FDA Will Soon Take Greater Action Against Unapproved Regenerative Medicines

Peter Marks, MD, PhD

A policy allowing enforcement discretion for cellular-derived therapies, including stem cell-based products, will end on May 31, 2021, allowing the FDA to take more action against unapproved regenerative medicines. The expiring policy, which went into effect in 2017, was designed to give manufacturers time to submit investigational new drug (IND) and premarket approval applications for products fitting the FDA's criteria for human cell, tissue, and cellular and tissue-based products.

The policy was initially scheduled to expire in July 2020 but was extended through November 2020 and then subsequently into May 2021, to give manufacturers extra time during the COVID-19 pandemic. Throughout the time of the policy, the agency continued to issue compliance actions for manufacturers of regenerative medicines that resulted in reported safety concerns. Since December 2019, the agency issued more than 350 letters to manufacturers, clinics, and health care providers.

"These regenerative medicine products are not without risk and are often marketed by clinics as being safe and effective for the treatment of a wide range of diseases or conditions, even though they haven’t been adequately studied in clinical trials," wrote Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. "We’ve said previously and want to reiterate here – there is no room for manufacturers, clinics, or health care practitioners to place patients at risk through products that violate the law, including by not having an IND in effect or an approved biologics license."

Despite allowing more than 3 years, Marks noted that broad marketing of unapproved products still existed. In many cases, adverse outcomes with stem cell therapy are brought about by non-homologous use of cells, such as extracting stem cells from adipose for injection into the eye or spinal cord. Since adipose stem cells, which are a type of mesenchymal stem cell, are programmed to work in a predefined fashion it is unknown how they may behave in these environments, without a rigorously conducted clinical trial under an FDA-approved IND.

In a consumer alert in July 2020, the FDA noted that the only approved stem cell products were those from hematopoietic progenitor cells derived from umbilical cord blood. Moreover, this warning extended to exosome products. Specifically, the FDA warned of these products being marketed as treatments for COVID-19, along with a number of arthritic, neurologic, and respiratory conditions.

"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," Marks wrote. "We will continue to take action regarding unlawfully marketed products. Our oversight of cellular and related products has included taking compliance actions, including numerous warning and untitled letters, and pursuing enforcement action for serious violations of the law.”

Prior to the expiration of the enforcement discretion policy, the FDA focused primarily on higher risk products, with potentially dangerous methods of administration, such as directly into the eye or central nervous system. With the expiration of the policy, the FDA will more broadly enforce regulations, even for those administered at lower risk, such as intradermal and subcutaneous.

"The FDA remains committed to helping advance the development of safe and effective regenerative medicine products, including stem cell-based products, to benefit individuals in need," Marks concluded. "We look forward to working with those who share this goal."