FDA Draft Stem Cell Guidance Documents Exposed as Improper Rulemaking, Bad Science and Heartless Public Policy
Today was a good day for people who want continued access stem cells outside of clinic trials, and also for people who want the FDA to allow faster access to this promising technology.
There was a wide spectrum of opinions. Some stem cell companies involved in clinical trials wanted the non-clinical trials clinics shut down. But at least there were representatives from some of these “unproven” clinics and interest groups who made some important points about the rights of patients and how the needs of patients are not being met by the current clinical trials model as it applies to stem cells. I heard a number like 250,000 people are not getting the stem cell treatments they need because of clogged research and regulatory hold-ups. There were numerous calls from very serious, highly credentialed people for the FDA loosen its death grip (my term) restricting access to these therapies, and the thrust of most of these presenters was that these draft guidance documents make thinks much worse.
The guidance document are really bad and deny access for many
And that was the big takeaway for me; that the guidelines were much, much worse than even I thought. I understood that the guidelines would make illegal the 21 CFR 1271.15 exempt same surgical procedures provided by many of the 600 plus unregulated stem cell clinics.
But what I didn’t understand until Monday’s hearing is that the FDA intends to radically change the rules so that, for example, the most popular form of breast reconstruction surgery post mastectomy (flap something) would become illegal under the new guidelines. Many other popular and widely successful procedures in other areas like orthopedics would be eliminated (outside of clinical trials). We’re not talking unboarded docs with no relevant experience who take a weekend course and starts shooting people up with stem cells. We’re talking about big-time breast reconstructive surgeons, highly regarded orthopedists and other highly skilled and specialized physicians who have successfully worked with tens of thousands of patients. If the FDA gets its way, according to these folks, Poof! These best practices transplant procedures are gone.
Fortunately, there were some very smart professionals making presentations, including an extremely knowledgeable law professor from Boston College, Mary Ann Chirba. She and several other people with regulatory expertise made the case that this whole guidance exercise was an illegitimate attempt to pass new rules without complying with the rulemaking requirements under federal law. Works for me!
They and others honed in on the radical revisions to the two key preexisting terms/concepts used by the FDA to work its illegal magic: homologous use and more than minimal manipulation.
What’s a “main function?”
It was also pointed out that the guidance documents invented a new concept not existing in the statute or rule, namely the “main function” of a cell or HCT/P which is used as a way of forcing stem cell procedures from just registration under 362 into the IND/NDA drug approval path. It was argued persuasively by several regulatory experts that the creation of this new concept and its resulting transfer of many heretofore legal uses of stem cells into illegal new drug products turns the guidance documents into rulemaking without following federal administrative rulemaking procedures.
The FDA doesn’t understand what fat does
Another extremely cogent criticism made by a variety of people including Professor Chirba, other regulators and by both of the two top presenting stem cell researchers, Arnold Caplan and Keith March had to do with the FDA’s view of fat. According to the guidance documents, fat just has a structural function. But these presenters and especially March and Caplan showed that the FDA’s view was biologically unsound. Fat has definite, known and extremely important non-structural uses, starting with energy storage and continuing to assistance in the healing function. The FDA’s unscientific, unsubstantiated restriction on fat allows it to find most of the important uses of fat and fat stem cells illegal as either non-homologous or as a more than minimally manipulated product. The FDA was absolutely and repeatedly pummeled on this point by my count, at least a half dozen very, smart experts. I don’t see how even the FDA, which has a very particular agenda, is going to be able to hold on to its limitations/restrictions on fat/adipose tissue.
The Big Guys say regulations are holding back progress
The two big-time researchers (Caplan and March) also made the point that the regulatory climate is holding back research. Caplan said that some bone marrow pioneers had observed that if they had the regulatory environment back then as what exists today, bone marrow transplants might never have taken off. Ouch!
Interestingly, Peter Rubin, the plastic surgeon who last Thursday presented the inspiring cases of reconstruction work from fat transfers, presented again. This time he was more critical of the FDA and stated that many of the most successful reconstructive plastic surgery procedures, including breast reconstruction would become illegal under the draft guidance documents. He and many other excoriated the draft homologous document which classifies fat tissue for breast reconstruction as non-homologous because the primary purpose of the breast is lactation. Several of the female presenters had some polite but pointed words to the FDA about that. Most of the day’s presenters agreed that regulation/regulatory expense was delaying bringing this technology to patients.
The 3 Billion Dollar Player Weighs-in
The biggest dollar player was the California Stem Cell Institute which has a 3 billion dollar budget and 12 research centers. Its director spoke, and his message was clear, concise and right on the money (and with 3 billion, it should be). The FDA has to loosen-up its grip and find an intermediate path between unregulated stem cell clinics and full-on clinical trials, because there is a desperate unsatisfied need and that need will be satisfied – just as water flowing down a hill will find a path – with or without the FDA’s help. He was very persuasive. Reminds me of an old TV ad: “When EF Hutton talks, people listen.”
