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For the Same Surgical Procedure Autologous Stem Cell Transplant Crowd, Big Decisions are a-coming

For the Same Surgical Procedure Autologous Stem Cell Transplant Crowd, Big Decisions are a-coming

If you are in the business of providing autologous stem cell transplants during the same surgical procedure for therapeutic purposes, the next couple of months are going to be very consequential for you because of the decisions in the two big cases in the field.

The appeal of the US Stem cell case is now under consideration by the appellate court. Oral argument was held on January 13th. By some accounts, the judges gave the government a hard time. But you can judge for yourself. Here is a link to the 30-minute oral argument. (its on page 2)

I have always thought that the FDA was in the wrong on the basic issue of whether under its regulations, MSC or SVF same surgical procedures were regulatable under the FDA’s new drug. And that’s for a pretty simple reason. I asked the FDA several times when I was pondering whether to issue what I think might have been the first opinion letter for a facility back in the early 2000s. I was assured a couple of times by different FDA personnel that as long as it was all done in the same surgical procedure (which precluded meaningful expansion/culturing of the cells), the FDA had no jurisdiction over the procedure.

But alas, things changed with the proliferation of these clinics and the increasingly shall I say aggressive advertising engaged by some. The FDA tried to reinterpret its position and tried to amend the regulations with a clever one-word change which it argued made it all subject to the New Drug laws. Since that time, there have been numerous warning letters, and of course, the final FDA’s guidance documents explaining why when a doctor removes a body part and reimplants it, somehow that body part gets transformed into an FDA regulatable drug which cannot be put back into you unless and until the FDA approves testing with other people whose more or less similar body parts are safe to put back into those other persons and does something helpful.  I felt that could only make sense to a regulator, bench scientists, or people who can’t see the forest for the trees.  But that’s just my opinion.

On the other hand, the feds and the states have what I consider to be a nasty doctrine called judicial deference to administrative agencies. It is what it sounds like, and it is a big reason why many complain about the power of the administrative state. To lawyers like me who practice before administrative agencies and/or challenge administrative findings in court, it is always an uphill and frustrating battle. Frankly, it is not a fair fight. And thus, despite believing that the FDA was wrong, under judicial deference to administrative agencies’ determination of the meaning of their own regulations, I thought the FDA would prevail in the US Stem Cell case and in the California case as well.

However, in the last few years, the increasingly conservative Supreme Court has taken notice of the issue, and slowly, a few judges starting writing dissents complaining about it. One or two of them have started to call for the elimination of the whole deference to administrative agency program (and here like in pandemic law, Justice Gorsuch is leading the charge).  But in the summer of 2019, the Supremes limited judicial deference to an agency’s interpretation of its own regulation to cases where the regulation is ambiguous. That’s a start but didn’t go far enough for the vocal minority.

That decision came a month after the district court in the US Stem Cell case issued its summary judgment ruling granting the FDA’s request for a permanent injunction on the grounds that the FDA law and regulations make SVF (stromal vascular fraction) a drug, and that was in part based on the fact that the FDA said so in its Guidance documents, in other words, judicial deference to the all-knowing (or at least all-powerful) FDA.

You all know by now that California District Judge Jessie Bernal took a different view and held that as long as the SVF removed was the same SVF reimplanted that it would not be subject to FDA oversight under the SSP (same surgical procedure) exemption under 21 CFR 1271.15, or at least so he thought and expressed in his opinion denying summary judgment.

Well folks, on Tuesday, January 26, 2021, the FDA’s injunction trial will start against Cell Surgical Network. All the pre-trial paperwork has been on file for many months.  It seems like the trial will take place by Zoom, but that’s more of an assumption on my part since I have not seen anything official about that in the docket. Since the paperwork is already on file (including the parties’ proposed findings of fact and conclusions of law), and because the judge has already ruled on the core issue, I wouldn’t expect him to take too long to issue his decision. I would say inside of 30 days, maybe 45 at the latest.

There is another factor that might propel the judge to issue a quick decision, namely the fact that the Eleventh Circuit Court of Appeals will be issuing its decision on the US stem cell case in the next couple of months. District Judge Bernal may want to give his views on this core issue before the appellate court does and might prefer that the appellate court reacts to his decision, rather than the other way around, given the fact that his is the “inferior” court.

If one of the two court cases resolve in favor of the stem cell transplanters, of course, look to a resurgence of these facilities offering and further aggressively advertising of these services.  That will lead to further action by the state AG’s against these facilities under state consumer protection laws, and possibly by the FTC, though it has not been a significant player in the space. I would guess the FTC is allowing the FDA to clean-up the field via the warning letters.  If both stem cell transplanters lose, then the field will just stick to the new HCT/P’s being used like bone marrow and other more exotic products which are a half step ahead of the FDA (for now).  Either way, I do not see any major restriction on the field, in the short to medium term, and as suggested, I think things could open-up big time if one or both decisions hold that these same surgical procedures are not regulatable by the FDA, But (and there is usually a but), even if that happens, that might just switch the battle to the medical boards, which is probably where the fight should have always been.   And on and on it will go.

