The US Food and Drug Administration's (FDA) Commissioner Scott Gottlieb said Monday the agency will advance a new framework to better regulate stem cell therapies this fall.
"This comprehensive policy will establish clearer lines around when these regenerative medicine products have sufficient complexity to fall under the agency's current authority, and then define an efficient process for how these products should be evaluated for safety and effectiveness," Gottlieb said.
The statement was sent out alongside a warning letter for a Florida stem cell clinic, known as US Stem Cell Clinic, LLC, and a news release on US Marshalls seizing five vials of a vaccine FDA says is reserved for people at high risk for smallpox, such as some military personnel.
The seizure of the vaccine vials from StemImmune, Inc. in California on Friday came as they were being used to create unapproved products that were injected intravenously into patients' cancer tumors. StemImmune did not respond to a request for comment. US Stem Cell Clinic said in a press release that it is "not manufacturing a drug and therefore medical clinics are not required to follow cGMP."
Gottlieb added: "The FDA will not allow deceitful actors to take advantage of vulnerable patients by purporting to have treatments or cures for serious diseases without any proof that they actually work. I especially won't allow cases such as this one to go unchallenged, where we have good medical reasons to believe these purported treatments can actually harm patients and make their conditions worse."
He added that the new policies will be set via a series of guidance documents to "give current product developers a very reasonable period of time" to interact with FDA to determine if they need to submit a marketing application.
He also said the agency is developing a novel approach to FDA approval of stem cell therapies that "we believe will allow very small product developers to gain all the benefits of FDA approval through a process that is minimally burdensome and less costly."
But the comments and crackdown come as FDA has so far let these direct-to-consumer stem cell clinics flourish and has only issued a limited number of warning letters. Texas also recently passed a new law to allow companies to sell unproven stem cell treatments without FDA approval. Other clinics have been found in California and Florida, experts say.
Leigh Turner, an assistant professor of bioethics at the University of Minnesota, who has co-written an article in Cell about direct-to-consumer stem cell clinics, told Focus that FDA’s enforcement push and statements issued Monday seem to make the claim that there are a few bad actors but there are actually hundreds of these unscrupulous companies.
And though these companies "are not that difficult to find," Turner said, "the bigger problem is once you find the businesses, what do you do, wait until there are patient complaints to issue a warning letter? Or do you issue a warning letter when dubious marketing claims are made?"
He noted that Florida’s US Stem Cell Clinic has been in operation for years and there is still a lack of clarity on "where the lines will be drawn" by FDA. And the StemImmune seizure is representative of "outrageous behavior," he added, but "not a good example" of the larger issue.
Gottlieb also offered the examples of when cells or tissues are taken from and given back to the same individual or when the cells or tissues do not undergo significant manufacturing and are not combined with another drug or device, among other factors, noting that such products "may not require premarket review under current law.
"However, when significant manufacturing is performed on the cells or tissues, or when the cells or tissues are not intended to perform the same basic functions, far greater uncertainty exists as to the benefits and risks involved. In these cases, it's necessary to understand the benefits and risks in clinical trials prior to widespread use of the products. Therefore, premarket review is required," Gottlieb said.
FDA also will launch a new working group to pursue unscrupulous clinics through "whatever legally enforceable means" are necessary to protect the public, he said.
But concerns linger around a whack-a-mole type environment where FDA takes action against bad actors but they crop up as different companies.
"If it’s a small clinic, are they going to care when draft becomes final guidance? Or about a warning letter?" Turner said. "My sense is warning letters may work for some," but there might be more of an impact if criminal charges are filed.
21st Century Cures Act and RMAT
And beyond the unscrupulous actors, FDA has already begun working with the regenerative medicine industry by offering the Regenerative Medicine Advanced Therapy (RMAT) designation thanks to the 21st Century Cures Act.
Several sections (3033-3036) of the law require FDA to update its regenerative medicine guidance, regulations and standards.
The pathway expedites programs to help foster the development and approval of these novel products.
"Among other things, we plan to include certain gene therapy products that permanently alter tissue and produce a sustained therapeutic benefit as part of the products that will meet the definition of being eligible to come under the pathway enabled by RMAT. This is part of our broader commitment to pursue efforts that will advance innovation in this space. We encourage sponsors who are seeking FDA approval of their product to consider this pathway," the agency said.
Humacyte and Vericel are two examples of companies that have already received the RMAT designation.