Challenges and Triumphs of BFS Success: ISPE-CASA 2018 Technology Conference

1. ISPE – CASA - 2018 Technology Conference 13MAR2018

2. the Challenges & triumphs of bfs Success is at hand

3. Earlene Gibbons • Senior Director, Operational Technology, Local Pharmaceutical Company in RTP • Ingrid Marshall • Project Manager, Avid Solutions, Inc. • Presenters

4. What is bfs

5. BLOW - Forms the container using a resin and mold What is bfs

6. FILL – Aseptic fill of container What is bfs

7. SEAL – Aseptic fill of container What is bfs

8. IN ONE MACHINE! What is bfs

9. Multi-step continuous process in one sterile machine • Produces small (.01 mL) to large volume liquid filled containers

10. BLOW FILL SEAL BENEFITS STERILITY -STUDIES OF PERFORMANCE BFS VS TRADITIONAL FLEXIBILITY (TYPE, SIZE) REGULATORY CONSIDERATIONS STANDARD OF QUALITY PRODUCT PERFORMANCE DIFFERENT TYPES OF RESINS (FOR DIFFERENT TYPES OF PRODUCTS) ECOLOGICAL RESIN IS RECYCLABLE

11. BLOW FILL SEAL BENEFITS SAFETY BREAKAGE CONTAMINANTS NO PRE-WASHING RESIN IS STERILE MADE, FILLED & SEALED IN ONE SEQUENTIAL OPERATION NO CONTAINER STORAGE BEFORE FILLING “MUCH LOWER FREQUENCY (ON-TENTH) OF CONTAMINATED MEDIA FILLS COMPARED TO CONVENTIONAL PROCESSES” –7. B. Ljungqvist et al., PDA J. Pharm. Sci. Technol. 60 (4), 254–258 (2006).

12. Logistics Transportation of resin only Storage of resin only No special consideration for storage of resin Cost of shipping product is significantly reduced Breakage

13. BFS • Expanding the usage of an OSD facility was risky. • Why? • Design challenges – new disciplines, new concepts, new • Utilities Expansion – No WFI • Building Renovation • Control system & SCADA architecture

14. WHAT ABOUT THE E-STOP

15. BE PREPARED TO TALK ABOUT Things FOREVER THAT HARDLY MATTER THERE’S A SIMPLE SOLUTION USE Common sense DON’T BE AFRAID TO START OVER STOP FIGHTING SOMETHING THAT WILL NEVER WORK GET AN EXPERT

16. Secrets to success Planning, planning, planning Having time to design before the schedule demands a solution Process knowledge Solution planning Control system & scada architecture – have a plan Controls systems are complete before mechanical completion Documentation completion after control system completion Documents approved before commissioning

17. Cost of change

18. THE COST MAGNIFIES AS TIME PROGRESSES Cost of change

19. THE COST ESCALATION - WHY • IT DEPENDS ON THE STAGE • WHY’S • EFFECTS EVERYTHING THAT CAME BEFORE & THE DOMINO EFFECT • LEAD TIMES FOR EQUIPMENT • UTILITIES INFRASTRUCTURE • CONTROL SYSTEM • PENN STATE UNIVERSITY STUDIES SHOW 10X MULTIPLIER OF COST COMPARED TO IF DESIGNED UP FRONT

20. Lessons learned

21. The importance of the basis of design • Foundation of the project • Functional design • Define connections between systems Lessons learned

22. Importance of choosing the right integrator Lessons learned

23. Importance of the team • Skill sets • Same objectives for success • Working together toward the same goal Lessons learned

24. Questions

25. Thank you