1. Increased Use of Third Party Audits For Improved Control Topic C Closing Presentation

2. Acceptance of 3 rd Party Audit Excipient Manufacturers Excipient Manufacturers Reduced site auditsReduced site audits Reduced questionnairesReduced questionnaires 2 nd party auditors not always familiar with excipients2 nd party auditors not always familiar with excipients 3 rd party more consistent between auditors3 rd party more consistent between auditors Do excipient manufacturers prepare more for 3 rd party audit? Do excipient manufacturers prepare more for 3 rd party audit? Negative first impression Negative first impression

3. Acceptance of 3 rd Party Audit Pharmaceutical Manufacturers Pharmaceutical Manufacturers Quality 3 rd Party Audit programQuality 3 rd Party Audit program Excipient manufacturer specificExcipient manufacturer specific Previously audited Previously audited Good Receiving and Production History Good Receiving and Production History Issues with supplier not passed to audit groupIssues with supplier not passed to audit group No regulatory issues to discuss-e.g. Residual SolventsNo regulatory issues to discuss-e.g. Residual Solvents

4. Acceptance of 3 rd Party Audit Pharmaceutical Manufacturers Pharmaceutical Manufacturers Audits of more excipient manufacturersAudits of more excipient manufacturers 3 rd Party auditor allowed more time on- site=more thorough assessment3 rd Party auditor allowed more time on- site=more thorough assessment Avoid risk management for deciding who to auditAvoid risk management for deciding who to audit FDA Position FDA Position Acceptable with proper controlsAcceptable with proper controls

5. Acceptance of 3 rd Party Audit Types of audits: Types of audits: Initial Qualification-2 nd or 3 rd partyInitial Qualification-2 nd or 3 rd party For Cause-probably 2 nd partyFor Cause-probably 2 nd party Surveillance-preferably 3 rd partySurveillance-preferably 3 rd party Response to Regulatory Action-2 nd PartyResponse to Regulatory Action-2 nd Party Non-manufacturing scope-3 rd PartyNon-manufacturing scope-3 rd Party Consumers benefit from assurance of excipient conformance Consumers benefit from assurance of excipient conformance

6. Acceptance of 3 rd Party Audit 3 rd Parties already being used for: 3 rd Parties already being used for: PackagingPackaging TestingTesting ManufacturingManufacturing Obstacle: Supplier Audit SOPs often preclude 3 rd Party Audit Obstacle: Supplier Audit SOPs often preclude 3 rd Party Audit Security Security

7. 3 rd Party Audit and Supplier Qualification 3 rd party audit must be equivalent to 2 nd Party 3 rd party audit must be equivalent to 2 nd Party 3 rd party audit adds new perspective 3 rd party audit adds new perspective How do you handle serious adverse findings? How do you handle serious adverse findings? Who is notified of findings?Who is notified of findings?

8. 3 rd Party Audit and Supplier Qualification Pharmaceutical firm must be able to action the report Pharmaceutical firm must be able to action the report Excipient Audit of manufacturers with low volumes Excipient Audit of manufacturers with low volumes ISO 9001 certified program ISO 9001 certified program

9. Expectations of a 3 rd Party Audit Program SOPs describing program operation SOPs describing program operation Pre-Audit QuestionnairePre-Audit Questionnaire Established Audit StandardEstablished Audit Standard Report ContentReport Content Confidentiality of audits Confidentiality of audits Independent and unbiased organization and auditors Independent and unbiased organization and auditors Qualification and reputation of the organization and auditors Qualification and reputation of the organization and auditors

10. Expectations of a 3 rd Party Audit Program Qualify 3 rd Party Audit Program by comparing reports for same excipient Qualify 3 rd Party Audit Program by comparing reports for same excipient Firm doing 3 rd Party Audit should not consult Firm doing 3 rd Party Audit should not consult Mock or sample audit report Mock or sample audit report Mechanism to confirm the veracity of the findings Mechanism to confirm the veracity of the findings Excipient manufacturer audit report reviewExcipient manufacturer audit report review

11. Qualifications of the 3 rd Party Auditor Training Training General AuditGeneral Audit ASQ Certified Quality Auditor ASQ Certified Quality Auditor ISO 9001 Certified Lead Auditor ISO 9001 Certified Lead Auditor Recognized Auditor Training Course Recognized Auditor Training Course Excipient GMPsExcipient GMPs Experience Experience Appropriate backgroundAppropriate background including API including API Understanding of regulated environment Understanding of regulated environment

12. Qualifications of the 3 rd Party Auditor Knowledgeable on difference between 21 CFR Part 211 and USP General Information Chapter Knowledgeable on difference between 21 CFR Part 211 and USP General Information Chapter Prioritize/categorize audit observations Prioritize/categorize audit observations Know what is important to auditKnow what is important to audit Know what findings are importantKnow what findings are important Demonstrate audit competency Demonstrate audit competency

13. Benefits to Small Manufacturers Pharmaceutical Manufacturers Pharmaceutical Manufacturers Audit has more credibility than questionnaireAudit has more credibility than questionnaire How do you know answers are truthful? How do you know answers are truthful? Small customers cannot audit excipient manufacturerSmall customers cannot audit excipient manufacturer Avoid staff of auditorsAvoid staff of auditors Reduced number of audits especially outside the US.Reduced number of audits especially outside the US. Allows generics to assess more excipient producersAllows generics to assess more excipient producers

14. Benefits to Small Manufacturers Excipient manufacturers Excipient manufacturers Audit helps assure their conformanceAudit helps assure their conformance

15. Closing Comments / Questions Web sites: Web sites: Third Party Audits Third Party Audits WWW.IPEAINC.comWWW.IPEAINC.comWWW.IPEAINC.com WWW.USP.orgWWW.USP.org