Crackdown On Bad Regenerative Medicine Could Benefit Gene Therapy

US FDA is vowing a crackdown on "unscrupulous actors" in the regenerative medicine industry as part of a policy that could also benefit honest manufacturers.

Coming on the heels of a series of recent enforcement actions against stem cell centers in Florida and California, agency Commissioner Scott Gottlieb announced that FDA is establish a working group to pursue deceitful clinics in the field "through whatever legally enforceable means are necessary to protect the public health."

The most recent enforcement actions "are examples of a larger pool of actors who claim that their unproven and unsafe products will address a serious disease, but instead put patients at significant risk," Gottlieb said in an Aug. 28 statement. "We will seek to take additional actions in the coming months as we address this field, and target those who are clearly stepping over the line, at the same time that they create a potential danger to patients."

FDA issued a warning letter dated Aug. 24 to Sunrise, Fla.-based US Stem Cell Clinic's chief scientific officer Kristin Comella, chiding the center for marketing unapproved stem cell products and for current good manufacturing practice (cGMP) and current good tissue practice (cGTP) violations.

Specifically, inspectors found the clinic was processing body fat into stem cells, and administering the product both intravenously or directly into patients' spinal cords to treat conditions such Parkinson’s disease, amyotrophic lateral sclerosis, chronic obstructive pulmonary disease and heart disease. FDA notes it has not approved any products manufactured by the clinic.

The warning letter also cites 14 different cGMP and cGTP violations, including failure to establish and follow appropriate written procedures to prevent microbiological contamination of products, failure to perform appropriate laboratory testing of each batch of drug product required to be free of objectionable microorganisms and failure to establish a quality control unit.

FDA further alleges that the clinic "impaired" the inspectors from conducting their inspection, which took place in April and May.

"For example, you delayed the inspection by refusing to allow entry except by appointment only and denied the investigators access to your employees," the letter reads.

"As the vaccine is not commercially available, the FDA has serious concerns about how StemImmune obtained the product for use as part of an unapproved and potentially dangerous treatment," the agency said.

Separately, FDA announced that the U.S. Marshals Service seized five vials of a live vaccinia virus vaccine that was being administered to patients at the California Stem Cell Treatment Centers in Rancho Mirage and Beverly Hills, Calif.

The vaccine – which is only reserved for people at high risk for smallpox, including certain military members – is not commercially available, and belonged to StemImmune Inc., a San Diego, Calif.-based stem cell-based immunotherapy company.

"As the vaccine is not commercially available, the FDA has serious concerns about how StemImmune obtained the product for use as part of an unapproved and potentially dangerous treatment," the agency said in an Aug. 28 announcement. "The FDA is actively investigating the circumstances by which StemImmune came to possess the vaccine."

FDA's inspections of StemImmune and the California Stem Cell Treatment Centers revealed that the vaccine was combined with stem cells derived from body fat to create an unapproved stem cell product which was administered to cancer patients. These patients had "potentially compromised immune systems" for whom "the vaccine posed a potential for harm, including myocarditis and pericarditis (inflammation and swelling of the heart and surrounding tissues)."

Center for Biologics Evaluation and Research Director Peter Marks had previously echoed FDA's sentiments on unscrupulous actors in the arena, noting that the Food and Drug Law Institute’s (FDLI) annual conference in May that there are some "shady practices" going on in the cell therapy world. (Also see "Regenerative Medicines Provisions Of Cures Act A Top Priority For CBER" - Pink Sheet, 9 Jun, 2017.)

Guidances To Come

Gottlieb's announcement also notes that FDA will be issuing a series of guidances this coming fall as part of the advancing the agency's regenerative medicines regulatory framework.

The purpose of the advanced framework is two-fold. For one, it hopes to clarify when a treatment is a medical product subject to an FDA premarket review. Gottlieb notes that certain individualized treatments performed by a physician are in the scope of his or her medical practice, and do not require such a review.

Premarket review is required "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," Gottlieb says.

The second purpose of the guidances, Gottlieb adds, is to "define an efficient process for how these products should be evaluated for safety and effectiveness."

Gottlieb further states that FDA will also issue a compliance policy that that will give product developers "a very reasonable period of time to interact with the FDA in order to determine if they need to submit an application for marketing authorization and to come into the agency and work on a path toward approval."

The agency is issuing the guidances as part of the 21^st Century Cures Act, which requires FDA to update guidance and regulations on regenerative therapeutic products. (Also see "The Evolution Of 21^st Century Cures Legislation" - Pink Sheet, 29 Nov, 2016.)

Benefits For Industry

The new policy could ultimately bring a number of benefits to the rule followers in the regenerative medicine industry.

Michael Werner, executive director of the Alliance for Regenerative Medicines tells the Pink Sheet in an interview that the commissioner's announcement sends a powerful message that the agency will work with honest product developers to help get products that are safe and effective to market.

Werner also touted the explicit acknowledgement of the bad actors in the regenerative medicine field by Gottlieb.

"Clearly what we've got by having the commissioner say it is, No. 1, it shows that the highest level of the agency is focused on it," Werner says. "No. 2, I think it really sends a strong message to people in the field that, 'If you are stepping over the line, the FDA is watching.'"

Werner further noted that the announcement was significant in that it specifically says that certain gene therapy products are eligible for the Regenerative Medicine Advanced Therapy (RMAT) designation, which allows for early and frequent communication between sponsors and FDA. Gottlieb says that the agency plans to include gene therapy products "that permanently alter tissue and produce a sustained therapeutic benefit."

There were initially questions as to how the RMAT designation would apply to such therapies, as the statutory language does not expressly mention gene therapies. (Also see "Will US FDA User Fee Reauthorization Bring More RATS?" - Pink Sheet, 5 Mar, 2017.)

"We know that the field of gene therapy is starting to really fulfill its promise," Werner says. "And so making sure that those technologies also have access to the expedited approval process at FDA really is a significant development."

A spokeswoman for the alliance added that a current negative impact bad actors have on its members is that a lay audience may conflate unscrupulous developers with honest developers when it hears phrases such as "stem cell." FDA's explicit focus on the bad actors could help to alleviate this notion.

"The negative impact that it can have on industry is that they are all tarred with the same brush," the spokeswoman said. "We don't want the two to be conflated."

Former FDA Commissioner Robert Califf was another proponent of the announcement, tweeting that, "Stopping illegitimate fake tx will make room for the proven stem cell uses as they evolve."