Singapore High Purity Water Course

Temple University Singapore High Purity Water Course Topic Summary

Session No. 1

 Definition of Compendial Waters o USP o EP o JP o BP o Other  “Bulk” Compendial Waters o Purified Water o Water for Injection o EP Highly Purified Water  “Other” Pharmaceutical Waters o “Drinking Water” o “RO” Water o “Softened” Water  Research/Laboratory Grade Waters o ACS, NCCLS, ASTM Reagent Grade, CAP  Specifications and Expectations for Bulk Compendial Water o Purified Water (USP, EP, JP) . Total Organic Carbon (TOC) . Conductivity . Nitrates (EP) . Total Viable Bacteria (USP, EP, JP)  Action Level  Alert Level o Highly Purified Water (EP) . Total Organic Carbon (TOC) . Conductivity . Nitrates . Bacterial Endotoxins . Total Viable Bacteria  Action Level  Alert Level o Water for Injection (USP, EP, JP) . Method of Production (JP, EP, USP) . Total Organic Carbon (TOC)

Singapore High Purity Water Course 1 William V. Collentro . Conductivity . Nitrates (EP) . Bacterial Endotoxins . Total Viable Bacteria  Action Level  Alert Level

Session No. 2

 Regulatory Expectations o Basis of Design/User Requirement Specification o Drawings o Design Documents o Installation Documents o Examples of Installation Criteria Discussed Throughout Course . Dead Legs . Sample Valves . Feed Water Chemical and Microbial Quality . Drains with Air Breaks . Valve Selection . Materials of Construction . Sampling Provisions . Cross Contamination . Pump Selection . Microbial/Biofilm Control . Sanitization Frequency and Effectiveness . Monitoring from Feed Water to “Delivered” Water . Added Substances . Foreign Substances and Impurities  Validation o Installation Qualification o Operation Qualification o Performance Qualification o Standard Operating Procedures o Maintenance Manual with Procedures o Training Manual o Summary Report

Session No. 3

 Impurities in Raw Water o Particulate Matter

Singapore High Purity Water Course 2 William V. Collentro o Ionic Material o Dissolved Gases – Non Reactive o Dissolved Gases – Reactive o Microorganisms o Bacterial Endotoxins o Organic Material o Colloids o Residual Disinfecting Agent o Disinfection By-Products  Surface Sources versus Ground Water Sources

Session 4

 Pretreatment Techniques (Design, Operating and Maintenance Considerations) o Chemical Injection Systems . Disinfecting Agent (Raw Water Treatment) . Reducing Agent (Pre RO) . pH Adjustment (Monochloramine Removal & Pre RO) o Thermal Blending Systems o Heat Exchangers o Particulate Removal Filters o Activated Carbon Units o Water Softeners o Organic Scavengers o Inline Ultraviolet Units o Recirculation/Repressurization Pumps o Cartridge Filtration Systems

Session 5

 Ion Removal Techniques – Reverse Osmosis o Theory and Application . Basic Theory . MF, UF, NF, and RO Comparison . RO Membrane ‘Flux” . Salt Passage . Membrane Types and Configuration . Fouling and Scaling . Langelier Saturation Index and Silt Density Index . Feed Water Chemical Injection . Membrane Chemical Cleaning . Membrane Hot Water Sanitization o Design Considerations

Singapore High Purity Water Course 3 William V. Collentro . General . Feed Water Microbial Control . Importance of Residual Disinfecting Agent Removal – TFC Membranes . Feed Water Pre-filtration – Type and Selection . Sampling Provisions . High Pressure Feed Water Pump . Pressure Vessels, End Adapters, and Interconnectors . Piping/Tubing . Integral Cleaning System . Accessories o Operating and Maintenance Considerations . General . Monitoring and Trending of Operating Data . Cleaning Considerations . Troubleshooting

Session 6

 Ion Removal Techniques – Ion Exchange o Introduction o Description and Classification of Ion Exchange Resins . Strong Acid Cation Exchange Resin . Weak Acid Cation Exchange Resin . Strong Base Anion Exchange Resin . Weak Base Anion Exchange Resin . Gellular and Macroporous Resins . Styrenic and Acrylic Resins o Basic Theory . Ion Exchange, Demineralization, and Deionization . Affinity of Ion for Resin Site . Physical Factors Affecting Ion Exchange . Pharmaceutical Water System Applications . Water Softeners o Two-Bed Systems – Co-Current Regeneration . Theory and Application . Design Considerations . Operating and Maintenance Considerations o Two-Bed Systems – Countercurrent Regeneration . Theory and Application . Design Considerations . Operating and Maintenance Considerations o Cation Polishers . Theory and Application . Design, Operating, and Maintenance Considerations

