American Academy of Orthopaedic Surgeons by Barbara D. Boyan, Ph.D.

Slide 1 - 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

Slide 2 -

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

Slide 3 - 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

Slide 4 - 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

Slide 5 - 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-

Slide 6 - Osteogenesis

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

Slide 7 - 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.

Slide 8 - Osteoconduction

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

Slide 9 - 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

Slide 10 - 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.

Slide 11 - 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

Slide 12 - Adverse Event Reporting (continued)

• AAOS suggests that FDA work with experienced clinicians to define the term “adverse event” for procedures.
• FDA’s 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.

Slide 13 - General Principles

• Consistency
• Predictability
• FDA Accountability
• Don’t change rules midstream- very difficult for companies to have the regulatory status changed.
• One application

Slide 14 -

AAOS looks forward to working with the FDA on bringing new products to market and ensuring patient safety.

Slide 15 -

AAOS appreciates the opportunity to participate in this open public meeting.

Thank You