New data on stem cell clinics, INDs, & more including from FDA itself

The International Society for Cell & Gene Therapy or ISCT held a really interesting webinar yesterday on the FDA and unproven stem cell clinics. It was focused on the expiration of the FDA’s discretionary period on unproven stem cell clinics.

What will the FDA do now?

The webinar included some ideas and also quite a bit of important data that I had never seen before.

Let’s dig in.

ISCT webinar on stem cell clinics

What the discretionary period being over means in English is that the FDA gave clinics three and a half years to become more compliant and that’s over.

Can the FDA or other entities like states make a real dent in the clinic industry?

Speakers at the webinar tackled this question and gave important background. They included:

  • Dr. Laertis Ikonomou
  • Dr. Wilson Bryan, Director of the FDA’s OTAT Office
  • Vermont State Senator Dr. Virginia Lyons
  • Michael Lehmicke, Senior Director at ARM
  • Dr. Leigh Turner

It was a great meeting with substantial new information. Dr. Ikonomou chaired the webinar and posed some good questions to the others.

fda period of enforcement discretion stem cell clinics
FDA actions during period of enforcement discretion on stem cell clinics. Screenshot of slide from Dr. Bryan.

From FDA OTAT office on clinics and INDs

I took notes on this meeting and some screenshots. I’m just going to give some of the highlights of what I thought were the most interesting parts.

The FDA’s Dr. Bryan provided some new data that I thought were striking. Note that OTOT at FDA means the Office of Tissues and Advanced Therapies, which I believe is a branch of CBER.

The FDA has been very busy during the “grace period” as I’ve called. It’s not like they have just been waiting around. Bryan put up a slide enumerating their actions during this time. See above.

To say that’s many letters is an understatement. Those 400 mini-warning letters of a sort (they don’t seem to have a name as a type of letter) are unprecedented in this field. The FDA deserves kudos for these actions. These actions illustrate that although there was a grace period of a sort, the FDA had the authority to take actions on any clinics during this time.

I wonder more broadly has the FDA ever sent out 400 letters to firms in any space? Maybe e-cigs? Maybe not.

I’m hoping is that FDA now uses them as a foundation to get busy taking strong enforcement actions. It would be along the lines of, “Look we already sent you a letter indicating your non-compliance, you are still non-compliant now, so now here’s your $50,000 fine.”

fda cell therapy inds
FDA data on cell therapy INDs cleared over time. Note the huge jump in 2020, probably related to COVID-19. Screenshot of slide from Bryan presentation at ISCT webinar.

A slide he put up on INDs was also striking. See screenshot above. You can see the general trend of the cell therapy field expanding as indicated by the steady increases in cleared INDs, but that jump in 2020 is unusual. He mentioned it being related in part to COVID-19.

Dr. Bryan characterized the increasing number of cleared INDs as a positive. Maybe so in part. However, I’m not so sure one can make that blanket assessment.

Did the FDA lower the bar too far during the pandemic for cell therapy INDs? I think it’s likely.

Some of the clearances of INDs related to the pandemic have been problematic in my view. A few COVID-19-related INDs from stem cell clinics were even green-lighted.

In the Q&A in the chat I asked Dr. Bryan if he could provide data on the total number of cell therapy-related IND applications, but didn’t get a reply. I’m going to ask him directly for this data. I’m curious if the FDA approved a much higher percentage during the pandemic. I’m sure part of it was that they received a lot more INDs, but the approval rate is key.

Leigh Turner: staggering new clinic numbers

I found Leigh Turner’s talk to be fascinating.

In addition to placing all of this in the appropriate context and presenting some ideas about approaches to the problem, Leigh presented actual data. It’s become clear over the past 5 years or so that we need concrete data on this problem.

When Leigh and I published our 2016 Cell Stem Cell paper for the first time with data on clinic numbers many people were shocked. In 2016, we found 351 businesses operating 570 clinics. By March 2017, Leigh reported a big jump: 432 clinic firms running 716 clinics.

What caught even me off guard was Leigh’s numbers for 2019, which he presented at this webinar. My sense is that there were around 1,000 clinics in the U.S.

He reported 748 firms running 1263 clinics.

