Open Public Meeting - Human Bone Allograft
August 2, 2000 - Slide Presentation
Summary
Ruth Solomon, M.D.
CBER, FDA
Notice of public meeting held August 2, 2000
- Purpose: to provide CBER and CDRH with information concerning the characteristics of bone products as they relate to the proposed definitions of "minimal manipulation" and "homologous use"
- Such information will be considered for possible future guidance to industry.
Four Sessions
- Background information: proposed approach, history of regulation as a tissue, history of regulation as a device, overview of comments to dockets of proposed rules
- Professional associations overview: bone processing (AATB); uses of bone allograft in spine repair (AAOS, AANS)
- Public discussion /comments
- Public discussion /comments
1. Which processing procedures applied to human bone allograft
fall within, or outside of, FDA's proposed definition for "minimal manipulation"?
Minimal manipulation
- For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue's utility for reconstruction, repair, or replacement
- Examples in preamble: cutting, grinding, shaping, soaking, sterilizing, lyophilizing, cryopreserving, freezing
Public Discussion/Comments on Manipulation
- eliminate this criterion
- re-propose the definition with more specificity and examples
- re-propose definitions for each product type
- pre-shaping/threading bone, whether in the tissue bank or in the operating room, does not alter its original relevant characteristics
- any process which does not alter the essential microstructural elements of the allograft is a "minimal" process
- the result of manipulation should be more important than the fact of manipulation
- validation to ensure that processing does not affect the product
- MMM--bone products modified by genes
2. Which uses of human bone allograft fall within, or outside of, FDA's proposed definition for "homologous use"?
Promotion or labeling for any use other than Homologous Use
- The use of a cellular or tissue-based product for replacement or supplementation and for structural tissue-based products, occurs when the tissue is used for the same basic function that it fulfills in its native state, in a location where such structural function normally occurs
Examples in preamble
- Homologous use claims--bone allograft from a long bone labeled for use in a vertebra; skin allograft from the arm labeled for use on the face
- Nonhomologous use claim--cartilage labeled for use in the submucosa of urinary bladder to change the angle of ureter
Public Discussion/Comments on Homologous Use
- eliminate this criterion
- re-propose the definition with more specificity and examples
- re-propose definitions for each product
- allograft used in the same manner as autograft ("gold standard") is homologous
- same basic characteristics (instead of "same basic functions")-support; lattice
- fusing bone to bone is homologous (location doesn't matter); not trying to replace disc
- long history of safe and effective use of allograft for spinal fusion; much literature
- use of bone anywhere in the skeleton (or in any orthopedic procedure) is homologous use
3. What risks to health have been identified and characterized for human bone allograft products?
Public Discussion/Comments on Risks
- no risk or significant public health issues
- no mechanism to report graft failures
- difficult to analyze why a graft failed--graft or surgical technique
- evaluate risk by looking at alternatives--autograft (10-20% morbidity vs. 2%) or metal graft (weakens over time)
- Risks include:
- infectious disease transmission
- biomechanical failure--collapse
- biologic potency failure--non-fusion
- immunologic risk--graft vs. host response
- standardized risk assessment--if significant new risk exists, then have additional reg.
4. What controls have been identified to adequately address the risk to health of human bone allograft products?
Public Discussion/Comments on Controls to address risks
- industry standards--ASTM, AATB
- quality systems--ISO 9001 certification: includes design control, risk assessment, complaint files, corrective action system
- peer-review of literature articles
- experience--many cases with no reports of collapse
5. What industry standards for bone allograft products are available, and what standards will be needed in the future?
Public Discussion/Comments on Industry Standards
- Existing Standards:
- AATB--manufacturing (processing) standards; standards aimed at infectious disease control--not all tissue banks are members; ? followed by all
- ASTM--TEMP standards--exist for metal implants--?allografts held to same stds.
- Standards Needed:
- standards aimed at performance
- standards for biologic activity/potency --standardized biologic assays
- standards for mechanical performance--standardized assays
- standards for processing; donor age/bone density
Perceived Disadvantages of Regulation as a Medical Device
- decreased patient access to treatment
- decreased availability/supply
- increased cost
- increased reliance on autografts or metal
- slowing of ongoing industry standards development
- interference with practice of medicine
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