakly bound" by Protein A. carries little or no charge (e.g., pH 6.5-9.0). The data MEP HYPERCEL is "antibody selective". Nevertheless, its demonstrate that typical feedstock may be loaded selectivity is sufficiently broad to provide high binding without adjustment of ionic strength. Neither diafiltra- capacity for a broad range of IgG variants. tion nor addition of lyotropic salt is required. Viscous feedstocks such as animal sera or ascites fluids may be diluted. Purity Antibodies are eluted using dilute buffer (e.g., 50 mM When antibody is isolated from protein-free cell culture sodium acetate or sodium citrate, pH 4). supernatant using MEP HYPERCEL, product of >90% puri- ty (SDS-PAGE) is typically obtained. In the example • Capacity and antibody concentration shown in table 3, product of 99% purity was recovered The influence of IgG concentration on dynamic binding capacity is illustrated in figure 4. Concentration ranges TABLE 2. MEP HYPERCEL Capacities. from 50 µg/ml to 5 mg/ml. No significant variation in Binding capacity capacity is observed. MEP HYPERCEL supports efficient capture of antibody from highly dilute feedstock. Human polyclonal IgG 32 mg/ml Murine monoclonal IgG1 (from ascites fluid) 37 mg/ml Murine monoclonal IgG2a (from cell culture) 34 mg/ml Figure 3. Influence of pH and ionic strength on the binding capacity of MEP HYPERCEL. Figure 4. Influence of human IgG concentration on the binding ABcapacity of MEP HYPERCEL. 35 35 (mg/ml) 25 25 40
(mg/ml) 30 15 15
20
DBC at 10% breakthrough 5 5 10 4 5678910 00.2 0.4 0.6 0.8 1 DBC at 10% breakthrough
pH NaCl (M) 0 12345
IgG capacities obtained at 10% breakthrough on MEP HYPERCEL vs. pH (A) and IgG (mg/ml) ionic strength (B) of the binding buffer. Experimental conditions : Column 1.1 cm ID x 9 cm ; Sample : IgG (2 mg/ml) ; Flow rate: 90 cm/h. Working buffer : PBS, pH 7 ; Flow rate : 70 cm/h.
TABLE 3. Examples of Purifications on MEP HYPERCEL. Total proteins IgG content IgG initial Final IgG Recovered Overall IgG Purification Feedstock (mg) (mg) purity (%) purity (%) IgG (mg) yield (%) factor CCS* with FBS 1740 30 1.7 69 23 76 40 Protein-free CCS* 330** 17 5** 99 17 99 19** Bovine serum 440 121 28 75 105 87 3 Ascites fluid 55 9 16 83 7 79 5
* CCS = Cell culture supernatant ** BCA methodology
3 in a single chromatographic step. Isolation included in schemes for antibody purifica- from crude feedstock – bovine serum and tion, this approach is convenient and ascites fluid or CCS supplemented with FBS effective. – is also illustrated, with purity values rang- ing from 69 to 83%. When antibody is iso- Stability and Cleaning lated from albumin-containing feedstock, albumin is the principal remaining impurity. The physical and chemical properties of In such applications, product of 70 to >90% MEP HYPERCEL are well suited to both labora- purity is generally obtained in including an tory and process scale use. MEP HYPERCEL is additional washing step with water or sodium compatible with systems routinely used for caprylate to selectively desorb the albumin. low or medium-pressure process chromato- If a simple anion exchange procedure is graphy. Sorbent-related backpressure is less used to bind residual albumin, product of than 0.5 bar in practical application at linear 99% purity can be obtained. Since anion velocities up to 200 cm/h. Pressure/flow exchange chromatography is frequently curves for columns up to 300 mm I.D. are shown in figure 5. To assure best capture efficiency, it is recommended that initial Figure 5. Backpressure as a function of flow rate. loading studies be conducted at 70 cm/h. MEP HYPERCEL is chemically stable from pH 4 ------ID 90 mm column ------ID 300 mm column to 14. Sodium hydroxide, 0.5-1.0 M, is 0.3 ------ID 25 mm column recommended for cleaning. Submitted to a 0.2 series of 200 clean-in-place cycles with 1 M Pressure (bar) 0.1 sodium hydroxide (1 hour contact/cycle), the sorbent maintained its initial properties. 0 50 100 150 200 Ligand density was unchanged. Flow rate (cm/h) Other useful cleaning agents include 4-6 M Column height 150 mm ; PBS, pH 7.4. guanidine, 8 M urea and 50/50 ethylene glycol/ water. Figure 6. Monoclonal antibodies purification on MEP HYPERCEL from cell culture supernatants. Applications
A - MEP HYPERCEL provides excellent selectivity for a broad range of antibody variants. H Representative applications are summarized 280nm
A below.
L • Direct capture from cell culture super-
A 280 nm 12 natant.
+ Capture of antibody from both protein-free ml and serum-supplemented (5% fetal bovine - serum) cell culture supernatant (CCS) is B described. In both cases, clarified samples 280nm
A were loaded without concentration or H adjustment of composition. The IgG con- a b centration in the protein-free CCS was L 114 µg/ml. Chromatograms are shown in 12 figure 6 and results are summarized in + ml table 3. ml In both applications, the column was equili-
Sample A = 300 ml protein-free cell culture supernatant. brated with 50 mM Tris-buffer, pH 8.0. After Sample B = 300 ml cell culture supernatant containing 5% fetal loading, the column was washed with the bovine serum ; Equilibration : 50 mM Tris-HCl, pH 8 ; Elution : same buffer. PBS, pH 7.4 may also be used. 50 mM acetate, pH 4 ; Flow rate : 70 cm/h. In curve B, (a) and (b) are respectively water and 25 mM sodium caprylate washings ; During chromatography of serum-supple- SDS-PAGE (reduced conditions) : (1) = crude sample, (2) = purified mented cell culture supernatant, two IgG. H = Heavy chain ; L = Light chain.
4 BIOSEPRA® MEP HYPERCEL® using DEAECeramicH in theIgGfractioncanbeaccomplished Efficient removalofresidualalbuminpresent on MEPH Figure 7.Immunoglobulincapturefromascitesfluid • MEPH marized below. using theanionexchangeproceduresum- the IgGfractioncouldbebroughtto98% 3. Isolatedproductwas83%pure.Purityof in figure7.Resultsaresummarizedtable prior toloading.Thechromatogramappears with anequalvolumeofequilibrationbuffer reduce viscosity, thesamplewasdiluted with serum-supplementedCCS.Inorderto same procedureasdescribedaboveforuse IgG wasisolatedfromascitesfluidusingthe • PurificationofmonoclonalIgGfrom cedure. application ofasimpleanionexchangepro- ter couldbebroughtto99%purityby supplemented CCSwas69%pure.Thelat- the feedstock, Despite the tein-free CCSwas99%pure(SDS-PAGE). acetate, pH4.0.Productisolatedfrompro- under theinfluenceof50mMsodium In bothcases,theIgGfractionwaseluted to promotedesorptionofalbumin. additional washsteps(figure6)wereadded tions) analysis:(1)= crudesample;(2)=purifiedIgG. Same conditionsas those offigure6.SDS-PAGE (reducedcondi- (a), (b)=Contaminant elutionpeaksafterthe2washingsteps ; Exchange Chromatography. ascites fluid.
