FDA Getting Tougher on Birth Tissue Companies

The FDA may be getting tougher on birth tissue injection companies, experts in stem cells and regenerative medicine said.

In its most recent warning letter to one such company, Re-Gen Active Lab, FDA stated outright that use of its products for “orthopedic diseases or conditions” would not be considered homologous use of human tissue — and thus would need to be regulated in the more stringent class of biologics.

“The key is the blunt, ‘You can’t deploy these products for ortho applications’ statement because it’s non-homologous use. The FDA is rarely that clear, so this is refreshing,” Paul Knoepfler, PhD, a stem cell expert at the University of California Davis, told MedPage Today.

“The language in this warning letter and the multi-year trend of more untitled and warning letters in this specific space suggests the FDA, finally, is moving to shut this down,” he added.

Though the Re-Gen Active Labs warning letter was issued in late May, it recently garnered attention when Chris Centeno, MD — a physician who owns stem cell clinics across the U.S. and who was sued by the FDA about a decade ago over certain stem cell treatments — posted about it on his blog.

“The FDA this week hopefully put the final nail in this coffin with new language that should make anybody selling these products very nervous,” Centeno wrote.

In order to be considered a “361” human tissue product rather than a “351” biologic drug — which requires more substantial regulation — a company must show that its product is used the same way in the patient as it is in the donor, and that it’s been minimally manipulated.

Centeno noted that previously, FDA warning letters to birth tissue companies were vague, and focused on manufacturers’ use of terms such as “cushioning” to promote the appearance of homologous use. But now, he said, the language is much more focused.

In the letter, FDA wrote, “Your products are not intended to perform the same basic function or functions of umbilical cord or amniotic membrane in the recipient as in the donor, such as serving as a conduit (for umbilical cord); or serving as a selective barrier for the movement of nutrients between the external and in utero environment, protecting the fetus from the surrounding maternal environment, and serving as a covering to enclose the fetus and retain fluid in utero (for amniotic membrane).”

The letter also stated that the product fails to meet criteria for minimal manipulation, “because your processing alters the original relevant characteristics of the umbilical cord and/or amniotic membrane related to their utility for reconstruction, repair, or replacement.”

Finally, the agency stated specifically that use of the products in orthopedic indications would not be considered homologous use.

Centeno called the new language “epic” on his blog. “This eliminates all orthopedic marketing for these tissues, which is one of their biggest markets.”

“If I were a birth tissue company focusing on the orthopedic space, I would either fold up shop or raise tens of millions of dollars for a clinical trial,” he wrote.

Centeno said he would expect more warning letters to follow, now that FDA has “very narrowly defined what homologous use is for these products.”

FDA’s new regenerative medicine guidelines went into effect in May 2021 after a 3.5-year compliance period. While the agency has done “surprisingly little” on stem cell clinics since the regulations took effect, Knoepfler wrote on his blog, “a pattern seems to be emerging of warnings and other actions targeting birth-related cell manufacturers.”

He pointed to a February warning letter to Idaho-based Smart Surgical, as well as earlier letters to Utah Cord Bank, Predictive Biotech, and Liveyon.

“I think we’ll see more aggressive action in the coming year, but it may continue to be slower than many of us would have hoped,” Knoepfler said. “COVID and other issues have really slowed the agency down on the stem cell clinic front.”

Leigh Turner, PhD, executive director of the bioethics program at University of California Irvine, agreed that there does appear to be a “general pattern of FDA enforcement activity” aimed at birth tissue companies.

“It looks as though the FDA is investigating and issuing warning letters to a subset of businesses selling non-compliant birth tissue-derived ‘stem cell’ products,” Turner told MedPage Today. “There are many more suppliers and direct-to-consumer clinics still selling such products, and so what I see is a laudable uptick in FDA enforcement activity that is still nowhere close to making a significant dent in what by now is a very large marketplace.”

“I hope FDA, FTC, and state Attorney General offices continue to pursue such businesses and get more aggressive in their enforcement actions,” Turner added, “because all signs indicate that limited enforcement actions encourage such companies and clinics to proliferate with little fear of being investigated or disciplined in any way.”