CPPT 9010: Facility Design & Operation

1. CPPT 9010: Facility Design & Operation D.I.T. DT275 Masters in Chemical andPharmaceutical Process Technology 26th November 2009 Clement Farrar BA BAI MSc MIEI

2. Assignment Overview • Introduction • Workshops • Presentation • Reference Material • Marking Scheme • Timelines • Where do you start?

3. Introduction ‘Conceptual Design of Syringe Fill Finish Pharmaceutical Plant’

4. Introduction 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.

5. Introduction • 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.

6. Introduction 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

7. Introduction Sections Breakdown 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)

8. Introduction Sections Breakdown 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)

9. Introduction Sections Breakdown Overall Assignment Layout (20 Marks) • General Layout/ Structure (5) • Integration of sections (5) • Spelling/ Grammar (3) • References (4) • Appendices (3)

10. Introduction Format: • 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). • 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.

11. Introduction Advice: • Advise use of Diagrams, Flow Charts, Pictures – easy to understand /read (may be more applicable to some sections than others) • Use Takeda Site Visit to ask questions relating to assignment – great opportunity to see a facility first hand!

12. Workshops • Generally last hour of lectures (8.30 – 9.30) • Opportunity to work together and progress the assignment • Also opportunity to ask questions, discuss ideas & work through any issues

13. Presentations • 10-15 Minutes Long • Keep text on slides to a minimum – don’t read off an essay! • Illustrations/ pictures always help • Each team member to speak • Try to make it interesting for the listeners • 1 cohesive presentation - not 5 individual pieces! • Introduction & Conclusion important

14. Reference Material • Always use references! • References don’t have to be limited to thise detailed in assignment

15. Assignment Marking Scheme (Individual v Group) • 5 individual sections to the assignment, each section is marked out of 15, and this will then be calculated as a percentage. X/15 x 100/1 = Y% (Individual Mark) • The overall assignment 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) • (Individual Mark %) + (Overall Assignment %) = Actual Mark % 2 2

16. Timelines • Assignment Workshops • Thurs Nov 26th • Tues Dec 1st • Thurs Dec 3rd • Tues Dec 8th • Tues Dec 15th • Thurs Dec 17th (TBC) • Report Submission no later than Friday 8th January • Assignment Presentation – will be during 1st week of term in January 2010, date to be confirmed

17. Where do you start ?

18. Where do you start ? • Decide on who does what sections - if someone has experience in a certain area, maybe that person can take that aspect of the assignment • Work Together: • Example: Decide on Process – what utilities does it require? • Demonstrate assignment was a team effort • Keep minutes of decisions/ meetings and include in report appendices

19. And Finally……..