Center for Drug Evaluation and Research

July 19, 2001

CDER Advisory Committee Conference Room

5630 Fishers Lane

Rockville, Maryland

PARTICIPANTS

Members Present Executive Secretary

Stephen R. Byrn, Ph.D., Chair Nancy Chamberlin, Pharm.D.

Judy Boehlert, Ph.D.

Joseph Bloom, Ph.D. FDA

John Doull, M.D., Ph.D. Wallace P. Adams, Ph.D.

Nair Rodriquez-Hornedo, Ph.D. Yuan-yuan Chiu, Ph.D.

William J. Jusko, Ph.D. Badrul Chowdhury, M.D.,Ph.D.

Vincent H. L. Lee, Ph.D. Eric P. Duffy, Ph.D.

Jürgen Venitz, M.D., Ph.D. Ajaz S. Hussain, Ph.D.

Capt. David Hussong, Ph.D.

Consumer Representative Robert J. Meyer, M.D.

Gloria L. Anderson, Ph.D. Bryan S. Riley, Ph.D.

Vilayat A. Sayeed, Ph.D.

Invited SGE Consultant Helen N. Winkle

William H. Barr, Pharm.D., Ph.D.

Invited Guests Participants Leon Shargel, Ph.D., R.Ph.

(Robert) Gary Hollenbeck, Ph.D. Gordon Holt, Ph.D.

Williams Kerns, D.V.M., M.S.,D.A.C.V.P.

Leon Lachman, Ph.D.

Marvin C. Meyer, Ph.D.

Jeanne Moldenhauer, Ph.D.

Kenneth H. Muhvich, M.S., Ph.D.

G.K. Raju, Ph.D.

These summary minutes for the July 19, 2001 meeting of the Advisory Committee for Pharmaceutical Sciences were approved on October 2, 2001.

I certify that I attended the July 19, 2001 of the Advisory Committee for Pharmaceutical Sciences and that these minutes accurately reflect what transpired.

__________|S|__________________ _____|S|______________

Nancy Chamberlin, Pharm.D. Stephen R. Byrn, Ph.D.

Executive Secretary Chair

Summary Minutes of the July 19, 2001 of the Advisory Committee for Pharmaceutical Science

Page 2

On July 19, 2001, the Advisory Committee for Pharmaceutical Science met in an open public session at the CDER Advisory Committee Conference Room, 5630 Fishers Lane, Rockville, Maryland. Prior to the meeting, the members, consultants and invited guests had reviewed background material from the FDA. There were approximately 110 people in attendance.

Helen Winkle introduced the topics and presented FDA’s objectives for the meeting.

Vincent H. L. Lee, Ph.D., provided an overview of The June 1999 BA/BE Guidance for Nasal Aerosols and Nasal Sprays. This was followed by Badrul Chowdhury, M.D., Ph.D.’s presentation of Difficulties in Showing a Dose-Response with Locally-Acting Nasal Sprays and Aerosols for Allergic Rhinitis. Robert J. Meyer, M.D., presented Clinical Study Options for Locally Acting Nasal Suspension Products. Then Wallace P. Adams, Ph.D., reported on the conclusions from the July 17, 2001 OINDP Subcommittee Advisory Committee Meeting during his presentation of The June 1999 BA/BE Guidance for Nasal Aerosols and Nasal Sprays: Recommendations of the OINDP Subcommittee. Following the presentations was the committee discussion regarding clinical BE studies for comparison of local delivery of suspension nasal products for allergic rhinitis.

John Doull, M.D., Ph.D. updated the committee on the NCSS subcommittee and introduced the speakers for the two Expert Working Groups (EWGs). Gordon Holt, Ph.D. reported on the NCSS Fact Finding Cardiotoxicity Expert Working Group. While Williams Kerns, D.V.M., M.S.,D.A.C.V.P., reported on the NCSS Vascular Injury Expert Working Group. Then

Helen Winkle, presented the Nonclinical Studies Subcommittee Next Steps.

Yuan-yuan Chiu, Ph.D., presented An Introduction and Overview of Risk-Based CMC Review. Eric P. Duffy, Ph.D., reported on the Risk-Based CMC Review AAPS Workshop Report: Drug Substance Issues. Vilayat A. Sayeed, Ph.D., provided an Update on Risk-Based CMC Review. While David Hussong, Ph.D., provided the Risk-Based CMC Microbiology Review and the Risk-Based CMC Review, GMP Breakout Sessions Summary. Then Yuan-yuan Chiu, Ph.D., concluding with her presentation of the Next Steps: Risk-Based CMC Reviews. The presentations were followed by committee discussion of the questions for Risk-Based CMC Reviews.

Ajaz S. Hussain, Ph.D., presented on Optimal Applications of "In-Line" or "At-Line" Manufacturing Controls in Pharmaceutical Production. Then G. K. Raju,. Ph.D., reported on

Continuous Quality Verification (CQV). After discussion by the committee, there was a proposal to create an in-line and at-line control production subcommittee under the Pharmaceutical Science Advisory Committee.

David Hussong, Ph.D., presented on New Microbiological Technologies. Then Bryan S. Riley, Ph.D., gave the Microbial Limit Testing Technology Overview. Followed by Kenneth H. Muhvich, Ph.D., describing Validation Issues of Rapid Methods. While Jean Moldenhauer, Ph.D., provided a presentation on Rapid Microbiology Methods: Industry Concerns. After discussion by the committee, there was a proposal for a creating a microbiology subcommittee under the Pharmaceutical Science Advisory Committee to look at new technology and validation issues.

The AAPS Inhalation Technology Focus Group (ITFG)/ International Pharmaceutical Aerosol Consortium (IPAC) Collaboration Technical Teams representatives presented information on Bioequivalence Studies and Other Recommendations for Orally Inhaled and Nasal Drug Products. David Radspinner, Ph.D., Aventis Pharma, presented an Update of ITFG/IPAC-RS Dose Content Uniformity (DCU) Working Group Progress. Carole Evans, Ph.D., Magellan Laboratories, presented an Update on Progress of Particle Size Distribution (PSD) Working Group and Tests and Methods Team. James D. Blanchard, Ph.D., Aradigm Corporation, presented an Update on Progress of Leachables and Extractables Team. Then Joel Sequeira, Ph.D., Schering Plough Research Institute, presented the concluding presentation on Bioequivalence Studies for Locally Acting Nasal Drug Products which contained comments from the BA/BE Team on the Issue of Dose Response.

The meeting adjourned on July 19, 2001 at 5:02 p.m.

For more detailed information see the verbatim transcript of this meeting on the FDA’s Docket Management Branch Website address:

Prepared by:

Nancy Chamberlin, PharmD., Executive Secretary

The Advisory Committee for Pharmaceutical Science