A 280 nm YPER YPER C presence ofabundantalbuminin EL C . product isolatedfromserum- EL ab followed byAnion YPER ml D. Thecolumnis 12 + - L H 5 of validationprocedures. information toassistusersindevelopment age isavailableandprovidesnecessary For industrialapplications,avalidationpack- teins. IsolationofIgAandselectedfusionpro- - plant andanimalsources. Isolationofantibodiesfromtransgenic - and colostrum. Isolationofantibodiesfromsweet-whey - range ofapplications,including: MEP H • AdditionalApplications: containing 0.5-1.0Msodiumchloride,pH8.8. latter isdesorbedusing25mMTris buffer tained peak,whilealbuminisretained.The above buffer. Antibodyappearsasanunre- After loading,elutioniscontinuedwiththe applied tothecolumn. with twovolumesofthesamebufferand fraction obtainedfollowingHCICisdiluted vide aconductivityof10mS.TheIgG containing sodiumchloridesufficienttopro- equilibrated with25mMTris buffer, pH8.8, Ordering Information .Boschetti,E., 9. .Schwartz,W,. etal., 6. .Guerrier, L.,etal., 8. .Guerrier, L.,etal., 7. .Scholz,G.H., etal., 5. Scholz,G.H., et al., 4. .Burton,S.C.,Hardling,D.R.K., 3. .Manzke,O.,etal., 2. Boschetti, E.,Jungbauer, 1. References 361. (1998) 71. 65. cd Press Acad. rdc a.N.Size Cat.No. MEP H Product YPER YPER C (2000) 535. C EL EL .Biochem.Biophys.Methods49 J. has beenstudiedinabroad J. Chromatogr. B755 Bioseparation 9 J. Immunol.Meth.219 J. ImmunolMethods208 J. Chromatogr. A908 J. Chromatogr. 709 23-4 10L 5L 1L 12035-044 12035-040 100ml 25ml 12035-036 5ml 12035-028 12035-010 12035-069 Sep. Sci.&Tech. 2No.15, J. Chromatogr. 814 (2000) 211 (1998) 189. (2000) 37 (2001) 251. (1998) 109. (1997) (2001) PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN PN702-002 - 12/2004
6 BIOSEPRA® MBI HYPERCEL™ Chromatography (MEPHyperCel Hydrophobic ChargeInduction Mixed-mode ligandcomplements (obtained byalcoholprecipitation). from humanplasmaCohnfractions recombinant expressionsystemsor milk fromhyper-immunizedanimals, tional sources suchassweetwhey, natant andfromothernonconven- rate antibodiesfromcellculturesuper- MBI HyperCel aration ofIgGsensitivetoacidicelution. graphy –onMEPHyperCel phobic ChargeInductionChromato- introduced approaches(HCIC–Hydro- sources. Complementingrecently and polyclonalantibodiesfromvarious ture andpurificationofmonoclonal bent, speciallydesignedforthecap- selectivity, scalablemixed-modesor- HyperCel ues orlimitedpH-stability. MBI options forproteinsofvariouspIval- expands therangeofchromatographic tive selectivitycharacteristicsand mixed-mode sorbentprovidesalterna- HyperCel note Product MBI HyperCel Mixed-mode sorbentfordirectcaptureofantibodies. MBI H The MBIHyperCel sorbent MEPHyperCel Induction Chromatography (HCIC) ment totheHydrophobic Charge • • • • No albumincontaminationifpresentinthefeedstock. Complement toHydrophobicChargeInductionChromatography(MEPHyperCel Alternative toProteinAsorbents. Designed fordirectcaptureofmonoclonalandpolyclonalIgG. ™ ™ can beusedaloneasa is particularlysuitedtosep- LPN PN702-002).MBI ™ ™ YPER can beusedtosepa- is ahighcapacity, high ™ ligand isacomple- ™ C (refer toour ™ EL ), MBI ™ ™ ). 1 strength forIgGcapture,MBIHyperCel 9.5).Whileoperatingatphysiological ionic (8.0- andIgGiselutedatalkalinepH range of5.0-5.5), antibodies atmildlyacidicpH(typicallyinthe elutes atslightlyacidicpH(pH4.0).MBIadsorbs HyperCel sorbents forthecaptureofantibodies.MEP sent cost-effectivealternativestoProteinA-based (MEP)andmixedmodeligands (MBI)repre- HCIC exchange). other standardchromatographicsteps(e.g.ion direct capturestep,orinasequence,combinedto 700 cm/h. ** With buffer, backpressuresof<1barareobtainedatlinearflowrates500- acetate, pH5.5,capacityisequalto25mg/mlfor5minresidencetime. dence time,i.e.forhumanpolyclonalIgG(5mg/ml)ina50mMsodium * Capacity variesaccordingtotheIgGtype,concentrationandresi- precipitation duringthepurification process. of acidic-sensitiveIgGs,or limit aggregationand thebiologicalactivity alkaline elutionmaypreserve and pH-sensitivityoftheir specific antibody. This users moreoptionstoexplore, accordingtothepI yai idn aaiyfr20-40mg/ml Dynamic bindingcapacityfor laigp 3-14 3 Cleaning pH atcesz 80-100µm Particle size Table I.MBIHyperCel rsuerssac <3bar(44psi) pH5.0-5.5 Adsorption: <1bar(14psi) Typical working pressure** Pressure resistance Working pH Ligand 2-mercapto-5-benzimida- hu IgG(10%breakthrough)* ™ binds IgGatneutralpH,andtypically PRODUCT NOTE ™ Main Properties. lto:pH8.0-9.5 Elution: zole sulfonicacid(MBI) ™ gives the ™ ). BIOSEPRA® MBI HYPERCEL™ Figure 1. in See pressurevsflowratecurve (<3 bar)inmltomulti-literpackings. be operatedatlowback bent iseasytopackandrun,can orprocess-scale:thesor- laboratory philic intheMBIHyperCel and theligandheadarebothhydro- toHCICsorbents,thespacer Contrary spacer andalbumindonotoccur. hydrophobic associationsbetweenthe (e.g.polyvinyl alcohol)suggeststhat inhibitors ofhydrophobicassociations perature andcompetitionusing binding capacityasafunctionoftem- Experimental databasedonprotein Figure 3. of theadsorptionpHisshownin IgG andhumanalbuminasafunction ionic effect.Theseparationbetween and thereforedoesnotinteractby whereas albuminisnegativelycharged positively chargedaroundpH5.5, 5.5).Mostoftheantibodiesare - (5.0 recommended adsorptionpHrange which isnegativelychargedoverthe group presentonthearomaticring bodies. TheMBIligandhasasulfonate edly describedforthecaptureofanti- were amongthosemoleculesrepeat- review, itappearedthatheterocycles described intheliterature.Fromthis extensive numberofsyntheticligands globulin Gwasdeducedfroman ligand fortheadsorptionofimmuno- acid (MBI)–seeFigure2usedasa 2-mercapto-5-benzimidazole sulfonic albumin. and segregationbetweenIgG Antibody selectivityofMBIHyperCel MBI HyperCel ™ can beusedatboth pressure ™ sorbent. ® 2 Other important parametersincludethe natureand time around5mintoget an optimumcapacity. should beadjustedtoallow anaverageresidence andflowrate multiple parameters:column geometry Figure 2.StructureoftheMBIligand. Column: 15.6cmx2.5I.D.,50mMsodiumacetate,0.14MNaCl,pH5.5. Figure 1.Pressurevs.FlowRate. The capacityofMBIHyperCel Dynamic bindingcapacity forIgG. found. at pHvaluesabove5.0,wheretheoptimalbindingcapacitiesforIgGare binding capacityforhumanalbuminisobtainedatpH4.0.HSAnotbound Data usingsolutionsofpureHSAandhuIgG(5mg/ml)showsthatthehighest human IgGandalbumin. 3. Figure Dynamic binding capacity (mg/ml)
10 15 20 25 30 35 40 45 50 Pressure 0 5 12.5 2.5 7.5 psi 2345678 15 10 0 5 Effect ofbindingpHondiscriminationbetween bar 0.2 0.4 0.6 0.8 0 0 0 0 0 0 0 700 600 500 400 300 200 100 1 HSA PRODUCT NOTE ™ for IgGdependson IgG Flow rate(cm/h) pH concentration of the IgG itself as well as the relative 2. Influence of ionic strength. isoelectric points of the IgG and feedstream proteic MBI HyperCel™ is suited to direct capture of IgG at contaminants. physiological ionic strength. The optimal capacity is MBI HyperCel™ has a dynamic capacity of 20-40 mg/ml typically obtained in the presence of 0.14 M NaCl, with concentrated hu IgG (standard residence times as shown in Figure 4. around 5 min and adsorption in 50 mM acetate, 0.14 M NaCl, pH 5.5). Higher capacities may be Figure 5. IgG dynamic binding capacity vs. pH. observed by increasing the residence time.
30 Figure 4. IgG dynamic binding capacity vs. ionic strength.
20
80 0.14 M NaCl 10
60
30 DBC at 10% BT (mg IgG/ml)
4.5 5.56.0 7.5 8.5 pH 20 40 5 mg/ml hu IgG in 50 mM sodium acetate, 0.14 M NaCl, pH 5.5. Conductivity 17.5 mS/cm. Flow rate 100 cm/h. 10 20 Conductivity (mS/cm) Dynamic binding capacity (mg/ml) 00.5 1.00 NaCl (M) 3. Influence of IgG concentration.
™ Hu IgG (5 mg/ml) in 50 mM sodium acetate, pH 5.5 containing 0 - 0.07 - 0.14 MBI HyperCel capacity and purity performance - 0.28 or 1 M NaCl. may vary according to the IgG concentration in the feedstream. When using human polyclonal IgG at concentrations from 0.05 to 1 mg/ml, capacity at 1. Influence of pH. pH 5.0 was found higher than at pH 5.5, as shown The adjustment of the adsorption pH is a critical in Figure 6. parameter to achieve the optimum purity and When MBI HyperCel™ is used to capture dilute IgG capacity performance. The MBI ligand does not (<250 µg/ml) from serum-supplemented feedstream, normally co-adsorb albumin at pH 5.5 (pH usually a binding pH optimization is recommended to find recommended to start experiments). With pure the best purity/capacity compromise (see Figure 9 concentrated IgG, the capacity of MBI at pH 5.5 is and Table II). in the range of 30 mg/ml, as shown in Figures 3 and 5. However, with crude feedstreams, this "standard" Figure 6. Binding capacity as a function of IgG concentration. recommended adsorption pH of 5.5 may not lead to the best purity/capacity ratio. Therefore, a pH 30 pH 5.0 adjustment (typically in the pH range of 5-6) is 25 recommended (refer to Table II). 20 pH 5.5
15 Table II. Guidelines for adsorption pH optimization
according to feedstream composition and IgG 10 concentration. 5 Type of feedstream Recommended binding pH Dynamic binding capacity (mg/ml) No albumin present pH 5.0 0 0 0.2 0.4 0.6 0.8 1 Albumin present IgG <250 µg/ml pH 5.0 - pH 5.5 IgG concentration (mg/ml) optimization Albumin present IgG ≥250 µg/ml pH ≥ 5.5 0.05, 0.25 and 1 mg/ml hu IgG in 50 mM sodium acetate, 0.14 M NaCl, pH 5.0 or 5.5 containing 0.14 M NaCl.
