CBER Presentation
FDA Update: Regulation of Reproductive Establishments
AATB Annual Meeting
Sept. 2006
Martha A Wells, MPH
Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research (CBER), FDA
Applicable 1271 Requirements
- Registration and listing if the establishment performs any of the manufacturing functions and doesn't fit any 1271.15 exemptions
- Donor eligibility required for donors of semen and oocytes if anonymous or directed
- DE required for donors of embryos if oocyte or semen donor utilized
- DE recommended for donors of embryos if both gametes were from the sexually intimate partner GTPs - only
- 1271.150(c ) manufacturing arrangements
- 1271.155 exemptions and alternatives
- Inspections and enforcement
Registration and Listing
- 606 list reproductive HCT/Ps/2322 total HCT/P establishments
- Semen banks - 72 registered that list semen
- 68 indicate only semen
- 26 identified as probably cryobanks
- Rest appear to be associated with IVF clinics - probably andrology labs that store semen for procedures for intimate couples
- Note that AATB identified 39 semen banks for their survey
- Oocytes -13 establishments registered that only list oocytes (? If banks or only perform donor eligibility)
- Others on the web - not sure if they cryopreserve or just find donors
- IVF Clinics - 481 list embryo
Inspections and Enforcement
21 CFR Part 1271, Subpart F
- Required by regulation
- Frequency at Agency discretion
- Generally unannounced
- Performed by trained investigators from FDA's District Offices
- Investigator may take samples, review and copy records
- List of observations generated if practices are not in compliance
Focus for FDA Inspections - Reproductive Tissue Establishments
- Record review
- Donor eligibility determination -Screening and testing
- Standard operating procedure review
- For all steps in determining donor eligibility
- Focus on preventing circumstances that might increase risk of introduction, transmission, or spread of communicable disease
Enforcement Actions by FDA
- Can order establishment to recall, destroy or retain products
- Can take possession of and/or destroy the violative tissue/cells
- Can order establishment to cease manufacturing
- Other actions
- Untitled and warning letters
- Regulatory meeting with FDA
- Prosecution and fines
Relevant Publications
- Compliance Program 7341.002- Inspection of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
covers human tissue recovered after 5/25/2005) - Attachment H- Reproductive tissue
- Import Alert #57-19 "Importation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)" - 3/10/2006
- Prompt release of reproductive HCT/Ps
- Not applicable to reproductive HCT/Ps donated by a sexually intimate partner
- No FDA review at point of entry to verify compliance
FY06 Inspections to Date (7/31/06)
HCT/P | Repro | Semen Banks | ART Clinics | |
---|---|---|---|---|
TOTAL | 287 | 57 | 11 | 46 |
Observations (%) | 77 (26%) | 16 (28%) | 3 (27%) | 13 (28%) |
Inspectional Observations
- SOP for screening, testing were not established and maintained
- Procedures for all steps performed in the screening of donor eligibility of HCT/P donors were not followed
- Documentation of donor screening for communicable diseases was not maintained
- Eligibility of an HCT/P donor was not documented by a responsible person based on results of donor screening and testing.
More
- Donors were not screened by a review of relevant medical records for risk factors of communicable disease agents and diseases
- Abbreviated donor screening procedure was used for anonymous semen donors who had no complete donor screening procedure in the previous six months
- Communicable disease agent tests were not FDA licensed, approved or cleared donor screening tests
- Testing for communicable disease agents was not performed in accordance with the manufacturer's instructions
- Communicable disease testing is incomplete (CMV, HIV-2, Chlamydia not tested)
- Donor specimens used for testing of communicable disease agents were not collected at the appropriate time.
- Lack of ensuring that testing lab is compliant with tissue regs ( use FDA approved test kit, follow instructions.)
Relevant Issues/Interpretations
- Failure to register - 95 repro/ 368 total
- Improper testing of donors
- Use of diagnostic tests rather than donor screening tests
- NAT testing using pooled samples rather than individual test samples
- Distribution of gametes from donors residing in countries where there is a CJD/vCJD risk identified
Identified Issues to Address
- Embryo donation where a 3rd party gamete donor used - 1271.90(a)(4)
- Release of embryos where problems in donor eligibility
- Donor eligibility and gestational carriers.
- Release of HCT/Ps from CMV positive donors
CONTACT INFORMATION
Martha A. Wells, MPH
Chief, Human Tissues and Reproduction Branch
Division of Human Tissues, OCTGT
CBER/FDA
1401 Rockville Pike (HFM 775)
Rockville, MD 20852-1448
Martha.Wells@fda.hhs.gov
301-827-6106