Quality by Design & Question-Based Review: Observations by the Generic Pharmaceutical Industry

1. Quality by Design & Question-Based Review: Observations by the Generic Pharmaceutical Industry Advisory Committee for Pharmaceutical Science October 5, 2006 Gordon Johnston Generic Pharmaceutical Association

2. Outline • Introduction • Quality by Design • Question-Based Review • Summary

3. Introduction • QbD/QbR • Requires significant changes to cross-functional coordination within firms • Shift to QbR content represents a major change • Cautiously optimistic • A steep learning curve for industry • Conversion to CTD format • Aggressive implementation schedule by FDA • ~ 800 ANDAs expected in CY 2006 • Increased burden for industry

4. Quality by Design • Extensive manufacturing expertise in the industry • Generic firms often manufacture 50 - >100 products • Product and process understanding is critical for efficiency • Concepts of QbD have been in use by industry for many years • QbD represents a more organized and integrated approach to product development

5. Quality by Design • Opportunities • Value in ‘prior knowledge’ • Extensive experience with common formulations • Excipient properties well understood • Critical attributes impacting manufacturing process known

6. Quality by Design • Opportunities (cont’d) • Keen knowledge of equipment and common manufacturing processes • Blending, coating, etc. • Potential for reduced review time • Potential for reduced post-approval burden

7. Quality by Design • Are QbD expectations clearly defined? • GMP implications? • Experience to date is mixed • ICH Q8 concepts still being integrated by Field • Field often expects full design space validation • Prior knowledge not universally accepted by investigators at this time

8. Quality by Design • Should FDA modify its focus? • Generic industry still required to accept FDA dissolution specifications • Continued requirements to set specifications typically based on process capabilities and not product performance • For example, residual solvents • More guidance on non-oral dosage forms needed

9. Question-Based Review • Represents a tool to efficiently assess QbD approach • Industry is supportive of the initiative • Industry and OGD still learning

10. Question-Based Review • OGD Model QOS • 2 years in the making • Open dialogue between OGD and generic industry during evolution • OGD responsive to Q&A sessions

11. Question-Based Review • OGD Model QOS • OGD-industry collaboration has accelerated industry’s understanding of QbR • Ongoing communication critical during full implementation

12. Question-Based Review • OGD Model QOSs • Help industry recognize issues OGD generally considers critical • Guide industry toward quality by design • Assist industry to prepare a high quality QOS

13. Question-Based Review • OGD Questions • Allow industry to address some questions with prior knowledge • Industry has been active in submitting QbR applications • Over 35 ANDAs • First ANDA Approval last month

14. Question-Based Review • Challenges • Simultaneous conversion to CTD format and QBR data elements • Implementation schedule has been challenging for some companies • Some companies have been submitting QbR applications since this summer • Substantial internal training and coordination required for implementation

15. Question-Based Review • Challenges • Still uncertain on OGD expectations for QOS and product development reports • Oct 20 OGD training on how to prepare a high quality QOS • Initial response is very positive • More OGD training if needed

16. Question-Based Review • Recommendation • Post-approval reduction in regulatory burden? • Industry requests clarity on types of supplements where regulatory burden may be ‘downgraded’ • Extending QbR concept to already approved products (>8000)? • Extending QbR concept to drug substance DMF

17. Summary • Excellent communications by OGD • Numerous meetings, webcasts, teleconferences during development phase of QbR • Ongoing industry-OGD communications critical • Increased burden

18. Summary • Need to expand QbR to already approved ANDAs and drug substance DMF • Post-approval regulatory relief a critical outcome of initiative • Industry remains cooperative and hopeful • Reassess in a year