1. Drug Quality Regulations for the 21 st Century PhRMA Perspective Manufacturing Subcommittee Meeting – May 21, 2003 Gerry Migliaccio Pfizer Inc

2. PhRMA Perspective Significant progress to date Industry is supportive and contributing to the process Conceptual agreement on many issues FDA/PQRI Workshop considered a success

3. PQRI Workshop Risk-Based cGMPs Integrated Quality System Approach Changes Without Prior Approval Manufacturing Science Significant overlap in discussions and findings.

4. Now it is time to operationalize the concepts!

5. High Low LessMore Manufacturing Science Effort Impact Risk Manufacturing Science & Risk Model I II III Regulatory Process Category I- High; II-Medium; III-Low

6. Manufacturing and Risk Model Prerequisites –Culture change –Knowledge sharing –Risk management principles –Integrated quality system

7. Culture Change Trust Open communications Move from “Change is Bad” to “Change is Good” Fitness-for-use by patient has to be the primary driver for FDA and Industry

8. Knowledge Sharing What does FDA need to ascertain the level of understanding that a firm has about the formulation and process, and the potential impact of changes on fitness for use? (i.e. what does FDA need to assess risk?) How will knowledge be handled in the regulatory process?

9. Knowledge Sharing Development pharmaceutics Critical-to-quality process parameters and product attributes Impact of variation in critical-to-quality parameters on fitness-for-use Process capability

10. Risk Management Principles Risk assessment process Risk mitigation strategies Risk classification Definition of risk still a work in process Risk changes through product life cycle

11. Integrated Quality System Science and risk-based cGMP guidance documents Knowledge transfer between Center and Field –Pharmaceutical inspectorate Specification lifecycle concept –Interim specification Flexible regulatory change management process –Based upon original knowledge base –Changes without prior approval where appropriate

12. Integrated Quality System Inspections based upon risk assessment –Prior compliance record –Product type and process complexity (risk) –Facilities and technology –Focus on more value-added systems inspections

13. Next Steps Several focused workshops are recommended to begin to operationalize the quality initiative.

14. Workshops Recommended 1.Define the knowledge base required to assess risk. Agree on how information will be handled in the regulatory process. 2.Define risk, develop a risk assessment process and agree on risk mitigation strategies.

15. Workshops Recommended 3.Continue focused workshops related to proposals for science-based cGMP guidance (e.g. PAT, aseptic, OOS, cleaning validation) 4.Develop proposed guidance for specification lifecycle. 5.Develop risk-based regulatory change management process.

16. Questions?