There has been general concern around the reports of untested stem cell treatments being sold before they have been proven safe and effective. A recent publication by the US' Food and Drug Administration (FDA) represents an informal forewarning to the rogue doctors operating outside of the regulatory regime that they may not get extra time to comply with the agency's strict regulation of regenerative medicine products.
This piece, which uses strong language, underscores the regulatory agency's firm commitment to evidence-based regenerative products.
In 2017, the FDA articulated the regulatory criteria for product marketing through the publication of four guidance documents. These documents build upon the agency's existing risk-based, flexible regulatory regime. They enable stakeholders to understand better how the regulatory criteria apply to their products by clarifying complex technical definitions such as 'minimal manipulation' and 'homologous use'.
This coming November will mark the end of the three years of enforcement discretion announced by the FDA when it first set up this stringent regulatory framework. This approach allows product manufacturers sufficient time to engage with the agency to comply with the requirements, eg, to determine whether they must submit a marketing authorisation application to the FDA for their approval. In the recent piece, there is no indication of a deadline extension.
The authors, Dr Stephen Hahn (FDA's new commissioner) and Dr Peter Marks (Centre for Biologics and Evaluation and Research (CBER) director), state that '... these products, whether autologous (taken from the patient) or allogeneic (donated), are not inherently safe and may be associated with serious adverse consequences'. This piece places the unproven stem cell therapy issue in the context of the COVID-19 pandemic, during which some clinics selling unproven stem cell therapies have exploited the fears of the vulnerable public.
It also indicates that 'the increasing number of adverse events being reported following the widespread use of unapproved regenerative medicine therapies at hundreds of clinics across the country make it necessary for the FDA to act to prevent harm to individuals receiving them.' This point is indeed commendable as it represents the increasingly proactive measures being taken by the FDA in taking enforcement action.
The authors request engagement from patients, their family and friends as well as clinicians 'to help to ensure that instead of remaining unintentionally or intentionally hidden, potentially harmful unapproved regenerative medicine therapies are identified and then removed from the market.' Some clinics may attempt to avoid being on the FDA's radar, however, there is reliable research that should help inform the FDA about the emergence of hundreds, if not a thousand such centres in the US.
Crucially, the article provides some useful and practical guidelines for patients to refer to when evaluating whether a cellular product is offered in compliance with the FDA regulations. For patients contemplating therapies involving a cellular product, the authors recommend the following steps as appropriate practices: first, they need to verify whether the product is FDA-approved or whether an investigational new drug (IND) application for the product is currently on file with the FDA. Next, the patient must provide written informed consent to participate in a clinical trial under that IND and compliance with institutional review board (IRB) requirements.
Moreover, the patient must not be charged for either the unapproved product or for participation in the clinical trial unless there is evidence of benefit to the patient, in which case the amount charged must not exceed the actual direct costs to create the product (cost recovery). And this must be documented by a certified public accountant.
On a critical note, patients (and family, friends and clinicians) are encouraged to report adverse medical events after receiving the product and the health care provider must clearly explain the specific steps for doing so, such as filling in patient-friendly forms to report the matter. Such reports will enable the FDA to get a complete picture of the range of dubious activities.
Finally, patients enrolled in the clinical trial should receive a summary of results after the clinical trial. Transparency, it is felt, will engender trust.
Interestingly, the authors state that medical professionals, including primary care physicians and nurses, are in the best position to assist patients in identifying whether the particular regenerative medicine treatment is appropriate for them to pursue. It is doubtful whether this represents an accurate position as there may be a wide range of knowledge and awareness of stem cell interventions even among the doctors.
The article, written amid a pandemic when the FDA is occupied with other pressing matters, reiterates the agency's obligation to its fundamental mission. Collectively, this piece and the recent escalation in warnings, as well as untitled letters sent by FDA to clinics proffering unapproved stem cell treatments, may indicate that these companies may not be granted more time to comply with the requirements. The remaining months may provide some inkling into what the enforcement situation is likely to be as the FDA's enforcement discretion period finishes in November 2020.