3 BIOSEPRA® MBI HYPERCEL™ of toxicitytheMBIHyperCel (1992) standardshowedtheabsence accordingtoISO10993-5 performed Ligand andsorbenttoxicity:astudy eration. ficient forcleaningandcolumnregen- cedures using0.5-1MNaOHaresuf- In mostcases,30to60minwashpro- cleaning with1Msodiumhydroxide. contact ourtechnicalservice. packageisavailable,please regulatory For industrialapplications,avalidation sorbent. MBI HyperCel support forindustrialapplications. Stability, cleaningandregulatory mended. containing 0.14MNaClisrecom- sodiumbicarbonate,pH9.0 mM 50 influence therecovery, typically The natureoftheelutionbuffermay buffers, inthepHrangeof8.0-9.5. withalkaline Elution isperformed protein-free cellculturesupernatants. obtained inasinglestepwhenusing Higher purities(95-98%)canbe are typicalwithcrudefeedstreams. Purity valuesof80-95%(SDS-PAGE) andpurityfactors Elution :recovery ™ is stabletorepeated ™ 4 bound byMBIHyperCel 95% bySDS-PAGE. Albuminfromserumwasnot with ProteinA:IgGpuritywasestimatedhigherthan in thepresenceoffetalbovineserum,contrast Figure 7.SeparationofRatIgGonMBIHyperCel MBI HyperCel serum –acomparisonwithProteinA. from ahybridomacellculturecontaining10% Example 1.PurificationofRatmonoclonalIgG APPLICATION EXAMPLES Load: DirectsampleloadonProteinACeramicHyperD 1 =Crudefeesdstock.2Columnflowthrough.3Eluate. Elution: 50mMbicarbonatebuffer, 0.14MNaCl,pH9.0. Wash: 50mM Load:19 mlsample,adjustedtopH5.2byadditionofaceticacid. Protein A-basedsorbent 0.1 Maceticacid. in theMBIHyperCel A B
A280 nm A280 nm 0.25 0.50 0.75 0.1 0.2 0.3 0.4 0 0 0
acetate buffer, 0.14MNaCl,pH5.2. 02 ml 20 10 ™ allows anefficientcaptureofRatIgG 060 30 (B) ™ PRODUCT NOTE column flowthrough. . ™ 30 , notraceofIgGwasfound 50mM bicarbonate pH9, 0.14 M NaCl
0.1M acetic acid 40 ml ® F. Wash: PBS. Elution: ™ (A) Non reducing Non reducing SDS-PAGE SDS-PAGE and ona Example 2. Purification of monoclonal IgG1 from Example 4. Capture of Mouse monoclonal IgG1 ascites fluid. from a low expression hybridoma cell super- natant – Influence of adsorption pH.
™ Figure 8. Mouse Monoclonal IgG1 purification on MBI HyperCel . Low expression Mouse IgG1 cell culture supernatant (150 µg/ml) was loaded on MBI HyperCel™ at two Non-reducing Reducing SDS-PAGE SDS-PAGE IgG different adsorption pH (5.0 and 5.2). Figure 9 shows the RC-SELDI-MS analysis of chromatography frac- tions on NP20 ProteinChip® Array.
HC The data shows that the capture of this low IgG1 titre ™
Cleaning 1M NaOH can be performed on MBI HyperCel at both pH 5.0 Elution pH 9 Load or 5.2, but differences in recoveries exist according LC to the binding pH. 0 5 10 15 ml 132132 When adsorption is performed at pH 5.2, some loss 1: Crude feedstream 2: MBI HyperCel™ eluted fraction of IgG is found in the flowthrough (FT) and in the 3: Protein A resin eluted fraction wash (W). In contrast, when pH 5.0 is used during the adsorp- tion step, a better capture is observed. IgG is eluted MBI HyperCel™ chromatography resulted in an effi- in one fraction (pH 9.0 elution), and no IgG loss is cient capture of Mouse IgG from a complex mixture found. This data highlights the importance of fine- such as ascites fluid. Purity was higher than that tuning the pH in order to achieve the best capture obtained on Protein A Ceramic HyperD® F and albu- and recovery efficiencies when using dilute IgG. min was not bound by MBI HyperCel™.
Figure 9. Capture of Mouse monoclonal IgG1 from a low expres- sion feedstream – Influence of adsorption pH (RC-SELDI-MS analysis of eluted fractions from MBI HyperCel™ column). Example 3. Use of MBI HyperCel in a three-step sequence as alternative to Protein A for clinical Adsorption at pH 5.0 grade IgG purification. 120000 140000 160000 IgG F0 ™ MBI HyperCel was evaluated as a potential replace- FT ment to a conventional Protein A sorbent in a three- FT step “generic” purification. IgG purity, host cell W E impurity removal and Protein A leakage were evalu- MW (Da) 120000 140000 160000 ated. Data suggests that MBI HyperCel™ capture step is compatible with the needs of preclinical antibody purification. Adsorption at pH 5.2 IgG 120000 140000 160000 F0 ™ Table III. Use of MBI HyperCel in a three-step FT sequence as alternative to Protein A for clinical FT grade IgG purification. W Process IgG purity HCP Protein A E (%) (ng/mg IgG) (ng/mg IgG) MW (Da) 120000 140000 160000
MBI HyperCel 99.3 3.52 NR Sample: 150 µg/ml IgG1 in cell culture supernatant, protein-free medium; + IEX1 + IEX2 40 ml of cell culture supernatant (CCS) are filtered and loaded on an MBI HyperCel™ column (10 cm x 0.3 cm ID). Equilibration buffer: 50 mM sodium Protein A sorbent 99.9 < 0.64 < 0.15 acetate, 0.14 M NaCl, pH 5.0 or 5.2. Elution buffer: 50 mM sodium bicarbon- + IEX1 + IEX2 ate, 0.14 M NaCl, pH 9.0. Column regeneration and cleaning: 1 M NaOH (10 CV). Linear flow rate : 150 cm/h; Residence time: 4 min. Analysis per- Data courtesy of Dr. Philippe Marschal, Novartis Pharma AG. formed on normal phase (NP20) ProteinChip® Arrays. IEX = Ion Exchange step, HCP = Host Cell Proteins, NR = Non Relevant. F0 = load, FT = flowthrough, W= wash, E= elution.
5 BIOSEPRA® MBI HYPERCEL™ MBI HyperCel In Figure10A,IgGwascapturedon total solubleproteinsinthisfraction. estimated torepresentabout40%of Cohn FractionII+IIIonMBIHyperCel polyclonal IgGfromhumanplasma Figure 10showstheseparationof HyperCel and MEP comparison withaProteinAsorbent HyperD onaProteinACeramic performed Figure 10Bshowsthesameseparation of non-specificallyadsorbedproteins. resulted inelutionofalargeamount step using1Msodiumhydroxide 0.14 M desorbed in50mMbicarbonate, 0.14 MNaClatpH5.5andtotally sorbent. and about95%withtheProteinA 90% intheMBIHyperCel bodies wasestimatedtobeabout conditions: purityofpolyclonalanti- the elutedfractionsinnon-reducing Figure 10CshowstheSDS-PAGE of acetic acid,pH3.0. adsorbed inPBSandelutedby0.1M and ProteinACeramicHyperD fractions onMBIHyperCel al IgGfromhumanplasmaCohn Example 5.Purificationofpolyclon- ferrin and ing mainlyimmunoglobulins,trans- ethanol precipitatedfraction,contain- Fraction II+IIIisaprotein-rich,19% ® NaCl atpH9.5.Acleaning F sorbent,whereIgGwere α and ™ in 50mMacetate, β -globulins. IgGare ™ . ™ eluate, ™ and ® F. ™ 6 plasma Cohnfraction. Figure 10.Purificationofpolyclonalantibodiesfromhuman apecuts fD.AndreaBuchacher, Octapharma, Austria. Sample courtesyofDr. ineach caseusing1Msodiumhydroxide. A columncleaningwas performed ed around120mg, linearflowrate:50cm/h. Column dimensions:11mmIDx65 (6.5mlsorbent);Proteinloadinject- 100 mMaceticacid,pH3.0. Purification onProteinACeramicHyperD F pH 5.5;Elution:50mMbicarbonatebuffer, 0.14MNaCl,pH9.5 Purification onMBIHyperCel C B A
A 280 nm A 280 nm 0.5 1.0 1.5 0.5 1.0 1.5 0 0 0.14M NaCl,pH9.5 0.14M 0mMbicarbonate 50 04 080 60 40 20 20 0.1M aceticacid 0.1M : Equilibration:50mMacetate,0.14M NaCl, PRODUCT NOTE 06 80 60 40 IgG purifiedon IgG purifiedon Paste II+III Standard puretransferrin Standard purealbumin Standard pureIgG IgG IgG : Equilibration:PBS;Elution: (non denaturingconditions) of elutedfractions Gel analysis MNaOH 1 Ceramic HyperDF MNaOH 1 MBI HyperCel Protein A Protein A MBI HyperCel ml ml Example 6. Separation of IgG light and heavy Figure 11B. Purification of a monoclonal humanized IgG1a from chains. a CHO cell line grown in protein-free medium (stirred reactor tank). Analysis using RC-SELDI-MS of collected fractions during Figure 11A shows the chromatographic profile corre- chromatography on MBI HyperCel™on an NP 20 ProteinChip® sponding to the purification of a humanized mono- Array. clonal IgG1 expressed in CHO cells which were pH 7.0 pH 7.5 pH 8.0 pH 8.5 pH 9.0 grown in a protein-free cell culture medium. Figures L FT 11B and 11C show RC-SELDI-MS profiles of the frac- Intact 150000 tions collected along the chromatography: heavy IgG and light chains are collected at pH 7.0 and 7.5, whereas the intact antibody was primarily eluted at higher pH (8.0 - 8.5). 100000
HC 50000 Figure 11A. Purification of a monoclonal humanized IgG1a from CHO cells in a protein-free medium on MBI HyperCel™ chro- LC matography sorbent. MW (Da)
1600
1400 Figure 11C. Separation of light and heavy chains from intact 1200 antibody using pH step elution on MBI HyperCel™. 1000
800
Absorbance, mAU pH 7.5 pH 8.5 80 600 pH 7.0 pH 8.0 pH 9.0 Heavy chain 400 70 Light chain 200 Intact IgG 60 0 0 50 100 150 200 50 Elution (ml) 40 Relative peak intensity
Conditions (Figures 11A, 11B & 11C) : 1 cm ID column; 7 ml of sorbent; Flow 30 rate: 100 cm/h. Equilibration/Wash: 50 mM sodium acetate with 0.14 M NaCl, pH 5.2. Step elutions using 50 mM Tris buffer at pH 7.0, 7.5, 8.0, 8.5 and 9.0. 20
10
0
FT pH 7.0 pH 7.5 pH 8.0 pH 8.5 pH 9.0 Load Collected fractions
Ordering Information
Product Cat. No. Size
MBI HyperCel 20194-069 5 ml 20194-010 25 ml 20194-028 100 ml 20194-036 1 L
Bulk quantities available on request.
