Food and Drug Administration

Center for Drug Evaluation and Research

 

Summary Minutes of the

Pediatrics Subcommittee of the Anti-Infective Drugs Advisory Committee

Advisory Committee Conference Room, Rm. 1066, 5630 Fishers Lane, Rockville, MD.

March 3, 2003

 

 

AntiInfective Drugs Advisory Committee Member Present

Mary Glode, M.D.

 

AntiViral Drugs Advisory Committee Members Present

Lauren Wood, M.D.                              Jan Englund, M.D.                     Courtney Fletcher, M.D.

 

Consultants

Patricia Chesney, M.D.                         Robert Fink, M.D.                     Mark Hudak, M.D.

Robert Nelson, M.D., Ph.D.                   David Danford, M.D.                Victor Santana, M.D.

Richard Gorman, M.D., FAAP               Keith Rodvold, Pharm.D.           Ellen Chadwick, M.D.

Norman Fost, M.D.                               John Sever, M.D.

 

Guests

Lynne Mofenson, M.D.             Benjamin Wilfond M.D. Steven Spielberg, M.D.(Industry Rep.)

 

FDA Participants

Dianne Murphy, M.D.                           Linda Lewis, M.D.                    Shirley Murphy, M.D.

Melissa Baylor, M.D.                            Solomon Iyasu, M.D.

 

 

These summary minutes for the March 3, 2003 meeting of the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee were approved on March 14, 2003.

 

I certify that I attended the March 3, 2003 meeting of the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee, and that these minutes accurately reflect what transpired.

 

 

 

_______________________________                      _______________________________

Thomas H. Perez, M.P.H., R.Ph.                                   Patricia Chesney, M.D.

Executive Secretary                                                             Chair
The Pediatric Subcommittee of the AntiInfective Drugs Advisory Committee, of the Food and Drug Administration, Center for Drug Evaluation and Research met March 3, 2003 at the Advisory Committee Conference Room, Rm. 1066, 5630 Fishers Lane, Rockville, MD.

 

The Committee discussed the development of antiretroviral drugs in HIV-infected and HIV-exposed neonates younger than four weeks of age.  Following this at 2:40 p.m., the agency provided an update to the subcommittee on the Adverse Event Reporting plan as mandated in Section 17 of the Best Pharmaceuticals for Children Act.  After this presentation, at approximately 4:00 p.m., the agency provided an update on pediatric initiatives within the agency.

 

The Committee and invited guests received a briefing document from the FDA in preparation for this meeting.

 

There were approximately 70 persons present.  The meeting was called to order at 8:20 a.m. by the Chair, Joan Chesney, M.D.  The Committee members and discussants introduced themselves. Thomas H. Perez, Executive Secretary of the Pediatric Subcommittee of the AntiInfective Drugs Advisory Committee read the Meeting Statement.   A welcome and opening comments were provided by Dianne Murphy, M.D., Director, Office of Pediatric Therapeutics.

 

Presentations began at 8:30 a.m. and proceeded as follows.

 

  State of the Art: Perinatal Transmission        Lynne Mofenson, M.D., National Institute of Child Health

 and Human Development

  Ethics of Neonatal Research                            John Sever, M.D., Children’s Hospital National Med. Ctr.

  FDA Perspective                                                Linda Lewis, M.D., Division of Antiviral Drug Products

 

After a 15 minute break the meeting was reconvened at 10:40 with the Open Public Hearing.  The committee heard from one participant, James M. Oleske, MD, M.P.H., Francois‑Xavier Bagnoud Professor of Pediatrics.  An additional 4 statements that were received from the public were read into the record by the Chair.

 

Linda Lewis, M.D., provided an introduction to the questions that FDA presented to the Subcommittee for discussion.  The Subcommittee discussed the questions and broke for lunch at 12:20 p.m.  The Subommittee reconvened at 1:10 p.m. and continued the discussion of the question.  At 2:20 the Subcommittee concluded its discussion of the questions.

 

After a 20 minute break the meeting resumed with the Pediatric Update to the Subcommittee and the following presentations.

 

  Overview: Division of Pediatric Drug Development                    Dianne Murphy, M.D.,

      Office of Pediatric Therapeutics                  Director, Office of Pediatric Therapeutics

 

  Medwatch                                                                                           Min Chen, M.S., Division of Drug Risk Evaluation

  Adverse Event Reporting                                                                 Solomon Iyasu, M.D.,

                                                                                                                Division of Pediatric Drug Development

  Division of Pediatric Drug Development – Update                      Shirley Murphy, M.D.

                                                                                                                Division of Pediatric Drug Development

  New Exclusivity / Rule Statistics                                                     Terrie Crescenzi, R.Ph., Office of Counter-Terrorism

 & Pediatric Drug Development

The presentations ended and the meeting was adjourned at 4:30 p.m.

 

The Subcommittee discussed the following questions to which no votes were requested or taken.  The discussion will be made available through the meeting transcripts and placed on the web in approximately three weeks.  Transcripts may be accessed at the following web address.

www.fda.gov/ohrms/dockets/ac/acmenu.htm.

 

Questions to the Committee

 

1.       Given that an estimated 300 to 400 HIV-infected infants are born annually in the U.S., that some of these infants are diagnosed after the first months of life, and that it is difficult to enroll neonates in studies:

·         Are there too few HIV-infected infants born each year in the U.S. or too little public health benefit to justify requesting studies in neonates?

Committee’s Vote:        0 Yes               15 No

The Committee expressed the need to develop strategies to allow for enrichment of the population recruited, and that studies should be done when they are needed where the risk benefit ratio is justified.

 

2.       Since neonates born to HIV-infected mothers may be tested for HIV infection in the first 48 hours and at 4 weeks, HIV-infected infants can be diagnosed within the first month of life.

·         Should only HIV-infected neonates be studied?

Committee’s Vote:        0 Yes               15 No

 

·         If an HIV-exposed population is to be studied, please discuss the risk/benefit assessment for HIV-exposed neonates who might be enrolled in a clinical trial?

Refer to the transcript for the committee’s discussion of this question.

 

·         If studies are conducted in resource poor countries (where the rate of underlying diseases, malnutrition, infant mortality, and pharmacogenetics may differ substantially from the U.S.), can we extrapolate results from these studies to the U.S. population?

Committee’s Vote:        15 Yes             0 No

The Committee indicated that would depend on the control of study variables found in the populations, compliance and overall quality of the data.

 

3.       Should we continue to request pharmacokinetic and safety studies for every antiretroviral drug under development? 

The Committee consensus was yes, assuming that the study issue is ethical, and with a public health benefit.

 

If not, what criteria would you suggest for deciding which drugs should be studied in the neonate (new class, resistance profile, safety issues, pharmacokinetic parameters)?

The committee also included the following additional criterias; formulation availability, breast feeding, tolerable toxicity, and bioavailability.  Refer to the transcript for the committee’s discussion of this question.