Food and Drug Administration Amendments Act of 2007 Reauthorization of Pediatric Initiatives

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

2. 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 FDAAA: ODAC Pediatric Subcommittee April 08

3. Objectives • Brief Overview of Pediatric History at FDA • 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) FDAAA: ODAC Pediatric Subcommittee April 08

4. FDA and Pediatrics • 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) FDAAA: ODAC Pediatric Subcommittee April 08

5. Childhood Cancer Mortality 1975-2003 FDAAA: ODAC Pediatric Subcommittee April 08

6. BPCA 2007 FDAAA: ODAC Pediatric Subcommittee April 08

7. 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 • Previouspriority list was for off patent drugs only FDAAA: ODAC Pediatric Subcommittee April 08

8. Internal Review CommitteePediatric Review Committee (PeRC) • Established to provide oversight to required and requested pediatric activities within CBER/CDER • Expertise mandated • Pediatric Oncology is represented FDAAA: ODAC Pediatric Subcommittee April 08

9. 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 FDAAA: ODAC Pediatric Subcommittee April 08

10. 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 FDAAA: ODAC Pediatric Subcommittee April 08

11. 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 FDAAA: ODAC Pediatric Subcommittee April 08

12. Improvements to BPCA (cont) BPCA 2007 • All adverse events must be submitted with application • 6 months to review studies and determine if terms of WR met • Must have 9 months of exclusivity at time of determination • Written requests become public • Studies must be added to label • Full 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 FDAAA: ODAC Pediatric Subcommittee April 08

13. PREA 2007 FDAAA: ODAC Pediatric Subcommittee April 08

14. Improvements to PREAbasics remain the same PREA 2007 • Drugs and biologics • Studies mandatory • Studies for orphan indications exempt • Required 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 review FDAAA: ODAC Pediatric Subcommittee April 08

15. 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 FDAAA: ODAC Pediatric Subcommittee April 08

16. Application of PREA • Indications that are likely to be studied under PREA • Leukemia/Lymphoma • Supportive care • Pegfilgrastim FDAAA: ODAC Pediatric Subcommittee April 08

17. Improvements to PREA (con’t) PREA 2007 • Age appropriate formulation required • Study results must be included in labeling • Full reviews posted • Pediatric adverse events reviewed and presented to PAC PREA 2003 • Age appropriate formulation required Sunset for PREA and BPCA Oct 1, 2012 FDAAA: ODAC Pediatric Subcommittee April 08

18. 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 FDAAA: ODAC Pediatric Subcommittee April 08