Module 9010: Facility Design and Operation Assignment - ‘Conceptual design of Syringe Fill Finish Pharmaceutical Plant’

Process Description:

The key steps in the Syringe Fill Finish (SFF) process are Equipment Preparation, Formulation, Filling and Inspection. The technology in SFF includes modular clean room construction, a high level of process automation, pre-sterilised Hypak syringes, a filling line and fully automatic syringe inspection.

The active ingredients are the vaccine conjugates which are produced in a separate Drug Substance site. The filled syringes will then be shipped to a contract facility for final packaging and labelling.

The vaccine conjugates are formulated with a saline buffer solution and then sterile filtered together into a product vessel. Aluminium Phosphate suspension is bulk manufactured, terminally sterilised by heating and transferred into 20 litre cans. The suspension is added aseptically to a mobile product vessel to give a batch size of 150 liters. This corresponds to approx 260k syringes per batch.

The product vessel is connected to the filling machine. The empty sterile syringes arrive in sealed Hypak tubs. Stoppers arrive in sealed bags. Each Hypak tub contains 100 syringes in a nest. The sealed tubs are conveyed through the E-Beam steriliser before entering the filling line. An E-Beam machine uses electron beam technology to sterilise the exterior surfaces of the sealed tubs. The filling machine fills the syringes to a volume of 0.58 ml and inserts the stoppers at approx 300 per minute.

A Grade A environment is required for filling and stoppering the syringes. This can be carried out in a grade A room, or in an isolator in a grade C room. The lid and liner of the Hypak tubs are automatically removed as part of the filling line.

The filled syringe tubs are de-nested, and the syringes loaded in single file on the conveyor to the automatic inspection machine. Each syringe is inspected for foreign particles in the liquid and cosmetic defects such as cracks. After inspection the syringes are put back in the nest. The tubs are then packed for shipping to the packaging.

Task: A new Green Field Syringe Fill Finish Facility (SFF) is required to be built to facilitate the above process description. Your task is to prepare the conceptual design for this facility, part of which will include the headings below:

 Process Equipment - Design  Process Layout - Design  Site Master Plan  Safety & Organisational Structure  Schedule & Start Up

1 Notes: The Conceptual design is to be presented in a report format (Minimum 6000 Words), and an oral presentation (80% of the marks are for the report and 20% for the presentation). Note: Presentations are to be no more than 15 minutes long.

The assignment will be marked on an individual basis and also from a group perspective, as described below, and as per attached marking scheme

Reports are to be clearly laid our in standard format, including cover page, introduction, references, and appendices. It is very important that the assignment reads as one cohesive report.

Clear, well illustrated diagrams are very important.

A large portion of the lecture material (including site visit) links directly to the assignment

A number of lectures in this module will have 1 Hour as a workshop to work on the assignment.

Schedule:  Report Submission: Friday 08Jan (Penalties will be incurred for late submissions as per standard DIT recommendations)  Presentations during 1 week of term in January 2010 (Date TBC)

Assignment Marking (Individual v Group): There are 5 sections to the assignment; you can decide among your group who is taking which section. Each section is marked out of 15, and this will then be calculated as a percentage. The overall report will also be given a percentage. Your overall individual percentage for the assignment will be a combination of your individual and overall assignment marks (i.e. individual and groups percentages added together and divided by 2).

2 Assignment Marking Scheme

Report (80 Marks)

Process Design - Equipment (12 Marks)  Equipment Description (4)  Utilities (4) Consider EPA Licence  Process Flow Diagram (4)

Process Design - Layout (12 Marks)  Room Classification & Floor Layout (Equipment, Personnel, Material Flows) and explanations (4)  Additional Detail (Cleaning, Sanitisation, Sampling, Transport of materials/ equipment, Novel/ Alternative Technology) (8)

Site Master Plan (12 Marks)  Location & justification (4)  Overall Facility Layout (Schematic & Description) (4)  Quality/ Compliance Philosophy/ Considerations (4)

Safety & Org Structure (12 Marks)  Diagrams (4)  Philosophy (Budget, Staff, Contractors, reporting structure) (4)  Safety Statement, Safety Philosophy, Training - ref HSA (4)

Schedule & Start Up (12 Marks)  Construction, Commissioning & Qualification Considerations (FAT, SAT, IQ, OQ, Media Trials, PQ) (Schedule for 1 batch - Buffer & Product) No. syringes per batch, run rate, no of syringe per year (4)  Tech Transfer Plan & Start Up (4)  Maintenance, Contingency, Shutdown (4)

Overall Assignment Layout (20 Marks)  General Layout/ Structure (5)  Integration of sections (5)  Spelling/ Grammar (3)  References (4)  Appendices (3)

Presentation (20 Marks)  Technical Content (8)  Clarity/ Cohesion/ Presentation (6)  Overall Effort (6)

3 Essential Reading: ISPE Baseline Guide vol. 3 Sterile Manufacturing Facilities, 1999 ISPE Vol. 2 Oral Solid Dosage Forms, 1998

Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice (FDA) ASME BPE 2002

EUDRALEX Volume 4 - Medicinal Products for Human and Veterinary Use : Good Manufacturing Practice Introduction to Contamination Control and Cleanroom Technology, M. Ramstorp, Wiley-VCH, 2000 Containment Systems: A Design Guide, N. Hirst et al, IChemE, 2002

Supplemental Reading: Pharmaceutical Production Facilities – Design and Applications, G. M. Cole, Taylor and Francis, 2nd edition, 1998 Pharmaceutical Engineering Vol. 1 – 12, Edwards, Butterworth Heinemann, 2005 Encyclopedia of Pharmaceutical Technology, J. Swarbrick, Marcel Dekker, 2002 Health and Safety at Work Regulations 2006. FDA (especially CFR part 11 guidelines)

Web references, journals and other: http://www.rsc.org/lic/knovel_library.htm http://www.fda.gov Pharmaceutical Technology Europe

Sample Vendor/ References:  Filling Machines: Groninger  Inspection Machines: Eisai  Isolators: Skan  E-Beams: Linac  Process Vessels: BCD/ Bioengineering  Mechanical contractor: H A O’Neills, Mercury, BCD  Electrical Contractor: Mercury, Suir  Clean Room Modular Walls: Daldrop

Feel free to use any others vendors, that you choose or may be familiar with.

(Disclaimer: The equipment vendors listed above are not meant in any way to represent endorsement or promotion of their equipment, products or materials).

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