Singapore High Purity Water Course 4 William V. Collentro o Mixed Bed Deionization Units . Theory and Applications . Design Consideration – Regenerative Units . Operating and Maintenance Considerations – Regenerative Units . Design, Operating, and Maintenance Considerations – Rechargeable Units

Session 7

 Additional Ion Removal Techniques o Electrodialysis and Electrodialysis Reversal . Historical Overview . Theory and Application . Design Considerations . Limitations of Technology o Continuous Electrodeionization . History, Theory, and Application . Design Considerations . Operating and Maintenance Considerations

Session 8

 Distillation and Pure Steam Generation o Theory and Application o Design Considerations . Single Effect Distillation Units . Multiple-Effect Distillation Units . Vapor Compression Distillation Units . Pure Steam Generators . Condensing Units o Operating and Maintenance Considerations . Single Effect Distillation Units . Multiple-Effect Distillation Units . Vapor Compression Distillation Units . Pure Steam Generators . Condensing Units

Section 9

 Storage Systems and Accessories o Theory and Application o Design Consideration . Tank Size . Tank Dimensions

Singapore High Purity Water Course 5 William V. Collentro . Pressure Vessel Rating . Materials of Construction . Tank Orientation . Heat Transfer Provisions . Surface (Interior/Exterior) Finish . Tank Access . Spray Ball Assemblies . Sensing/Control Devices . Utility Parameters . Tank Support . Fittings . Tank Pressure . Hydrophobic Vent Filtration Systems . Nitrogen Blanketing . Materials of Construction o Operating and Maintenance Considerations

Session 10

 Ozone Systems and Accessories o General Theory and Application o Theory and Application – Gaseous Ozone Generation o Theory and Application – Dissolved Ozone Generation o General Design Considerations o Design Considerations – Gaseous Ozone Systems o Design Consideration – Electrolytic Ozone Systems o Operating and Maintenance Considerations  Polishing Components o Distribution Pumps . Theory and Application . Design Considerations . Operating and Maintenance Considerations o Inline Ultraviolet Sanitization Units . Theory and Application . Design Considerations . Operating and Maintenance Considerations o Polishing Ion Removal . Theory and Application . Design Considerations . Operating and Maintenance Considerations o Final Membrane Filtration . Theory and Application . Design Considerations

Singapore High Purity Water Course 6 William V. Collentro . Operating and Maintenance Considerations o Ultrafiltration . Theory and Application . Design Considerations . Operating and Maintenance Considerations

Session 11

 Distribution Systems – Design, Installation, and Material Selection o Introduction o Theory and Application o Biofilm o Design Considerations . Stainless Steel Distribution Loops . Seamless Plastic Distribution Loops . Socket Welded Plastic Distribution Loops . Plastic Tubing with Sanitary Ferrule Distribution Loops o Additional Design Considerations o Operating and Maintenance Considerations

Session 12

 Controls and Instrumentation o Overview o Symbols o Process and Instrumentation Diagrams (P&IDs) o Control Functions for Pharmaceutical Water Purifications Systems o “Screen Shots” o Data Acquisition o Data Logger o Purified Water and Water for Injection . Conductivity Measurement . TOC Measurement  System Design and Specification Guidelines o Overview o General Requirements o Drawing Requirements o Control System Requirements o Operation and Maintenance Requirements o Quality Control/Assurance Requirements o Commercial Considerations  System Start-up and Commissioning

Singapore High Purity Water Course 7 William V. Collentro o Overview o System Installation . Facility Considerations . Technical Considerations . Utility Considerations o Start-up and Commissioning Considerations System Validation

 Introduction  General Discussion – Start of Project (Review) o Validation Master Plan o User Requirement Specification o Risk Assessment Document  Factory Acceptance Test  Site Acceptance Test  Protocols – End of Project o Types of Validation . Prospective . Concurrent . Retrospective o Revalidation o Installation Qualification o Operation Qualification o Performance Qualification . Chemical . Bacteria . Bacterial Endotoxins . Frequency . Duration . Bacteria Enumeration Methods . “One Year Guideline” o Standard Operating Procedures o Maintenance Manual o Training Manual .

Singapore High Purity Water Course 8 William V. Collentro