7 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN PN704-008 - 12/2004
8 BIOSEPRA® Protein A Ceramic HYPERD® F bent The rigidityofProteinACeramic HyperDF immunoglobulins. processes andisneverincontact with is purifiedbystandardchromatographic with cGMPrequirements.TherecProteinA gin andisproducedinstrictcompliance The ProteinAligandisofrecombinantori- lowleakageofrecombinantProtein A. very providesasorbentthatexhibits chemistry capacity. Theunique,multi-pointcoupling employed withonlylimitedlossofbinding procedures usingsodiumhydroxidemaybe ditions. Cleaning-in-placeandsanitization chemically stableoverabroadrangeofcon- linkage usedfortheProteinAcouplingare The ceramicbead,thehydrogel,and gel withintheporousceramicbead. immobilized toaspeciallyformulatedhydro- ceramic bead.RecombinantProteinAis bent ispreparedusingarigidproprietary BioSepra ProteinACeramicHyperDFsor- concentration. applied withoutpreliminary Dilute feedstock(~100µgIgG/ml)maybe fluid inasinglechromatographicstep. ed fromcellculturesupernatantorascites bodies ofgreaterthan95%purityareisolat- ing capacityandexcellentscalability. Anti- bent combineseaseofusewithhighbind- purification ofimmunoglobulinsG.Thesor- affinity sorbentdesignedforprocess-scale BioSepra Affinity ChromatographySorbent Protein ACeramicHyperD • • • • • • Easy topack. Low backpressure. Rigid. High selectivitywithnonon-specificbinding. High bindingcapacityforhumanandmurineIgGs. Ideal forlarge-scaleantibodypurification. available fromPall ® Protein ACeramicHyperD ® is ahighcapacity ® F sor- 1 available onrequest. meet specificmanufacturing requirementsis range ofpackagesizes.Special packagingto taining 20%ethanolandis availableina The materialisshippedin1MNaClcon- changes inpH,ionicstrengthorflowrate. does notshrinkorswellinresponseto columns. Equallyimportant,thematerial settles quicklyandpackseasily, eveninlarge purification. Thedenseceramicmaterial The sorbentisidealforproductionscale time andenhancedcaptureefficiency. increased toprovideresidence velocity. Similarly, beddepthmaybe sorbent facilitatesoperationathighlinear with 0.1Msodiumcitrate,pH2.5.Column:4.6IDx100mm. Determinedusing10mg/mlhuIgGinPBS,pH7.4;Elution * iad RecombinantProteinA Ligand al :MainPropertiesofProteinACeramic Table 1: rsuerssac 70bar(1,000psi) 13 - 2 11 - 2 Pressure resistance Noncompressible and ionicstrength 5mg/mlofsorbent Volume changesduetopH - 4 Cleaning pH 50µm(av.) Working pH Immobilized ProteinA 100 cm/h) >30mg/ml hu IgG*(10%breakthrough, Dynamic bindingcapacityfor Particle size . ® F HyperD Fsorbent. PRODUCT NOTE BIOSEPRA® Protein A Ceramic HYPERD® F capacity (flowrate:75cm/h). Figure 1.InfluenceofhuIgGconcentrationonbinding 3.6 mg/mlforIgG ture supernatant.Thecapacityrangesfrom IgGsubclassesfromascitesorcellcul- ferent Table 2showsbindingcapacityvaluesfordif- ties rangingfrom100to300cm/h. exceeds 30mg/ml(figure2)atlinearveloci- Dynamic bindingcapacityforhumanIgG capacities withavarietyofsamples. HyperD Fsorbentexhibitshighbinding (figure 1).Nevertheless,ProteinACeramic and theIgGconcentrationinfeedstock position ofthesample,IgGsubclass, binding capacityisinfluencedbythecom- As withallProteinAsorbents,thedynamic Capacity • high linearvelocityforprocess-scaleuse. compromise betweenhighcapacityand operated at300cm/hprovidesagood utes (figure3).Acolumn15-20cmdeep, dence timeinthecolumnisabout3-5min- tivity isobtainedwhentheaverageIgGresi- Studies haveshownthatthebestproduc-
Dynamic binding capacity (mg/ml) hu lgGconcentration(mg/ml) 2a to 19mg/mlforIgG 0.1 M 2MNaCl, pH8.9;Elution: Column: 3mmID x 100mm;Volume: 0.7ml; Loading:1Mglycine/ sie li .0IgG 4.00 Ascites fluid sie li .0IgG IgG 4.10 2.43 Capacity IgG Subclass IgGconc.inthe Ascites fluid 0.05 Ascites fluid Cell culturesupernatant Source 2. Table sie li .4IgG 6.34 Ascites fluid acetic acid,pH3. Binding CapacitiesforIgGSubclassesat300cm/h. 3 . 2 for huIgG Figure 3.Capacityvs.linearvelocityorresidencetime tion offlowrate(huIgG:1mg/ml). Figure 2.DynamichuIgGbindingcapacityasafunc- Experimental: 2.55mg/mlhuIgG
ape(gm)(mg/ml) sample (mg/ml) DBC at 50% breakthrough DBC at 50% breakthrough (mg/ml) (mg/ml) Dynamic binding capacity (mg/ml) 1 . PRODUCT NOTE Linear Velocity (cm/h) 1 Linear velocity(cm/h) Residence time(min) ; Column:1.0x11.7cm. 2b 3 2a 1 1 19.0 12.7 13.4 9.5 3.6 • Purity Table 3. Preparative Purification of Monoclonal IgG on Protein A Ceramic HYPERD F. During studies with various IgG Source Origin IgG Initial IgG Eluted IgG Purity subclasses and feedstocks, Protein A Subclass conc. (mg/ml) (mg) SDS-PAGE Ceramic HyperD F sorbent provided Ascites fluid murine IgG1 kappa 6.34 37 > 98% high purity product, even at high Ascites fluid murine IgG1* 2.26 20 > 98% column loading. Results are summa- Ascites fluid murine IgG1* 3.86 31 > 98% rized in table 3. In all cases, the Ascites fluid murine IgG2b** 2.31 6 > 98% purity was greater than 98% as Ascites fluid murine IgG2a** 2.43 10 > 98% determined by SDS-PAGE. No albu- Ascites fluid murine IgG2a* 2.86 28 > 98% Cell culture supernatant murine IgG1* 0.05 15 > 98% min was detected in IgG1 isolated Cell culture supernatant humanized IgG * 0.20 30 > 98% from ascites fluid. Isolation of anti- 1 body from serum-containing cell Column: 6.6 mm ID x 120 mm; Volume: 4 ml, 10-30 mg IgG per run; Loading: 1 M glycine / 2 M NaCl (*), pH culture supernatant is illustrated in 8.9 or PBS (**); Elution: 0.1 M acetic acid. figure 4. Analysis by SDS-PAGE is shown in figure 5. Figure 4. Isolation of IgG1 from serum-con- Figure 5. SDS-PAGE analysis of feedstock (1), Despite the relatively high selectivi- taining cell culture supernatant on Protein A flowthrough (2), recovered IgG1 (3). Ceramic HyperD F sorbent. ty of Protein A, isolation of high 12 3 purity product, suitable for thera- peutic use requires further, ortho- UV gonal chromatographic steps. Cation exchange chromatography may be conducted using CM or S Ceramic HyperD F sorbents. Typically, the cation exchange pro- cedure is designed to bind IgG while impurities are selectively des- Time (min) orbed. Anion exchange chromatog- The arrow indicates introduction of elution buffer. raphy on Q or DEAE Ceramic Column: 3 mm ID x 100 mm. Loading and wash: 1 M HyperD F sorbents may be glycine / 2 M NaCl, pH 8.9. Elution: 100 mM acetate buffer, pH 4.6. Linear velocity: 300 cm/h. Sample: employed to bind a variety of rela- 50 ml cell culture supernatant. Figure 6. Pressure vs. number of cycles. tively acidic impurities while the antibody passes unretained in the flowthrough fraction.
