Next Monday and Tuesday, September 12 and 13th is a widely acknowledged big day in the stem cell world; it’s the two day public hearing on the FDA’s four draft guidance documents. (Here is a link to the FDA’s announcement. http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm462125.htm. The entire event will be live broadcast via a link on this FDA page.
The draft guidances are a big deal because, as I’ve said before, http://rickjaffeesq.com/2016/04/21/stemcells/, they will make illegal almost all autologous cell transplants outside of FDA approved clinical trials, including the ever popular stem cell transplants from adipose tissue. It’s been reported that there might be over 500 U.S. clinics physicians/clinics doing some form of autologous stem cell transplants for a wide variety of conditions, so you can bet that this new industry is watching closing and worrying. They have plenty to worry. Let’s start with what’s out there.
The lines are drawn
For at least the past year, there has been what I would call an institutional attack on the clinical use of autologous stem cells, and by that I mean the use of autologous stem cells outside of FDA approved clinical trials. Thought leading papers, especially the New York Times have run articles against the stem cell clinics both here and abroad. The most recent article, in July, 2016, http://www.nytimes.com/2016/07/28/upshot/stem-cell-therapies-are-still-mostly-theory-yet-clinics-are-flourishing.html?_r=0 seemed more like a retweet or bump of an article by one of the main anti-stem cell talking heads, Paul Knoepfler, a PhD who works at U C Davis. Just google “stem cells and false hope” and see what comes up. Knoepfler published an article which is the source of the now widely reported 500 or 600 plus clinics in the United States performing autologous stem cell transplants outside of clinical trials. But other news media outlets have also taken up the call to ban the clinical use of stem cells until they go through the complete drug approval process. http://www.webmd.com/a-to-z-guides/features/stem-cell-treatments-false-hope-warning-signs
Apart and together with the media outcry are ethicists and public policy position papers decrying the unregulated stem cell business. (Here is one from the Texas Baker Institute http://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-015-0069-x ).
The knock on the clinical stem cell business is that it is unproven and untested and hence might be dangerous or ineffective and shouldn’t be given outside of clinical trials until proven safe and effective. This is same criticism leveled against the “right to try” state and federal legislative initiatives. (See my post on the federal right to try:: http://rickjaffeesq.com/2016/05/24/federal-right-try-hopefully-not/
Maybe the Really Important Meeting Is Not What We Think It Is
What hasn’t received as much attention from the stakeholders is the stem cell workshop which will take place tomorrow. Thursday September 8th which I think will be as or more important. http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm518541.htm.
This workshop will be presentations from the scientific/policy/ethics luminaries and thought leaders. From what I can tell, none of them are directly involved in the clinical use of stem cells beyond what is in accordance with FDA approved use. My guess is that all of the speakers are against the clinical use of stem cells except in clinical trials, and until they pass through the full approval process.
The two lectures I’m most interested in hearing about are : Jonathan Kimmelman, PhD, Ethics, Evidence, and Regulatory Approval for Cell-Based Interventions and Massimo Dominici, MD, Dissecting Unproven Cellular Therapies: The International Society for Cellular Therapy (ISCT) Position.
My guess is that, consistent with the talking heads in the past media articles, their conclusion will be that it’s unethical and dangerous to allow the unregulated use of autologous stem cell transplants outside of clinical trials and before FDA approval.
Why this is important is because I think the FDA is going to cite the workshop position papers as a reason to make the draft guidance documents final without substantial changes. And these speeches will justify the FDA’s position to make adipose stem cell transplants illegal outside of clinical trials.
Why do I think that’s going to happen? Well first the obvious. That’s the import of the draft guidelines and the FDA has had a few years to think about the problem. The problem is that the originally thought-to-be tiny regulatory loophole in 21 CFR 1271.15 (which says that autologous same day procedure transplants aren’t regulated by the FDA) has mushroomed into an entire industry with all kinds of wild west claims and with virtually no barriers to entry stopping any doc from cashing in. That has the FDA very, very nervous.
But beyond the obvious and the din of media and institutional based criticism of the field, there is a broader FDA context, which I am aware of because I do a lot of stuff beyond stem cells.
Let’s look at two other big things the FDA is working on right now.
FDA tries to tame the Wild West of Dietary Supplements
A month ago, the FDA released its long awaited revised draft guidance on dietary supplement NDIs (New Drug Ingredients). The guidance document is highly restrictive and, if enacted, will severely limit access to dietary supplements. (See my recent blog on this http://rickjaffeesq.com/2016/08/16/maybe-glass-still-less-half-full-water-might-start-leaking/
The FDA’s concerns about supplements is basically the same as its concerns with stem cells, namely unsubstantiated claims for products which haven’t been adequately tested for safety and efficacy. The proposed solution: make supplements with “new dietary ingredients” (broadly defined) subject to rigorous testing. Sound familiar?
Pharmacy Compounders Get Unwanted Federal Attention
Second, in 2012, a compounding pharmacy literally killed over 60 people from a contaminated batch of a compounded product. Up until that time, compounders were largely unregulated by the FDA and were overseen by the state pharmacy boards. But many compounders were blurring the lines between a compounded drug for patients and drug manufacturing.
As a result of the outcry over these deaths, there were congressional hearing, new legislation, new regulations, and proposed draft guidances. Bottom line. Increased regulation and scrutiny of these pharmacies by the FDA. This example is different from the NDI supplement and stem cell guidance documents in that there was actual severe harm, but it still shows that if the FDA believes there is an abuse and a regulatory vacuum, they will regulate.
Of course, autologous stem cells are different from supplements or compounded drugs for the obvious reason that the source is the person’s own body, which presumably eliminates contamination from the source issues. But it doesn’t address the claims issue which I think is at the heart of the FDA’s and institutional opposition to the clinical use of stem cells. And admittedly, there are probably still some safety issues, and most likely some training issues, because anyone with a valid medical license can become a stem cell transplanter, and it’s a lot easier logistically than doing brain surgery which requires a real surgical center. In fact, stem cell transplants are commonly done in regular medical offices. Some might view that as not a good thing.
Perhaps interestingly, in the 1997 FDA modernization act, there were advertising restrictions placed on compounders as a compromise solution, but those restrictions were ruled unconstitutional by the U.S. Supreme Court. (Western States. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/UCM155167.pdf. Because of Western States, my guess is that the FDA is not going to offer a compromise by limiting stem cell advertising because of its past negative experience.
For all these reasons, I think the FDA’s mind in pretty much made up. Tomorrow’s stem cell workshop will provide a nice piece of cover, and I expect it to be relied upon by the FDA when the final guidance documents come out.
The FDA has to give stakeholders the right to comment, but there’s no law that says the FDA has to really listen.
Circling back to the dietary supplement NDI draft guidance document, the original one came out many years ago, but due to the enormous public outcry complaining about them, the original draft guidance was rescinded. That bought the field many years of a guidance free existence. Sometimes that’s about as good as you can get, and I think with the stem cell draft guidance documents, that’s as good a strategy as any I’ve heard.
Rick Jaffe, Esq.