1. PQRI Workshop Discussion D Discuss Strategies to Increase the Number of Excipients Labeled USP-NF

2. PQRI Workshop Discussion D Current Situation Increasing danger that excipient manufacturers will stop producing excipients that meet USP-NF standards Increasing danger that excipient manufacturers will stop producing excipients that meet USP-NF standards May result in deletion of USP-NF monograph for such excipients May result in deletion of USP-NF monograph for such excipients

3. PQRI Workshop Discussion D Current Situation Problematic for drug product manufacturers Problematic for drug product manufacturers Additional regulatory burden for excipient information in regulatory filings Additional regulatory burden for excipient information in regulatory filings methods and acceptance criteriamethods and acceptance criteria methods validationmethods validation justification of specificationsjustification of specifications

4. PQRI Workshop Discussion D Current Situation Contrary to FDA’s cGMP Initiative to: Contrary to FDA’s cGMP Initiative to: strategically reduce industry’s regulatory and paperwork concerns, andstrategically reduce industry’s regulatory and paperwork concerns, and change the regulatory focus to concentrate on those aspects of manufacturing that pose the greatest risk to product qualitychange the regulatory focus to concentrate on those aspects of manufacturing that pose the greatest risk to product quality such as unique attributes of an excipient needed for manufacturing such as unique attributes of an excipient needed for manufacturing

5. PQRI Workshop Discussion D Survey Results Most (>80%) excipient manufacturers, distributors and drug product manufacturers make their products for global distribution Most (>80%) excipient manufacturers, distributors and drug product manufacturers make their products for global distribution Most (>80%) test excipients according to USP-NF Most (>80%) test excipients according to USP-NF Almost all (97%) drug product manufacturers test excipients per USP-NF Almost all (97%) drug product manufacturers test excipients per USP-NF

6. PQRI Workshop Discussion D Survey Results Most (89%) excipient manufacturers label their excipients as compendial grade Most (89%) excipient manufacturers label their excipients as compendial grade survey may not be reflective of all excipient manufacturerssurvey may not be reflective of all excipient manufacturers Most (80%) distributors label their excipients as compendial grade Most (80%) distributors label their excipients as compendial grade

7. PQRI Workshop Discussion D Survey Results Difficulty finding a manufacturer of at least 1 USP-NF grade excipient? Difficulty finding a manufacturer of at least 1 USP-NF grade excipient? 40% of drug product manufacturers40% of drug product manufacturers 25% of distributors25% of distributors

8. PQRI Workshop Discussion D Survey Results When no USP-NF grade excipient is available, drug product manufacturers: When no USP-NF grade excipient is available, drug product manufacturers: 80%use best grade available80%use best grade available 80%test excipient per USP-NF monograph80%test excipient per USP-NF monograph 90%conduct audit of excipient manufacturer90%conduct audit of excipient manufacturer 78%do not reformulate product78%do not reformulate product 90%do not contact FDA for direction90%do not contact FDA for direction

9. PQRI Workshop Discussion D Survey Results Reasons for not labeling excipients as USP-NF Reasons for not labeling excipients as USP-NF 35%low demand for USP-NF grade35%low demand for USP-NF grade 30%GMP requirements too restrictive30%GMP requirements too restrictive 30%internal time/resources for audits30%internal time/resources for audits 30%potential to be inspected by FDA30%potential to be inspected by FDA 5% can’t meet monograph5% can’t meet monograph

10. PQRI Workshop Discussion D For Discussion What are the barriers to labeling an excipient as USP-NF grade? How can the barriers be reduced? What are the barriers to labeling an excipient as USP-NF grade? How can the barriers be reduced? What excipients are no longer available as USP-NF grade? What excipients are no longer available as USP-NF grade?

11. PQRI Workshop Discussion D For Discussion What are the implications when an excipient user moves from a compendial grade excipient to noncompendial grade (i.e., not designated through labeling suffix, namely USP-NF, Ph. Eur. or JP)? What are the implications when an excipient user moves from a compendial grade excipient to noncompendial grade (i.e., not designated through labeling suffix, namely USP-NF, Ph. Eur. or JP)? What is industry’s burden in supplying analytical method validation data to regulatory agency for excipients no longer labeled USP-NF? What is industry’s burden in supplying analytical method validation data to regulatory agency for excipients no longer labeled USP-NF?

12. PQRI Workshop Discussion D For Discussion What test methods are used when an excipient user must replace a compendial grade excipient with noncompendial grade? What test methods are used when an excipient user must replace a compendial grade excipient with noncompendial grade? What are the ongoing initiatives at the USP to address these problems? What are the ongoing initiatives at the USP to address these problems?