• Stability chromatography described in figure
BioSepra Protein A Ceramic HyperD F 6 is accomplished at less than 0.4 Pressure (bar) sorbent is a dense, rigid, non com- bar at 300 cm/h. The pressure pressible material. Packing is faster remained consistent for more than than for conventional Protein A 30 cycles. Agarose. The sorbent typically set- Pressure/flow rate characteristics of Number of cycles tles in a few minutes, i.e. less than Protein A Ceramic HyperD F sor- 10 min are needed to pack a 10 ml bent facilitate process-scale applica- hu IgG capacity at 10% breakthrough; Linear flow column. rate: 300 cm/h; Bed height: 25 cm; Residence time: tion. For example, at large scale, 5 min; Loading: 35 mg/ml. Protein A Ceramic HyperD F sor- bed heights of 20-50 cm can be bent allows the use of flow rates used at flow rates up to 200 cm/h higher than 300 cm/h at backpres- to maximize capacity of the sorbent sure less than 3 bar. Indeed, the by optimising the residence time.
3 • Cleaning Figure 7. Tentative schematic structure of immobilized Protein A on Ceramic HyperD. Recombinant Protein A, rich in carboxylic side chains, is coupled to the primary- amine-containing hydrogel via stable sec- ondary-amide linkages. The procedure has been tailored to give optimized multi-point attachment, as illustrated in figure 7. This unique multi-point coupling chemistry confers high chemical stability. Cleaning with sodium hydroxide from 1 to 100 mM can be performed repeatedly. Modest decreases in binding capacity can occur over time depending upon the concentration of sodium hydroxide and the total contact time. Alternatively, cleaning may be conducted using 6 M guanidine hydrochloride for some/all cleaning cycles.
The arrows represent proteolysis sensitive locations of Protein A • Ligand leakage between sub-units responsible for Fc binding. As a consequence of the Protein A coupling chemistry, the ligand leakage is low. An independent study of Protein A Ceramic Figure 8. Separation of spiked Protein A from IgG1 HyperD F sorbent showed less than 10 ng using a Q Ceramic HyperD F column. Protein A per mg of purified hu IgG (aver- age value). A non-competitive ELISA procedure was used to determine native Protein A in the IgG eluate. These findings reflect the high UV abosrbance stability of Protein A Ceramic HyperD F sor- bent. In many pharmaceutical applications, an anion exchange procedure is employed to assure removal of trace quantities of leached rec Protein A. Q Ceramic HyperD F sorbent is well suited to this application. The proce- dure is conducted under conditions which Time (s) promote dissociation of the IgG-Protein A Sample: IgG1 (7.9 mg) purified from a cell culture supernatant complex. As illustrated in figure 8, IgG is using Protein A Ceramic HyperD F sorbent spiked with 850 µg unretained, while the relatively acidic Protein A. As required, the mobile phase can contain up to 2 M urea and 50% ethylene glycol. A sodium chloride gradient up to Protein A (pI < 5) is bound. The study was 2.6 mS can be employed. performed using IgG1 spiked with 107 µg of rec Protein A per mg of IgG1.
4 BIOSEPRA® Protein A Ceramic HYPERD® F A doesnotinteractwithhumanIgG SeparationofIgGsubclasses(e.g.Protein - Other applicationsinclude: transgenic milk,andvariousanimalsera. from ascitesfluid,cellculturesupernatant, suited toisolationandpurificationofIgG Protein ACeramicHyperDFsorbentiswell plied withtheproduct. found intheProductInsertwhichissup- Detailed recommendationsforusecanbe mum bedheightandlinearvelocity. umn diameterwhilemaintainingtheopti- up isaccomplishedbyincreasingthecol- Once conditionshavebeenoptimized,scale weakly adsorbedIgGssuchasmouseIgG pH (2.5-3.0).Mildercanbeusedfor Elution isnormallyaccomplishedatacidic mented withglycineandsodiumchloride. pH (~8.5-9.0)usingamobilephaseaug- efficient bindingisaccomplishedathigher acting immunoglobulins(e.g.murineIgG physiological conditions.Forweaklyinter- applications, bindingisconductedunder the IgGsubclasstobepurified.Inmost Optimum bindingconditionsdependupon Applications cell culture. RemovalofbovineIgGfromhybridoma - Purificationofenzymeconjugates. - Separationofimmunecomplexes. - clonal antibodies. Purificationofhumanizedormousemono- - enzymatic hydrolysis. of FcandFabfragmentsobtainedafter SeparationofFcfragmentsfromamixture - 3 ). 1 1 . ), 5 . Watanabe, M.,etal., 5. Akerstrom,B., 4. .Eliasson,M.,etal., 3. .Guerrier, L.,etal., 2. Boschetti,E.,Jungbauer, A., 1. References Ordering Information 1 Kronvall,G.,Seal,U.S.,etal., 11. Sjoquist,J.,Movitz,etal., 10. . Lindmark,R.,Movitz,J.,Sjoquist, 9. Medgyesi,G.A.,Fust,G., et al., 8. 7. Ledbetter, J.A., .DerBalian,G.P., etal., 6. rdc a.N.Size Cat.No. Protein ACeramicH Product Technology, AcademicPressVol. 2 (1970), 140. (1972) 190. 74 (1978) 125. (1977) 623. J. Biol.Chem.261 Immunol. Rev. 47 J. Chromatogr. B755 YPER J. Biol.Chem.263 Japan J.Exp.Med.225 07-3 5ml 20078-036 D F J. Exp.Med.152 Separation Science& Eur. J.Biochem.30 07-6 10L 5L 1L 20078-069 20078-051 20078-044 100ml 25 ml 20078-010 20078-028 J. Immunol.104 Immunochemistry 15 Immunochemistry (1986) 10240. (1979) 63. (2000) 535. J., Eur. J.Biochem. (1988) 4323. (2000) 37. (1980) 209. (1981) 51. PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, HyperD, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN PN702-004 - 12/2004
6 BIOSEPRA® Heparin HyperD® M Affinity ChromatographySorbent Heparin HyperD Heparin HyperD flow rates. high bindingcapacityat teins... Thesorbentprovides factors, growthlipopro- heparin, suchascoagulation logical moleculesthatbindto bents forthepurificationofbio- capacity affinitypreparativesor- advanced highspeed, bent isthemosttechnologically composite chromatographysor- properties ofHyperD (1993) coveringtheunique holds U.S.patent5,268,097 hydrogel filledpores.BioSepra containing heparinbound of aporousrigidmineralbead pressure. high flowrateswithlowback- hundred litersandoperated at sizes frommltomorethan bent canbepackedincolumn purification ofATIII. Thesor- and isusedforpreparativescale average particlesizeof80µm HyperD capacity athighlinearvelocities. to providesuperiordynamic composite structurewaschosen BioSepra Heparin HyperD gel” or“gel-in-a-shell”sorbents. (1987) onother“supported and U.S.patent5,234,991 ® ® sorbent iscomprised Heparin HyperD ® ® M hasan M unique ® sorbents ® M Figure 1:Dynamicbindingcapacityvs.linearvelocity. flow rateof600cm/h,10cmbedheight. 0.3 MNaCl,pH7.4.Elutionwith20mMTris-HCl, 2MNaCl,pH7.4ata Capacitydeterminedusinghu ATIII at72.5UI/mlin20mMTris-HCl, * 7.4. 7.4; Elutionbuffer:20mMTris-HCl containing2MNaCl,pH UI/ml; Equilibrationbuffer:20mMTris-HCl containing0.3MNaCl,pH at72.5 Column dimensions:0.46cmI.D.x10cm;Sample:huATIII ® Particle size Table 1.HeparinHyperD Pressure resistance and ionicstrength Volume changesduetopH Recommended operatingpHrange Ligand hu ATIII (600cm/h) Dynamic bindingcapacityfor Hu ATIII dynamic binding capacity
(UI/ml) M 1 30 10 20 40 ...... 200 ...... 300 PRODUCT NOTE 400 ® M MainProperties. 500 ...... Linear velocity(cm/h) 70 bar(1,000psi) Non compressible 3-13 Porcine heparin > 25mg/ml* 80 µm(av.) 600 700 800 PRODUCT NOTE
The main benefits of Heparin HyperD® M Figure 2: Pressure vs. linear flow velocity. sorbent are: Pressure ● Rapid packing due to the high density of psi bar heparin sorbent which settles in a few minutes. 45 3 30 2 ● HyperD® sorbent is very rigid and allows 15 1 M the use of high flow rates without pres-
sure increase or shrinking or swelling of the 200 600 1000 1400 1800 2200 ® sorbent. Linear velocity (cm/h)
