The FDA started off 2018 with a bang on the direct-to-consumer stem cell clinic front with a warning letter on January 3rd to American CryoStem, a firm involved in processing and distributing adipose stem cells. The company’s ATCELL™ adipose stem cell product was the focus of much of letter.
The FDA indicated in the warning letter and in an accompanying press release (PR) that ATCELL™ is not minimally manipulated and that its administration did not qualify as homologous use. For these reasons, the letter said that ATCELL™ is a drug product, but the firm does not have an IND or other required drug approval. The FDA inspected the company last summer and you can read the 483 inspection report here.
In the bigger picture, the FDA’s recent final guidances and oversight actions paint a consistent picture that adipose stem cells, most commonly referred to as stromal vascular fraction (SVF; you can see my illustration of SVF production at right), are biological drugs requiring FDA pre-market approval. Adipose stem cell businesses, including direct-to-consumer clinics that lack INDs and firms associated with the clinics, generally disagree about SVF being a drug.
In my view, it’s hard to see how such businesses can continue to sell SVF now in 2018 and still be compliant with FDA regs given the steps taken by the agency in the past year and now this warning letter. The FDA’s view of SVF is very clear at this point so there’s little if any gray area left there. On the other hand, most dubious clinics will likely continue selling SVF to vulnerable patients anyway unless there are stronger, consistent steps from regulators. Perhaps the clinics hope that since there are 100s of such businesses that the FDA may not act on their particular firm.
As to American CryoStem, the FDA warning letter and PR noted numerous issues including expansion of the SVF In culture, but also other factors:
“The unapproved product, Atcell, is being distributed directly to physicians to treat patients for a variety of serious or life-threatening diseases or conditions, including anoxic brain injury (caused by lack of oxygen), Parkinson’s disease, amyotrophic lateral sclerosis (ALS), stroke, and multiple sclerosis (MS). Physicians are directed by the company to administer Atcell by various routes of administration, including intravenously, intrathecally (injection or infusion into the central nervous system) and by aerosol inhalation.”
and the agency raised more concerns including related to GMP practices:
“Compounding these risks, the FDA’s inspection also uncovered evidence of significant deviations from current good manufacturing practice requirements in the manufacture of Atcell that pose significant additional risks, such as potentially being contaminated with microorganisms or having other serious product quality defects. Specific deviations included unvalidated processes, an inadequately controlled environment, lack of control of components used in production, and a lack of sufficient and validated product testing.”
The FDA PR on the warning letter quotes both Commissioner Scott Gottlieb and CBER Director, Peter Marks about the agency’s current perspectives on regenerative medicine and risky businesses:
“As part of our comprehensive policy framework for the efficient development and regulation of cell-based regenerative medicine, we’re going to be stepping up enforcement activities against those who manufacture and market products in ways that put patients at risk,” said FDA Commissioner Scott Gottlieb, M.D. “We see great promise from the field of cell based regenerative medicine, but there are also novel risks. Our goal is to implement our new policy framework in a way that helps this promising field advance, while making sure that we address issues that can put patients at risk. It also means taking an efficient, risk-based approach to making sure that products undergoing more than minimal manipulation, which makes them subject to FDA’s review and approval, and particularly products intended to treat serious and/or life-threatening disease or conditions, must prove that they deliver the benefits they’re promising to patients.”
These words from top FDA leadership are encouraging to those of us who are concerned about the big for-profit stem cell clinic industry out there with so many firms lacking INDs and pre-clinical data. However, this quote also hints, as has been suggested in other recent FDA statements, that the agency won’t be going directly after all non-compliant stem cell clinics. Is it possible that the agency believes that issuing a warning letter to a supplier of non-FDA approved stem cells could have relatively large impact? What other firms might be viewed by the FDA as warranting quick action to reduce risks to patients?
Let’s see what else 2018 brings, but I see this warning letter as a positive step and expect more warning letters in the near future.