The U.S. Food and Drug Administration (FDA) plays a critical role in ensuring the safety of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) by regulating donor eligibility and screening protocols. These products, which include bone, skin, corneas, heart valves, hematopoietic stem cells, and reproductive cells such as sperm and oocytes, are widely used in medical procedures, transplants, and regenerative medicine.
In January 2025, the FDA released several draft guidances to update recommendations on donor eligibility determinations for HCT/Ps. The primary goal of these updates is to reduce the risk of communicable disease transmission, particularly HIV, Hepatitis B (HBV), and Hepatitis C (HCV), while also addressing advancements in donor screening technologies and evolving public health concerns.
This blog explores the key updates in the FDA’s latest guidance, their impact on industry stakeholders, and what healthcare professionals need to know about compliance with donor eligibility regulations.
Why Donor Eligibility Matters: Protecting Public Health
HCT/Ps are sourced from human donors and carry inherent risks of transmitting infectious diseases if proper screening and testing are not performed. The FDA requires establishments handling HCT/Ps to implement rigorous donor screening and testing protocols to prevent the transmission of diseases such as:
- Human Immunodeficiency Virus (HIV-1, HIV-2)
- Hepatitis B Virus (HBV)
- Hepatitis C Virus (HCV)
- Syphilis, West Nile Virus (WNV), and other relevant communicable diseases
The FDA’s updated guidance reflects scientific advancements in testing methodologies, improved risk assessment tools, and new concerns about emerging infectious diseases. These updates aim to strengthen the integrity of the HCT/P supply chain while maintaining access to life-saving therapies.
Key Updates in the FDA’s Draft Guidance on Donor Eligibility for HCT/Ps
The new draft guidance addresses four critical areas related to donor eligibility.
Expanded Infectious Disease Testing Requirements
The FDA is proposing stricter infectious disease screening and testing protocols to enhance patient safety. The updated recommendations include:
- Expanded NAT (Nucleic Acid Testing), which requires all donors to undergo NAT-based testing for HIV, HBV, and HCV, as this method offers higher sensitivity than traditional serological tests.
- Syphilis screening enhancements, with new requirements for confirmatory testing in cases of ambiguous initial results.
- Considerations for West Nile Virus (WNV) testing, particularly in donors from high-risk geographic areas where seasonal outbreaks occur.
- Refinements to Cytomegalovirus (CMV) testing, focusing on its application in immunocompromised recipients.
HCT/P establishments will need to update their donor testing protocols and ensure laboratories are equipped with the latest NAT-based screening technologies.
Strengthened Donor Risk Assessment Criteria
The FDA is introducing more comprehensive donor risk assessments to reduce disease transmission risks. Updates include:
- Revised behavioral risk factors, extending deferral periods for donors with recent high-risk exposures such as unprotected sexual contact with HIV-positive individuals or intravenous drug use.
- Geographic exposure risks, requiring closer evaluation of donor travel history in relation to emerging infectious disease outbreaks.
- Expanded screening for variant strains of hepatitis, with additional genetic testing for drug-resistant HBV and HCV variants.
HCT/P establishments must revise donor screening questionnaires and risk assessment protocols to align with updated criteria. Staff training on new risk factor considerations will also be essential.
Guidance on Donor Eligibility Determinations for Reproductive Cells and Tissues
The FDA’s new draft guidance introduces specific recommendations for donor screening in reproductive medicine, particularly for:
- Sperm and oocyte donors, requiring enhanced screening for sexually transmitted infections (STIs) to improve the safety of assisted reproductive technologies (ART).
- Use of directed (known) donors, with new considerations for informed consent regarding potential risks.
- Adjustments to sperm and egg quarantine periods based on advancements in testing technologies.
Fertility clinics and ART facilities must implement updated infectious disease screening protocols to remain compliant with new FDA guidelines.
Clarification on HCT/P Exceptions and Special Cases
The new guidance also clarifies exemptions and special cases, including:
- Autologous HCT/P donations, where patients donate their own cells or tissues for future use. In these cases, standard infectious disease screening may not apply, but contamination risks must still be managed.
- Emergent life-threatening cases, where alternative donor eligibility pathways may be permitted to prioritize patient survival while balancing safety.
- HCT/Ps from deceased donors, requiring enhanced post-mortem donor screening, including new post-mortem infectious disease testing techniques.
HCT/P establishments handling exceptional cases must have clear protocols in place to ensure compliance with FDA requirements while maintaining patient safety.
How HCT/P Establishments Should Prepare for Compliance
With the FDA’s updated donor eligibility guidance, organizations involved in HCT/P collection, processing, and distribution should take the following steps:
- Update infectious disease testing protocols to incorporate enhanced NAT-based screening for HIV, HBV, HCV, and other required pathogens.
- Revise donor screening questionnaires to ensure new behavioral and geographic risk assessments are included in donor evaluations.
- Enhance staff training to educate personnel on updated donor eligibility criteria and changes in reproductive HCT/P screening.
- Engage with the FDA early by participating in pre-submission meetings to discuss compliance strategies for novel HCT/P applications.
- Strengthen recordkeeping and documentation by maintaining comprehensive records of donor screening results, risk assessments, and testing methodologies.
Conclusion: Strengthening the Safety of HCT/Ps
The FDA’s updated draft guidance on donor eligibility for HCT/Ps underscores the need for rigorous infectious disease screening and enhanced risk assessment criteria. By incorporating advancements in diagnostic testing, refined risk evaluation methods, and updated reproductive tissue regulations, the FDA aims to protect both recipients and the integrity of the HCT/P supply chain.
For HCT/P establishments, compliance with these evolving guidelines will require proactive updates to testing protocols, staff education, and enhanced regulatory engagement. By staying ahead of regulatory expectations, the industry can continue to provide safe, effective, and ethically sourced human tissue products for medical and therapeutic use.
