Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

Advisory Committee for Pharmaceutical Science October 21, 2002 Rockville, MD

CDER

Introductory Remarks
Helen N. Winkle Acting Director Office of Pharmaceutical Science Center for Drug Evaluation and Research
FDA
Food and Drug Administration

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HHS

Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Accomplishments of Committee in the Last Three Years

• Provided input into food effect guidance • Provided input on Biopharmaceutical Classification System (BCS) • Helped in establishing Process Analytical Technologies (PAT) subcommittee
FDA
Food and Drug Administration

2

HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Accomplishments (cont.)

• Discussed dermatopharmacokinetics (DPK) and helped in making decision to withdraw draft guidance and focus on more general bioequivalence methodology for topicals • Discussed PQRI project on blend uniformity assisting OPS in determining acceptability of recommendations
FDA
Food and Drug Administration

3

HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Accomplishments (cont.)

• Debated individual bioequivalence and replicate design and provided OPS with feedback that served as background for making changes to General BA/BE Guidance • Orally Inhaled and Nasal Drug Products (OINDP) - recommendations for BA/BE and chemistry guidances
FDA
Food and Drug Administration

4

HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Accomplishments (cont.)
• Participated in awareness sessions on the following topics: – lactation – polymorphism – liposomes – risk based CMC review
FDA
Food and Drug Administration

5

HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Current Subcommittees
• PAT • OINDP • NCSS

FDA
Food and Drug Administration

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HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Vision for Subcommittee Structure of ACPS
ACPS

Manufacturing

Clinical Pharm

Pharm/ Tox

Microbiology

Biopharm

PAT

NCSS

OINDP

FDA
Food and Drug Administration

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HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Future Focus
• GMP Initiative - includes manufacturing practices and policies • CBER/CDER Consolidation • Developing policies and practices to regulate new products, new delivery systems, etc.
FDA
Food and Drug Administration

8

HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Future Focus (cont.)
• Development and revision of new standards/guidances • Focus on generic products - developing bioequivalence methods, etc. • Evaluation of future PQRI recommendations
FDA
Food and Drug Administration

9

HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

CDER

Changes in Membership
• Last Meeting: – Dr. Lee – Dr. Anderson – Dr. Berg – Dr. Doull – Dr. Boehlert – Dr. Jusko
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• Sabbatical: – Dr. Venitz

FDA

HHS
Health and Human Services

Food and Drug Administration

Office of Pharmaceutical Science

Center for Drug Evaluation and Research
Call to Order Conflict of Interest Vincent H. L. Lee, Ph.D., Chair Kathleen Reedy, Exec. Sec. Helen Winkle, Acting Director OPS

OPS

Day 1: Monday, October 21, 2002 8:30

CDER

8:45 9:00

Introduction to Meeting Subcommittee Reports 9:00 9:45 Non-Clinical Studies Process Analytical Technologies

Frank Sistare, Ph.D. Robert Osterberg, Ph.D. Thomas Layloff, Ph.D.

10:30 Break 10:45 Other Updates 10:45 Risk Based CMC Review 11:15 Blend Uniformity Invited Guests: Tobias Massa, Ph.D., Eli Lilly Thomas Garcia, Ph.D., Pfizer 11:45 Open Public Hearing 12:45 Lunch 1:45 Regulatory issues related to crystal habits - polymorphism 1:45 2:00 2:45 Introduction Gary Buehler, R.Ph. Yuan-yuan Chiu, Ph.D. Vilayat Sayeed, Ph.D. Ajaz Hussain, Ph.D.

Scientific considerations of pharmaceutical solid polymorphism Lawrence Yu, Ph.D. Expert comments Kenneth R Morris, Ph.D. Purdue Harry G. Brittain, Ph.D. Center for Pharmaceutical Physics Leslie Benet, Ph.D. UCSF

3:15 3:30

Break Polymorphism cont. Committee Discussion

FDA

4:45

Conclusions and Summary Remarks

Food and Drug Administration

11

Ajaz Hussain, Ph.D.

HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

Day 2: Tuesday, October 22, 2002 8:30 Call to Order Conflict of Interest 8:45 Vincent H. L. Lee, Ph.D., Chair Kathleen Reedy Exec.Sec.