Rick Jaffe, Esq.







The Sleeping Giant Awakens: The FDA starts its final push to eliminate practice of medicine stem cell clinics

The Sleeping Giant Awakens: The FDA starts its final push to eliminate practice of medicine stem cell clinics

In late August, the FDA issued a trilogy of pubic actions and announcements advancing its goal of shutting down what I’ll call the practice of medicine stem cell clinics (“POM”). These clinics provide autologous stem cells and other autologous tissue or tissue based products which have not been approved by the FDA. These clinics have exploded in popularity over the past dozen years, which has caused the FDA and the stem cell institutional players much angst. The FDA’s efforts to close these clinics started a couple years ago when it sent warning letters and issued four draft stem cell guidance documents which, if followed, would all but eliminate the ability of patients to use their own stem cells for therapeutic purposes. I’ve discussed these guidance documents often and at length. Here are a few:

The guidance documents propose dramatic changes to critical terms, such as what constitutes homologous vs non-homologous use of a stem cell (or other tissue) and the definition of “more than minimal manipulation.” The purpose of these proposed definitional changes is to render illegal most same day autologous therapeutic transplant procedures.

Last September, the FDA held a two-day public comment hearing on the draft guidance documents. Many of the stakeholders on both sides of the issue testified.

Then there was nothing

Since September 2016, there’s been nary a peep out of the FDA. Of course there was the little matter of the election, and the resulting interesting times. In due course, a new FDA commissioner was appointed.

And then the sleeping giant awoke

In late August, the FDA made three dramatic pronouncements, which have the same underlying message: the FDA is going after the POM clinics. Here they are:

1. Warning Letter to Kristina Comella and the US Stem Cell Clinic in Sunrise, Florida
On August 24, 2017, the FDA issued a warning letter to US Stem Cell Clinic in Sunrise, Florida and its head, Kristina Comella.
Here it is:

Ms. Comella and her clinic had become infamous after an anti-POM clinic New York Times story reported that several patients had gone partially or totally blind as a result of the clinic’s nurse practitioner (NP) injecting the patients’ eyeballs with stem cells (actually a stromal vascular fraction derived from adipose tissue) for therapeutic purposes (macular degeneration). Given these seemingly egregious facts, it was just a matter of time until the feds went after the clinic.

The warning letter had several parts. First, in line with the draft guidance documents, the FDA said that the clinic’s SVF (stromal vascular fraction) was a drug and not exempt from regulation under 21 CFR 1271.15 (see my prior discussions on this regulation listed above).

The FDA’s drug determination had two bases: First, the SVF product was more than minimally manipulated because it altered the relevant characteristics of the adipose tissue (i.e. fat). Second, the use of the fat derived product was “non-homologous” since it was used to treat an eye condition, which is not a homologous use of fat. Thus, the FDA’s conclusion that the product was an unapproved new drug, and not something which is exempt from the FDA’s new drug laws.

The FDA’s other disconcerting finding was that that the clinic was deficient in terms of its CGMP (Current Good Manufacturing Practices) and CGTP (Current Good Tissue Practices) standards, compliance of which is presumably required under federal law. The FDA cited fourteen areas of CGMP and/or CGTP deficiencies.

Based on my experience, it is going to be very hard for a regular medical clinic to be fully CGMP and CGTP compliant. Further, I can’t think of any other examples of types of clinics in which such rigorous standards are applied by the FDA to medical clinics. Also, I have firsthand experience that early on, the FDA took the position that if the 21 CFR 1271.15 exemption criteria are met, the FDA did not have jurisdiction over the procedure or the clinic because it was the practice of medicine. Obviously, the FDA has changed its view.

The warning letter documented the clinic’s impeding the FDA’s inspection, which is never a good idea, since as the FDA pointed out in the warning letter, such actions can administratively transform approved drugs into adulterated ones.

The warning letter acknowledged the clinic’s prior response to these violations (presumably noted in the 483 (i.e. the inspection report issued by FDA inspectors at the conclusion of the inspection)). The clinic argued that it was engaged in the practice of medicine and hence exempt from all FDA drug and inspection requirements. The warning letter rejected the clinic’s contention.

This was the same argument used by the Regenerative Science clinic in Colorado a few years back when it tried to argue that the culturing/expansion of autologous stem cells was the practice of medicine and exempt from federal regulation. Regrettably, the federal court rejected the argument which surely emboldened the FDA in its current mission.

And that brings up an annoying point: Bad Cases Make Bad Law

The Regenerative Science case was a bad case in the sense that under current regulations culturing stem cells seems like more than minimal manipulation. The decision fed the beast, which from my perspective was a bad thing.

The problem with the FDA’s choice of using this particular Florida stem cell clinic is that the case involves nasty, and almost inexplicable facts. A nurse practitioner injecting tissue products into people’s eyeballs! What genius thought that was a good idea, legal though it may be under the Florida scope of practice laws. So when patients were harmed by the NP, the FDA could not have found a better poster child to show the dangers of these unregulated and “illegal” clinics.

