HCT/P donors must meet specific eligibility criteria outlined by the FDA in 21 CFR 1271 Subpart C. The criteria are intended to ensure that the prospective HCT/P donor is healthy and the patient receives a safe product. The FDA requires that all HCT/P donors must be screened for relevant communicable disease agents or diseases (RCDADs) and that a determination of the donor's eligibility be made prior to product distribution. When the regulations (21 CFR 1271 Subpart C) were published, certain RCDADs were listed. New agents or diseases have been, or will be, identified by the FDA, usually through the publication of Guidance for Industry documents. The August 2007 FDA guidance document titled "Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products" contains overarching recommendations for compliance with the regulations for determining donor eligibility found in Subpart C.
Donor History Questionnaires have been developed by an AABB interorganizational task force to provide establishments with a standardized tool to screen donors. The task force developed these questionnaires based on current FDA regulations and guidance documents, and incorporated requirements of accrediting organizations (AABB and the Foundation for the Accreditation of Cellular Therapy) and the National Marrow Donor Program. FDA liaisons collaborated with the task force in the development of the questionnaires. The FDA does not mandate the use of any particular screening tool to fulfill the requirements set forth in Subpart C for screening donors for communicable disease risks.
Per FDA requirements, all HCT/P donors must be tested for the following infectious diseases: HIV, types 1 and 2; HBV; HCV; and Treponema pallidum. Viable leukocyte-rich HCT/P donors must be tested for HTLV, types 1 and 2, and CMV. In the case of reproductive HCT/Ps, donors who are not sexually intimate with the recipient must be tested for Chlamydia trachomatis and Neisseria gonorrhea. A donor who tests positive or reactive for CMV is not necessarily ineligible to donate HCT/Ps. The positive or reactive CMV test result should be communicated to the physician responsible for accepting the HCT/P.
Zika virus (ZIKV) emerged as a global public health threat in 2016 and was quickly identified as an RCDAD by FDA. A final guidance recommended screening potential donors of all HCT/Ps for risk factors associated with transmitting ZIKV. There is no currently approved ZIKV screening test for HCT/P donors. However, a screening test for ZIKV is available for blood products and HCT/Ps under IND.
West Nile virus (WNV) is another RCDAD that the FDA requires donors be screened for — see the guidance document for determining donor eligibility. A final guidance published in 2016 recommended establishments within the United States to perform nucleic acid test (NAT) screening on all HCT/P donors recovered from June 1st through October 31st and all year for establishments collecting HCT/Ps outside of the U.S.
HCT/P donors may be ineligible because of reactive test results. However, under the provisions of 21 CFR 1271.65, the product may be made available for 1) cases of urgent medical need as defined in 21 CFR 1271.3(u) — if no comparable HCT/P is available and the recipient is likely to suffer death or serious morbidity without the HCT/P; 2) allogeneic use in a first or second-degree blood relative; or 3) directed reproductive use.
The FDA maintains a list of assays available for testing HCT/P donors for relevant communicable agents and diseases — see FDA-Licensed Donor Screening Tests with Approved Indications for Testing HCT/P Donors List. After new products are licensed or cleared for use, they may not immediately appear on the FDA Web page; however, the product package insert clearly will state if the assay can be used for screening donors of HCT/Ps, or "other living donors." Additional information is available in 21 CFR 1271.80(c).