● Heparin leakage is minimized due to the stable chemical link of the heparin mole- Column: 0.46 cm I.D. x 10 cm; Buffer: 20 mM Tris-HCl cule to the sorbent. containing 0.3 M NaCl, pH 7.4. Heparin HyperD® M is available as ready-to- use labpacks suspended in 1 M sodium even at high linear velocity, assures direct, chloride with 20 % ethanol as bacteriostat- predictable scale up to any volume (see ic. Larger bulk quantities are also available Figure 2). upon request. Mechanical and chemical stability. Capacity. The pH stability is the same as for the free Heparin HyperD® M maintains high binding soluble heparin: between 3 and 13. capacity, even at extremely high linear Dissociating agents and detergents have velocity. It is commonly used at large scale generally no effect on heparin sorbent. for the production of pharmaceutical grade Treatments of Heparin HyperD® M sorbent ATIII. Production scale columns (>100 L) can with 8 M urea, 6 M guanidine hydrochlo- be operated at high linear velocities (>200 ride and 1% Triton X-100 led to no change cm/h) while maintaining capacity with mini- when tested with bovine ATIII or Hu ATIII. mal backpressure (Figure 2). Its capacity is Heparin HyperD® M can be cleaned with sodi- higher than 25 UI/ml even at 600 cm/h um hydroxide in concentrations of 0.01 to Heparin HyperD with a 10 cm bed height (Figure 1). 0.1 M. ® Stability. Validation. The non compressible HyperD® matrix can The heparin used for the production of withstand very high flow rates without any Heparin HyperD® M has a North American risk of bed collapse. As a result, Heparin origin and is from porcine intestinal EPRA HyperD® M can be used with LPLC, MPLC mucosa. The heparin is produced in compli-
S or HPLC systems. An HPLC purification can ance with the applicable requirements of be performed in less than 10 minutes using the FDA’s Good Laboratory Practices and a 0.46 I.D. x 5 cm column. Faster purifica-
IO Good Manufacturing Practices regulations. tion saves user time and preserves the bio- A validation file can be provided to industri-
B logical integrity of the purified proteins. The al customers to support the regulatory mechanical properties of Heparin HyperD® requirements for producing clinical and M sorbent remain constant across a wide approved therapeutics. range of velocities. Minimum pressure drop,
2 Applications. ● Lipoproteins (LDL, VLDL, VLDL apoprotein, HDL) Heparin is a mucopolysaccharide known for its antico- may form an insoluble complex with heparin in the agulant and clarifying actions. presence of divalent cations. This property is exploited in the separation of serum lipoproteins on Heparin is essentially composed of equimolar quanti- immobilized heparin (e.g. lipoprotein elimination ties of glucosamine and glucuronic acid, alternatively from serum to reduce interference with enzymatic linked by α-1,4 glycosic bonds. assays). A certain number of its hydroxyl groups are esterified ● Growth hormones. with sulfuric acid, especially those on C-6 of glu- cosamine. Other groups are also sulfated, including ● Growth factors: FGF, ECGF. C-3 of glucosamine and C-2 of glucuronic acid. The ● DNA- and RNA-related enzymes as heparin is an main characteristic of heparin is that it contains a inhibitor of DNA and RNA polymerases, and inter- large number of amino groups combined with sulfate acts with numerous DNA- and RNA-dependent groups, the latter being quite labile in acidic medium. enzymes. These properties are used to purify a wide The molecule contains small quantities of other sugar, variety of enzymes (polymerases, restriction such as galactose and xylose, and amino acids, e.g. endonucleases,...). serine, which explains positive ninhydrin reactions. ● Other applications: immobilized heparin has been As a result of its composition and its biochemical role, used for the purification of various other enzymes α heparin has the property to combine with a number (collagenase, -L-iduronidase, hyaluronidase and of proteins, enzymes and in general with polycationic lysozyme), fibronectin, fibronectin fragments and organic compounds. It is also combined with alka- hormones receptors. loids, antibiotics, stains and hormones. There are many fields of applications of Heparin HyperD® M sorbent which are related to the different types of interactions of native heparin.These interac- tions may be specific as with certain coagulation factors Ordering Information or may be due to a more complex ionic interaction. Product Cat. No. Size Seven major groups of proteins can be purified on ® Heparin HyperD® M: Heparin HyperD M 20029-039 25 ml 20029-021 100 ml ● Coagulation factors such as ATIII, Factor IX, Factor 20029-013 1 L VII, Factor XI, Factor XII and XIIa. 20029-054 10 L
● Lipoprotein lipases are enzymes which participate in lipid metabolism. Forming ionic complexes with heparin, immobilized heparin provides a suitable means for their purification. There are numerous References reports on the purification of lipoprotein lipases from serum, mammalian heart, adipose tissue and 1. Lebing, W.R. et al., Vox Sang 67 (1994) 117. 2. Josic, D., Bal, F., Schwinn, H., J. Chromatogr. 632 (1993) 1. bovine milk. 3. Kisiel, W., Davie, E.W., Biochemistry 14 (1975) 4928. 4. Lindon, J., et al., J. Lab. Clin. Med. 253 (1978) 5946. 5. Augustin, J., Freeze, H., J. Biol., Chem. 253 (1978) 2912. 6. Ashby, P., et al., Biochem. J. 171 (1978) 305. 7. Bengtson, G., Olivecrona, T., J. Biochem. 167 (1977) 109. 8. Pan, Y.T., et al., Arch. Biochem. Biophys. 189 (1978) 231. 9. Huet, J. et al., Meth. Enzymol. 273 Part A, 249.
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, HyperD, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN BT200080 - 12/2004
4 BioSepra® Blue Trisacryl® the dyeinnormalworkingconditions. agent. Thistypeofcouplingpreventsanyleakage withtheEEDQcoupling The reactionisperformed matrix throughasixcarbonspacerarm(Figure1). Cibacron blueF3GAdyeisstronglyboundtothe sion andimprovesexchangekinetics. form. Itsmacroporousstructureallowsagooddiffu- amino-2 hydroxymethyl-1,3-propane-diolinbead The initialmatrixisacopolymerofN-acryloyl-2- lently immobilized. non ionicsorbentonwhichCibacronBlueiscova- from IgGdepletedplasma. over 700cyclesintheproduction ofhumanalbumin The excellentchemicalstabilityofBlueTrisacryl Chemical andmechanicalstability BioSepra BlueTrisacryl Introduction Affinity ChromatographySorbent Blue Trisacryl Due totheirextendedlifetime,BlueTrisacryl the columnheight. according to its relationtoworkingpressurewillvary per hour. However, theabsolutelinearflowrateand increases linearlywithpressureuptoabout40cm Experimental resultshaveshownthattheflowrate can beused. High flowrateswithworkingpressuresupto3bar The sorbenthasanexcellentmechanicalstability. mechanism. and theenhancedstabilityofligandcoupling a functionofthesyntheticnatureTrisacryl sorbent On anindustrialscale,BlueTrisacryl whole plasma. more than100cyclesofalbumin separationfrom chromatographic propertiesofthesorbentafter Experimental resultsshowednomodificationofthe cost- andlabour-saving. columns donotrequirefrequentrepacking,whichis The basicmatrixisTrisacryl andsomecoagulationfactors. albumin, interferons, variety ofenzymesandproteinssuchaskinases, graphic sorbentusedforthepurificationofawide ® M isanaffinitychromato- ® GF2000, amacroporous ® M wasused ® M ® M ® M is 1 rate, BlueTrisacryl Due toitsbindingcapacityandoutstandingflow working conditions,especiallypH(seeFigure2). according to the Binding capacitycanalsovary bovine albuminislowerthanforhumanalbumin. mal species.Forexample,thebindingcapacityfor for agivenproteinmaydifferaccordingtotheani- on theproteininvolved.Additionally, thecapacity Figure 1.StructureofBlueTrisacryl M. The bindingcapacityofBlueTrisacryl Capacity * CapacitydeterminedinPBSbufferusing5mg/ml. improve yields. absence ofnon-specificadsorption contributeto commonly usedsorbent.Itslong lifetimeandthe eauigaet ...... Excellent . denaturing agents Stability todetergentsand Upto3bar(45psi) . Pressure stability –20°Cto+121°C . Heat stabibity 1-10 . pH stability 5-7mg/ml . Capacity torbovinealbumin* 10-15mg/ml . Capacity forhumanalbumin* xlso ii ...... 10 . Exclusion limit 40-80µm . Particle size Table 1.MainPropertiesofBlueTrisacryl M. O O NH NH 2 PRODUCT NOTE ® M ismoreefficientthanany SO 2 ONa SO NH 2 ONa N N Trisacryl M NH NH N 7 ® dt M depends R 2 R 1 PRODUCT NOTE
® Figure 2. Sorption capacity (Calb) and sodium chloride elution On the industrial level, Blue Trisacryl M is the ideal molarity (Melu) of human albumin at different pHs. sorbent for human albumin separation in a single step, for interferon purification and for TPA isolation. C alb ® (mg/ml) [NaCl] Blue Trisacryl M may be used in any other purifica- 30 2 tion of Cibacron Blue F3GA-affine proteins. Many other enzymes may be purified on Blue Trisacryl® M, Melu such as sulfatases, phosphatases, RNA polymerases, 20 mono-oxygenases, and oxydoreductases.
