1. Food and Drug Administration Amendments Act of 2007 Reauthorization of Pediatric Initiatives Lisa L. Mathis, M.D. Pediatric and Maternal Health Staff Office of New Drugs April 2008

2. FDAAA: ODAC Pediatric Subcommittee April 082 Acronyms BPCA – Best Pharmaceuticals for Children Act FDAAA – Food and Drug Administration Amendments Act PAC – Pediatric Advisory Committee PREA – Pediatric Research Equity Act WR – Written Request

3. FDAAA: ODAC Pediatric Subcommittee April 083 Objectives Brief Overview of Pediatric History at FDABrief Overview of Pediatric History at FDA Major changes to Title V: Best Pharmaceuticals for Children Act of 2007 (BPCA)Major changes to Title V: Best Pharmaceuticals for Children Act of 2007 (BPCA) Major changes to Title IV: Pediatric Research Equity Act of 2007 (PREA)Major changes to Title IV: Pediatric Research Equity Act of 2007 (PREA)

4. FDAAA: ODAC Pediatric Subcommittee April 084 1979 Labeling Requirement 1994 Pediatric Labeling Rule 1997 FDA Modernization Act (FDAMA) 1998 Pediatric Rule 2002 Best Pharmaceuticals for Children Act (BPCA) 2002 Pediatric Rule Enjoined 2003 Pediatric Research Equity Act (PREA) 2007 FDA Amendments Act of 2007 –Pediatric Medical Device Safety and Improvement Act –Pediatric Research Equity Act (PREA) –Best Pharmaceuticals for Children Act (BPCA) FDA and Pediatrics

5. FDAAA: ODAC Pediatric Subcommittee April 085 Childhood Cancer Mortality 1975-2003

6. FDAAA: ODAC Pediatric Subcommittee April 086 BPCA 2007

7. FDAAA: ODAC Pediatric Subcommittee April 087 Improvements to BPCA BPCA 2007 Pediatric Subcommittee of the Oncologic Drugs Advisory Committee –Extended Committee to 2012 –May make recommendations directly to the Internal Review Committee on the implementation of BPCA Expands role of NIH to “pediatric therapeutics” not just drugs BPCA 2003 Clarified role of the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee Previous priority list was for off patent drugs only

8. FDAAA: ODAC Pediatric Subcommittee April 088 Internal Review Committee Pediatric Review Committee (PeRC) Established to provide oversight to required and requested pediatric activities within CBER/CDER Expertise mandated Pediatric Oncology is represented

9. FDAAA: ODAC Pediatric Subcommittee April 089 National Institutes of Health Expanded role includes establishing a “List of Priority Issues in Pediatric Therapeutics” –Previously NIH was charged with a list of off patent drugs not eligible for market exclusivity –Expert meeting in June-July 2008 Law requires consideration of available information on drugs and biologics

10. FDAAA: ODAC Pediatric Subcommittee April 0810 Improvements to BPCA (cont) BPCA 2007 Drugs Studies voluntary Studies on entire active moiety May include on & off label indications WR may be issued for orphan indications Preclinical studies may be requested Priority review for all applications BPCA 2003 Drugs Studies voluntary Studies on entire active moiety Had to choose between on or off label indication WR may be issued for orphan indications Only includes studies in pediatrics Priority Review supplements only

11. FDAAA: ODAC Pediatric Subcommittee April 0811 Preclinical Studies Law states that pediatric studies and preclinical studies may be included in a Written Request –BPCA 2002 only allowed for the request of studies in the pediatric population –Could not previously require a preclinical study as a term of the WR Law does not allow for preclinical studies only

12. FDAAA: ODAC Pediatric Subcommittee April 0812 Improvements to BPCA (cont) BPCA 2007 All adverse events must be submitted with applicationAll adverse events must be submitted with application 6 months to review studies and determine if terms of WR met6 months to review studies and determine if terms of WR met Must have 9 months of exclusivity at time of determinationMust have 9 months of exclusivity at time of determination Written requests become publicWritten requests become public Studies must be added to labelStudies must be added to label Full reviews postedFull reviews posted Adverse events review for peds BPCA 2003 No requirement to submit adverse events 3 months to review studies and determine if terms of WR met Could submit on day of patent expiration Written request confidential Labeling not required Summaries of reviews posted Adverse events reviewed for peds Sunset for PREA and BPCA Oct 1, 2012

13. FDAAA: ODAC Pediatric Subcommittee April 0813 PREA 2007

14. FDAAA: ODAC Pediatric Subcommittee April 0814 Improvements to PREA basics remain the same PREA 2007 Drugs and biologics Studies mandatory Studies for orphan indications exempt Required studies only on drug/ indication under reviewRequired studies only on drug/ indication under review PREA 2003 Drugs and biologics Studies mandatory Studies for orphan indications exempt Required studies only on drug/ indication under reviewRequired studies only on drug/ indication under review

15. FDAAA: ODAC Pediatric Subcommittee April 0815 Required Studies Only on Drug/ Indication Under Review: Application of PREA Pediatric studies required and a pediatric assessment must be submitted for NDA/BLA or supplements with –New active ingredient –New indication –New dosage form –New dosing regimen or –New route of administration Applies only to the indication included in the submission –Limits scope of required studies

16. FDAAA: ODAC Pediatric Subcommittee April 0816 Application of PREA Indications that are likely to be studied under PREA –Leukemia/Lymphoma –Supportive care Pegfilgrastim

17. FDAAA: ODAC Pediatric Subcommittee April 0817 Improvements to PREA (con’t) PREA 2007 Age appropriate formulation requiredAge appropriate formulation required Study results must be included in labelingStudy results must be included in labeling Full reviews postedFull reviews posted Pediatric adverse events reviewed and presented to PACPediatric adverse events reviewed and presented to PAC PREA 2003 Age appropriate formulation required Sunset for PREA and BPCA Oct 1, 2012

18. FDAAA: ODAC Pediatric Subcommittee April 0818 Conclusions Reauthorization provides continued incentive and requirement for pediatric studies and pediatric oncology still plays a major role in the new legislation Despite progress in pediatric oncology drug development specifically, improvements in survival rates have slowed Scientists in every sector must collaborate using tools available to them to provide new opportunities for treatment We can use legislation to improve this collaboration