Open Public Meeting - Human Bone Allograft August 2, 2000 - Slide Presentation Manipulation and Homologous Use in Spine and Other Orthopedic Reconstruction Ruth Solomon, M.D. CBER, FDA PROPOSED APPROACH TO THE REGULATION OF CELLULAR AND TISSUE-BASED PRODUCTS February 28, 1997 PURPOSE comprehensive approach wide spectrum of products protect public health permit innovations without unnecessary burden therefore--TIERED; RISK-BASED CELLS/TISSUES INCLUDED ALREADY FDA-REGULATED: musculoskeletal tissue; skin; ocular tissue [21 CFR 1270--Final Rule] human heart valves; dura mater [medical devices] somatic cell and gene therapy products; manipulated bone marrow stem cells [licensed biological products] combination products [21 CFR , Part 3] CELLS/ TISSUES INCLUDED NOT CURRENTLY FDA-REGULATED: hematopoietic stem cells from peripheral blood and cord blood reproductive cells/tissue NOT INCLUDED vascularized human organs whole blood/blood components/blood derivatives secreted or extracted products (human milk, collagen, cell factors) minimally manipulated bone marrow ancillary products used in manufacture cell, tissues, organs from animals in vitro diagnostic products PUBLIC HEALTH AND REGULATORY CONCERNS Transmission of communicable disease Processing controls to prevent contamination and preserve product integrity and function Clinical safety and efficacy Promotional claims/Labeling Monitoring and education of industry TRANSMISSION OF COMMUNICABLE DISEASE Surgery (unbanked)---no requirement Autologous (banked)--recommend donor testing and screening Reproductive cells/tissue from sexually-intimate partners--recommend donor testing and screening Allogeneic --require donor testing and screening PROCESSING CONTROL Surgery (unbanked)--no requirement IF product is regulated solely under section 361 of PHS Act--GTP IF product is regulated under FDC Act and/or section 351 of PHS Act--GTP and GMP/QS CLINICAL SAFETY/EFFICACY IF product is regulated solely under section 361 of PHS Act--no submission to FDA; no premarket approval required IF product is regulated under FDC Act and/or section 351 of PHS Act--submission to FDA [IND; IDE; BLA; PMA; 510(k)] and premarket approval required PROMOTION AND LABELING Surgery (unbanked)--no requirement IF product is regulated solely under section 361 of PHS Act--no submission to FDA, but labeling must be clear, accurate, balanced, and non-misleading IF product is regulated under FDC Act and/or section 351 of PHS Act--labeling submitted to FDA for approval IMPLEMENTATION OF PROPOSED APPROACH 3 PROPOSED RULES: Establishment Registration and Listing of Human Cellular and Tissue-based Products--63 FR 26744 May 14, 1998 Suitability Determination for Donors of Human Cellular and Tissue-based Products--64 FR 52696 Sept. 30, 1999 Current Good Tissue Practice (GTP); Inspection and Enforcement ESTABLISHMENT REGISTRATION AND LISTING Purpose and Scope Definitions Establishments subject to this part; criteria for regulation solely under section 361 of the PHS Act Criteria for regulation under FDC Act and/or section 351 of the PHS Act Establishments not required to comply with the requirements of this part 1271.3(e) Human cellular or tissue-based product A product containing or consisting of human cells or tissues intended for implantation, transplantation, infusion, or transfer into a human recipient not considered human cellular or tissue-based products (see previous slide) 1271.3(d) Homologous use- for replacement/supplementation 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; For cellular and nonstructural tissue-based products, occurs when the cells or tissue is used to perform the function(s) that it performs in the donor 1271.3(g) 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; For cells and nonstructural tissue, processing that does not alter the relevant biological characteristics of cells or tissue 1271.10 regulation solely under section 361 of the PHSA is minimally manipulated is not promoted or labeled for any use other than a homologous use is not combined with or modified by the addition of any component that is a drug or a device; and either does not have a systemic effect, or has a systemic effect and is for autologous, family-related allogeneic, or reproductive 1271.15 regulation under FDC Act and/or section 351 of PHS Act Is more than minimally manipulated is promoted or labeled for any use other than a homologous use is combined with or modified by the addition of any component that is a drug or a device has a systemic effect and is not for autologous, family-related allogeneic, or reproductive use ESTABLISHMENT REGISTRATION--PROCEDURES When to register and list How and where to register and list Information required for registration and listing Amendments to registration Assignment of a registration number Inspection of registration and product lists DONOR SUITABILITY Determination of donor suitability Records of donor suitability Quarantine Disposition of product from a donor determined to be unsuitable Donor screening Donor testing--general; specific Exceptions--recommended screening and testing; labeling requirements CURRENT GOOD TISSUE PRACTICE General; exemptions and alternatives Quality program Organization and Personnel; procedures Facilities; environmental control Equipment; supplies and reagents Process controls, changes and validation Labeling controls Storage; receipt, distribution Records; tracking; complaint file ADDITIONAL REQUIREMENTS; INSPECTION AND ENFORCEMENT Reporting Labeling and claims Inspections Imports Orders TISSUE REFERENCE GROUP (TRG) Established March '97; proposed approach CBER/CDRH/Ombudsman rep/ Exec sec single reference point for product-specific questions re: jurisdiction, policy, regulation makes recommendations to centers/OCMO proprietary information--not public if decision affects a class of products--guidance/revision of regulations SOP; annual update on CBER website

Updated April 9, 2001

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