In November 2017 the United States Food and Drug Administration finalised a four-document Comprehensive Regenerative Medicine Policy Framework that has shaped how the autologous-biologics space operates ever since. The guidance was several years in the making. It clarified one of the most consequential lines the FDA draws in this field: the line between Section 361 and Section 351 of the Public Health Service Act.
Under Section 361, products derived from human cells, tissues, and cellular or tissue-based material are subject to a lighter regulatory framework focused on safety and on preventing the transmission of communicable disease. They do not require premarket approval. They do, however, have to satisfy a set of criteria. The product has to be minimally manipulated. It has to be autologous, meaning derived from and used on the same individual, or used in a homologous way that performs the same basic function in the recipient as it did in the donor. It cannot have a metabolic or systemic effect outside its homologous use. And it must be combined only with other materials that do not change the relevant biological characteristics of the cell or tissue.
Section 351 is the heavier regulatory pathway. Products that fall outside the Section 361 criteria are treated as biologics or drugs and require a Biologics License Application. That means full preclinical safety work, controlled clinical trials, characterisation against the standards expected of a pharmaceutical product, and ongoing post-market surveillance. The path from laboratory to approved Section 351 product typically runs to many years and significant capital.
The November 2017 framework did not change the underlying statute. What it did was clarify how the FDA intended to interpret the four key tests of Section 361 eligibility: minimal manipulation, homologous use, the systemic-effect rule, and the combination-product rule. The guidance walked through specific examples of cell and tissue products and explained where the agency saw them falling. The intent was to remove ambiguity. Many of the products that had been operating in regulatory grey areas through the 2010s were, after the framework, clearly on one side or the other.
For autologous cell-free preparations, drawn from a person’s own biological material and reinfused without expansion or chemical modification, the framework provided a structure for how to think about eligibility. It did not approve any particular product or programme. What it did was set the discipline. If the preparation is autologous, minimally manipulated, homologous in use, and does not exert a metabolic effect outside its homologous use, it can sit under Section 361. If any of those tests fails, the preparation is in Section 351 territory.
Alongside the framework, the FDA announced a three-year period of enforcement discretion. Existing manufacturers and clinics offering cell and tissue products that might fall outside Section 361 were given time to come into compliance, either by aligning to the 361 criteria or by initiating the Section 351 process. The enforcement-discretion period ran from November 2017 to May 2021, and the agency made clear that after that window closed, enforcement action against non-compliant products would follow. The agency held to that timeline.
Wellbeing’s positioning under this framework has been conservative from the outset. The current research programme operates around blood-derived autologous biology, minimally manipulated, and prepared for homologous biological use. The 361 criteria are not treated as a finish line but as a continuing discipline applied to every aspect of preparation, characterisation and delivery. Wellbeing has not pursued and is not pursuing a Section 351 pathway, because the work is fundamentally structured around the autologous, minimally manipulated principle.
Readers interested in the framework itself can find the four guidance documents on the FDA website, indexed under the Center for Biologics Evaluation and Research. The guidance is technical but accessible, and remains the single most useful starting point for anyone trying to understand how human cell and tissue products are regulated in the United States.