History Form Pediatric Office - PowerPoint

							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
                            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   2
                         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   3
                    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       4
Childhood Cancer Mortality 1975-2003




FDAAA: ODAC Pediatric Subcommittee April 08   5
 BPCA 2007




FDAAA: ODAC Pediatric Subcommittee April 08   6
              Improvements to BPCA
         BPCA 2007                                     BPCA 2003
• Pediatric Subcommittee of                 • Clarified role of the Pediatric
  the Oncologic Drugs                         Subcommittee of the Oncologic
                                              Drugs Advisory Committee
  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       • Previous priority list was for
  “pediatric therapeutics” not   off patent drugs only
  just drugs

        FDAAA: ODAC Pediatric Subcommittee April 08                    7
       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



    FDAAA: ODAC Pediatric Subcommittee April 08   8
     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   9
        Improvements to BPCA (cont)
           BPCA 2007                                      BPCA 2003
• Drugs                                        • Drugs
• Studies voluntary                            • Studies voluntary
• Studies on entire active moiety              • Studies on entire active moiety

• May include on & off label                   • Had to choose between on or
  indications                                    off label indication
• WR may be issued for orphan                  • WR may be issued for orphan
  indications                                    indications

• Preclinical studies may be                   • Only includes studies in
  requested                                      pediatrics
• Priority review for all                      • Priority Review supplements
  applications                                   only

        FDAAA: ODAC Pediatric Subcommittee April 08                      10
                   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         11
       Improvements to BPCA (cont)
          BPCA 2007                                     BPCA 2003
• All adverse events must be                • No requirement to submit adverse
  submitted with application                  events
• 6 months to review studies and            • 3 months to review studies and
  determine if terms of WR met                determine if terms of WR met
• Must have 9 months of                     • Could submit on day of patent
  exclusivity at time of                      expiration
  determination
• Written requests become                   • Written request confidential
  public
• Studies must be added to label            • Labeling not required
• Full reviews posted                       • Summaries of reviews posted
• Adverse events review for peds            • Adverse events reviewed for peds

                   Sunset for PREA and BPCA Oct 1, 2012
       FDAAA: ODAC Pediatric Subcommittee April 08                      12
                                 PREA 2007




FDAAA: ODAC Pediatric Subcommittee April 08   13
       Improvements to PREA
                 basics remain the same
        PREA 2007                                     PREA 2003
•   Drugs and biologics                      •    Drugs and biologics
•   Studies mandatory                        •    Studies mandatory
•   Studies for orphan                       •    Studies for orphan
    indications exempt                            indications exempt
•   Required studies only on                 •    Required studies only on
    drug/ indication under                        drug/ indication under
    review                                        review




    FDAAA: ODAC Pediatric Subcommittee April 08                        14
 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         15
              Application of PREA

• Indications that are likely to be studied
  under PREA
  – Leukemia/Lymphoma
  – Supportive care
       • Pegfilgrastim




  FDAAA: ODAC Pediatric Subcommittee April 08   16
   Improvements to PREA (con’t)
         PREA 2007                                   PREA 2003
• Age appropriate formulation                • Age appropriate
  required                                     formulation required
• Study results must be
  included in labeling
• Full reviews posted
• Pediatric adverse events
  reviewed and presented to
  PAC


                  Sunset for PREA and BPCA Oct 1, 2012

      FDAAA: ODAC Pediatric Subcommittee April 08                     17
                        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   18