On May 26, 2021 the United States Food and Drug Administration closed a window that had been open since November 2017. The three-year enforcement-discretion period the agency had announced alongside its Comprehensive Regenerative Medicine Policy Framework was over. The agency had used the intervening years to clarify its thinking, to engage with operators in the space, and to give manufacturers and clinics offering cell and tissue products time to come into compliance. From May 26 forward the agency’s position was clear. Products that fell outside Section 361 eligibility without an approved Biologics License Application were subject to enforcement action.
The pattern of enforcement that followed in the months and years after May 2021 is worth understanding in some detail. The agency did not move uniformly across the field. Its initial focus was on products being marketed for specific therapeutic claims, particularly products marketed for orthopaedic, ophthalmological, or neurological conditions, where the claims being made placed the product clearly in Section 351 territory while the product was being offered under Section 361 framing. Warning letters and untitled letters were issued to specific manufacturers and clinic operators in the months following the deadline. In some cases, product seizures and injunctive action followed.
What the agency did not do, and what some operators in the space had hoped it would do, was suspend its position on what counted as Section 361 eligibility. The four criteria, minimal manipulation, autologous, homologous use, and no metabolic or systemic effect outside homologous use, continued to be applied as written. The clearest message the agency sent through its post-2021 enforcement pattern was that the criteria were not negotiable, but that compliant operations within them were welcome to continue.
For Wellbeing the May 2021 date was less a turning point than a clarifying one. Research programmes already structured around minimally manipulated, autologous, homologous-use criteria carried on without significant operational change. Programmes built around culture-expanded cell populations, chemically modified preparations, or non-homologous applications had a harder conversation to have with their regulators, and many of those programmes have since restructured, paused, or moved into the Section 351 pathway with all that entails.
The broader effect on the regenerative-medicine landscape in the United States has been significant. The unregulated end of the field, in which clinics offered loosely characterised stem-cell preparations for a wide range of claimed indications without meaningful regulatory oversight, has shrunk considerably since 2021. Most of the worst operators have been the targets of enforcement action. Some have closed. Some have restructured into legitimate Section 361 or Section 351 programmes. The signal-to-noise ratio in the public conversation about regenerative medicine in the United States has improved meaningfully, although the field still carries the reputational weight of the period when that was not true.
Wellbeing does not operate in the United States as a clinic and does not directly offer the kind of products the FDA’s enforcement work has focused on. Wellbeing’s clinical relationships in the United States run through licensed clinicians operating within their own jurisdictions and regulatory frameworks. The relevance of the FDA framework to Wellbeing is at the level of how the underlying preparation is structured, characterised, and prepared. That work has always been organised around the principles the framework codifies.
There has been continued movement in the framework since 2021. The agency has issued additional guidance and clarifications, particularly around specific cell types and preparation methods. Industry conversation has continued through trade associations and academic-clinical convening. The field has not stood still. But the basic structure the November 2017 framework set out has held, and most of the post-2021 development has been about operating within it rather than altering it.
For readers interested in following the regulatory side of the field more closely, the FDA’s Center for Biologics Evaluation and Research maintains current guidance and enforcement records on its website. The agency’s public meetings and town-halls, which run periodically, are a useful direct source for how the agency is thinking about emerging questions in the space. Several of the trade associations active in the field also publish useful summaries.