CDER

Future Subcommittee - GMP/Manufacturing 8:45 9:00 Introduction and Overview Industry Perspective: PhRMA Gerry Migliaccio GPhA 9:30 Ken Lavin Ajaz Hussain, Ph.D. Deputy Director, OPS

Committee discussion

10:15 Break 10:30 Manufacturing Issues: Sterile Drug Products Produced by Aseptic Processing 10:30 Introduction 10:55 Contamination Risk Factors 11:20 Microbiology Review Perspective 11:25 Industry Perspective 11:40 Design, Control and Contamination 12:00 Lunch 1:00 2:00 Open Public Hearing Manufacturing Issues cont. Discussants: Sandra Lowery Anne Marie Dixon Terry Munson Michael Korczynski, Ph.D. Don Burstyn, Ph.D. Jeanne Moldenhauer, Ph.D. 2:00 Committee Discussion (Design) 2:25 Presentation - Sterilization Options Kris Evans Ajaz Hussain, Ph.D. Joseph Famulare Richard Friedman David Hussong, Ph.D. Russ Madsen Berit Reinmuller, Ph.D.

FDA
Food and Drug Administration

2:30 Committee Discussion

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HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

PAT Subcommittee Wednesday, October 23, 2002 8:30 Call to Order Conflict of Interest 8:40 9:00 Introd uction to Meeting Thomas Layloff, Ph.D., Acting Chair Kathleen Reedy, Exec.Sec. Ajaz Hussain, Ph.D. Deputy Dir. OPS

CDER

Computer systems validation - Part 11 issues p ertinent to PAT Invited speakers: Guy Wingate, Ph.D. Debbie T homas John Murra y

10:30 Break 10:45 Computer systems validation - Part 11 issues pertinent to PAT cont. Subcommittee Discussion 11:30 Open Public Hearing 12:30 Lunch 1:30 Breakout Sessions A. PAT Mock Subm ission B. Rapid M icrobiolog y Testing

(Break 3:00 - 3:15) 3:45 Breakout Sessions Presen tations to Subcommittee PAT Mock Subm ission - 15 minutes Rapid M icrobiolog y Testing - 15 minutes 4:15 4:50 Subcommittee Discu ssion and Summary Closing Remarks Adjourn Ajaz Hussain, Ph.D.

FDA

5:00

Food and Drug Administration

13

HHS
Health and Human Services

Office of Pharmaceutical Science

Center for Drug Evaluation and Research

OPS

FDA

Clinical Pharmacology Subcommittee Wednesday, October 23, 2002 8:00 Call to Order William Jusko, Ph.D., Acting Chair Conflict of Interest Kathleen Reedy, Exec.Sec. 8:10 Welcome Helen Winkle, Acting Director OPS 8:15 Introduction to Meeting Lawrence Lesko, Ph.D., Director OCBP 8:45 Topic # 1 Consideration of investigational pharmacokinetic studies to identify patient populations at risk: Methods used to adjust dosing given the availability of exposure-response information 8:45 FDA presentation: case studies and a model for the future Peter Lee, Ph.D. 9:45 Evaluation of methods and clarifying questions Richard LaLonde, Pharm.D.. Lewis Sheiner, M.D., Ph.D. (10:15 -10:30 Break) 10:30 Committee discussion 11:30 Using exposure-response relationships to define therapeutic index: a preliminary approach based on utility function Jurgen Venitz, M.D., Ph.D. 12:00 Open Public Hearing 1:00 Lunch 2:00 Topic # 2 Use of exposure-response relationships in the Pediatric Study Decision Tree: Questions to be asked using the FDA pediatric database 2:00 Medical and clinical pharmacology perspective on the pediatric study decision tree and experience to date Rosemary Roberts, M.D. 2:20 Efforts to optimize pediatric clinical pharmacology studies Arzu Selen, Ph.D. 2:30 Committee Discussion 3:00 Break 3:15 Topic # 3 Scientific and practical considerations in the use of pharmacogenetic tests to determine drug dosage and administration 3:15 Current experience and clinical pharmacology perspective: questions to the committee Lawrence Lesko, Ph.D. 3:30 Assessment of TPMT testing and impact on risk management Richard Weinshilboum, M.D. Mary Relling, Pharm.D. 4:00 Committee discussion 4:30 Concluding Remarks Lawrence Lesko, Ph.D. 5:00 Adjourn William Jusko, Ph.D.

CDER

Food and Drug Administration

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HHS

Health and Human Services