1. cGMP Update Presented by: Karen Ginsbury For IFF, Denmark October 2014

2. Do you consider yourself expert in GMP? Are you a QP? Is GMP really compatible with an effective, company-wide Quality System? Discuss…

3. What is Quality

4. What is a Quality System And who owns it?

5. What is the Role of QA / Quality Unit? To set up, monitor, report and continually improve the quality system To ensure compliance with the quality system and that the quality system complies with regulatory requirements Ensure that there are no contradictions or resolve conflicts

6. Quality is… Meeting all the requirements all the time Therefore – not meeting the requirements at any time is not quality Don’t use “high” or “low” quality – it cheapens the term

7. Waivers the act of intentionally [and voluntarily] relinquishing or abandoning a known right, claim, or privilege So a “planned” deviation or “temporary” change or “special” release is a waiver of “quality” which is meeting requirements (all of them all the time)

8. Have you Heard About…ISO2001:2015?

9. Changes: Use of RISK Management and PREVENTION – decrease documentation

10. New Structure

11. Context Internal and External issues that affect intended outcomes of the quality system Added emphasis on control of outsourcing Ensure that externally provided goods and services satisfy the requirements – includes outsourcing

12. Context

13. What are the 9 chapters of EU GMP? Write them down

14. What about Annexes?

15. GMP/GDP Inspectors Working Group

16. What changes in last 12 months Part 1 Cap 2: Personnel Cap 3: Premises and Equipt Cap 5: Production Cap 6: Quality Control Cap 8: Complaints, Recalls Part 2 APIs Annex 15 Annex 16 Effective: 16 Feb 2014 01 Mar 2015 01 Oct 2014 01 Mar 2015 01 Sep 2014 Draft out

17. 2 - Personnel Effective Feb 2014 Changes: – Integrate principles of quality system i.e. ICH Q10

18. 3 – Premises and Equipment 3.6 as part of improved guidance on prevention of cross-contamination involving Cap 5

19. 5 - Production

20. 6 – Quality Control

21. 8 – Complaints, Quality Defects and Product Recalls

22. Annex 15 draft - Validation

23. Annex 16 draft– QP Release

24. Part 2 – Active Substance / API

25. Other US GMPs: 21CFR parts 210, 211, part 11 and part 820 FDA guidances: – Quality system guidance vs ICH Q8, 9, 10 – Process validation guidance – Contract Manufacture

26. Other MHRA Compliance Report program and FDA on quality metrics WHO Guidances PIC/s Guidances USP, European Pharmacopoeia Pulling together the threads and staying updated

27. Hot Topics – Data Integrity

28. Measurement is the basis of the Quality Process What do we measure What could we measure What should we measure What can we measure

29. How many metrics BE CAREFUL – if everything is important then nothing is important

30. About Measurement “Measurement is the first step that leads to control and eventually to improvement If you can’t measure something, you can’t understand it If you can’t understand it, you can’t control it If you can’t control it, you can’t improve it.” H. James Harrington

31. Measureable…But Meaningful If a measurement matters at all, it is because it must have some conceivable effect on decisions and behavior If we can't identify a decision that could be affected by a proposed measurement and how it could change those decisions, then the measurement simply has no value Douglas W. HubbardDouglas W. Hubbard, How to Measure Anything: Finding the Value of Intangibles in BusinessHow to Measure Anything: Finding the Value of Intangibles in Business

32. Data Collection Plans Who decides what data to collect? How do they make that decision? How do they COMMUNICATE the decision? (what are the tools) How do they educate for compliance with the data collection plan?

33. Dashboards Dashboards are reporting tools that consolidate and arrange numbers, metrics and sometimes scorecards on a single screen Usually tailored for a specific role Display metrics targeted for a single point of view or department

34. Dashboards

35. Product vs Process Control Product Is controlled at the end of the process and you can do nothing about it – you have already made the quality – so you test and if it is ok – release and if it is not ok – you SHOULD reject but you probably get into an OOS fight Process Is controlled through understanding where the variability is and controlling critical process parameters such that all three cakes come out the same even when baked by three different students in three different ovens

36. The toolbox – Fabulous 14 Tools Process flow diagram Cause and effect (fishbone) Pareto chart Check sheets Location diagrams Tally count Time plot Scatter diagram Histogram Stem and Leaf Box and Whisper plot Regression analysis Control Chart Conformance chart

37. The Power of Walking the Floor Thoughts?

38. The Power of Walking the Floor “You see but you do not observe” Just stand and watch a production operation and ask questions about what you see Talk to operators and LISTEN to their comments

39. In Conclusion GMP isn’t enough even if “c” Keep it Simple: – Define requirements – Use Risk Management to identify risks and prevent them from happening – Monitor and improve in a PDCA cycle

40. In Conclusion Few KEY metrics Define data collection, analysis and presentation in a Data Collection Plan with standardized templates Management review and leadership of the program Follow up and feedback Walk the floor and LISTEN

41. THANK YOU FOR LISTENING!