Volume 40 Number 2 | April 2026
Summary

The article outlines the FDA’s comprehensive regulatory framework ensuring the safety of the U.S. blood supply through strict donor eligibility criteria, infectious disease testing, and routine inspections. It highlights updates to the Donor History Questionnaire, the shift to individualized risk‑based screening, and the TTIMS surveillance system, which together strengthen transfusion safety and guide evidence‑based policy.

Yan Zheng, PhD, MLS(ASCP)CM, Patient Safety and Diagnostic Stewardship Committee

Yan ZhengBlood transfusion is a critical component of modern health care, supporting a wide range of medical and surgical interventions. In the United States, blood and blood products are regulated as biologic drugs, and their collection, testing, and distribution are overseen by the U.S. Food and Drug Administration (FDA). Through a comprehensive regulatory framework that includes donor eligibility criteria, standardized screening procedures, mandatory infectious disease testing, and continuous surveillance, the FDA works to ensure the safety, purity, and potency of the nation’s blood supply.

The FDA requires that all donated blood be screened using licensed assays for specific transfusion-transmissible infections (TTIs).1 For each donation, testing is performed for at least seven infectious agents, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-lymphotropic virus (HTLV), Chagas disease, and West Nile virus, with additional testing such as Babesia screening required in certain endemic regions. Only units that test nonreactive for all required markers are released for transfusion. In addition, blood centers are required to maintain and enforce donor deferral registries to prevent future donations from individuals who do not meet established safety criteria.

Oversight of blood establishments is rigorous and comparable to standards applied to pharmaceutical manufacturers. All FDA-registered blood facilities are inspected at least biennially, with more frequent inspections conducted for facilities identified as higher risk. These inspections evaluate compliance with current good manufacturing practices, donor screening procedures, testing protocols, and donor record requirements. Over time, this regulatory structure has contributed to substantial improvements in transfusion safety and public confidence in the U.S. blood system.

“Over time, this regulatory structure has contributed to substantial improvements in transfusion safety and public confidence in the U.S. blood system.”

Donor eligibility assessment is a cornerstone of blood safety. The Donor History Questionnaire (DHQ) is a standardized screening instrument developed by an AABB (Association for the Advancement of Blood & Biotherapies) task force in collaboration with the FDA and representatives from the blood and plasma industry.2 The DHQ is required for all blood donations and includes questions addressing medical history, potential exposure to TTIs, sexual and behavioral risk factors, travel history, medications and vaccinations, and donation frequency. Multiple versions of the DHQ have been released over time to reflect evolving scientific evidence and regulatory guidance, particularly regarding HIV risk assessment.

In May 2023, the FDA implemented the Donor History Questionnaire version 4.0 (DHQ v4.0), marking a significant shift in donor screening policy.3 This update replaced time-based deferrals for men who have sex with men (MSM) with a uniform, individual risk-based assessment applied to all donors, regardless of sex assigned at birth, sexual orientation, or gender identity. DHQ v4.0 eliminated MSM-specific questions and introduced gender-neutral, behavior-based screening focused on recent sexual behaviors associated with higher HIV transmission risk, such as having new or multiple sexual partners and engaging in anal sex within the prior three months. The updated questionnaire also incorporated screening questions related to the use of HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), with defined deferral periods based on current scientific evidence.2,4

Complementing regulatory oversight and donor screening is national surveillance through the Transfusion-Transmissible Infections Monitoring System (TTIMS). Established in 2015 as a public-private partnership between U.S. government agencies and blood collection and testing organizations, TTIMS integrates donation data, laboratory testing results, and epidemiologic research to monitor trends in HIV, HBV, HCV, and syphilis among U.S. blood donors. TTIMS consists of two core components: the Donation Database Coordinating Center (DDCC) and the Laboratory and Risk Coordinating Center (LRCC). Four large blood collection organizations and their affiliated laboratories, representing more than 60 percent of approximately 11 million annual U.S. blood donations, contribute data and specimens to this system.5

Functioning as both a surveillance mechanism and a research platform, TTIMS generates longitudinal data that inform regulatory decision-making and policy refinement. Analyses derived from TTIMS were instrumental in supporting the FDA’s 2020 reduction of MSM deferral periods from 12 months to three months and the 2023 adoption of individualized donor assessment. Beyond HIV policy, TTIMS provides a flexible infrastructure for identifying emerging infectious threats and guiding timely responses to protect transfusion safety.

Together, FDA regulation, standardized donor screening through the DHQ, rigorous laboratory testing, and continuous surveillance via TTIMS form an integrated system designed to minimize transfusion-transmitted risks. This multilayered approach reflects advances in laboratory science, evolving epidemiologic evidence, and a commitment to balancing donor inclusivity with the highest standards of blood safety in the United States.

References
  1. S. Food & Drug Administration. Infectious Disease Test. Available at: https://www.fda.gov/vaccines-blood-biologics/infectious-disease-tests
  2. Association for the Advancement of Blood & Biotherapies. Blood Donor History Questionnaires. Available at: https://www.aabb.org/news-resources/resources/donor-history-questionnaires/blood-donor-history-questionnaires
  3. S. Food & Drug Administration. Recommendations for Evaluating Donor Eligibility Using Individual Risk-Based Questions to Reduce the Risk of Human Immunodeficiency Virus Transmission by Blood and Blood Products. May 2023. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-evaluating-donor-eligibility-using-individual-risk-based-questions-reduce-risk-human
  4. Association for the Advancement of Blood & Biotherapies. Full-Length Blood Donor History Questionnaires(DHQ) v4.0. Available at: https://www.aabb.org/docs/default-source/default-document-library/resources/dhq-v4-0/pdfs/dhq-v4-0.pdf?sfvrsn=c8022a9f_0
  5. Custer B. The Transfusion-Transmissible Infections Monitoring System (TTIMS): 10 Years of Key Insights in Policy Change and Blood Safety. 2025 AABB Annual Meeting. October 25-28, San Diego, CA,

Yan Zheng is Clinical Assistant Professor in the Department of Clinical Laboratory Sciences at the University of Kansas Medical Center in Kansas City, Kansas.