FDA Regulation of Combination Products

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FDA Regulation of Combination Products

• Barbara D. Boyan, Ph.D.
• American Academy of Orthopaedic Surgeons
• Professor and Deputy Director for Research for
  the Georgia Tech/Emory Center for the Engineering
  of Living Tissues
• November 25, 2002

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• AAOS has a commitment to quality care and patient
  safety initiatives.
• AAOS suggestions for the regulation of
  combination products.

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Decrease regulatory burden

• Combination products provide unique challenges to
  FDA- under current scheme it will be difficult to
  get products to market.
• Large start up capital
• Tissue-engineered products have a smaller
  potential market (except cartilage subs.)
• 2 TE companies filed for bankruptcy- regulatory
  problems
• Coordinate with CMS

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Team Approach

• Both in-house and 3rd party reviews
• Multidisciplinary Coordination
• Materials Scientist
• Biologist
• Clinician
• Engineer
• Odd number of reviewers
• Sponsor should have the opportunity to provide
  additional information with the FDA Homework
  packet

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Focus more on safety than effectiveness

• Effectiveness could take 10-20 years in
  orthopaedic products.
• Single and consistent regulatory pathway over
  time.
• For mode of action in bone products-

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Osteogenesis

• Cellular elements, either from the host or from
  the TE product, which survive transplantation and
  synthesize new bone at recipient site.

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Osteoinduction

• New bone realized through the active recruitment
  of host mesenchymal stem cells from the
  surrounding tissue, which differentiate into
  bone-forming osteoblasts or form bone by
  endochondral ossification. Facilitated by
  presence of growth factors, principally BMPs.

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Osteoconduction

• The facilitation of blood-vessel incursion and
  new-bone formation into a defined trellis
  structure

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Use foresight in preparing for global
harmonization

• CBER should work with the TEMPS subcommittees of
  ASTM on tissue standards
• Several standards have already been finalized
• Encourage global harmonization efforts

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Create Advisory Panel

• Consider the establishment of an FDA Advisory
  Panel with biological and device expertise.
• FDA biologist and engineer reviewers should work
  side-by-side during the review process.
• The review should consider method of use as well
  as primary mode of action.
• TEMPs are not the same as drugs or biologics.

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Adverse Event Reporting

• Patient Safety movement
• AAOS supports legislation introduced into the
  106th 107th Congress that will encourage a
  nonpunitive approach for reporting that ensures
  appropriate confidentiality peer review
  protections
• AAOS encourages the finalization of the Donor
  Suitability Good Tissue Practice regulations

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Adverse Event Reporting (continued)

• AAOS suggests that FDA work with experienced
  clinicians to define the term adverse event for
  procedures.
• FDAs interpretations of adverse events are too
  broad.
• For combination products, users will not readily
  understand the regulatory class- coordinate
  reporting within FDA.
• FDA mechanism is not interactive.

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General Principles

• Consistency
• Predictability
• FDA Accountability
• Dont change rules midstream- very difficult for
  companies to have the regulatory status changed.
• One application

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AAOS looks forward to working with the FDA on
bringing new products to market and ensuring
patient safety.
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AAOS appreciates the opportunity to participate
in this open public meeting.

• Thank You