As widely reported yesterday, the FDA finalized the draft guidance documents concerning stem cells, or as the FDA refers to the category broadly, HCT/P’s.
The draft guidance documents proposed a couple years ago made it very hard for what I call unregulated stem cell clinics to operate. Based on recent FDA action against a couple of these clinics (see my prior post at http://rickjaffeesq.com/2017/09/22/sleeping-giant-awakens-fda-starts-final-push-eliminate-practice-medicine-stem-cell-clinics/),the tea leaves weren’t looking good for the FDA loosening-up the rules in the final version. Well, the final documents are out and the feds didn’t (lossen them up). The final guidance documents are at least as bad as the drafts, and in one important respect, worse.
Here is the main guidance document on minimal manipulation and homologous use.
The FDA also issued a final guidance document on same day surgical procedures, but practically speaking, that one is irrelevant, based on the main guidance document. And that’s because, per many of my previous posts, the two critical concepts which determine the legality/illegality of the delivery of HCT/P’s to patients outside of clinical trials are: homologous vs. non homologous use, and more than minimally manipulation (“MMM”).
What’s a Non Homologous Use? Answer: It’s what you’re all doing!
If there is one sentence in the FDA guidance document which sums up the FDA’s position on the use of HCT/P’s by the heretofore unregulated clinics, this is it:
“If an HCT/P is intended for use as an unproven treatment for a myriad of diseases or conditions, the HCT/P is likely not intended for homologous use only.” (Page 15 of “Regulatory Considerations for Human Cell, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use”, here is the link again: https://pactgroup.net/system/files/GD_HCTs_20171116_UCM585403.pdf )
To remind you, if the use is non-homologous, (meaning not the same function as from where the HCT/P derived), it’s a drug, requiring the IND/NDA path, and the non-homologous use of which is a violation of the regulation, the law which leads to bad things.
Every unregulated stem cell clinic that I am aware of falls within this FDA statement, and I wouldn’t get my hopes up based on the FDA’s “likely” qualification. If you’re using an HCT/P to cure a disease and it’s not something like hematopoietic cells or bone marrow for blood conditions, blood related cancers, or immune system issues, your use is non-homologous according the guidance documents (draft and final).
When is an HCT/P More than Minimally Manipulated? Answer: Every process used on an HCT/P unless there is scientific proof to the contrary
The nastiest thing in the final guidance document is that the FDA has created in effect an irrebuttable presumption that anytime you do anything to an HCT/P, it’s MMM unless there is information that that the process is minimal manipulation, or as the FDA puts it:
“Please note that if information does not exist to show that the processing meets the definition of minimal manipulation, FDA considers the processing of an HCT/P to be “more than minimal manipulation”, (which basically makes the HCT/P a drug)
For structural tissue like fat, MM is defined by the FDA as “processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement.”
For sure, when you separate the mesenchymal stem cell (“MSC”) from the adipose substrate, that’s MMM, let alone when the MSC is further processed into something like SVF or some other derivative product.
Prior to the draft guidance documents and even under the draft guidances, you were more or less free to argue that what you were doing to the HCT/P was not changing its relevant characteristics or MMM (more than minimally manipulating it), and then presumably force the FDA to prove that you were. Under the final guidance document, if there’s no “information” that what you’re doing is MM, then it’s not.
What Kind of Information is Needed Exactly?
Frankly, I’m not sure. Part of my uncertainty is there is some fuzziness, in my mind at least, about what are the relevant characteristics, etc. It’s an FDA created concept or administrative conclusion, rather than a biological fact or physical thing like a stem cell or HCT/P. Or it’s a question of where you draws the line. So is there a new business in creating “information” that some process doesn’t alter relevant characteristics?
How broad is the Guidance Document? Answer: Broad enough to cover basically any human tissue used by the unregulated clinics.
The guidance document covers almost every conceivable human tissue except some specific things like vascularized human organs, blood and blood components as listed in the regs, secretions or extracts like milk or other bodily fluids, bone marrow not MMM and a couple other things which are not of interest to the unregulated stem cell clinics. All other human tissue is subject to the guideline and the resulting restrictions. (See footnote 3 of page 2 of the guidance document for the list of excluded products).
So is there any Good News in the Final Guidance Document? Maybe, if you’re a Super Optimist
Perhaps to lessen the sting to the unregulated stem cell clinics, (or more cynically, to give them a false sense of hope), right in the beginning of the guidance document, the FDA says that in some cases it will use its enforcement discretion, and not enforce its interpretation of the regulations for three years to give stakeholders time to decide whether they are in compliance with the law or need to go the IND/NDA route. Later in the document, the FDA lists some factors which it will use to decide who it will not go after during these three years. (See pages 21-22).
The good of it is that autologous use lowers the risk.
The really bad of it is that high on the FDA hit list is non-homologous uses for serious and life threatening diseases and where the HCT/P’s are delivered by “high risk” methods like IV, infusion and some other methods. (See page 21 paragraph V B). The FDA considers the unapproved use of HCT’s for such life threatening conditions particularly nefarious since it might delay patients receiving “safe and effective medical treatment.” That’s an unfunny joke because the main, if not the only reason people seek out HCT/P treatment is because there are no safe and effective treatment for such conditions.
So basically, if you’re using HCT/P’s for curing or mitigating diseases other than blood or immune conditions, I’d say you’re not going to be the beneficiary of the FDA’s enforcement discretion largess.
Does that mean you should expect to receive a visit or letter from the FDA in the next year or three?
Not necessarily. There are hundreds of you clinics out there. It takes a lot of man-hours (sorry, person-hours) by many line investigators and back office federales to do each investigation. The FDA’s resources are insufficient to open up investigations and engage in the process of finding violations for anywhere near the number of clinics out there.
So what’s going to happen?
The FDA will continue with the administrative process of the high profile clinics which it has recently targeted. I think it will start the investigatory process with a few other high visibility clinics, as time and person-power permits. This will reinforce the message that the FDA is out there and remind the clinics that what they are doing is illegal (according to the FDA).
It will probably take almost a year or two before there is a judicial decision on the validity or enforceability of the guidance document. A safe bet is that the FDA will bring an injunction action against one of these clinics for not, in effect, closing. Injunction cases are tried to the judge, not a jury.
If the first case involves the Florida clinic where a nurse practitioner injected eyeballs with HCT/P’s and caused blindness, well you don’t have to have a crystal ball to know the result. Like I say, bad cases make bad law.
It’s going to interesting times for the unregulated stem cell folks.
More to follow.
Rick Jaffe, Esq.