This obviously presents a massive problem for the FDA, patients, and our country. It’s also a threat to the legit stem cell field. Note that some of these unproven clinic firms are technically FDA-compliant even if they don’t have solid data to back up what they are selling.

I’m thinking the pandemic has made a small dent in clinic numbers just as it has been so hard on legit businesses. However, it’s likely that the clinic industry is already bouncing back. My small, informal phone survey of stem cell clinics during the pandemic found that many were still open for business. Some weren’t.

arm slide fda trip program
ARM slide with data including on FDA TRIP program. Screenshot of slide from Lehmicke presentation at ISCT webinar.

Looking ahead on stem cell clinics

Vermont State Senator Virginia Lyons (who is a Ph.D. scientist) and Michael Lehmicke, Senior Director at ARM, also made interesting points. Vermont has passed a law on stem cell clinics requiring in part signage to inform patients.

Dr. Lyons noted that before the law the state had 3 clinics and now it only has one. I’m not sure if the law played a role in that. She also noted that the one remaining clinic seemed to want to fight it out. It’s likely to end up in the courts.

I thought Lehmicke’s most interesting slide was related to the FDA’s Tissue Reference Group Rapid Inquiry Program. This TRIP mechanism was operational also during the discretion period. As you can see in the screenshot above, TRIP has gotten many inquiries. Most products assessed by trip have been 351s. These are interesting data that I had not seen before.

The big remaining question is what the FDA is going to do about all these stem cell clinics now that the grace period is over.

What do you think is going to happen now?

Recently I wrote that I think the FDA needs to ‘go big’ on the most serious offenders now that grace period is over. Even if the agency “goes medium” on this problem it could still have a big positive impact if it targets the riskiest clinics with actions that have some real teeth. Fines and injunctions are needed for them.

7 thoughts on “New data on stem cell clinics, INDs, & more including from FDA itself”

  1. “There are risks of contamination and spread of disease as we saw with Liveyon and I’m aware of other cases of infections.”

    Dr. Knoepfler. What does your statement above have at all anything to do with the autologous use of one’s own stem cells? You’ve brought up essentially the allogeneic use of a biological product, I will agree that the FDA should regulate a company similar to Liveyon because they are involved in the mass manufacturing/distribution of a product to the masses across state lines. Similar to what drug companies do. But , how did you get there from what I am talking about? Specifically the autologous use of one’s own stem cells. I am sure there are risks of contamination in terms of using one’s own stem cells also but that is also true with regard to the practice of medicine which should be regulated by the state medical boards. Not the FDA. The risk of contamination from invasive surgeries for instance like knee and hip replacements is I’m sure greater than that of trying something less invasive first like PRP or stem cell injections into those anatomical areas. And my point is that Liveyon would likely not even exist as a company had the FDA not made their one word change in its’ Codes of Federal Regulations suddenly giving themselves authority into the practice of medicine and essentially a person’s own body. After all, what need would most folks have for a Liveyon product if allowed use of their own for instance, adipose derived stem cells?

    “As to “never been litigated”, what about US v. Regenerative Sciences? And now US v. US Stem Cell? The FDA prevailed in both cases and as to the newer case, an appeals court just supported the ruling in the FDA’s favor.”

    To my knowledge FDA’s impropriety in violating the Administrative Procedures Act bypassing the extensive public comment making period before making changes to CFR 21-1271 was not mentioned in either the Regenexx or the US Stem cell cases decided in 2014 and 2021 respectively. FDA prevailed in these instances as you mention above. But as far as I know, neither case involved FDA’s improper change to their codes of Federal Regulations. Perhaps they were just dismissed by the Judges involved. I read nothing about FDA impropriety at this link regarding the 11th circuit court of appeals decision here Perhaps you can send me a better link?

    “State medical boards are not authorized to regulate drugs. While some offerings of stem cell clinics may not be drugs, many others clearly are and that again has been supported by federal courts”

    I think you are begging the question here with regard to adipose derived stem cells. California has yet to weigh in on this notion of whether or not adipose derived stem cells constitute a drug. And with the exception of the most recent ruling by the 11th court of appeals in Georgia, judges having decided in favor of the FDA thus far did so under judicial deference to a federal regulatory authority. The Judge in California may not exercise that same option. I’ll wait and see whether or not he brings up FDA’s impropriety with regard to the the Administrative Procedures Act of the 1940’s.

