1. Regulatory Aspects of Pharmaceutical Excipients PQRI Workshop Nick Buhay Acting Director Division of Manufacturing and Product Quality Office of Compliance Center for Drug Evaluation and Research Food and Drug Administration Marriott Hotel and Convention Center October 10, 2006

2. Oversight of Excipient Manufacturing Quality • Current oversight program • Monitoring the uses/types of excipients • Monitoring excipient quality • Monitoring of manufacturing problems based on excipient quality • Recognition of use of Voluntary CGMP • Participation in review of standards, industry input • Oversight of user control of excipients: application conditions of approval, CGMP • ‘For cause’ inspection of excipient mfg as drug; other regulators’/other FDA inspection

3. Excipient Manufacturing • Subject to statutory requirements in section 510 (a) (2) (B) of the Food, Drug and Cosmetic Act • Excipients must be manufactured, processed, packaged and held in conformity with Current Good Manufacturing Practice (CGMP)

4. Models for CGMP Conformance • FDA has not developed regulations or specific guidance on CGMP conformance for excipients • ICH Q7A GMP Guidance for APIs contains applicable guidance • However, FDA is supportive of the IPEC GMP Guide for Bulk Pharmaceutical Excipients

5. Drug Excipient Quality • Quality characteristics of excipients are significant to the overall quality of the drug products in which they are used • Drug product manufacturers rely on excipient manufacturers to provide excipients of uniform quality, physical and chemical characteristics, e.g., levels of impurities

6. Drug Excipient Manufacturers • Specification development based on critical quality attributes • Process controls that ensure consistent conformance with specifications • Every batch is tested to ensure conformance with all specifications • Provide reliable test data to drug product manufacturers

7. Drug Product Manufacturers • Identify excipients needed for drug product formulations, including physical and chemical characteristics • Conformance with the CGMP regulations in 21 CFR 211.84 • Qualify sources of excipients

8. Drug Product Manufacturers • 21 CFR 211.84(d)(2) requires the user/drug product manufacturer to test every batch of drug excipient for conformity with written specifications, for purity, strength and quality • However, drug product manufacturers can rely on their suppliers for this testing, provided that the reliability of the suppliers’ test results is validated at appropriate intervals

9. Drug Product Manufacturers • The CGMPs are not specific as to the method and frequency of validating test results provided by suppliers • Drug product manufacturers should have SOPs detailing a scientifically sound approach to ensure periodic validation of suppliers’ test results

10. Drug Product Manufacturers • For excipients that are critical to the quality of the finished dosage form, testing by the drug product manufacturer may be necessary to verify the critical attributes of every batch

11. Drug Excipient Quality • Send us information • Contribute input • Science-based • Risk assessment • Questions????