CBER Presentation

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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

 
Updated: March 13, 2007