Another FDA letter to a stem cell clinic supplier: what’s the agency’s long game?

The FDA just sent another untitled letter to a producer of a potentially non-compliant perinatal “stem cell” product that may be an unapproved drug. This follows past non-warning letters and/or inspection reports made public to Liveyon, R3 Stem Cell, Stemell, and others. RAPS has more on the story of the new letter here.

This newest untitled letter went to RichSource Stem Cells, Inc. and its CEO Sara Oracle, a firm which markets an unusual “combo” product described this way by the FDA, “a combination of amniotic fluid and membrane, Wharton’s jelly, and placental tissue.”

In my view it’s very difficult to see how such a complex allogeneic product would not be considered a drug. Also, do all the different components come from a single donor source in each case? I kind of doubt it, and if they come from different donors that makes the product even more likely to be a drug in my view.

Plus, it seems that RichSource is marketing this RICHGEN product for many health conditions having little-to-nothing to do with the inherent nature of the constituents, invoking nonhomologous use. Thus, overall RICHGEN sure seems to me to be a drug. The FDA makes some of these points in its letter (emphasis mine):

“Based on a review of your website, it appears that no exception in 21 CFR 1271.15 applies, and the products offered by RichSource Stem Cells, Inc. are intended for nonhomologous uses. Additionally, they appear to not meet all the other criteria at 21 CFR 1271.10(a), and accordingly, would be regulated as drugs as defined in section 201(g) of the FD&C Act [21 U.S.C. 321(g)] and biological products as defined in section 351(i) of the PHS Act [42 U.S.C. 262(i)]. In order to lawfully market a drug that is also a biological product, a valid biologics license must be in effect [42 U.S.C. 262(a)].”

As with the other perinatal suppliers, I don’t quite understand why the FDA is sending them each an untitled letter. Such letters don’t have much in the way of teeth, so to speak. Earlier I was upbeat about the FDA sending so many of these letters (dozens now it seems), but where has it gotten us?

Are these scads of untitled letters to various unproven stem cell clinic-related firms doing any good? It’s hard to say if they are changing many corporate behaviors. Maybe in a few cases. Does an individual firm care that much if it gets an untitled letter? Also, not all of these letters have been publicly released by the FDA so if they in part are intended to raise awareness, how much has that been helpful?

Or maybe the agency agenda here is that these letters lay the foundation for robust, rapid actions once the FDA’s 3-year “grace period” of a sort ends next year?

At that point maybe the FDA is going to send dozens of warning letters to firms that haven’t “shaped up” into compliance? Or maybe the agency will even directly seek injunctions against many firms?

Perhaps the agency is thinking they can more easily take these kinds of bold steps without having to do standard, lengthy inspections of every one of these firms in advance since it already sent them the untitled letters? Technically, the FDA could take more bold steps any time it sees particularly risky non-compliance even during the grace period and even without having sent untitled letters first.

As to the grace period itself, many of us feel the FDA erred in establishing such a long period during which many forms of non-compliance can apparently flourish. Unproven stem cell clinic and supplier firms have seemed to keep on going and new firms have even popped up during the 3-year period. RAPS quoted long-time fellow stem cell clinic critic, bioethicist Leigh Turner:

“Turner added that he thinks the 36-month period “was too lengthy” and has “provided a period where many more businesses are entering the marketplace.” Corporate records for RichSource show the company was incorporated in 2018, just months after FDA released its regenerative medicines framework and announced the 36-month enforcement discretion window.”

During this window are non-compliant firms at most subject to untitled or more rarely warning letters? As long as what they are doing does not reach a certain level of risk, business as usual can proceed even though there’s an unapproved drug involved?

What does it take for the FDA to be spurred to take more robust action such as the suits against Cell Surgical Network/California Stem Cell Treatment Center (still pending) and US Stem Cell Inc (FDA prevailed and case has been appealed)?

How does the agency decide, “Okay, these 700 noncompliant firms will get no action, these other 60 firms will get untitled letters, these few get warning letters, and then these handful of firms will get sued for permanent injunction?”

What’s the logic behind the different responses? A range of perceived risk?

I hope the FDA has a long game in place. Next year when the grace period ends there are likely to be hundreds of clinics and supplier firms that are actively non-compliant. Hopefully these untitled letters will have some positive role.