1 ® 10 Calb Application examples
0 Example I. Separation of phytohemagglutinin- 4567891011pH induced interferon (-IFN) on Blue Trisacryl® M. Courtesy of S. Stefanos, J. Wietzerbin, published by Mary Ann Liebert Inc. Publications, NY.
Presentation and storage 1.5 M PB PBS NaCl EG -3 Blue Trisacryl® M is supplied as ready-to-use labpacks 80 3 suspended in 1 M sodium chloride and 20% ethanol
as bacteriostatic. 60 2
Before the first use, the sorbent can be stored at prot. (mg/ml) IFN units/ml x10 room temperature. –– 40 Once opened, Blue Trisacryl® sorbent or columns --- 1 must be stored at +4°C in a neutral buffer contain- ing a bacteriostatic agent. They must never be 20 frozen.
0 20 40 60 Fraction Blue Trisacryl Applications ––– Protein concentration ---- Interferon activity ® PB = 0.02 M phosphate buffer, pH 7.2
® Blue Trisacryl M can be used for the purification of PBS = phosphate buffer saline many proteins. Generally speaking, the Cibacron EG = ethylene-glycol mixed with PBS (50:50) Blue F3GA chromophore interacts with most enzymes which need NAD as cofactor (kinases, dehydrogenases, phosphatases). Other proteins with a non-enzymatic activity can also be separated: Example II. Analytical separation of human plas- albumins, lipoproteins, growth factors such as matu- ma proteins on Blue Trisacryl® M. ration promoting factor and heparin-binding growth %T factors, clotting factors, interferons (Example I) and (280 nm) [NaCl] plasma proteins. IgG Transferrin Albumin The interaction mechanism between Cibacron Blue 2 F3GA and proteins involves one or more of the fol- 50 lowing:
BioSepra - Stereospecific recognition of NAD analogs, - Electrostatic and hydrophobic interaction, 1 - Electron exchange. Due to its high selectivity and resolution power, Blue ® Trisacryl M may be used on the laboratory level for 0 rapid analytical and preparative separations of 100 1 2 3 numerous proteins (Example II). The separation Hours speed allows several chromatographic cycles to be performed in a single day. Column: 1.6 cm I.D. x 10 cm; Buffer: 0 05 M Tris-HCI, pH 8 8; Elution performed by a continuous sodium chloride gradient from 0 to 3 M; Flow rate: 100 cm/h; Separation time: 180 min; Temperature: 20°C.
2 Example III. Automatic separation of Example IV. Purification of phospho- Example V. Purification of MPF human albumin from plasma on Blue fructokinase-2/fructose-2,6-bisphos- (Maturation-Promoting Factors) on a Trisacryl® M by step elution chroma- phatase (PFK 2/FBP) on a Blue Blue Trisacryl® M column from a tography. Trisacryl® M column from an anion hydroxyapatite fraction obtained exchange chromatography of a using a x.laevis unfertilized egg spinach extract. extract. %T (280 nm) [NaCl] pH (Courtesy of Y. Larondelle, E. Mertens, E. Van Courtesy of P. Nguyen-Gia, M. Bomsel, J.P. INJECTION 1 INJECTION 2 Schaftingen & H.G. Hers, Université Labrouase, C.L. Gallien & H. Weintraub, 3 Catholique de Louvain, Eur. J. of Biochem.). CNRS, Unité d'Enseignement et de Recherche Biomédicale des Saints-Pères, Paris, Eur. J. of 9 PFK2 or Biochem. 2 FBPase2 Protein (mU/ml) (µg/ml) 8 C A (280 nm) 1.5 8 A (280 nm) PFK2 0.16 0.04 1 7 NaCl 6 1 (2 M) 0.12 0.03 6 4 0 0.08 0.02 0.5 B D F Elution volume E 2 A 0.04 0.01
FBPase 0 0 A B C Column: 2.5 cm I.D. x 6 cm; Adsorption buffer: 0 10 20 30 40 50 0 0 Fraction No. 0 10 20 30 40 50 0.05 M Tris-HCl, 0 5 M NaCI, pH 8; Albumin elution Fraction No. buffer: 2.5 M NaCl in the same buffer; Regeneration solution: water-ethylene glycol mixture (50:50). 21 mU ot PFK 2/FBP were injected into a 2 cm I.D. x 7 ml (12 mg/ml) of the MPF extract were applied to —— UV absorbance at 280 nm 0.9 cm Blue Trisacryl M column pre-equilibrated a 10 ml Blue Trisacryl M column pre-equilibrated - — - lonic strength ---- pH with 25 mM Tris-acetate buffer, pH 7.8 containing with 80 mM sodium glycerol-2-phosphate, 20 mM 5 mM magnesium acetate, 5 mM dithiothreitol and EGTA, 15 m M MgCI , 1 mM dithiothreitol, ATP and 0.2% Triton X-100. Elution was performed by a sodi- 2 phenylmethylsulfonylfluoride. The MPF activity was um chloride gradient up to 2 M. For the determina- retained and eluted with the same buffer containing tion of proteins (histograms), six pools (A to F) were 500 mM NaCI. prepared and concentrated. The purification factor The horizontal lines show fractions pooled to give from the previous column was 27.6; The recovery three sets: Inactive peaks A and B (emerging with was approximately 44%. the flowthrough and eluted with extraction buffer containing 100 mM NaCI), and the active MPF (peak C) eluted with extraction buffer and 500 mM NaCI. Left absorbance axis relates to peak A, right axis to peaks B and C. Purification factor from the previous References column was 12. Recovery was 51%.
1. Travis, J., Pannell, R., Clin. Chim. Acta 49 (1973) 49. 2. Saint-Blancard, J., et al., Proc. Int. Symp. Aff. Chromatogr., Veldhoven (1981) 546. 3. Stefanos, S., et al., J. Interferon Res. 2 (1982) 447. 4. Barot-Ciorbaru, R., et al., Science Tools 29 (1982) 20. 5. Bohme, J.J., et al., J. Chromatogr. 60 (1972) 209. 6. Clonis, Y.D., Biochim. Biophys. Acta 659 (1981) 86. 7. Carne, A., Anal. Biochem. 121 (1982) 227. 8. Travis, J., et al., J. Biochem. 157 (1976) 301. 9. Roschlau, P., Hess, B., Z. Physiol. Chem., Hoppe Seyler's 353 (1972) 441. 10. Lowe, C.R., J. Chromatogr. 216 (1981) 175. 11. Trisacryl GF05 BioSepra Product Note No. BT B202915. 13. Wille, L.E., Clin. Chim. Acta 71 (1976) 355. Ordering Information 14. Barritault, D., et al., J. Neurosci. Res. 8 (1982) 477. 15. Ahmad, A., et al., Biochim. Biophys. Acta 481 (1977) 542. Product Cat. No. Size 16. Shaw, D.J., et al., Biochem. J. 187 (1980) 181. 17. Bouriotis, V., J. Chromatogr. 206 (1981) 521. Blue Trisacryl® M 25896-010 100 ml 18. Bull, R., et al., Biochim. Biophys. Acta 653 (1981) 368. 25896-028 1 L 19. Skotland, T., Biochim. Biophys. Acta, 659 (1981) 312. 20. Carillo, N., Vallejos, R.H., Biochim. Biophys. Acta 742 (1983) 285. 25896-036 10 L 21. Saint-Blancard, J., et al., Sci Tools 32 (1985) 87. 22. Lau, D., et al., Biotechnology 5 (1987) 953. 23. Nguyen-Gia, R, et al., Eur. J. Biochem. 161 (1986) 771. 24. Larondelle, Y., et al., Eur. J. Biochem. 161 (1986) 351. 25. Lobb R.R., et al., Anal. Biochem. 154 (1986) 1. 26. Iberg, N., Fluckiger, R., J. Biol. Chem. 261 (1986) 13542.
