1. Ajaz S. Hussain, Ph.D. Deputy Director Office of Pharmaceutical Science, CDER, FDA ACPS Subcommittee on Manufacturing Science: Identification and Prioritization of Topics for Discussion

2. Subcommittee Work Planning This afternoon –“Desired State” outlined by FDA Does this reflect a “shared vision” for the future? –Identify and prioritize topics for discussion –Recommend a format and background information FDA should prepare for discussion of identified topics

3. Subcommittee Work Planing Tomorrow –Update on current activities PAT Initiative and its role in the Drug Quality System for the 21st Century Comparability Protocols as tool for continuous improvement A perspective on risk analysis –Committee discussion on the relationship between process understanding, change management, and risk to quality –Update on aseptic processing guidance

4. A Drug Quality System for the 21 st Century: Objectives [1] Risk Management [2] Quality System [3] Recognize and encourage scientific advancement and innovation (continuous improvement) [4] Review & Inspection programs are coordinated, synergistic, and consistent [5] Effective and efficient utilization of FDA and (industry) resources

5. Begin with the end in mind…. The “Desired State” for Pharmaceutical Manufacturing and Associated Regulatory Processes in the 21st Century

6. Defining the “desired state” As we move forward with this initiative it is essential to define what we wish to achieve –What should be the “desired state” of pharmaceutical manufacturing and associated regulatory policies in the 21 st Century? A shared vision to guide further evolution of this initiative Enroll all stakeholders in this journey to better serve the patients Highlight, for the academic and research community, the scientific needs in pharmaceutical engineering

7. Approach We Use Must... Strengthen the public health protection achieved by FDA’s regulation of drug product manufacturing Not interfere with strong enforcement of the existing regulatory requirements Be risk based Be science based –(Win Win)

8. Science Provides a Win Win Approach Pharmaceutical manufacturing is evolving from an art form to one that is now science and engineering based. Effectively using this knowledge in regulatory decisions in establishing specifications and evaluating manufacturing processes can substantially improve the efficiency of both manufacturing and regulatory processes. This initiative is designed to do just that through an integrated systems approach to product quality regulation founded on sound science and engineering principles for assessing and mitigating risks of poor product and process quality in the context of the intended use of pharmaceutical products. http://www.fda.gov/cder/gmp/21stcenturysummary.htm

9. Desired State  Product quality and performance achieved and assured by design of effective and efficient manufacturing processes  Product specifications based on mechanistic understanding of how formulation and process factors impact product performance  Continuous "real time" assurance of quality http://www.fda.gov/cder/gmp/21stcenturysummary.htm

10. Desired State  Regulatory policies tailored to recognize the level of scientific knowledge supporting product applications, process validation, and process capability  Risk based regulatory scrutiny relate to the:  level of scientific understanding of how formulation and manufacturing process factors affect product quality and performance, and  the capability of process control strategies to prevent or mitigate risk of producing a poor quality product http://www.fda.gov/cder/gmp/21stcenturysummary.htm

11. Shared Vision for the future? FDA articulated the “desired state” based on discussions at several advisory committees (ACPS-PAT and FDA Sci. Board) Presented it at several public workshops and meetings We believe it now represents a “shared vision” of the pharmaceutical community Does the subcommittee agree?

12. Topics and Priorities Definition of “Quality” and “Risk” Risk models and management approaches Manufacturing science and process understanding –Process understanding and control strategies for mitigating “risk” –Process validation and capability

13. Topics and Priorities (Cont.) Manufacturing science and process understanding (Cont.) –Continuous improvement Use of prior knowledge (e.g., development) for risk mitigation and justification for less burdensome reporting (e.g., “Make Your Own SUPAC”) Design of experiments and failure mode analysis for assessing and mitigating risk –Specifications and in-process controls interim and final specifications risk and mechanism based approaches

14. Subcommittee Discussions Additional Background Information –Summary Reports from the April 2003 FDA/PQRI Workshop Subcommittee membership reflects diverse backgrounds. It will help FDA and other subcommittee members if each member first shares their individual perspectives on the initiative and the proposed topics and challenges they believe FDA will need to address

15. Subcommittee Discussions Subcommittee discussions and recommendations on the list of proposed topics for discussion –Objectives of these discussions will range from addressing specific questions posed by FDA working groups to broader discussion of FDA proposals –These recommendations will be shared with FDA working groups