1. How characterization of excipient physical and chemical properties helps build quality into drug products How characterization of excipient physical and chemical properties helps build quality into drug products Topic B Closing Presentation Dr. Brian Carlin

2. Highlights Responsibility for testing Responsibility for testing Legal liability rests with userLegal liability rests with user No regulatory restriction on whether user or supplier does the testingNo regulatory restriction on whether user or supplier does the testing No requirement to duplicate other than IDNo requirement to duplicate other than ID What to test/why to test/how to test as a part of inclusion in QbD-based applicationsWhat to test/why to test/how to test as a part of inclusion in QbD-based applications

3. Highlights Additional cost should be borne by excipient user; offset by increased efficiency (eg. Reduced rejection of drug product batches) Additional cost should be borne by excipient user; offset by increased efficiency (eg. Reduced rejection of drug product batches)

4. Highlights 21 st Century cGMP initiative is beneficial to all parties 21 st Century cGMP initiative is beneficial to all parties Reduced regulatory oversightReduced regulatory oversight Flexibility, continuous improvementFlexibility, continuous improvement Requires informed user-supplier collaborationRequires informed user-supplier collaboration

5. Highlights Functionality transcends the excipient Functionality transcends the excipient As applied to formulation and manufacturer processAs applied to formulation and manufacturer process Not to be included in monograph Not to be included in monograph Testing methodology should be in general chapter Testing methodology should be in general chapter Customized between supplier and user Customized between supplier and user

6. Highlights Change notification Change notification All “significant” changes should be notified by excipient manufacturer and impact assessed and monitored by drug product manufacturer.All “significant” changes should be notified by excipient manufacturer and impact assessed and monitored by drug product manufacturer. Who defines significant?Who defines significant? Supplier often unaware of applicationSupplier often unaware of application

7. Highlights The onus of evaluating multiple source excipients lies with the user The onus of evaluating multiple source excipients lies with the user Assumption of new supplier as a minor change often not validAssumption of new supplier as a minor change often not valid “non-critical” excipients can become critical if detrimental, eg. drug degradation“non-critical” excipients can become critical if detrimental, eg. drug degradation

8. Actions IPEC/USP to challenge EP Functionality Related Characteristics (FRCs) whether non-mandatory or not IPEC/USP to challenge EP Functionality Related Characteristics (FRCs) whether non-mandatory or not More early interaction between center, field, and sponsor for QbD- based applications More early interaction between center, field, and sponsor for QbD- based applications

9. Actions Clarify who defines significant change Clarify who defines significant change Users to ensure oversight of purchasing decisions by R&D and other QA/technical groups Users to ensure oversight of purchasing decisions by R&D and other QA/technical groups Improve communication between purchasing and technical functions Improve communication between purchasing and technical functions Improve communication between user and supplier Improve communication between user and supplier

10. Actions Change control should be part of the quality agreement between user and supplier Change control should be part of the quality agreement between user and supplier Audits of suppliers should be a team effort which, in addition to GMP compliance, includes technical functions. Audits of suppliers should be a team effort which, in addition to GMP compliance, includes technical functions.

11. Actions Develop education programs focusing on formulation science/QbD collaboratively between academia and industry Develop education programs focusing on formulation science/QbD collaboratively between academia and industry

12. Closing Questions / Comments Need to define Significant Change in Quality agreements. Need to define Significant Change in Quality agreements.