1. Pharmaceutical Quality Systems (ICH Q10) Concepts & Implementation SAPRAA Meeting 19 th June 2009 Chris Stubbs

2. Presentation Outline What is the objective of any System ? What is expected of us in terms of Quality Systems? Fundamentals of ICH Q10 ? Implementation advice Summary

3. What is the Objective of any System? (Using ICH Q10 as an example) Development + Tech transfer + Commercial + Discontinuation Product Realization State of Control Continual Improvement Compliance ORGANIZATIONAL OPTIMIZATION System Boundaries ie full Life Cycle “Quality is a side effect of a system that is running well”

4. What is expected of us in terms of Quality Systems?

5. MEDICINES CONTROL COUNCIL GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINES IN SOUTH AFRICA

6. SA Guide to GMP (Common to all GMP Guides) CHAPTER 1 QUALITY MANAGEMENT 1.1PRINCIPLE 1.1.1The holder of a manufacturing licence must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the medicine registration and do not place patients at risk due to inadequate safety, quality or efficacy. 1.1.2The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company's suppliers and by the distributors. 1.1.3To achieve the quality objective reliably, there must be a comprehensively designed and correctly implemented system of Quality Assurance, Incorporating Good Manufacturing Practice and thus Quality Control and Quality Risk Management.

7. QUALITY MANAGEMENT GMP – MCC/PICs Guide PRODUCTS & MATERIALS FACILITIES QUALITY UNIT EQUIPMENT PRODUCTION MNGMENT PEOPLE

8. FDA – 6 Systems Approach Quality System Production System Facilities & Equipment System Laboratory Controls System Materials System Packaging & Labeling System

9. FUNDAMENTALS OF ICH Q10 FDA for the 21 st Century approach provides the road map for Q10

11. ICH Q10 OBJECTIVES Product Realization State of Control Continual Improvement (Compliance)

12. manag Fundamentals of Q10 DevelopmentTech TransferDiscontinue Commercial Supply GMP

13. manag Fundamentals of Q10 DevelopmentTech TransferDiscontinue Commercial Supply Monitoring Systems GMP

15. manag Fundamentals of Q10 DevelopmentTech TransferDiscontinue Commercial Supply Monitoring Systems CAPA Systems GMP

17. manag Fundamentals of Q10 DevelopmentTech TransferDiscontinue Commercial Supply Monitoring Systems CAPA Systems Change Management GMP

19. manag Fundamentals of Q10 DevelopmentTech TransferDiscontinue Commercial Supply Monitoring Systems CAPA Systems Management Review Change Management GMP

21. manag Fundamentals of Q10 DevelopmentTech TransferDiscontinue Commercial Supply Monitoring Systems CAPA Systems Management Review Change Management Quality Risk Management GMP

22. Q9 Risk Based Approach (2005)

23. manag Fundamentals of Q10 DevelopmentTech TransferDiscontinue Commercial Supply Monitoring Systems CAPA Systems Management Review Change Management Quality Risk Management Knowledge Management GMP

24. Integrity Uniformity Weight Control In vitro Dissolution Chemical Purity API, Excipients, Manufacturing Process Pharmaceutics Profile API Particle Size API Salt Selection Chemical Compatibility Degradation Pathway Prediction Material Property Characterization Process Simulation Design Christopher Sinko, Ph.D. Pfizer Global Research & Development Knowledge Management Example: Quality By Design

25. manag Fundamentals of Q10 DevelopmentTech TransferDiscontinue Commercial Supply Monitoring Systems CAPA Systems Management Review Change Management Quality Risk Management Knowledge Management SENIOR MANAGEMENT RESPONSIBILITY GMP

26. Q10 Management Responsibilities for a Pharmaceutical Quality System (P4 Section 2) Senior Management has ultimate responsibility Have to participate Demonstrate strong & visible support Effective communication to appropriate levels of management Define roles, responsibilities authorities & inter-relationships Conduct Management reviews of product Quality, Process performance & Pharmaceutical Quality System performance Advocate continual improvement Commit appropriate resource Why do we need more guidance when the is all covered in GMP – refer section 1.1.2 & 1.1.3 of the GMP Guide ?

28. IMPLEMENTATION ADVICE FOR Q 10

29. IMPLEMENTATION REALITIES The guidance specifically states that: "ICH Q10 is not intended to create any new expectations beyond current regulatory requirements", and anything within ICH Q10 that is additional to current GMP requirements is "optional" rather than obligatory Implementation of these initiatives on top of current “rules based Quality Management Systems” will drown your Company in additional Resources and associated expenses Re-implementation of your Quality Management System based on these initiatives can create innovative ways to explore the latest efficiency improvements while still complying to GMP

30. Quality System Implementation Start End Management Team Leadership High Low Advice on how NOT to start Kick Off Fanfare Get System Ready Management Team will See Value and Integrate Into Daily Performance

31. Quality System Implementation Start End Management Team Leadership High Low Advice on What Works Kick Off Fanfare Get System Ready Integrate into Business Objectives STOP Management Team see Value and have Integrated Into Daily Performance

32. Advice on approaches that work The Head of the Unit and not the QA Manager/RP has to be seen as the driver of any implementation (think like a fox!) Always have a separate meeting (called by Head) to discuss the status of your QMS until implementation is complete: paradox- NOT at normal management meetings as QMS issues will be diluted by “more important issues” STOP and wait if you have to – Sub optimization leads to negative perceptions of value & results in management doubts A good Quality System should eventually be the backbone of a “Business Excellence System” but if it gets weighed down too early it will breakdown – Allow it to get strong before adding additional “modules” - irony: As the management team get excited they will want to use it for more (and break it) so you have to defend the system until the entire system is strong enough (and mature enough) to take on more processes

33. Summary ICH Q10 requires an understanding of FDA for the 21 st Century, ICH Q8 (Design), ICH Q9 (Risk) as well as ISO 9000 (2005) to maximize benefit ICH Q10 is an ISO SYSTEMS approach to GMP NOT additional to GMP but integral to GMP Covers full life Cycle of a Product Objectives: Product Realization, Control & Improvement DEMANDS Management Team to lead Quality System Seek compliance only and you will get compliance only The toughest implementation battles are internal so look for internal Allies before going outside for support

34. THANK YOU Selected References follow

35. References GMP for the 21 st century www.fda.gov/cder/gmp/gmp2004/GMP_finalreport2004.htm International Conference on Harmonisation, ICH Q8: Pharmaceutical Development, November 2005. http://www.ich.org/ http://www.ich.org/ International Conference on Harmonisation, ICH Q9: Quality Risk Management, November 2005. http://www.ich.org/http://www.ich.org/ International Conference on Harmonisation, Draft Consensus Guideline, ICH Q10: Pharmaceutical Quality System, May 2007. http://www.ich.org/ http://www.ich.org/ FDA, Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations, September 2006. http://www.fda.gov/ http://www.fda.gov/ 01 January 2008By:Adrian KirkPharmaceutical Technology EuropeAdrian Kirk