The development and marketing of human cells, tissues, and cellular and tissue-based products (HCT/Ps) in the United States require a clear understanding of FDA’s risk-based regulatory framework. HCT/Ps may include bone, skin, corneas, tendons, ligaments, heart valves, hematopoietic stem/progenitor cells from peripheral or cord blood, and reproductive tissues. Depending on how a product is processed and intended to be used, it may be regulated solely under section 361 of the Public Health Service (PHS) Act and 21 CFR Part 1271 or may require FDA premarket review as a drug, biological product, or medical device.

A critical first step in HCT/P development is determining the product’s regulatory classification. FDA evaluates whether an HCT/P meets the criteria in 21 CFR 1271.10, including requirements related to minimal manipulation, homologous use, combination with certain substances, and systemic effect or dependence on the metabolic activity of living cells. Products meeting the applicable criteria may be regulated solely under section 361, while products outside that framework may require premarket authorization under section 351 of the PHS Act and/or the Federal Food, Drug, and Cosmetic Act.

For companies developing cell and tissue products, regulatory strategy should therefore be established before significant clinical or commercial investment. FDA’s guidance on minimal manipulation and homologous use is particularly important because processing methods and intended use can determine whether an HCT/P remains within the 361 framework or becomes subject to a more extensive premarket pathway. A defensible classification assessment should be supported by documented scientific and regulatory rationale rather than relying solely on product terminology or marketing claims. FDA HCT/P requirements also extend to donor eligibility and communicable disease risk controls. Under 21 CFR Part 1271, Subpart C, establishments must follow requirements for donor screening and testing, with applicable exceptions. FDA states that donors generally must be tested for relevant communicable disease agents or diseases using appropriate FDA-licensed, approved, or cleared donor screening tests when available. Robust donor qualification, testing records, traceability, and eligibility determinations are therefore fundamental components of an effective compliance program.

Manufacturing controls represent another major area of regulatory scrutiny. Current Good Tissue Practice (CGTP) requirements under 21 CFR Part 1271, Subpart D address practices intended to prevent contamination, cross-contamination, mix-ups, and transmission of communicable disease. Establishments should maintain appropriately controlled facilities, equipment, procedures, personnel practices, environmental controls, records, and quality systems. FDA’s CGTP guidance provides recommendations for implementing these requirements and emphasizes controls across relevant manufacturing activities. Registration and product listing are also important HCT/P compliance obligations. Establishments manufacturing HCT/Ps regulated solely under section 361 generally must register with FDA and list their HCT/Ps under 21 CFR Part 1271. FDA states that registration must be updated annually, while certain changes to establishment information or product listings require additional amendments. Importantly, FDA registration or listing does not mean that FDA has determined that the establishment is compliant or that the HCT/P has been approved or licensed.

For products that require clinical development and premarket authorization, regenerative medicine regulation becomes especially important. Depending on the product and its regulatory classification, sponsors may need to address IND requirements, clinical trial design, manufacturing controls, potency and characterization, safety monitoring, and ultimately an appropriate marketing application. Companies should avoid assuming that an innovative cellular therapy is exempt from FDA oversight simply because it is derived from human cells or tissues. Recent FDA activity demonstrates that donor safety and infectious disease prevention remain evolving areas of regulatory attention. In 2025, FDA issued several draft guidances addressing donor eligibility and risks associated with HIV, hepatitis B, hepatitis C, Mycobacterium tuberculosis, and sepsis. These documents are draft, nonbinding recommendations and should not be treated as final requirements; however, they demonstrate FDA’s continued focus on strengthening disease-transmission risk controls for HCT/Ps.

FDA’s regulatory focus also continues to respond to emerging public-health risks. In July 2026, FDA issued information concerning Ebola disease and HCT/P donation following an outbreak involving Bundibugyo virus. The communication highlights the importance of monitoring relevant disease risks when making donor eligibility determinations. For global manufacturers and tissue establishments, this reinforces the need for regulatory intelligence and procedures capable of responding to changing communicable disease information.

From a commercial perspective, HCT/P marketing compliance is closely connected to product classification and intended use. Promotional claims should remain consistent with the product’s authorized regulatory status and available evidence. Claims suggesting treatment, prevention, or diagnosis of disease can have significant regulatory implications, particularly when an establishment is relying on the 361 pathway. Companies should therefore coordinate regulatory, clinical, medical, quality, and marketing teams before launching promotional materials. Common compliance risks include incorrect product classification, inadequate donor screening, incomplete testing documentation, weak traceability, insufficient environmental or process controls, failure to maintain required records, inaccurate labeling, inappropriate promotional claims, and missed registration or listing obligations. International manufacturers may face additional challenges involving U.S. importation, U.S. agents, product listing, and alignment of overseas manufacturing controls with FDA expectations. FDA requires foreign establishments that import or offer HCT/Ps for import into the United States to meet applicable registration and listing requirements.

A practical compliance strategy should begin with a documented regulatory assessment, followed by donor eligibility controls, validated and controlled manufacturing processes where applicable, comprehensive quality documentation, traceability, adverse event and deviation management, and periodic regulatory review. Organizations should also distinguish carefully between legally binding regulations and FDA guidance. FDA guidance generally represents the Agency’s current thinking and does not itself establish legally enforceable requirements unless incorporated into applicable regulations or otherwise required by law. For pharmaceutical, biotech, medical device, and clinical research organizations, understanding the complete HCT/P regulatory pathway can reduce costly regulatory uncertainty and support better development decisions. Early classification and regulatory planning can help sponsors determine whether they can operate within the section 361 framework or need to prepare for a more extensive FDA development and marketing pathway.