1. CPPT 9010: Facility Design & Operation
D.I.T. DT275
Masters in Chemical and Pharmaceutical Process Technology
24th November 2009
Clement Farrar
BA BAI MSc MIEI

2. Lecture Overview 1) Introduction 2) Aseptic Processing
3) Process Stages
4) Utilities Introduction
5) Assignment Introduction/ Workshop

3. Qualifications
: B.A., B.A.I. - Mechanical & Manufacturing Engineering, TCD
: M.Sc. - Bioengineering, TCD

4. Work Experience
Present: Wyeth BioTech (now Pfizer), Grange Castle, Clondalkin
: Process Engineer - Drug Substance Start Up to Commercial Production
2009: Process Engineer - Syringe Fill Finish Start Up

5. Wyeth At A Glance
Founded in 1860 by two Wyeth brothers in Philadelphia
Became American Home Products Corporation in 1926
Changed to Wyeth in 2002
Corporate headquarters – Madison, New Jersey
2008 Sales – $22.8 billion
Approximately 47,400 employees worldwide: 22,600 U.S. and 24,600 international
2009 – Became part of the Pfizer

6. Wyeth Pharmaceuticals’ Leadership Positions
#1 Antidepressant
#1 RA & Psoriasis Biologic
#1 Vaccine
#1 HRT
#1 I.V. Antibiotic
#1 Hemophilia B
#1 Infant Formula (In Aggregate Market Where We Compete)

7. Ireland’s Pharmaceutical Industry… Then and Now
Exports less that €100 million
Employment less than 2000
1973

8. Ireland’s Pharmaceutical Industry… Then and Now
Exports €16.7 billion – Largest net exporter of pharmaceuticals in the world
Employment 24, out of every 5 pharmaceutical jobs created in Europe in 2008 were in Ireland - 50% hold a third level qualification
120 companies including 13 of the top 15 worldwide
Replacement value of the investment by the pharma sector in the Irish economy exceeds €40 billion – €3 billion in Corporation Tax
€7 billion invested in last nine years
2008
Exports less that €100 million
Employment less than 2,000
1973

9. Why Ireland? Availability of fully serviced 90 acre site
Quality and availability of workforce
Support from Government, IDA Ireland and South Dublin County Council
Corporation Tax regime in Ireland
Focus on Research in Ireland
35 years of manufacturing experience in Ireland.

10. Once a muddy field in Clondalkin…

11. Now… A Centre of Biotechnology Excellence

12. Grange Castle At-A-Glance
Largest capital investment ever undertaken by Wyeth
1,224 full time employees and 220 contractors
Producing some of the world’s top medicines
The anchor for the establishment of a biotechnology cluster in Ireland
One of the largest biotech campuses in the world

13. Aerial View of Grange Castle
Drug Substance
Central Utilities Building
Product Development Centre (PDC)
Warehouse
Manufacturing Suites
Vaccine Conjugation
Vial Fill/Finish
Syringe Fill/Finish
Quality & Administration Building (QA/QC)

14. Grange Castle Products
The first advance in 20 years for the treatment of moderately to severely active rheumatoid arthritis (RA) in adult and juvenile patients
Pneumococcal-Meningicoccal Vaccine
Relistor is a new product, which will be used for the treatment of opioid-induced side effects, including constipation and post-operative bowel dysfunction.
Antibiotic – for the treatment of complicated intra-abdominal infections

15. Recruitment 80,000 job applications to date
25,000 Interviews conducted to date
1,224 full time employees in place today
220 full time contractors
11% of employees relocated from international locations
Half of this group are Irish people returning home
95% with third level qualifications
55% male; 45% female
Average age 37

16. Aim of Module Experienced Process Engineer working in the industry
Invite any Questions I may be able to answer from my experience
Assignment - aim is to try to get you thinking in a real life ‘facility design’ frame of mind
Give you as much knowledge/ experience to allow you use your skills & knowledge

17. Facility Design & Operation
1) Introduction
2) Aseptic Processing
3) Process Stages
4) Utilities Introduction (inc HVAC)

18. Learning Outcomes At the end of this Lecture you should be able to …..
Describe what is meant by Aseptic Processing
Define what is meant by a Critical Process step
Define types and sources of Contamination in Aseptic operations
Describe how contamination risk is minimised
Describe key factors influencing facility design
Describe the process steps in a typical Aseptic process
Define the area Classification Requirements for typical process steps
Describe what is meant by ‘Direct’ and ‘Indirect’ impact utility systems

19. Sterile Processing Parenteral Drugs: Terminal Sterilisation:
Injectable drugs bypass the body’s natural defences so must be sterile
Terminal Sterilisation:
Sterilise drug in final container (after manufacture and packaging)
Preferred method of sterilisation
Moist Heat Sterilisation
Gamma Radiation
E-Beam
Microwave
Many drugs not suitable for this method of sterilisation
Aseptic Processing:
Individual components are sterilised separately and brought together in the final form in a sterile environment.

20. Aseptic vs. Sterile Definition of Aseptic
“Free of or using methods to keep free of Pathological Micro-organisms” synonym : sterile
Sterile processing area is also know as the Aseptic Processing Area, Critical Processing Area or Sterile Core.

21. Aseptic Facility Design
Aseptic Processing Area Area where critical process steps carried out
Critical Process Steps Activities during which the sterilised product and container / closure are exposed to atmosphere
Design must minimise challenge to Aseptic Processing Area – HOW?
Flow of raw materials, components, drug product containers, closures, in-process materials, drug products and people through the facility shall be designed to prevent contamination.

22. Contamination – Types & Sources
Non-Viable (Particulates) including Endotoxins
Sources: Equipment, Clothing, Water, Air
Viable (Micro-Organisms)
Sources: Equipment, People, Water, Air, Tools, Excipients, Active Ingredients

23. Contamination – Preventative Measures
Non Viable:
Contact Parts are cleaned and sterilised
Water is purified
Air is HEPA Filtered
Viable:
Interventions in sterile core are minimised
Solutions are sterile filtered through a 0.2m filter

24. Design concept to minimise challenge to Aseptic Processing Area
Fig 2.1 Nested Manufacturing Zone (ISPE Guideline Vol 3)

25. Aseptic Facility Design
Fig 2.2 Sterile Manufacturing Flowchart (ISPE Guideline Vol 3)
Highlights interdependence of operations in support of the core sterile activity
Highlights importance of support area design to GMP Compliance of Aseptic Processing Area

26. Exercise 1
You are members of a project team designing a new sterile product (s) facility –
Discuss what product / process information you would need to ensure the facility can handle this new product

27. Exercise Answer Key Factors Influencing Facility Design Product
Form - liquid/ powder (lyopholised)
Product Characteristics- light sensitive/ Excipients- number, quality, form, hazards etc.
Presentation- vials/ syringes
Market- market need, regulatory requirements- IMB/ FDA

28. Exercise Answer Key Factors Influencing Facility Design Process
Degradation with thermal sterilisation?
Process duration - will impact production capacity
Cross Contamination Issues - e.g. strong antibiotics
Current Facility Capacity - spare capacity or shortfall