FDA Economically Motivated Adulteration Conference 119

Excipient Industry Efforts to Stop EMA Develop trust in your excipient supplier BUT verify  IPEA Excipient Audit Program  IPEA Excipient Certification Program  Conformance to Good Manufacturing Practices (GMP)  Conformance to Good Distribution Practices (GDP)  Improve supply chain integrity  Confirm Excipient Pedigree  Enhance excipient receipt and approval The pharmaceutical company has ultimate responsibility for excipient suitability! 219

Supplier Qualification Direct from Manufacturer  Assess Manufacturer Purchased from Distributor  Must know manufacturer and site  Must know role of distributor  Warehousing  Packaging  Repackager  Assess Distributor and Manufacturer 319

Supplier Qualification Ideal: Pharmaceutical Manufacturers audit all excipient suppliers Impact: Each audit cycle  Pharmaceutical Manufacturer  Hundreds to thousands of sites to audit globally - Pfizer reported 4,000 suppliers after mergers  Excipient Supplier (ISP)  Host over 300 site audits at Texas City facility! Unsuitable: Questionnaire/paper audit! 419

Excipient Audit Program Objective: Substitute IPEA audit for Pharmaceutical manufacturer audit Goal: Reduce audit cost through report sharing Program:  1-Day audit by qualified auditors  Quality review of report by IPEA Executive Report available for 2 years 519

Excipient Certification Program Accredit to American National Standards Institute  Develop Auditable Standard  Document Certification Program  Create Program Administration  Establish Objective Expectations  Create Certification Body  Prepare Quality Manual  Host ANSI Assessment 619

ANSI Accreditation Process Procedures Assessment Application Standards Action Standards Action Standards Action Evaluation Task Force Accreditation APPROVED Preliminary Application 719

Excipient Certification Program Benefits  Accredited by nationally recognized organization (ANSI)  Audit duration 4 man-days (plus)  Enhanced assurance of quality system conformance  Quality review of report by IPEA Executive  Certification Board  Review of report  Validation of conclusion visa vie certification  Annual surveillance audit 819

IPEA Excipient Certification Process 9 Certified Application Planning Audit Report Review Certification Review Board 19

Supply Chain Integrity Excipient Pedigree  Verified Paper Trail  Already in-use All movements require paperwork (e.g. BOL)  Site audit  Verify distribution  Shipping papers back to original manufacturer  Periodically confirm 1019

Supply Chain Integrity Distributors  Good Distribution Practices  Unopened Package  Plus Good Manufacturing Practices where:  Packaged from bulk  Repackage 1119

Supply Chain Integrity Tamper -evident Seals  Boxes  Embossed Tape  Drums  Embossed Tape  Imprinted Dust Caps  Bulk  Numbered Seals 1219

Supply Chain Integrity Identification of the manufacturer and site  Paperwork (Bill of Lading) traced to Manufacturer  Audit entire supply chain  Certify excipient manufacturer  Certify all distributors  Periodic confirmation of manufacturer  Acknowledgement of Bill of Lading  Confirm Shipment of Lot to Distributor 1319

Supply Chain Integrity Approval of Excipients  Review of COA  Confirm identity of excipient  Identification test - No composite samples!  Periodic confirmation of COA validity  Perform tests  Return COA to manufacturer to confirm authenticity 1419

Enhance Excipient Receipt and Approval Approval of Components  Evaluation of Packaging  Label matches reference label  Tamper-evident seal matches reference seal  Packaging components match reference components 1519

Operating without supply chain integrity is like accepting currency without verifying its authenticity. 1619

Predicting EMA Reports of EMA lead to:  Assess potential impact to excipients, e.g. Melamine in pet food and milk  Digestion or combustion nitrogen analysis non- specific for protein  Digestion or combustion nitrogen analysis used for certain USP excipients - Evaluate the potential for certain excipients to be diluted with melamine Economic advantage? Pass Quality Control approval? 1719

Predicting Vulnerability Economic Advantage:  Technical vs. Excipient Grade  Latin American customers used PVP versus Povidone USP - Not for Pharmaceutical Use on PVP liners English and Spanish  Improved test methods  Heterocyclic nitrogen instead of non-specific digestion  Purchase through long supply chain vs. direct from manufacturer 1819

Thank you for your attention 19 wwwwww.ipecamericas.org Irwin Silverstein 19