1. PAT Progress Report: 13 April 2004 ACPS Meeting Ajaz S. Hussain, Ph.D. Deputy Director Office of Pharmaceutical Science CDER, FDA

2. Outline Brief historyBrief history Current Status and Next StepsCurrent Status and Next Steps –Finalizing PAT Guidance, Training and Certification Chris WattsChris Watts –Standards development Ali AfnanAli Afnan –Rapid microbial methods Brian RileyBrian Riley Committee discussion and recommendationsCommittee discussion and recommendations –Are we on the right track? –Any recommendations to improve our approach?

3. Historical Milestones October 1993, St. Louis, MissouriOctober 1993, St. Louis, Missouri –Pharmaceutical Process Control and Quality Assurance by Non-traditional Means (AOAC Symposium) February 2000, San Francisco, CaliforniaFebruary 2000, San Francisco, California –FIP’s Millennium World Congress of the Pharmaceutical Sciences March 2001, London, United KingdomMarch 2001, London, United Kingdom –RPS NTF#4: Process Measurement and Control

4. The message has not changed! FIP Millennium Conference San Francisco

5. FIP Millennium Conference San Francisco The message has not changed!

6. ACPS Meeting November 28, 2001 G.K. Raju, MIT and CAMP

8. ACPS Meeting November 28, 2001 October 23, 2002 June 12-13, 2002 February 25-26, 2002

9. Arthur H. Kibbe, Acting Chair PAT Application Benefits Working Group PAT Application Benefits Working Group Judy P. Boehlert, Acting Chair Judy P. Boehlert, Acting Chair PAT Product and Process Development Working Group PAT Product and Process Development Working Group Leon Lachman, Acting Chair Leon Lachman, Acting Chair PAT Process and Analytical Validation Working Group Melvin Koch, Acting Chair Melvin Koch, Acting Chair PAT Chemometric Working Group PAT Chemometric Working Group Tom Layloff, PAT Sub-Committee Acting Chair

10. FDA Sci Board, April 9, 2002 Dr. Woodcock Ray Sherzer

12. The PAT Team: The Engine of Success A team is a group of interdependent individuals with complimentary skills who are organized and committed to: 1. Achieving a common purpose 2. Applying a common process, and 3. Sharing a common destiny Quality of Relationship Thinking Action Results

13. PATRIOT: ORA, CDER & CVM PAT Steering Committee Doug Ellsworth, ORA/FDA Dennis Bensley, CVM/FDA Mike Olson, ORA/FDA Joe Famulare, CDER/FDA Keith Webber, CDER/FDA Frank Holcomb, CDER/FDA Moheb Nasr, CDER/FDA Ajaz Hussain Chair, CDER/FDA PAT Review - Inspection Team Investigators: Robert Coleman (ORA/ATL-DO) Rebeca Rodriguez (ORA/SJN-DO) Erin McCaffery (ORA/NWJ-DO) George Pyramides (PHI-DO) Dennis Guilfoyle (ORA/NERL) Compliance Officers: Albinus D’Sa (CDER) Mike Gavini (CDER) William Bargo (CVM) Brenda Uratani (CDER) Reviewers: Norman Schmuff (CDER) Lorenzo Rocca (CDER) Vibhakar Shah (CDER) Rosario D’Costa (CDER) Raafat Fahmy (CVM) Brian Riley (CDER) PAT Policy, Consultant, Support Team Raj Uppoor, OPS/CDER Chris Watts, OPS/CDER Huiquan Wu, OPS/CDER Ali Afnan, OPS/CDER PAT Training Coordinators John Simmons, Karen Bernard and See Lam

17. Current State Several successful workshops (e.g., AAPS Arden House, IFPAC, ISPE, PDA,…)Several successful workshops (e.g., AAPS Arden House, IFPAC, ISPE, PDA,…) Several proposals, one approvalSeveral proposals, one approval First training session complete, certification process ongoingFirst training session complete, certification process ongoing Ongoing Interagency Agreement with NSFOngoing Interagency Agreement with NSF Ongoing CRADA with Pfizer on Chemical ImagingOngoing CRADA with Pfizer on Chemical Imaging Ongoing communication and cooperation with other regulatory agencies (e.g., EMEA PAT Team, Health Canada, MHLW)Ongoing communication and cooperation with other regulatory agencies (e.g., EMEA PAT Team, Health Canada, MHLW)

18. Current State ASTM Committee E55: Pharmaceutical Applications of PAT ( http://www.astm.org)ASTM Committee E55: Pharmaceutical Applications of PAT ( http://www.astm.org) http://www.astm.org Growing external collaborations and emerging support structureGrowing external collaborations and emerging support structure –ISPE and PDA interest in PAT, PAT Group in AAPS, discussion on AAPS-ISPE collaboration,, strong support from IFPAC and formation of IPFAC MA or IFPAT MA, AIChE,… –Growing number of academic programs with focus on PAT –Several “PAT” companies and training opportunities –Pharmacopeias are interested in PAT PAT now a part for the 21 st Century Initiative and FDA’s Strategic PlanPAT now a part for the 21 st Century Initiative and FDA’s Strategic Plan

19. Next Steps Final GuidanceFinal Guidance Quality System for PAT processQuality System for PAT process Participate in ASTMParticipate in ASTM Expand the scope of the guidance to include Office of Biotechnology Products OPS/CDER (discussions today)Expand the scope of the guidance to include Office of Biotechnology Products OPS/CDER (discussions today) –They were not part of the first training and certification program –Develop 2 nd Training and certification program In the next 2-3 years PAT is a regular part of the CMC & GMP programIn the next 2-3 years PAT is a regular part of the CMC & GMP program