My guess is the Florida clinic is not going to roll-over, and will either sue the FDA first (and that case will be dismissed) or wait for the FDA to sue the clinic. It’s going to be a tough job defending the clinic on those facts. If the clinic loses (and there’s a very excellent chance it will), that will be another nail in the coffin in the POM stem cell clinics.

2. FDA Raids California Stem Cell Clinics

Here is the headline from the FDA’s August 28th Press Release involving two California POM clinics:

“FDA acts to remove unproven, potentially harmful treatment used in “stem cell” centers targeting vulnerable patients”

Gulp (or hurray for the FDA, depending on your perspective).

Here is the press release:

According the press release, the clinics were using a live virus vaccine (Vaccinaia Virus Vaccine (Live) on patients, presumably as part of the stem cell or other autologous tissue treatment. The FDA contends that the vaccine is not commercially available and poses a danger to patients. I haven’t heard about the use of this kind of product in processing autologous stem cells, but I’m hoping the clinic has a good explanation, because it will need it.

My guess is that after investigation, the FDA will issue a warning letter/cease and desist, on the grounds that the autologous product which either contains the vaccine or is used to process the material constitutes the FDA trifecta of illegality (introducing into interstate commerce an unapproved new drug, adulteration, and misbranding). I think the FDA may seek to extract a formal cease and desist, then it’s entirely possible that a criminal case will be started, after the civil side is resolved. So watch out you guys!

3. The FDA Commissioner’s public statement

Here is the title of the Commissioner’s August 28th press release:
“Statement From FDA Commissioner Scott Gottlieb, M.D. on the FDA’s new policy steps and enforcement efforts to ensure proper oversight of stem cell therapies and regenerative medicine”
Here is the press release:

Here are some of my favorite parts of his statement:

“There are small number of unscrupulous actors who have seized on the clinical promise of regenerative medicine, while exploiting the uncertainty, in order to make deceptive and sometimes corrupt assurances to patients based on unproven and, in some cases, dangerously dubious products. These dishonest actors exploit the sincere reports of the significant clinical potential of properly developed products as a way of deceiving patients and preying on the optimism of patients facing bed illnesses. . . A select few often motivated by greed without regard to responsible patient care, are able to promote unproven, clearly illegal, and often expensive treatments that offer little hope, and, even worse, may pose significant risks to the health and safety of vulnerable patients.”

* * *

Commissioner Gottlieb further stated that while the FDA has taken action recent action against a few of these clinics, “but unfortunately, these are examples of a larger pool of actors who claim that there unproven and unsafe products will address a serious disease, but instead put patients at significant risk. We will seek to take additional actions in the coming months as we address this field, and target those who are clearly stepping over the line, at the same time that they created potential danger to patients.” (Emphasis added by me)

* * *

“I have directed the FDA to launch a new working group to pursue unscrupulous clinics through whatever and legally enforceable means are necessary to protect the public health.”
Double Gulp. The FDA has painted a target on all of the POM stem cell clinics and the Good Dr. Commissioner Gottlieb is not shy about saying so.

What’s next?

1. Expect the Final Guidance Documents soon

It’s been a year since the close of the public comment period on the draft guidance documents, and it’s been almost a month since the FDA issued its trilogy of announcements of its new campaign against the POM stem cell clinics. So I would expect in the next few weeks the FDA to issue the final guidance documents. We already see the big picture: the therapeutic use of stem cells and other tissue or tissue derived products will be regulated as drugs, meaning they will not be exempt under 21 CFR 1271.15. I hope and expect to see some small carve-outs, like for fat for breast reconstruction purposes. I also expect the FDA to clarify and/or reinforce its position that even for exempt uses under 21 CFR 1271.15, CGMP and CGTP regulations apply. That’s bad news for the POM clinics.

2. More FDA Inspections of POM clinics

I suspect that the FDA has obtained a list of the POM stem cell clinics from the authors of the study published on these clinics.

I would expect the FDA to conduct inspections of some of these clinics, to get the message out that the FDA means business. The initial targets will likely be the big, high visibility clinics whose only business is providing stem cells or such products to patients.

It might be a good idea for POM clinics to have an inspection plan in place before the FDA appears at the front door. FDA inspectors don’t have to make an appointment in advance. They just show up and demand entrance.

A relationship with knowledgeable counsel would be a good idea also. If the clinic is using materials imported from outside the U.S., FDA criminal experience would be good and useful in said counsel, because once the importation becomes known to the inspectors, OCI (Office of Criminal Investigations) is likely to get involved.

So what should the POM Clinics and its supporters do?

As stated, preparing for an inspection would be a good start. Warning letters and guidance documents are tricky regulator creatures. I suspect the founding fathers would have been very perplexed that the system they created could conceive such creatures. But alas, they have to be dealt with, and there’s only two ways to deal with them head on: the courts and Congress. Both avenues need to be explored, but more about that another time.

Rick Jaffe, Esq.