CBER Presentation
Guidance for Industry: Certain Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Recovered From Donors Who Were Tested For Communicable Diseases Using Pooled Specimens or Diagnostic Tests
Martha A Wells, MPH
Division of Human Tissues
OCTGT, CBER, FDA
Pharma Conference HCT/P Meeting
January 24, 2007
San Antonio, TX
Introduction
- Guidance issued January 24, 2007 for immediate implementation
- Certain HCT/Ps
- Hematopoietic stem cells
- Reproductive cells and tissues
- Pertains to those HCT/Ps recovered on or after May 25, 2005 and within 30 days of FR notice
Background
- Donor Screening and Testing became effective May 25, 2005 (21 CFR Part 1271, Subpart C)
- Since learned that some testing laboratories have tested HCT/Ps inconsistent with manufacturer's instructions for the tests
- Pooled NAT testing (HCT/P donors must be tested using individual NAT)
- Diagnostic vs. screening (HCT/P donors must be tested with donor screening tests)
- Both pooled and diagnostic tests are less sensitive and have potential for introducing additional risk of communicable disease transmission
Investigation & Corrective Actions
- Identify, quarantine, and do not distribute all HCT/Ps from such donors that are in inventory
- Identify all HCT/Ps from such donors that were distributed
- In-house testing
- Investigate, identify HCT/Ps and report those affected in deviation report (21 CFR 1271.350(b)); or
- Testing under contract/agreement
- Laboratory must notify affected HCT/P establishments (21 CFR 1271.160(b)(2)(ii))
- Establishment should investigate, identify HCT/Ps and report those affected in deviation report
- Appropriate corrective actions must be taken (21 CFR 1271.160(b)(2)&(3))
Do I Need to Submit a HCT/P Deviation Report?
- Must submit deviation reports related to core CGTP requirements
- Donor testing is a core CGTP requirement
- Deviations are only reported on HCT/Ps that have already been distributed
- Establishment that distributes HCT/Ps related to deficiency in donor testing must report the deviation
- Required:
- Hematopoietic stem cells derived from peripheral or cord blood, distributed for use in first or second-degree blood relatives (related allogeneic)
- -Per 21 CFR 1271.350(b)
- Not Required
- Reproductive HCT/Ps
- Reporting requirements do not apply (Subpart D and E do not apply to reproductive HCT/Ps at this time)
HCT/P Deviation Reports
Not Required For Hematopoietic Stem Cells
- Distributed for autologous use
- Donor testing not required under section 361 of PHS Act
- Distributed for use in unrelated allogeneic recipients
- Regulated under section 351 of PHS Act, when licensed, report under 21 CFR 600.14
- If under IND, amendment should be submitted to file (21 CFR 312.31)
How Do I Submit a Deviation Report?
- One report for all affected HCT/Ps
- Use Form FDA 3486 (Biological Product Deviation Reports)
- Electronically as directed on web at http://www.fda.gov/cber/biodev/biodev.htm
- By mail to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research (HFM-600), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448
What Information Must the Deviation Report Contain?
- Description of HCT/P deviation
- Information relevant to the event or manufacture of the HCT/P involved
- All follow-up action that has been or will be taken in response to the HCT/P deviation (21 CFR 1271.350(b)(2))
HCT/Ps in Inventory
When possible:
- Donor specimens originally pooled for NAT testing should be retested individually; or
- Donor specimens originally tested using diagnostic tests should be retested using the appropriate FDA approved screening tests
- Specimens used in retesting should be collected within the specified time frames when possible (21 CFR 1271.80(b))
- If these time frames have elapsed retesting should still be performed
Hematopoietic Stem Cell Donors (Other than Autologous)
- Should be retested
- If results are negative or non reactive FDA intends to exercise enforcement discretion
- If retesting is not feasible FDA intends to exercise enforcement discretion provided that:
- Accompanying records state the reason retesting could not be performed; file kept on record
- Establishment documents that recipient's physician was notified of results
- Labeling must include "WARNING: Advise patient of communicable disease risks"
Reproductive HCT/P Donors (Cryopreserved Embryos)
- Formed for sexually intimate partners using a third party gamete donor
- If the third party gamete donor is retested and results are negative or non reactive FDA intends to exercise enforcement discretion
- If retesting is not feasible FDA intends to exercise enforcement discretion provided that:
- Accompanying records state the reason retesting could not be performed; file kept on record
- Establishment documents that recipient's physician was notified of results
- Labeling must include "WARNING: Advise patient of communicable disease risks"
Reproductive HCT/P donors (Cryopreserved Semen or Oocytes)
- Directed or anonymous
- If results are negative or non reactive FDA intends to exercise enforcement discretion
- If retesting is not feasible, HCT/Ps must not be distributed
Required Labeling for Distribution Without Retesting
- "WARNING: Advise patient of communicable disease risks"
- Include original pooled NAT test results and name of test in the summary of records along with qualifier - "not performed according to manufacturer's instructions"; or
- Include diagnostic test results and name of test in the summary of records along with qualifier - "diagnostic tests used instead of donor screening tests"
Contact Information
Martha A. Wells, MPH
1401 Rockville Pike, HFM-775
Rockville, MD 20852
Martha.wells@fda.hhs.gov
301-827-6106
FAX b301-827-2844