FDA published on May 20, 2004 a new Final Rule on donor eligibility for human tissues and cells (Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products), and draft guidance (Guidance for Industry Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products) related to donor screening and eligibility. These documents include HIV, among a variety of conditions for which cell and tissue donor screening would be required. The final rule establishes donor eligibility criteria for donors of human cells, tissues, and cellular and tissue-based products (HCT/Ps) to help prevent the transmission of communicable disease when these products are transplanted. This new rule is part of the Agency's plan to regulate tissues and related products with a comprehensive, risk-based approach. The requirements are comprehensive, yet adequately flexible, and they provide needed protections for patients without imposing unnecessary regulation.

Along with the potential for great benefit, products derived from the human body such as HCT/Ps may pose risks of transmitting communicable diseases, especially if donors are not properly screened and tested. For this reason, this final rule requires that, before the use of most HCT/Ps, the cell or tissue donor must be found eligible, based on the results of screening for risk factors and testing for relevant communicable diseases. In most cases, a donor who tests positive for a particular disease or who possesses clinical signs or risk factors for such a disease would be considered ineligible, and cells and tissues from that donor would not ordinarily be used.

The new rule on donor eligibility expands the types of human-derived products that come under FDA regulation in an effort to prevent the transmission of diseases through transplantation. Some 350,000 transplants were performed in 1990. Approximately one million are expected to be performed in 2004. The rule pertains to donors of traditional tissues such as musculoskeletal, skin and eye tissues that have been required since 1993 to be screened and tested for HIV, Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Under this new rule, however, reproductive tissue (semen, ova, and embryos), hematopoietic stem cells derived from cord blood and peripheral blood sources (circulating blood sources as opposed to bone marrow), cellular therapies and other innovative products are also regulated.

In addition to including a broader range of tissues and cells, the new rule extends the scope of protection against additional communicable diseases that can be transmitted through transplanted tissues and cells. The new regulation adds requirements to screen for human transmissible spongiform encephalopathies, including Creutzfeldt-Jakob disease (CJD), and to screen and test for syphilis. Screening and testing for still other relevant communicable disease agents (human T-lymphotropic virus (HTLV) would be required for viable cells and tissue rich in leukocytes such as semen and hematopoietic stem cells. For reproductive tissues, Chlamydia trachomatis and Neisseria gonorrhoeae also pose potential risks and are included.

The new rule also provides a framework for identifying emerging diseases that may pose risks to recipients of transplanted HCT/Ps and for which appropriate screening measures or testing are available. Thus, this new regulation gives FDA the flexibility to rapidly address new disease threats as they appear, providing substantial new protections for patients receiving tissue transplants. Examples of such diseases include West Nile virus, Severe Acute Respiratory Syndrome (SARS) and sepsis.

The behavioral risk factors that are used to screen donors are consistent with 1994 Centers for Disease Control and Prevention (CDC) guidelines for preventing transmission of HIV through organ and tissue transplantation and with the scientific literature as reviewed by CDC in 2000. Professional groups, such as the American Association of Tissue Banks, have adopted the recommendations contained in the CDC guidelines.

The rule also contains requirements related to record-keeping, quarantine, storage and labeling of the HCT/Ps, all important to the prevention of disease transmission.

Certain exceptions from the requirements for donor eligibility testing and screening exist. These tissues and cells include: -autologous HCT/Ps (Cells or tissue removed from and transplanted back into the same person) -reproductive cells or tissues from a sexually intimate partner.

Other cells and tissues are subject to donor testing and screening, but may be used with appropriate communication, labeling and documentation of the relevant results even if the donor is determined to be ineligible. These are: -reproductive cells or tissues from a directed donor, -those for use in first or second-degree blood relatives, and -those that meet a documented urgent medical need.

The new framework does not include whole organs or minimally-manipulated bone marrow, which are regulated by the Health Resources and Services Administration (HRSA), another agency of the Department of Health and Human Services. It also does not cover blood products for transfusion or products derived from animals, which FDA regulates under the biologics license requirements and other applicable regulations.

The final rule becomes effective on May 25, 2005.

The new Final Rule is accompanied by draft guidance that provides recommendations for complying with the requirements in the donor eligibility rule. Comments on the draft guidance will be accepted until August 23, 2004 (90 days from the publication date) for consideration in the final guidance.

The Notice of Final Rule, and the draft guidance document are available on FDA's website: Federal Register Notice: http://www.fda.gov/OHRMS/DOCKETS/98fr/97N-484S-nfr0001.pdf Draft Guidance Document: http://www.fda.gov/cber/gdlns/tissdonor.pdf In addition, a "Questions and Answers" document has been prepared to address basic points about the Donor Eligibility Final Rule and the Draft Guidance.

Questions and Answers http://www.fda.gov/cber/rules/suitdonorq&a.htm Richard Klein, HIV/AIDS Program Director Office of Special Health Issues - Food and Drug Administration

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