Six more months tacked onto regenerative medicine enforcement date

 
 
The end of a discretionary enforcement period for regenerative medicine products was pushed back by another 6 months, according to a final guidance issued today by the US Food and Drug Administration (FDA).
 
Today’s updated guidance shifts the enforcement date but otherwise leaves unchanged a 2017 guidance addressing regulatory considerations for “minimal manipulation” and “homologous use” of human cells, tissues and cellular and tissue-based products (HCT/Ps).
 
The guidance provides examples of various types of HCT/Ps, explaining how the regulations which define and govern the minimal manipulation and homologous use criteria (21 CFR 1271.10(a)(1) and (2)) apply to a variety of regenerative medicine products. Specific use cases, such as changing the physical state of adipose tissue and ligament, are addressed in the guidance, which also lays out criteria for classification of both structural and nonstructural tissues.
 
In framing a comprehensive policy approach to regenerative medicine in 2017, FDA announced that it would employ a discretionary enforcement policy for the following 36 months. Today’s final guidance extends the period of discretionary enforcement, which was slated to end in November 2020, to 31 May 2021. (RELATED: FDA unveils new regenerative medicine framework, Regulatory Focus, 16 November 2017)
 
The enforcement discretion policy, said FDA in a statement, “does not apply to products that have been associated with reported safety concerns or have the potential to cause significant safety concerns to patients.”  Examples given in the guidance of such high-risk products include those administered by intravenous injection, inhalation, or intraocular or central nervous system injection or infusion.
 
In an interview, bioethicist Leigh Turner, PhD, offered a critique of the agency’s protracted period of discretionary enforcement: “The point of the enforcement discretion period was to give companies time to determine whether they needed biologics licenses for their purported stem cell therapies,” said Turner, associate professor at the University of Minnesota’s Center for Bioethics. “If they were selling products requiring licensure they could apply for licenses or submit Investigational New Drug applications to conduct the clinical trials needed to generate the safety and efficacy data needed to apply for product licensure. This decision was a mistake.”
 
Turner pointed out that there was already brisk trade in stem cell products when the initial framework was issued in 2017. He said, “Hundreds of U.S. companies were selling unlicensed and unproven stem cell products when the FDA’s policy of enforcement discretion was announced and hundreds more such businesses have entered the U.S. direct-to-consumer marketplace since this policy was implemented.”
 
Elsewhere, Turner documented that during the current novel coronavirus pandemic businesses are “preying on public fears and anxieties” by selling unproven and unlicensed stem cell-based products. He cited several such examples in a 7 May 2020 article published in Cell Stem Cell. In the article, Turner noted that FDA had at that point issued three untitled letters to businesses that were advertising unproven stem cell or exome products to treat or prevent COVID-19 and had sent warning letters to several others. FDA has continued to issue warning letters to firms, including those marketing regenerative medicine products, making such claims during the pandemic. (RELATED: Four homeopathic injectable producers warned by FDA, Regulatory Focus, 16 June 2020)
 
“Regulatory bodies such as the FDA and [Federal Trade Commission] must make challenging resource allocation decisions when deciding whether to investigate particular businesses,” acknowledged Turner in the article. Still, he wrote, “The commercial and clinical activities of businesses selling purported stem cell treatments and preventive measures for COVID-19 constitute sufficient risks to patient safety, public health, and truthfulness in advertising and commerce to warrant further investigations and enforcement actions.”
 
Regulatory Focus provided Turner’s interview responses to CBER and asked for commentary. In response, a media spokesperson referred to the agency’s press announcement of the extension of the enforcement policy discretion.
 
“To be clear, our policy of enforcement discretion only pertains to certain human cell, tissue and cellular and tissue-based products that do not raise potential significant safety concerns or reported safety concerns," said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER) in the announcement.
 
“This policy was never intended to provide a cover for bad actors, and we intend to continue to take action against manufacturers and health care providers who are offering unapproved regenerative medicine products that have the potential to put patients at significant risk,” said Marks.
 
From Turner’s perspective, the time is past for a sharper enforcement policy from FDA: “Often overlooked is the extent to which the FDA by insufficient regulatory action and tolerance of noncompliant activities helps enable and perpetuate 'Wild West' marketplaces," he said. “Reputable companies do not need 3 years to determine the regulatory status of the products they want to sell. They certainly don’t need three and a half years to make such determinations.”

Added Turner: “This extension doubles down on a misguided approach to a marketplace that has for a decade needed more robust oversight by the FDA.”