1. Pediatric Advisory Committee: Overview of Role and Evolution of Process Dr. Dianne Murphy Director, Office of Pediatric Therapeutics, OC, FDA November 16 th, 2006

2. Section 17 : The Best Pharmaceuticals for Children Act Drugs with Pediatric Market Exclusivity Drugs with Pediatric Market Exclusivity (1) In General.-During the 1-year beginning on the date on which a drug receives a period of market exclusivity under 505A Of the FD&C Act, any report of an adverse event regarding the drug that the Secretary of HHS receives shall be referred to the Office of Pediatric Therapeutics. In considering the report, the Director of such Office shall provide the review of the report by the PAC, including obtaining any recommendations of such Committee regarding whether the Secretary should take action under the FD&C Act in response to the report.

3. Section 5: BPCA Timely Labeling Changes for Drugs Granted Exclusivity (2) Dispute Resolution (2) Dispute Resolution (A) Request for Labeling Change and Failure to Agree.- (A) Request for Labeling Change and Failure to Agree.- Basically, if labeling is the only open issue for final action, no later than 180 days after submission of the application- (ii) if the sponsor of the application does not agree to make the labeling change requested by the Commissioner, the Commissioner shall refer the matter to the PAC. The PAC has 90 days to review and make recommendations. (ii) if the sponsor of the application does not agree to make the labeling change requested by the Commissioner, the Commissioner shall refer the matter to the PAC. The PAC has 90 days to review and make recommendations. We have not had to use this Section of the BPCA though we have told sponsors we were going this route and resolution was reached.

4. Evolution of Process DATABASE ISSUES: DATABASE ISSUES: -Dr. Rosemary Johann-Liang will be reviewing for you the limitations and strengths of AERS and other databases available to FDA; there have been some changes -We have no Active Surveillance pediatric program for AE’s related to drugs; there are limited data in this area -The PAC has expressed the need for a denominator and better context in relation to the reporting of adverse events REPORTING PRACTICES: REPORTING PRACTICES: -The PAC has stated they do not need to see all AE’s but definitely wanted to see all deaths and serious adverse events

5. Response to Requests of PAC Reviews no longer concentrate on the top 20 adverse events. Reviews no longer concentrate on the top 20 adverse events. Reviews do focus on deaths and serious AE’s. If required to provide a better understanding of what is happening, AE’s not only from the 1 year post exclusivity but from all years since marketing are presented. This includes integration of knowledge about what is occurring with adults when this information is thought to be relevant. Reviews do focus on deaths and serious AE’s. If required to provide a better understanding of what is happening, AE’s not only from the 1 year post exclusivity but from all years since marketing are presented. This includes integration of knowledge about what is occurring with adults when this information is thought to be relevant.

6. Response to PAC The pediatric trials conducted for pediatric exclusivity are provided to and reviewed for the PAC. This is an effort to provide the context of safety reporting during a controlled trial and to provide information on possible benefit(s) to be derived from use of the product. The pediatric trials conducted for pediatric exclusivity are provided to and reviewed for the PAC. This is an effort to provide the context of safety reporting during a controlled trial and to provide information on possible benefit(s) to be derived from use of the product.

7. Response to PAC Presentations are classified in 3 ways to permit focusing on the more interesting or controversial products. Presentations are classified in 3 ways to permit focusing on the more interesting or controversial products. Abbreviated, Standard & In-depth Committee receives the same complete package for all new exclusivity products, irrespective of the type of presentation. Committee receives the same complete package for all new exclusivity products, irrespective of the type of presentation. Follow-up reviews are provided in response to the Committee’s request Follow-up reviews are provided in response to the Committee’s request

8. 1-Year Post Pediatric Exclusivity Safety Reviews Status - to 11/06 Dates: June 2003 - November 2006 # of PAC meetings: 10 # of PAC meetings: 10 # of 1 st time Reviewed Drugs Total: 65 # of 1 st time Reviewed Drugs Total: 65 # of Committee Requested Follow-ups: 6 # of Committee Requested Follow-ups: 6 In-depth/Full PAC Reviews: 9 In-depth/Full PAC Reviews: 9 Drug Categories: 15 Drug Categories: 15 Drug Usage Estimates: Widely variable Drug Usage Estimates: Widely variable

9. Drug Categories: No./group GI: gastric; I: immunologic; R: reproductive; Rh: rheumatologic; H: hematologic; Pa: pain; U: urologic; N: neurologic; O: ophthalmologic; AP: allergy/pulmonary M: metabolic; AM: anti-microbial; P: psychiatric; CR: cardiorenal; Oc: oncologic

10. Today’s Activities Largest number of products (16) we have ever tried to review in one meeting. Largest number of products (16) we have ever tried to review in one meeting. There are 11 new exclusivity products and 5 PAC requested product updates. There are 11 new exclusivity products and 5 PAC requested product updates. 8 of the products will have Abbreviated presentations; the Committee receives the exact same complete package for all new products irrespective of the presentation. 8 of the products will have Abbreviated presentations; the Committee receives the exact same complete package for all new products irrespective of the presentation. Some products are in the midst of active reviews and the approach the agency is taking is being provided. For these we are providing information more than asking a question. Some products are in the midst of active reviews and the approach the agency is taking is being provided. For these we are providing information more than asking a question. Some products will have completed reviews and the Agency will be asking if the Committee is in agreement with returning these products to routine review. Some products will have completed reviews and the Agency will be asking if the Committee is in agreement with returning these products to routine review.