Human cells, tissues, and cellular and tissue-based products (HCT/Ps) occupy a complex regulatory space because their safety depends not only on the biological characteristics of the product but also on donor eligibility, collection, processing, storage, labeling, traceability, and controls against contamination and disease transmission. FDA regulates HCT/Ps under 21 CFR Parts 1270 and 1271, while cellular therapy products that do not qualify for regulation solely under section 361 of the Public Health Service Act may also be subject to drug and biological product requirements. A fundamental compliance question is whether an HCT/P meets all criteria in 21 CFR 1271.10(a) for regulation solely under section 361. These criteria include minimal manipulation, homologous use, appropriate combination requirements, and other specified conditions. If the product does not satisfy the applicable criteria and no exception under 21 CFR 1271.15 applies, additional FDA regulation may apply, including premarket review. Recent FDA enforcement actions demonstrate that sponsors and manufacturers cannot assume that describing a product as a “stem cell therapy” or “HCT/P” determines its regulatory pathway. For establishments operating under the HCT/P framework, Good Tissue Practices (GTP) are central to product safety and regulatory compliance. FDA’s Current Good Tissue Practice guidance addresses requirements under 21 CFR Part 1271, including controls covering facilities, environmental conditions, equipment, procedures, records, process controls, personnel, and prevention of contamination or cross-contamination. The objective is to ensure that HCT/Ps are recovered, processed, stored, labeled, packaged, and distributed in a manner that preserves their safety and quality.

GMP for HCT/Ps becomes particularly important when a cellular or tissue-based product is regulated as a drug or biological product in addition to, or rather than solely under, section 361. Manufacturing systems must then support appropriate quality controls, validated or qualified processes, contamination control, testing, documentation, deviation management, investigations, and batch or lot disposition. For more complex stem cell therapies, the manufacturing strategy should be linked closely to the product’s intended use, mechanism of action, critical quality attributes, and clinical development program rather than relying on generic tissue-processing controls. Donor eligibility is another critical component of the FDA framework. Establishments must maintain processes for donor screening and testing consistent with 21 CFR Part 1271, Subpart C. FDA’s 2025 draft guidance on reducing the risk of sepsis-associated disease transmission further illustrates the agency’s continuing focus on donor screening, testing, and infectious-disease risk management. Because the document is draft guidance, its recommendations are nonbinding unless and until incorporated into applicable requirements.

Traceability is equally important. A robust HCT/P compliance system should allow organizations to connect the donor, recovered material, processing activities, storage conditions, labeling, distribution, and recipient-related information through controlled records. Inadequate traceability can make investigations, recalls, adverse-event assessments, and root-cause analysis significantly more difficult. Documentation should therefore be treated as a component of product safety rather than simply an administrative requirement. For organizations developing cell and gene therapy manufacturing programs, contamination control deserves particular attention. Cellular materials may be highly sensitive to microbial, viral, or other contamination risks, while many products involve complex, patient-specific or donor-specific workflows. FDA has previously identified manufacturing deficiencies in unapproved cellular products involving conditions that could contribute to microbial contamination. Practical controls may include appropriate facility design, environmental monitoring where applicable, aseptic practices, equipment qualification, validated cleaning or sanitization processes, controlled material flows, personnel training, and documented investigation of excursions.

Regulatory classification also has direct implications for clinical development. A product requiring FDA approval cannot simply be commercially marketed because an IND has been submitted or because clinical investigation is underway. FDA states that an HCT/P requiring premarket approval may not lawfully be marketed merely because the sponsor has an IND or is pursuing an IND or BLA. Sponsors should therefore establish the regulatory pathway early and ensure that manufacturing controls support the requirements applicable to the clinical-stage product. Recent FDA enforcement activity reinforces the importance of correctly evaluating product claims and intended use. In 2026, FDA warning letters addressed companies marketing umbilical-cord-derived products and determined that certain products did not meet the criteria for regulation solely under section 361, including concerns involving nonhomologous use and other regulatory requirements. This demonstrates why promotional language, labeling, websites, and other communications can become relevant to FDA’s assessment of intended use.

For biotech and pharmaceutical companies, the practical lesson is that stem cell therapy compliance requires an integrated quality and regulatory strategy. Organizations should map the product’s classification, establish donor eligibility controls, define manufacturing and testing responsibilities, maintain complete records, qualify suppliers and contractors, investigate deviations systematically, and periodically assess whether manufacturing changes could affect regulatory status or product quality. Quality systems should evolve as the product progresses from research through clinical development and, where applicable, commercial manufacturing. Ultimately, compliance for HCT/Ps and stem cell therapies depends on more than laboratory procedures. A defensible program connects regulatory classification, Good Tissue Practices, current Good Manufacturing Practices, donor eligibility, contamination control, traceability, documentation, and clinical-development requirements into one quality framework. As FDA continues to scrutinize unapproved cellular products and manufacturing practices, organizations should build regulatory and quality controls into product development from the outset rather than treating compliance as a later-stage activity.