OVERVIEW OF FDA’S PEDIATRIC ADVISORY COMMITTEE ACTIVITIES

1. Pediatric Advisory Committee June 29, 2005 Dianne Murphy, MD Director, Office of Pediatric Therapeutics OC, FDA OVERVIEW OF FDA’S PEDIATRIC ADVISORY COMMITTEE ACTIVITIES

2. Review of Pediatric Expert Panel Activities: An Evolving Process • Pediatric Advisory Subcommittee of the Anti-infectives Advisory Committee- 1999 • Cadre of Ethicists who supplemented the Pediatric Advisory Subcommittee for specific ethical issues • Full Pediatric Advisory Committee- 2004 • Pediatric Ethics Subcommittee- 2004 • Re-evaluation of 1-year post-exclusivity safety reporting- February 2005

3. Ethical Issues • Pediatric Advisory Subcommittee Meetings have addressed: • Patients vs. subjects in pediatric trials (11/15/99) • Placebo controlled trials (9/11/00) • Vulnerable pediatric populations (4/24/01)

4. Pediatric Ethical IssuesSubpart D • September 2004: Effects of single dose Dextroamphetamine in ADHD and functional imaging • June 2005: Precursor Preference in Surfactant Synthesis of Newborns

5. Prior Peds AdvisorySubcommittee Discussions • November 1999: Issues regarding a Pediatric Drug Development Program for the Treatment of Insomnia • September 2000: Pediatric Psychotropic Drug Use Issues • April 2001: Treatment of Chronic Hepatitis C in Children

6. Prior Peds Advisory Subcommittee Discussion (cont.) • March 2003: Development of Antiretroviral Drugs in HIV-Infected and HIV-Exposed Neonates Younger than four weeks of age • June 2003: Current Epidemiology and Therapeutic Interventions Relevant to Hyperbilirubinemia in the Term and Near-Term Newborn • June 2002: Reflux disease; GERD-Template

7. Prior Peds Advisory Subcommittee Discussion (cont.) • February 2004: Use of Imaging Drugs in conjunction with cardiac imaging procedures in the pediatric population Suicidality in clinical trials for anti-depressant drugs in pediatric patients: the issues and the approach.

8. Prior Peds Advisory Committee Discussion (cont.) • October 2003: Clinical Risk Management of HPA Axis Suppression in Children with Atopic Dermatitis being treated with Topical Corticosteroids Tracking Cancer Risk among Children with Atopic Dermatitis who are treated with Topical Calcineurin Inhibitors

9. Prior Peds Advisory Committee Discussion (cont.) • June 2004: Safety report update: SSRI’s and the Neonatal withdrawal syndrome and Congenital Eye Malformations • September 2004: First full Pediatric Advisory Committee -- Suicidality in clinical trials for anti-depressant drugs in pediatric patients

10. Prior Peds Advisory Committee Discussion (cont.) • February 2005: Discussion of approach to improving BPCA safety reporting to the pediatric advisory committee • February 2005: Potential cancer risk in children from use of topical calcineurin inhibitors

11. Tamoxifen Quinapril Paroxetine Nefazodone Citalopram Pravastatin Vinorelbine Sertraline Oxybutynin Atorvastatin Simvastatin Busulfan Cetirizine Losartan 1-Year Post-ExclusivityReporting of Adverse EventsJune & October, 2003; February 2004

12. Topotecan Temozolomide Venlafaxine Moxifloxacin Ciprofloxacin Fosinopril Fexofenadine Fentanyl 1-Year Post-ExclusivityReporting of Adverse EventsJune 2004

13. Budesonide Desloratadine Fluticasone Ofloxacin Fludarabine Alendronate Benazepril Atovaquone/proguanil Esmolol Nelfinavir Orlistat Glyburide/metformin 1-Year Post-Exclusivity ReportingSeptember 2004 and February 2005

14. Ortho Tri-Cyclen- Norgestimate/ ethinyl estradiol Detrol and Detrol LA –Tolterodine tartrate Cipro –Ciprofloxacin Zemplar-Paricalcitol Zomig-Zolmitriptan Trusopt -Dorzolamide Arava – Leflunomide Concerta – OROS Methylphenidate 1-Year Post-ExclusivityReporting of Adverse EventsJune 2005

15. Summary: 1999 to June 2005 Pediatric Advisory Panels for either Ethical or Scientific Discussions: 19 Pediatric Advisory Panels to review adverse events for Exclusivity: 7 Products Reviewed for Adverse Events under BPCA mandate : 42 New safety information identified for almost a dozen products used to treat children. Examples are: antidepressants, pain patches, products for treatment of asthma

16. Evolving Process for Safety Reporting: BPCA 1-year Exclusivity • Committee will continue to receive ALL of the written reviews: ODS Adverse Event and Use Reviews Exclusivity Studies ( Medical and Pharmacology Reviews) Pediatric Division Slides Labeling

17. Evolving Process: Cont’d • FDA will provide an extensive assessment of products with possible new or increased safety signals. This may include additional information from both FDA and external experts. • FDA will provide a brief oral summary for the Committee on products with no new or less concerning safety signals and will state why it has come to the conclusion this approach is adequate.

18. Evolving Process: Cont’d • Today and tomorrow the Committee will have the opportunity to review products which fit into the above categories and a few products which fell in between these categories.

19. FDA’s Pediatric Advisory Experts Job very well done! But there is much more to come. Upcoming Issues: Obesity and therapeutic interventions More Ethical issues involving Trial Design Thank you