The Office of Orphan Products Development Grant Program Janet

							   The Office of Orphan
Products Development Grant
         Program
             Janet Whitley, Ph.D.
   Office of Orphan Products Development
        Food and Drug Administration


         FDA Office of Orphan Products Development
  Office of Orphan Products
         Development
1. Orphan Drug Designation
     Drugs/biologics
2. Orphan Products Grants
     Drugs, Biologics, Devices, Foods
3. Humanitarian Use Device Designation
     Humanitarian Device Exemption




          FDA Office of Orphan Products Development
    Grant Program Objective
   To fund clinical research that will accelerate or
    assist in the approval of products which
    demonstrate promise for rare diseases/disorders.

       Basic Research Funding




               FDA Office of Orphan Products Development
     Grant Program Objective
   To fund studies leading to publications in peer-
    reviewed journals.
   Supports mainly Phase 1 and 2 trials
      Funding may be used to cover portion of larger

       trial
      Importance of funding




                 FDA Office of Orphan Products Development
     Grant Support for Investigation
       of Rare Disease Treatment
   Awarded to both academic and industry-sponsored
    research
   FDA funds approximately 20-30 new grants per year
   Provides $150,000 to $300,000 in direct costs per year -
    - up to 3 years




                  FDA Office of Orphan Products Development
                 OPD Grant
   >50/400 grants awarded to industry sponsors
   Grantees are US and abroad
   Orphan Designation not required
   New drug/product or new use of approved product




            FDA Office of Orphan Products Development
                     Funding
FY 2003:
  101 responsive applications
  15 received funding
Currently: 65 Active grants




           FDA Office of Orphan Products Development
FDA Office of Orphan Products Development
    Orphan Grant Application
            Process
   Issue Federal Register notice (RFA).
   Meets program review criteria.
   Review panels:
      Ad hoc panels of outside experts review
       scientific merit
      Regulatory review

   Prepare summary statements.
   Present to Advisory Council.
   Advise - Fund - Monitor.

                FDA Office of Orphan Products Development
    Grant review: Responsive to Program
              Review Criteria?

   Study is a clinical trial.
   Prevalence is fewer than 200,000 U.S. patients.
   Study must be performed under an active
    IND/IDE (except medical foods).
   Budget is within limits.
   Availability of sufficient product.



                 FDA Office of Orphan Products Development
           Grant review: Scientific and
               Technical Merit?

   Soundness of the rationale
   Appropriateness of study design
   Statistical justification for proposed enrollment -
    POWER
   Potential for patient accrual
   Qualifications of investigator & support staff




                  FDA Office of Orphan Products Development
       Grant review: Scientific and
           Technical Merit?

   Adequacy of resources and environment
   Budget Justification
   Informed consent documents and IRB approval
   Potential for completion of study within stated
    time and budget




               FDA Office of Orphan Products Development
          Not funded because:
   Non-responsive application
   Overall quality of application – clarity and detail
   Scientific merit
      Preliminary data, poor study design, weak rationale,
       sketchy analysis plan
   Compelling nature of study
   Resubmissions that don’t follow/address panel’s
    suggestions/concerns
   Feasibility
      Number of patients, drug supply, too much to do in too
       little time
                FDA Office of Orphan Products Development
          Management of Funded
                Grants
   Assignment to Project Officer
     Liaison between grantee and FDA review division.

     Enrollment goals/achievement.

     Quarterly progress updates.

     Site visits to assure grant compliance.

     Sponsor acquisition.

   Continuation funding dependent on progress.


                  FDA Office of Orphan Products Development
               Grant Program
              Accomplishments
   36 product approvals supported by OPD
    grants
   Hundreds of publications, abstracts, and
    presentations have been produced as a result of
    orphan product grant studies.



                FDA Office of Orphan Products Development
          FY2005 Request for
          Applications (RFA)

   Federal Register Announcement
     August

     OPD website

   Application Due Dates:
       October 2004
       April 2005


                FDA Office of Orphan Products Development
 Responsibilities of the Office of
 Orphan Products Development
in Evaluating Humanitarian Use
        Devices (HUD)


        FDA Office of Orphan Products Development
                   Background
   Makers of new medical devices ordinarily must show
    that products are safe and effective.
   For humanitarian purposes, FDA will approve devices
    limited to use only in rare diseases/conditions if
    manufacturers demonstrate the safety and probable
    benefit to patients.




                  FDA Office of Orphan Products Development
                HUDs vs HDEs

Two-step process:
1 – HUD: FDA will consider the use and size of the
    proposed patient population

2- HDE: Device is evaluated for safety and probable
   benefit in the CDRH Office of Device Evaluation.



                FDA Office of Orphan Products Development
        What is a HUD?
   A Humanitarian Use Device (HUD) is a
    medical device intended to benefit patients
    in the diagnosis and/or treatment of a
    disease or condition that affects or is
    manifested in fewer than 4,000 patients per
    year in the United States.



            FDA Office of Orphan Products Development
                What is an HDE?
   A Humanitarian Device Exemption (HDE) is a
    provision that exempts sponsors of devices for orphan
    diseases from the effectiveness requirements of the
    medical device law, provided the device meets safety
    conditions and will not expose patients to significant
    or unreasonable risk.




                   FDA Office of Orphan Products Development
Diagnostic/prevention devices
   Sponsor must demonstrate that the less than 4,000
    patients/year would be subjected to diagnosis by
    the device in the U.S.
      PKU screening in newborns

         Rare disease

         4,000,000 newborns screened yearly




             FDA Office of Orphan Products Development
          How is a HUD Review
              Performed?

   Evaluate rationale and population.
   Approve, disapprove, or request additional
    information.
   Review clock: 45 days from receipt of
    request/supplemtent.




                  FDA Office of Orphan Products Development
    Refusal to approve HUD
             request
   Population >4,000
      OPD consults with review division re: use

   Sponsor points to approved HUD population
   Medically plausible basis to limit the use of a
    product to a particular population
      Usually risk-to-benefit

      Feasibility of assay/rationale

      Cost not a factor (not in regs)



             FDA Office of Orphan Products Development
                        Statistics
Since October 1996
   138 requests received.
   96 devices designated as HUDs by OPD.
   36 devices approved as HDEs by CDRH.




               FDA Office of Orphan Products Development
       Contact Information
   Website: www.fda.gov/orphan
      Information on HUDs, Orphan Designation,

       and grants (RFA)
   Phone: 301-827-3666

 Snail:      5600 Fishers Lane
              HF-35, Room 6A55
              Rockville, MD 20857

            FDA Office of Orphan Products Development