  2. Unfortunately, unless and until these restrictions are enforced and these predatory clinics that have no business treating patients get shut down, people will continue to permanently injured. We continue to see it first hand and it is not slowing down! Both, our patient population and those doing real research through clinical trials are at great risk!

  3. Restricting the autologous use of stem cells to the public really amounts to prohibition in my estimation. While all this condemnation on The Niche exists towards “Predatory Stem Cell Clinics” many who are eager to agree with the notion of a more muscular FDA fail to understand that FDA had a huge role in creating the very industry of stem cell clinics so often condemned on this blog in my opinion. This American time honored phenomena of prohibition creates the very problems it purports to address. Laws said to work in the interest of society end up instead elevating yet another bogey man and consequently a perpetual money pit with no end in sight in terms of adequate funding. Prohibition for its own sake ends up being the means to its own end. This has been true with regard to sex, gambling, alcohol, drugs and now regenerative medicine. Instead of simply allowing state medical boards to regulate the practice of medicine like they were mandated to, the FDA decided it also wants this authority which they were never created to regulate.
    The problem isn’t limited authority to the FDA, It is in allowing them authority that simply does not apply to them. FDA improperly made changes to their Codes of Federal Regulations that were originally supposed to apply only to the allogeneic use of human derived stem cells. FDA then unilaterally expanded this power to include the autologous use of our own stem cells. Then FDA, by extension, began referring to our own mesenchymal autologous stem cells as “drugs”. This was neither proper nor legal on their part and amounts to a veritable Code of Federal Regulation house of cards. Unfortunately FDA’s impropriety has never been litigated. (They Violated the Administrative Procedures Act of the 1940’s) This is not the sort of agency I’d like to further strengthen. IF given their way, the FDA will now be demanding more money every year just like the Coast Guard, DEA and police authorities do, to fight the war on drugs. Only this will be against the very stem cell clinics they likely helped to create. And thanks to the propaganda industry, we’ll keep hearing about how close FDA is to stopping this new bogey man of a shadow industry year after year particularly during tax season. Sound familiar? Sure. Just give the FDA more money, more resources, more authority, more technology etc and they will certainly defeat these dreaded and “predatory stem cell clinics”. How has that worked so far with regard to the shadow industries I just named?

    1. @Doug,
      Your claims are almost entirely incorrect.

      I can’t see any way that the FDA created the unproven stem cell clinic industry. That’s just false. Their slowness to act did give space for expansion, but that’s not the same thing.

      Second, when you say “prohibition for its own sake” regarding the FDA and the clinics, that’s also completely wrong. There are good common sense reasons for FDA oversight of stem cells. Let’s take just one type of risk: infectious disease. There are risks of contamination and spread of disease as we saw with Liveyon and I’m aware of other cases of infections. The FDA isn’t regulating clinics just because it can. In addition, there is no “prohibition”. There are just rules one has to follow to go down certain paths with a treatment.

      As to “never been litigated”, what about US v. Regenerative Sciences? And now US v. US Stem Cell? The FDA prevailed in both cases and as to the newer case, an appeals court just supported the ruling in the FDA’s favor. The appeal’s court ruling was very well written and logical. I recommend reading it.

      State medical boards are not authorized to regulate drugs. While some offerings of stem cell clinics may not be drugs, many others clearly are and that again has been supported by federal courts.

      I’m also not aware, as you suggest, of the FDA getting more money for its oversight of stem cell clinics.

      Overall, the comparison to Prohibition just doesn’t work.

  4. what good is a 50K fine (not to mention a 13K fine) for clinics that are charging around 20K (my guess and from what i have seen on the internet) for a treatment? they should have more like at 250K fine or even higher.

  5. I watched the presentation, too. It was dismaying to see the unintended consequences of FDA’s grace period. The number of predatory stem cell clinics continued to rise, and many added a new way to exploit people by claiming they had cures for Covid19. Because the FDA warnings lacked teeth, the clinics just disregarded the FDA, and most will continue to do so until there is some penalty. I think the solution is to strengthen the FDA so they can be more vigilant in investigating these clinics. The consequences of their actions or inactions are huge and have tremendous impact on our health.

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