Big spike in FDA warning letters to unproven biologics firms

This year already appears to be a record one for cell and tissue therapy-related warning letters the FDA. Directly or indirectly, these come from the FDA’s Center for Biologics Evaluation and Research or CBER.

Something unusual seems to be happening.

FDA’s CBER has been exceptionally active in 2024 including on cell & tissue products

I’ve never seen so many CBER warnings to biologics firms. Most of these are not typical stem cell clinic-type firms, but quite a few are.

Dr. Peter Marks, the Director of CBER, has shown commitment to overseeing biologics firms. It hasn’t always been easy for many reasons.

I count nine warnings so far this year just related to cell and tissue products and we still have three months left. There are many warnings on other biologics too.

For background, in the last few years CBER might issue three warning letters to cell and tissue firms in a year.

Historically, there have been long stretches where sometimes CBER issued none at all or just one or two warning letters to unproven cell firms in any given year. While CBER has been somewhat more active over the last few years, 2024 stands out.

Note that for these searches I’m going by the posted date being within 2024. Also, I searched under “issuing office” for both “biological” and “biologics” to hopefully capture all biologics letters.

Let’s start with the first new warning I recently noticed, which went to Berkeley Biologics. While this warning did not focus on a living cell product, it led me to search the FDA warning letter tool for all recent letters related to CBER.

Berkeley Biologics

Berkeley Biologics, LLC, previously operating as Elutia, Inc. – Orthobiologics Business Unit, formerly Aziyo Biologics, Inc. I had somehow missed this letter, which went to CEO Mesfin Mengesha.

The warning focused on “viable bone matrix products derived from human bone tissue and marketed as Viable Bone Matrix (VBM), Fiber Viable Bone Matrix (FVBM), Cellular Fiber Matrix (CFM)/Excel Viable Bone Matrix (EFM), and Osteo Viable Bone Matrix (OVM).”

I see these as fitting into the cell and tissue therapy category. The FDA said in the letter that these are drugs. In addition, the letter noted deviations from “current good tissue practice (CGTP) requirements.”

My search found warnings to eight other cell or tissue firms.

Other 2024 FDA warning letters in the cell and tissue therapy space

• In January, Kimera Labs and MiMedx got warning letters. So that’s two.
• The FDA warned Neobiosis via a letter to its leader Ian A. White, Ph.D.
• Regener-Eyes maker gets FDA warning on amniotic eye drops
• FDA warned Mother Stem Institute & Alvaro Skupin.This one was also SVF related.
• CARsgen Therapeutics Corporation. It’s uncommon to see a warning related to CAR-T cells. The letter says, “Further, it is a prohibited act under section 301(a) of the FD&C Act, 21 U.S.C.§ 331(a) to cause the introduction or delivery for introduction into interstate commerce of any drug that is adulterated or misbranded.” This seems serious to me and there are also CGMP violations noted.
• Akan Biosciences, Inc.  This one is notable as it is focused on SVF and was issued prior to the FDA winning a big court case on regulating SVF as a drug last Friday. However, here the product was allogeneic SVF and the injunctions sought by the FDA focused on autologous SVF.
• Safari Regenerative Therapy. This is for pets, but still it’s an important one.

Why all these warnings in and around 2024?

It may be that despite Commissioner Robert Califf being publicly quiet about unproven stem cell and other therapies, he has been busy behind the scenes. If that’s the case, it’s a good thing and public statements on this activity may just not be his style. He may have also given Dr. Marks more leeway to issue warnings. Another possibility is that somehow these warnings just kind of piled up behind the scenes only to be made public this year.

Part of me also wonders if the FDA had an early sense that it was going to win the SVF appeals case and so gave itself a freer hand to be more active.

Whatever the reason, I hope this high level of oversight activity continues because there remain somewhere between 1000-2000 unproven stem cell clinic firms in the U.S. While many of these clinics are compliant with FDA regs, hundreds are not.

Why does this matter?

The unproven stem cell clinic industry puts patients at risk.

It’s also bad for the legitimate stem cell research field.

References: additional CBER warning letters this year

• Konrad Rejdak, M.D., Ph.D.
• Massachusetts Institute of Technology MIT. This one is a surprise and relates to their IRB, which is potentially concerning. I may do a post just on this warning.
• Human Microbes
• Barkey GmbH & Co. KG
• New Mexico Lions Sight Conservation Foundation, Inc. dba New Mexico Lions Eye Bank and Indiana Lions Eye Bank, Inc. dba VisionFirst Indiana Lions Eye Bank.
• Washington Fertility Center

Reference: what is an FDA warning letter?

For more background, see this explainer post: What is an FDA warning letter & how should firms respond? The agency can also send untitled letters, which are a step below warnings in terms of seriousness. Often these warnings are sparked from an inspection, but that isn’t always the case.

I believe CBER should be warning more firms based on publicly-available content that shows they are marketing unapproved cell therapy drugs or related products.