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, Trisacryl, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN BT201138 - 12/2004
4 BIOSEPRA® SDR HYPERD® solvent detergentadsorption. Product descriptionandmechanismof SDR HyperD oils combinedtoreversephaseonC18. affinity orbatchextractionwithvegetable ing sorbentpartitioning,sizeexclusion, can beachievedbyvariousmethodsinclud- from biologicalfractionsisnecessary, and The eliminationofsolventanddetergent es). detergents (effectiveforlipid-coatedvirus- and treatmentwithnon-ionicsolvents sion removalofnon-lipidenvelopedviruses) by combiningnanofiltration(forsizeexclu- that areeffectivelyremovedandinactivated Plasma preparationsmaycontainviruses Solvent-detergent removalchromatographysorbent. SDR HyperD SDR HyperD – andTriton processes (i.e.Tri-n-Butyl Phosphate–TnBP gents typicallyusedinviral inactivation mized foraretentionofsolvents anddeter- the natureofpolymerhavebeenopti- the smallporesizeofsilicabeadsand The particlesizedistribution(40-100µm), polymer. three- combines asilica- logical fluids. to eliminatesolventanddetergentfrombio- • • • • Stable inacid,polarorganicandoxidizingsolutions. High sorptioncapacityforsmallhydrophobicmolecules. forproteins(exclusionlimit10kDa). High recovery (TnBP andTriton Binds solventanddetergentmoleculesusedinviralinactivationprocesses dimensional cross-linkedhydrophobic ® ® ® X-100). is acompositesorbentthat is auniquesorbentdesigned bead moietyfilledwitha ® X-100). ® 1 Triton X-100andTnBPonSDRHyperD Figure 1.Schematicinteractionmechanismof features ofSDRHyperD to theorganicpolymermoiety. Themain the adsorptionofTnBPislinked tobinding area,whereas portional tothesilicasurface mer. TheadsorptionofTriton X-100ispro- the silicamoietyandhydrophobicpoly- The adsorptionmechanisminvolvesboth hydrophobic polymerofthesorbent. polymer moiety. TnBPinteractsonlywiththe the polyoxyethylenechain)andwithhydrophobic mation ofhydrogenbondsbetweenthesilanolsand Triton (for- X-100interactsbothwiththesilicasurface mechanism represented inFigure1. marized inTable Iand the adsorption
Triton X-100 SILICA OH O OH O OH O OH O OH O OH O OH O OH O OH O OH O OH PRODUCT NOTE O O=P O=P O=P TnBP ® sorbent aresum- ® sorbent.
HYDROPHOBIC POLYMER BIOSEPRA® SDR HYPERD® m area(200 specific surface On theotherhand,high volume. tained inthecolumnvoid bent, andarefoundunre- "excluded" fromthesor- allows targetproteinstobe exclusion limitof10kDa mer cross-linking,alow of three-dimensionalpoly- Due tothespecificdegree solvent/detergent retention. engineered tooptimizethe 40-50 mg/ml mg/ml forTriton X-100and currently dynamic bindingcapacities Triton X-100andTnBP. The allows ahighcapacityfor HyperD The structureofSDR ciency. detergent removaleffi- Capacity andsolvent- Determinedusing5mg/mlTriton X-100inPBS,pH7.4,10%breakthrough,300cm/h. * 2 yia apela 2-3timesthecolumnvolumewithresidenceof Typical sampleload prtn Hrne2-12 70bar(1000psi) PBS Sorbent pressureresistance PBS/Ethanol(50/50)andEtOH or/andisopropanol Operating pHrange Solvent/detergent elutionbuffer 60-80mg/ml* Adsorption buffer Hydrophobic,longaliphaticchainsbindsolvents. Binding capacityforTriton X-100 40-100µm Sphericalsilicabeadsfilledwithathree-dimensional Nature ofpolymer Average particlesize Sorbent structure Table I.MainPropertiesofSDRHyperD eomne eiec ie5-15min Recommended residencetime g oftheporoussilica /g) ® sorbent hasbeen obtained are60-80 for TnBPat loads wereused. for Triton X-100; thisremovalefficiencywasdecreasedto80%when8CV supplemented withTriton X-100orTnBP),aremovalof95.5%wasobserved ing: i.e.whenusinga10cmcolumn at150cm/h(2CVloadofbovineserum NOTE Residence time:4min. Sample volume:3.6CV, Flowrate:150cm/h;Columnlength:10cm; are summarizedinTable II. Examples ofremovalefficienciesfromvariousfeedstreams bovine plasmaarerespectively10and5mg/ml). 100 cm/h(initialconcentrationofTriton X-100 g nP500pm<04pm99.9% <0.4ppm 5,000ppm Bovine serum TnBP IgG TI nP500pm<04pm99.9% <0.4ppm 5,000ppm TnBP ATIII Table II.Solvent-DetergentDepletionExample. : Theremovalefficiencyisalsodependentonflowrateandcolumnload- 10 kDalimitpreventsproteinsfrombeingretained. hydrophobic polymer. 5 minusingIgGorATIII treatedsolutions. 2 nP500pm<04pm99.9% <0.4ppm 5,000ppm TnBP rtnX101,0 p 0pm95.5% <10ppm 99.9% 10,000ppm Triton X-100 <10ppm 99.9% 10,000ppm Triton X-100 <10ppm 10,000ppm Triton X-100 ® sorbent. PRODUCT NOTE elto elto efficiency depletion depletion eoeAtrRemoval After Before and TnBPin Guidelines for binding capacity optimization. Cleaning in place and chemical stability. As for any sorbent, the dynamic binding capacity SDR HyperD® sorbent is insoluble in water and in (DBC) of SDR HyperD® sorbent is sensitive to the lin- organic solvents. It is also very stable to strong ear flow rate, to the residence time on the column denaturating agents and chaotropic agents. The sor- and to the nature of the sample. Therefore, it is bent can be treated with 0.01 to 0.1 M hydrochloric recommended to start trials by loading not more acid or water-miscible organic solvent. SDR HyperD® than 5 CV of sample on a column with a minimum sorbent can also be treated with oxidizing agents height of 15 cm, and a working flow rate not such as peracetic acid (1500 ppm in sodium acetate, exceeding 150 cm/h. Adsorption buffer sample load pH 5.0), which is a well-known bactericide and spo- and flow rate can be increased according to per- ricide. formance. Note that the rigid nature of SDR HyperD® sorbent allows to use higher flow rates Recommendations for sanitization are shown in (i.e. >600 cm/h) for washing and cleaning, with Table III. moderate backpressure (< 2 bar).
Desorption of retained solvent/detergent. SDR HyperD sorbent is supplied in a storage solution It is typically achieved by injecting 1-10 CV of containing 20% ethanol. PBS/Ethanol 95° (50/50), followed by 3-10 CV of For industrial applications, bulk quantities are avail- ethanol 95°. If necessary, 2-isopropanol can also be able on request. used (10 CV) in the washing sequence.
Table III. Recommended clean-in-place methods.
Method Procedure
Alcohol/acid treatment Wash with at least 3 CV of a solution of 20% (v/v) ethanol containing 1 M acetic acid. This solution should be injected after removal of dissolved gas at a flow rate of 10-20 cm/h (1 hour contact time). After treatment, reequilibrate with normal sterile pyrogen-free buffer.
Diethylpyrocarbonate/ Wash with 2 CV of PBS buffer containing 95% ethanol - 5% diethylpyrocarbonate solution. ethanol treatment Then wash the column with 3 CV of 3 M pyrogen-free sterile NaCI / 1 M acetic acid to remove pyrogens. Reequilibrate the column in sterile pyrogen-free buffer.
Reference
● Specific sorbent to remove solvent-detergent mixtures from virus-inactivated biological fluids. Guerrier, L., et al., J. Chromatogr. B, 664 (1995) 119.
Ordering Information
Product Cat. No. Size
SDR HyperD® 20033-031 25 ml 20033-023 100 ml 20033-015 1 L 20033-056 5 L 20033-049 10 L
3 PRODUCT NOTE
About BioSepra® Products & Collaborative Services BioSepra process chromatography sorbents are manu- factured and marketed by Pall Life Sciences. They great- ly simplify protein purification development and signifi- cantly improve biopharmaceutical manufacturing pro- ductivity.
Over the past 25 years, BioSepra® chromatography products and services have earned an outstanding reputation for product innovation and technical support. Our expanded R&D sorbent program, ISO 9001 manu- facturing plant and HyperCel™ sorbents represent our latest commitment to the biopharmaceutical industry.
With the acquisition of BioSepra® products and services, Pall combines chromatography development expertise with Ciphergen®'s SELDI-based ProteinChip® technology to set in motion an entirely new approach to protein purification development.
This single-step, on-chip approach dramatically acceler- ates and simplifies purification development and analy- sis. The future of Process Proteomics begins with Pall.
Pall has the most comprehensive family of scaleable separation products. 2200 Northern Boulevard Visit us on the web at www.pall.com/biopharmaceutical East Hills, New York 11548-1289 +1 800.717.7255 toll free +1 516.484.5400 phone These products are for laboratory research use only and are not intended for human or animal diagnostic, therapeutic, or other clinical uses, unless otherwise stated. The +1 516.801.9548 fax information contained in this brochure are subject to change without notice. [email protected] Pall Corporation has offices and plants throughout the world in locations including: Europa House, Havant Street Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, India, Portsmouth PO1 3PD, United Kingdom Indonesia, Ireland, Italy, Japan, Korea, Malaysia, Mexico, the Netherlands, New Zealand, +44 (0)23 9230 3303 phone Norway, Poland, Puerto Rico, Russia, Singapore, South Africa, Spain, Sweden, +44 (0)23 9230 2506 fax Switzerland, Taiwan, Thailand, United Kingdom, United States and Venezuela. [email protected] Distributors are located in all major industrial areas of the world. , Pall, BioSepra, HyperD, Hypercel are registered trademarks of Pall Corporation. BioSepra SA 48 avenue des Genottes Filtration. Separation. Solution. and UpScale are service marks of Pall Corporation. 95800 Cergy Saint Christophe, France ProteinChip is a trademark of Ciphergen Biosystems, Inc. +33 (0)1 34 20 78 00 phone +33 (0)1 34 20 78 78 fax
LPN PN704-009 - 12/2004
4