In my last post on stem cells, I painted a pretty bleak picture. Based on warning letters and recent FDA guidance documents, the clinical use of autologous stem cell therapeutics is essentially over. The only way patients are going to be able to receive autologous stem cell transplants for non-homologous use is either in FDA approved clinical trials or outside the United States.

This hasn’t gone unnoticed in Congress. In March, 2016, a bill was introduced, by Senator Mark Kirk and others which purports to help. It doesn’t. It creates an illusion of a solution that changes nothing. The bill does not address the core problem which is that autologous stem cells, even if cultured, should not be regulated as drugs, because under any reasonable analysis, they are not. As I suggested in my previous article, the feds are clamping down on stem cells because of the claims made by transplanters and because of the culturing of stem cells. The FDA’s response is draconian and the Kirk bill doesn’t help in any meaningful way.

Under the proposed bill, ostensibly a new regulatory pathway is created. But before we talk about the new path and why it’s nonsensical window dressing, let’s briefly review the traditional approval path. Under current FDA law, to get a drug approved, a drug sponsor needs to file an IND (investigational new drug application). This is a very big deal in terms of time, expense and volume of paperwork. All available information about the safety and efficacy of a drug must be submitted. Usually this information comes from animal studies.  (However, if there is controlled clinical use or foreign studies, such data is submitted which could bypass phase 1 and go right to phase 2 studies.)

All available pharmacokinetics information (basically mechanism of action and interactions) must also be submitted. A protocol setting out all of the details of the dosage, entry criteria, contraindications, endpoints, and a myriad of other aspects of intended use information must be included in the application. In addition, the proposed informed consent form must be submitted for FDA review, as well as information about the study’s IRB (Institutional Review Board). Also, the sponsor must include information about the principal investigators and sub investigators who will administer the investigational drug to the patients/study subjects. Basically, the IND has to convince the FDA that it is safe to administer the drug to humans, and there is some reason to believe that the drug will work as well in humans as it did in animals, (or in humans if there is prior controlled clinical use). In other words, that there is some reasonable expectation of efficacy.  After the IND is submitted (which usually consist of tens of thousands of pages), the FDA has 30 days to review the filing. If the sponsor doesn’t hear from the FDA in that time, the trials can proceed. Oftentimes, the FDA has questions which have to be answered, which begins the back and forth between the sponsor and FDA. This process can move with the alacrity of the shifting of tectonic plates.

Under the Kirk bill, a supposedly new and streamlined drug approval path is created. It’s called “conditional approval.” The bill gives the FDA one year to come up with some kind of framework to conditionally approve a stem cell application, if the sponsor demonstrates preliminary evidence of safety and a reasonable expectation of efficacy, short of phase 3 levels of proof. See section 351B (a) of the proposed bill. https://www.congress.gov/114/bills/s2689/BILLS-114s2689is.pdf).

On its face, this test seems similar to what is required to obtain an IND, except the Kirk bill seems to assume that the treatment has already been used on humans and there is some legitimate clinical trials data supporting safety and efficacy.

Hmmm. Odd. I thought the bill was supposed to make it easier for a person to get his/her own stem cells? But this seems to require more evidence of efficacy than might otherwise be required of a sponsor to obtain a regular old IND.

These two Kirk bill requirements (preliminary evidence of safety and controlled clinical evidence of a reasonable expectation of efficacy) of course give the FDA complete discretion in determining whether the proposed study meets the criteria. If the sponsor succeeds in this threshold showing, then it has five years to submit the data in an NDA (new drug application).

However, in detailing the additional requirements for obtaining “conditional approval”, Section 351B (b) (8) requires that that the sponsor submit an IND in order to treat any patients under the “conditional approval.”

OK, so everything which has to be submitted in a regular IND has to be submitted for “conditional approval” because you can’t get conditional approval without submitting an IND.

So in substance and paperwork requirements, the bill seems more cumbersome than the requirements for an IND, at least an IND with a couple different protocols.  So what’s the point of the conditional approval thing?  I haven’t figured that out yet.  Seems that the Kirk bill is a waste of time and energy, despite the fact that something like 80 organizations support it. Maybe the devil is in the details. One could always hope that the FDA will actually come-up with a more streamlined process to allow patients to receive stem cells, but I’m just not feeling it from what is in the bill.

My underlying problem is that I don’t think a person’s cells are drugs or should be regulated/prohibited as “unapproved new drugs.”  There seems to be something fundamentally odd and wrong about the federal government regulating a person’s own tissue when the tissue or part of it is reinjected. I get that the separation should be done in a sterile and effective way, (read that the cells aren’t contaminated or destroyed by the separation process) and that the centrifuges should be validated and FDA cleared. But regulating a person’s own biological material which is removed and then reinjected, well that just seems crazy intrusive, or just plain crazy to me, except in the Bizzaro regulatory world.  But actually, the FDA used to agree with my view, in part at least, because up until the first warning letter in 2012, the FDA interpreted 21 USC 1271.15 as stating that separating stem cells from tissue or structure was the practice of medicine and not subject to FDA regulation as long as the product was reinjected in the same surgical procedure. The FDA only changed this reasonable position based on the perceived abuse by stem cell transplanters  (my interpretation).

In that regard, I also get that government agencies might or should be concerned about these exaggerated claims. But the state medical boards can and do police physicians based on their web sites and information conveyed to patients. I think the state medical boards are in a better position to handle enforcement actions against unsupported claims. And of course, this is more in-line with the seeming intuitive notion that a person’s tissue or cells are not drugs just because the material is removed and reintroduced into the body. Both the FDA and the FTC have the statutory jurisdiction to go after the transplanters for false claims if they think the medical boards aren’t doing their job. But prohibiting what is essentially a surgical procedure seems like an unnecessary and complete overreaction to the problem.

So what needs to be done? It’s not complicated. Congress should statutorily overturn the FDA stem cell guidance documents and warning letters by passing a law that autologous stem cell transplantation is the practice of medicine, even for non-homologous use, and even when the cells are cultured/expanded.  Let the state medical boards police the autologous stem cell transplant physicians in terms of their claims and therapeutic use. Texas is already doing just that. Organizations or other sponsors can still do clinical trials. People will still enroll in trials the way they do now, (or did before the warning letters) because of the financial incentives to the patients in enrolling in clinical trials (the “drugs” are free and so are many associated costs). But at least those who decide to have their own stem cells reinjected in their bodies will have the option to do so without government interference, and in my view, that’s a good thing.

Any brave Congress folk willing to take on the FDA?

Richard Jaffe

rickjaffeesquire@gmail.com