June 18, 2021

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

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.

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

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

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

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