CBER Presentation

Printable Version

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

 
Updated: November 9, 2006