Report on “Pharmaceutical GMPs for the 21 st Century” Initiative

1. Report on “Pharmaceutical GMPs for the 21st Century” Initiative Janet Woodcock, M.D. Acting Deputy Commissioner for Operations November 5, 2004

2. History of Initiative • Announced August 2002 • Presented to FDA Science Board (pivotal event) • Progress Report August 2003 • Final Report September 2004

3. Major Theme: Modernizing Actual Practice and Regulation of Pharmaceutical Manufacturing • Manufacturing Science • Risk-based regulatory approach • “GMPs” as a Quality system • Public benefits

4. Initial Findings • Pharmaceutical manufacturing not fully utilizing modern manufacturing technologies and quality management approaches • Manufacturing expenses exceed R&D investment • Perceived regulatory barriers to improvement • Additional reasons for lack of investment

5. “21st Century” Announcement on September ‘04 • Establishment of FDA Council on Pharmaceutical Quality • Restructuring & refocusing CMC review process • Risk-based inspectional model • Draft & final guidances • Quality System model

6. Two Years of Effort: What have we achieved? • Formation of Pharmaceutical Inspectorate • Reform of Part 11 • Process (regulation revision) not finished • Focus on Manufacturing Science • PAT effort • White paper • Academic & industrial collaborations

7. What Have We Achieved? • Dispute resolution process • Improvement in warning letter process • Plan to institute quality system for further progress • Clarification of use of “process validation”

8. What Have We Achieved? • Final scientific guidances e.g., aseptic processing • Risk-based inspectional model • Extensive comparative analysis of quality and GMP regs both within FDA and internationally

9. What Have We Achieved? • Model of quality system for pharmaceutical manufacturing (draft) • Quick guidance process similar to “GMP notes” • Initiated international discussion in ICH • Approached PIC/s re: US membership

10. What Remains to be Done? • Council on Pharmaceutical Quality Process • Move ICH guidances along • Implementation of quality system within Agency • Proceed through PIC/s

11. What Remains to be Done? • Restructuring and refocusing CMC review process • Shift from detailed data analysis to overall quality assessment • Attention to specifications and possibility of interim specs • Plan to decrease number of required manufacturing supplements

12. What Remains to be Done? • Risk-Based Approach to Oversight • Manufacturers with good product and process knowledge and quality system • Commensurate decrease in submissions and inspection • Implementation of program is challenging

13. What Remains to be Done? • Pharmaceutical Inspectorate • Curriculum developed • Candidates undergoing training • Deployment and evaluation remain

14. The Future of Pharmaceutical Quality Regulation: • Can we make some “Quantum Transitions” ? • Most change will be incremental • Can we achieve a few breakthroughs? • Innovative manufacturing & control technology or processes? • Regulatory oversight via “virtual inspections”?

15. The Future of Pharmaceutical Quality Regulation: • Definition of “Pharmaceutical Quality” • Current definition constrains change & continuous improvement (Ajaz Hussain’s analysis) • Need to move toward acceptance of probabilistic definitions rather than pass or fail

16. The Future of Phamaceutical Quality Regulation: Role of Critical Path Initiative • “Industrialization” dimension an important one • Intent to support robust science at FDA and continued scientific evolution of regulatory standards • Also envisions collaborative research efforts to advance manufacturing science – e.g., consortia with universities, industry and FDA

17. SUMMARY • “21ST Century” Initiative had substantive accomplishments • Next phase – consolidation and institutionalization of changes • Nevertheless – we need some “quantum transitions” to model the path forward • As always – the science should guide us