The Role Of Flexible Technologies In Containment Presented by Hari Floura President

1. The Role Of Flexible Technologies In Containment Presented by Hari Floura President

2. Agenda • Introduction • Why Flexible Technologies? • Advantages • Disadvantages • Points to Consider • Available Technologies • Contained Transfer • Application • Case Studies/Examples • Conclusion

3. Introduction Flexible Technologies is the new ‘in technology’ in Biopharma. However Flexible Technologies have been in use in other industries for decades:

4. Why Flexible Technologies • The appeal of flexible technologies vs. hard wall systems in Biopharma is: • Relative low cost • Single/Multi use disposables • Cleaning validation and qualification may be eliminated or significantly reduced • Reduced turnaround time • Accelerated implementation • Not limited by size and shape

5. Advantages • Fast to prototype • Fast to implement • Size not a restriction • Easier to retrofit to existing facility & equipment • Low capital cost • Improved operator access when compared with hard-wall systems • Dry disposable waste

6. Advantages • Can easily be interfaced to equipment and allow equipment to be reverted to original condition quickly • Can be modified and repaired while in use • Design can be modified on an ongoing basis • Advantage for CMO - provide guarantee of a new device/container for each process to clients • Advantage for Client – No need to invest in costly containment equipment

7. Disadvantages • Potential high operational cost • If Product contact, potential regulatory issues: • Effect of plasticizers, antistatic agents, etc. • Can supplier provide data to show regulations met, DMF number for NDA submittal, Certificate of conformance? • Hazardous waste disposal cost

8. Disadvantages • Fails to danger • Limited tolerance to pressure & vacuum • Leak testing in-situ can be challenging • Limited temperature tolerance • Susceptibility to damage (cuts/abrasion) • Environmental impact • Potentially poor aesthetics • New industry to Pharmaceutical so vendor knowledge of needs is limited

9. Points To Consider • Does the vendor manufacturing space/process meet your requirements • Does the film material offered by the vendor pose challenges for disposal (e.g. toxins released when incinerated) • Testing plan to verify integrity when installed • If Product Contact: • Are there any special requirements: • Anti-Static • Unique material properties to meet NDA filing • Involve Quality early to confirm requirements • Allow time for stability testing

10. Available Technologies

12. Safe Change Filter Housings The ‘double tie & cut technique’ originated in the nuclear industry in the 1960’s as a method for safe change of filters.

13. ‘Double Tie & Cut’ Technique

14. ‘Double Tie’ Stainless Steel Crimp System

15. Crimp System Video File

16. Performance

17. GEA Hicoflex® Video File

18. GEA Hicoflex® - Real World Experience Results from several pilot studies by GSK(2005/2006) in R&D Pilot Plant, discharging small particle size compounds. Tasks conducted using ~900g of pure active ingredient and 2% active ingredient in a 3.0 kg blend.

19. Ezi-Dock® Video File

20. Ezi-Dock® - Ezi-Clip

21. Application Video File

22. Case Study – Compression Machine

23. Case Study – Compression Machine

24. Case Study – Compression Machine

25. Case Study – R&D Equipment

26. Case Study – R&D Equipment

27. Case Study – R&D Equipment

28. Case Study – R&D Equipment

29. Case Study – Glove Curtain

30. Conclusion • Flexible Technologies are an: • Effective control to be considered for mitigating risk during handling of high risk materials • Can be used as a ‘just in time’ technology • ‘They are not a magic cure all’ • Caution has to be exercised with some vendors as they have limited knowledge of Pharmaceutical Process and cGMP requirements • Ergonomics must still be given high consideration. Flexibles offer an advantage but they do not mitigate the need for ergonomic design and testing • If used for a ‘product contact’ application: • Obtain material certifications from vendors to confirm materials meet your needs • Involve Quality department day one

31. References References: • Making Flexible Containment Work For You – Brian G Ward - Case Studies in Flexible Containment Conference May 17 & 18, 2007 Comparative Capital & Operating Cost Advantages Incurred with a Potent Compound Dispensing Enclosure – Brian G Ward – Containment of Potent Compounds Conference, January 2008 • Identifying the Material Requirements and Gaining a Regulatory Understanding of Qualification of Materials When Processing with Flexible Containment - Mark Copeland, Eli Lilly, Brian Klecan, ILC Dover, Alan George, ILC Dover - Case Studies in Flexible Containment Conference May 17 & 18, 2007 • Flexible Containment Use In the Nuclear Industry A Historical Perspective - John Kremer and Frank Rebmann, Applied Engineering Controls - Case Studies in Flexible Containment Conference May 17 & 18, 2007 • The Use Of Flexible Containment Technology Transfer Technologies In The Pharmaceutical Industry – Hari Floura (IH data provided by LawrenzoHeit, BMS) • Hicoflex performance data compiled by Mandy H. Stone (Industrial Hygienist II, GlaxoSmithKline) and submitted to the ISPE Containment COP by Lisa Cardo (10 July 2007). Samples collected in accordance with The ISPE Good Practice Guide: Assessing the Particulate Containment Performance of Pharmaceutical Equipment.

32. Acknowledgements • Many thanks to the following companies in providing material used in this presentation: • Applied Engineering Controls • Camfil FAR • Ezi-Dock • GEA • ILC Dover • Panduit • Wyeth Inc –Special thanks to Steve Meszaros , Corporate Director EHS. Steve Meszaros has been responsible for spearheading the use of flexible technologies within Wyeth.

33. Questions Hari Floura President Floura LLC. Tel: 609-259-7136Fax: 609-249-5541Mobile: 908-896-1698 E-mail: hari@flourallc.com