Interestingly, no one picked up on what I though was the most egregious over reach in the draft guidelines, namely that the FDA guidelines silently incorporated or read the homologous and more than minimally manipulated requirements from 361 registration facilities (1270.10) into the exemption for same surgical procedure places (1271.15). Under the actual rule (1271.15) same day surgical procedures can do non-homologous and more than minimally manipulation. At least those two terms are not in that rule. Legal Method 101 instructs that if terms are in 1271.10 but not in 1271.15, then the 1271.10 terms and restrictions cannot be read into 1271.15 which is what the FDA is doing based on its interpretation of “‘such’ HCT/P’s.” (Maybe too technical. I’ll have more to say about that another time.)
Maybe there is a viable lawsuit
Something else I realized as a result of a couple of the astute presentations. I said in the last post that you can’t sue on a guidance document because it’s just the agency’s “current thinking.” However, if a guidance document is really disguised rulemaking without meeting the rule changing requirements, then maybe there is a lawsuit. Many presenters were clear about the fact that these guidance documents are disguised rule changes, so I’m now more optimistic about the chances of a legal challenge.
People are Mad and are going to do something about it
And speaking of possible legal challenges, while all of the presenters were very professional, very cordial, ostensibly courteous and complimentary to the FDA panel members on the dais, I sensed that quite a few, many in fact, were pretty upset by what the FDA is trying to do with the draft guidance documents.
So here is my prediction/wish/what I hope to make happen. There won’t be one lawsuit filed if the draft guidelines go into effect. There will many lawsuits. I don’t think these folks are going to go quietly. My sense is that the big players, sophisticated players, like Rubin, the fellow who started a society and has 5800 members, the guy with dozens of clinics, they have seen too many good results to give up their most effective tools. All these guys either run or are closely connected to prestigious professional societies and I predict that many of them are going to try to stop these guidance documents, in court or in Congress.
I hope for everyone’s sake the FDA really listened today, because people are mad as hell and they’re not going to take it. They want better and quicker access to this new technology, and my hope is they will get it.
Rick Jaffe, Esq.
10 thoughts on “FDA Draft Stem Cell Guidance Documents Exposed as Improper Rulemaking, Bad Science and Heartless Public Policy”
Great post. Aside from being an example of illegal rulemaking, the introduction of the undefined concept of “main function” by the FDA suggests that they believe themselves to be uniquely capable of discernment of the “main function” of any particular tissue. Most egregious example, of course, being the assertion that lactation is the “main function” of fat… Caplan and others did an excellent job of politely exposing their ignorance.
As the ASPS speaker mentioned, the fact that many states have legislation guaranteeing women the right to breast reconstruction will bring in an immediate conflict between FDA regulation and state laws that were enacted with the backing of HUGE advocacy groups. The new guidances, if enforced as written, would mean that TRAM flaps (which he termed the “gold standard” for reconstruction, already being done I think it was 150K times yearly) will no longer be legal, because they do not restore lactation.
I don’t understand your comment “Legal Method 101 says that if terms are in 1271.10 but not in 1271.15, then they’re in in 1271.15. ” If not a typo, I would appreciate an explanation.
see my post from sept 9th where I flushed out more how the FDA is attempting to introduce the 1271.10 concepts of mm and homologous use into 1271.15 via the “such” HCT/P’s.
re the 1271.10 and .15 point. checked it, there was a word missing. corrected it. hopefully it makes sense now. thanks
First, thank you for this very informative and thoughtful blog.
Now that the FDA meeting has concluded, what guidelines have been issued as a result and what does this mean to clinics practicing stem cell treatments. In particular, what has changed since this meeting has concluded for clinics practicing bone marrow derived stem cell treatments and platelet rich plasma treatments.
all good questions
I think stem cell tourism is probably going to be next on the FDA’s list regarding clinics they want to shut down outside of the U.S. We are a global society now and the FDA seem to have exactly that kind of influence/power. That their policies and the manner in which they arrive at them appear at the very least dysfunctional seem not to matter even where the legal authorities are concerned. As you know, the FDA unilaterally rewrote, without congressional or public approval/notification, Code of Federal Regulation 21-1271. As far as I know, this never became an issue in the courtroom when they were sued by Regenerative Sciences a number of years ago. Regenerative Sciences lost in that case which concerned the practice of medicine versus the creation of a drug. Richard, I hope you are right about legal action being an option against such nonsense. But so far that tactic has not been very promising when it comes to a regulatory body that seems not very accountable to its’ tax paying public.
Great blog. Appreciate all the great info.
Please put me on your list.