CBER Q&A addresses stem cell enforcement questions

Regulatory NewsRegulatory News | 12 July 2021 |  By 

The US Food and Drug Administration (FDA) issued a question-and-answer document on Monday to address issues that may arise now that the agency's enforcement discretion policy against unauthorized marketing of these products has come to an end.
The agency’s Center for Biologics Evaluation and Research (CBER) ended a period of enforcement discretion against purveyors of unauthorized human cells, tissues, or cellular or tissue- based products (HCT/Ps) on 31 May 2021. According to the question-and-answer document, “after May 31, 2021, FDA no longer intends to exercise enforcement discretion with respect to the IND and the premarket approval requirements,” as described in its compliance and enforcement policy. “If you market/offer for sale an HCT/P that requires premarket review as a drug and biological product, you do so at your own risk.” (RELATED: Time’s up for questionable cell and tissue products, says Marks, Regulatory Focus 22 April 2021)
However, according to the agency's general policy, FDA did not specify exactly what its compliance and enforcement plans will be for individuals and companies marketing unauthorized stem cell products.
FDA originally laid out its regulatory policy framework for regenerative medicine in November 2017, announcing a 3-year period of enforcement discretion at that time to allow manufacturers and providers of these products time to seek premarket approval and bring their practices into conformity with the new regulations.
The end of the enforcement discretion period came six months later than FDA had originally intended; the public health emergency of the COVID-19 pandemic prompted the additional abeyance. (RELATED: Six more months tacked onto regenerative medicine enforcement date, Regulatory Focus 20 July 2020)
FDA issued more than 300 warning letters during the period of enforcement discretion. “Despite all of the FDA’s efforts to engage industry, there continues to be broad marketing of these unapproved products for the treatment or cure of a wide range of diseases or medical conditions,” said CBER director Peter Marks in a statement released in advance of the end of the enforcement discretion period. “The wide extent of the marketing of such unapproved products is evidenced by their inappropriate advertisement in various media and by the number of consumer complaints about them submitted to the FDA.”
“FDA expects all establishments that manufacture HCT/Ps regulated as drugs or biological products to have an approved biologics license application (BLA) or an investigational new drug application (IND) in effect,” according to the question-and-answer document. If a product has an IND in effect, the product may be distributed for clinical use, but only as part of a clinical investigation.
Separate regulations, found in 21 CFR 312.8, cover whether sponsors may recoup costs associated with administration of an IND. The CBER document also points sponsors to an FDA guidance for further information, clarifying that each request to charge for a product covered by an IND must be authorized by FDA.
The document also makes clear the products that companies may no longer continue to market or offer for sale products that have not been granted a BLA or an IND, even if an IND or BLA has been submitted. This holds true for HCT/Ps that require, but do not currently have, premarket approval, even if a patient had been receiving the product and responding well to it before the period of enforcement discretion ended.
Also, even if an HCT/P product has an IND in effect, the product still cannot be used to treat patients outside of the IND. And HCT/Ps purchased from a manufacturer before the end of the enforcement discretion period cannot be administered to patients outside of an IND.
FDA does not have the authority to disclose the existence of an IND; the existence of an IND must be verified by the sponsor, who can provide the FDA-issued IND number and a copy of FDA communication acknowledging the IND, according to CBER.
Individuals with questions about HCT/P regulation should first consult the relevant FDA guidance, says the question-and-answer document. Those with further questions can file a request for recommendation with the Tissue Reference Group, or seek a request for designation from the Office of Combination Products (OCP), as appropriate.  OCP may also issue a preliminary assessment of a product if a pre-request for designation is submitted.
CBER clarified that platelet-rich plasms (PRP) is a blood product, and therefore not an HCT/P; therefore, PRP does not fall under these compliance and enforcement policies.


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