Is it the beginning of the end for dubious American clinics that sell transplants of unproven and non-FDA approved fat stem cells?
These new FDA guidances indicate that the stem cell products used by scores of dubious stem cell clinics in the US are almost certainly drugs for which pre-marketing approval and licensing (biological license application or BLA) from the FDA are required in advance of use on patients.
The clinics don’t have that licensing or approval, but they are transplanting stem cells into thousands of patients a year any way and making millions doing it.
In 2012 I imagined in a cartoon (below) a possible future if the stem cell clinics got their way for extreme deregulation. These new 2014 draft guidances are a strong signal that appropriate regulation of the stem cell clinic industry is not going away.
In fact, these new FDA guidances more squarely put scores of such dubious stem cell clinics in the US on a regulatory collision course with the agency.
Could the clinics win out in such a conflict?
It’s very unlikely.
The regulatory path may be a slow one and these are so far just draft guidances, but the eventual outcome is not in much doubt. It is not a question of if, but rather when.
These clinics and their doctors cannot continue with their status quo of using patients as guinea pigs for profit now without serious legal risks to themselves. Indeed, the one thing that could alter the impending collision is if the clinics change course and mend their ways to be compliant in a regulatory sense. It’s hard to imagine that happening, but it is possible that some will try. I hope so.
I suppose the clinics could also try to sue the FDA, but that would likely be a huge waste of money as the FDA would almost certainly prevail in court given legal precedent.
The newer of the two FDA guidances that came out at the end of the past year is specifically all about fat (or adipose) stem cells.
Fat stem cells are the stem cell product of choice for most dubious clinics in the US today. Their fat stem cell product is most often called “stromal vascular fraction” or SVF, which is made by enzymatically liquefying the fat tissue and spinning it through a column to isolate just the cellular “stem cell” part of the fat.
You can see a diagram that I drew of the method to make SVF from my book on stem cells. It’s hard to imagine the stem cell clinic argument that the SVF (cell pellet at the bottom of that tube) is the same thing as the starting fat tissue.
The new FDA guidance makes it crystal clear that regardless of other circumstances, if a clinic makes SVF it is a biological drug legally requiring pre-market approval and licensing by the FDA before you use it on patients.
Again, to my knowledge 100% of these clinics do not have such FDA approval.
The top rationales put forth by the clinics for why they do not need FDA approval seem even more outlandish today after these new guidances.
For example, clinics often claim that the fact that they transplant the fat stem cells in a “same day” surgical procedure makes the fat stem cells not qualify as drugs. The new guidance says that reasoning is invalid if the product is more than minimally manipulated and to be clear it says that fat stem cells are more than minimally manipulated.
Another important issue is non-homologous use of fat stem cells. The clinics often sell fat stem cell transplants to supposedly help a surprisingly wide array of conditions that generally have nothing in common with fat. For example, the clinics sell fat stem cells to treat neurologic or orthopedic conditions or for sexual dysfunction. The FDA draft guidance says that such non-homologous use automatically means that the fat stem cells are drugs regardless of other circumstances.
There is a compelling logic to the FDA guidance here. Fat is fat. It is not nerve or cartilage or other kinds of tissues. This doesn’t mean that fat stem cells cannot ever be used to treat other kinds of conditions, but rather it just means that there is an appropriately rigorous requirement for scientific data in advance before such use should occur.
What should the fat stem clinics do now? Given these new guidances, if I were such a stem cell clinic doctor, I would be stopping my clinic operations right away at this point so as to avoid serious legal ramifications. Otherwise there is a good chance in the future that you will receive a visit from the FDA, perhaps a warning letter, and they may shut you down. Such FDA action may also be a sound legal basis for patients to sue you for malpractice as well.
Below are some key quotes from the newest FDA guidances, which could give the clinics operators some sleepless nights because they sure seem to directly indicate that what the clinics are doing is making and using unapproved biological drugs, which is almost certainly contrary to FDA regulations and hence the law (emphasis mine):
“Example A-1: Adipose tissue is recovered by tumescent liposuction. The adipose tissue undergoes processing or manipulation (e.g., enzymatic digestion, mechanical disruption, etc.) to isolate cellular components, commonly referred to as stromal vascular fraction, which is considered a potential source of adipose-derived stromal/stem cells for clinical therapeutic uses. This processing breaks down and eliminates the structural components that function to provide cushioning and support, thereby altering the original relevant characteristics of the HCT/P relating to its utility for reconstruction, repair, or replacement. Therefore, based on the definition of minimal manipulation for structural tissue, this processing would generally be considered more than minimal manipulation.”
“Example B-2: Adipose tissue is recovered and processed for use, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent, to treat bone and joint disease. Because adipose tissue does not perform this function in the donor, using HCT/Ps from adipose tissue to treat bone and joint disease is generally considered a non-homologous use.”
“Example A-2: Adipose tissue is recovered by tumescent liposuction. Stem cells from the lipoaspirate are then isolated. Cell isolation would typically cause the adipose tissue to no longer be “such HCT/P.” Thus, even if this processed HCT/P from adipose tissue is injected into the same patient from whom it was removed during the same surgical procedure, the establishment would generally not be considered to qualify for the exception under 21 CFR 1271.15(b).”
In order to lawfully market a biological product, a biologics license must be in effect (42 USC 262(a)). Such licenses are issued only after a determination by FDA that the establishment(s) and the biological products meet the applicable requirements to ensure the continued safety, purity, and potency of such products (21 CFR 601.2(d)).
In the end, this new FDA guidance is appropriate and when finalized will further protect the public from dubious stem cell clinics that today are making big bucks off of vulnerable patients via unapproved as well as potentially harmful and ineffective stem cell “treatments”.
Some helpful background posts and FDA links: