1. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team ITFG/IPAC TECHNICAL TEAM: SUPPLIER QUALITY CONTROL (QUALIFICATION) Presented by: Gordon Hansen 26 April 2000 Rockville, MD

2. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team SUPPLIER QUALITY CONTROL TEAM Team membership is comprised of representatives from 9 pharma companies and 5 key component manufacturers.

3. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team SUPPLIER QUALITY CONTROL TEAM A core theme of the draft CMC guidances with respect to component, excipient, and raw material suppliers is summarized below: Tight standards and extensive testing by the pharma manufacturer are required in order to assure batch to batch quality of components and excipients.

4. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team TEAM’S THESIS The qualification and control of critical components (in the areas of performance related physical testing, extractables and leachables) and excipients should be achieved by a combination of appropriate scientific practices, cGMP controls and supplier qualification systems.

5. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team TEAM’S APPROACH: cGMP SURVEY A survey of suppliers was conducted to evaluate quality and compliance practices at all stages of component, excipient, raw materials, and active drug substance manufacture Survey requested assessment of performance related to 31 specific cGMP elements Circulated to all companies represented on Team Information obtained on 53 suppliers, from raw materials through finished component manufacture

6. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team TEAM’S APPROACH: cGMP SURVEY Results: Highest level of compliance is evident with active ingredient suppliers Level of cGMP awareness and compliance in the component and raw material supply chain is increasing, but needs to be improved Specific cGMP program elements remain to be generally accepted and implemented, especially early in supply chain

7. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team TEAM’S APPROACH: cGMP SURVEY Results: No generally accepted cGMP guidelines exist for the component supply chain cGMP guidelines have been drafted by IPEC (International Pharmaceutical Excipients Council)

8. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team PROPOSALS AND COMMITMENTS The Team endorses the IPEC Guideline for the control and cGMP compliance of excipients The Team proposes that an industry-wide initiative be established to develop a cGMP guideline for component suppliers

9. ITFG/IPAC Collaboration CMC Supplier Quality Control Technical Team PROPOSALS AND COMMITMENTS The Team requests that the Agency partner with the pharma industry and component suppliers by: Formally recognizing the value of a cGMP guideline for component suppliers by acknowledging in the guidance documents that if sufficient supplier control mechanisms are in place, appropriate reductions in testing will be considered. Establishing key elements and expectations for a cGMP guideline. Participation in reviewing and commenting on draft cGMP guidelines.