US Stem Cell Inc (USRM)

[Dragon Lady]

PhD Blogger SHREDS Comella FDA "Response", LOL !

TITLE:

"FDA Hammers A Flaunter of the Rules Against Making and Treating Patients with Fat Tissue-derived Stem Cells – "

LOL !! Freaking brilliant if you ask me....amazing...."FLAUNTER", LOL !

One of the most brilliant pieces of writing I've seen in a long, long time. This guy per his resume is extremely experienced at all types of "stem cell science" and also extremely experienced at "FDA REGULATORY MATTERS" related to same, and he "dissects" the so called "Comella response" to the FDA.

It's a real hoot and some very entertaining reading- as he, comes to the conclusion basically (just as the FDA did to prior Comella 483 "responses" if one reads the FDA FORMAL WARNING LETTER) that her "response" doesn't really address ANYTHING the FDA raised in their very, very serious and formal "warning letter".

I'm of the same opinion- I don't believe she addressed a single issue the FDA raised, nor does it look like any "WARNING LETTER" proper response that I've ever seen or read (basically arguing with THEE FDA and essentially telling um, "YOU'RE WRONG" and what you state is, NOT TRUE, etc...freaking mind blowing), nor did she lay out any formal plan, which would normally be PAGES and PAGES of extremely detailed process changes etc, laid-out in extreme detail to explain how they will STOP violating the violations the FDA cites in extreme detail, and the "WARNING LETTER" says that they already rejected her prior attempts at a similar "reply", stating basically, "WE RECEIVED YOUR REPLY AND IT DOESN'T ADDRESS A SINGLE THING WE CITED IN THE PRIOR 483 WARNING/OBSERVATIONS" (paraphrasing, but basically what it says)

Here is this PhD stem cell scientist (a real, bona fide scientist by the way, look at his credentials and resume and industry background) and he piece by piece, dismantles the "Comella Response" and it's a hoot, a real gut buster it's so damn well written IMO (done as a five part series so far, and looks like more to come):

https://www.greyledgebiotech.com/fda-hammers-treating-patients-fat-tissue-stem-cells-part-one/

https://www.greyledgebiotech.com/fda-warning-letter-treating-patients-fat-tissue-stem-cells-part-two/

https://www.greyledgebiotech.com/fda-warning-letter-comella-treating-patients-with-fat-tissue-derived-stem-cells-part-three/

https://www.greyledgebiotech.com/fda-warning-letter-treating-patients-with-fat-tissue-derived-stem-cells-part-four/

https://www.greyledgebiotech.com/fda-warning-letter-treating-patients-with-fat-tissue-derived-stem-cells-part-five/

Some quotes, it's just fantastically written IMO, just great stuff:

"Last Thursday, the FDA issued a Warning Letter to Ms. Kristin Comella, Chief Scientific Officer (CSO) of US Stem Cell Clinic, LLC (USSCC). And although it looks like your run-of-the-mill letter it actually is a hammer—a FDA hammer. The recipient, USSCC, is a subsidiary of US Stem Cell, LLC, for which Ms. Comella also is CSO. Apparently, the FDA got fed up with Ms. Comella running around the country flaunting her views about making stromal vascular fat (SVF) preparations from a patient’s fat tissue and treating patients. I was fed up a long time ago with her fantasies about being able to process a patient’s fat tissue to create SVF and treat patients at point-of-care."

"Glad I could help you out Ms. Comella, while you wait for the FDA to get around to answering your questions.

Now, I will go back through the Warning Letter to highlight the sins your clinic committed that don’t involve cGMP standards—the standards needed if you are making a drug. I am not saying the SVF you make in your clinic isn’t a drug, just that there are some disturbing examples the FDA cited that have nothing to do with the fact that your clinic falls well short of the quality framework needed when making a biologic drug."

"What I find so fascinating about this answer is that there is a fairly large discrepancy between the statement shown above and statements the FDA made in their Warning Letter. The company wants us to believe that they just perform a so-called “mini-lipo” and then centrifuge the lipoaspirate, which presumably produces a pellet of mechanically-released cells generated during the liposuction procedure. From the language I excerpted above, it would seem that USSCC doesn’t do any additional processing of a patient’s liposuction sample.

On the other hand, the FDA indicates that the USSCC processes a patient’s fat tissue to produce a stromal vascular fraction (SVF) preparation. I created, optimized, validated and commercialized a technology platform at Vet-Stem, Inc. in 2002/2003 that provided an autologous SVF preparation for veterinarians to treat horse, dog and cat patients. So I understand what it takes to make a SVF preparation. And it is a lot more than what the USSCC indicates they do to create a SVF, which is limited to centrifuging the lipoaspirate and treating the patient with (presumably) the pelleted cells. This procedure, as minimalist as it is, still is not compliant with 21 CFR 1271 in my opinion, but that is another post.

Here is what the FDA wrote specifically about the USSCC SVF procedure in the Warning Letter:"

"However, I will spare you the somewhat pedantic review for now that would be required to sort out what appears to be serious problems detected by the FDA in Comella’s clinic and its provision of stromal vascular fraction (SVF) therapy. Instead, I want to focus on what has to be one of the most brazen rebuttal letters made public in response to an FDA Warning Letter that I can recall, signed by K. Comella, which she offered up as a defense of her methods of working with a patient’s own fat tissue to produce SVF.

The letter is rather long and repetitious, but perhaps convincing if you buy into Ms. Comella’s bit about “my body, my cells”. Since I try to remain firmly rooted in reality, which is why I am a somewhat boring scientist, I found her letter to be a real scream. Instead of going line-by-line or section-by-section, which would take me to the end of the year to deal with all of the tautologies and contorted thinking, I will focus on answering the 12 questions that appear at the end of her diatribe. I will present her questions exactly as written."

"Comella Question Eleven: “Why is the FDA ignoring the requests of tens of thousands of citizens to keep these therapies available?”

My Response: The point is a fair one, since isn’t the FDA supposed to work for the American people? Kind of. The problem is the FDA doesn’t get a warm and fuzzy feeling from clinics like yours in view of the three patients who under your clinic’s care ended up blinded or with highly diminished eyesight after receiving SVF therapy for macular degeneration. I also don’t see eye to eye with you on using SVF to treat the myriad of other pathologies like ALS, Parkinson’s, etc. for which you believe SVF would be an effective therapy, with no justification provided anywhere. Since your clinic’s approach to offering SVF therapy has failed the “do no harm” ideal you mentioned, somewhat ironically, in your rebuttal letter, I don’t see why the FDA should give in to public sentiment, since the public doesn’t know what I suspect the FDA knows—medical clinics are less than ideal places to be manufacturing stuff like SVF with manual methods, and those clinics certainly shouldn’t be using it."

"She also has claimed that SVF can be used to treat an incredibly wide variety of pathologies, including autoimmune diseases, COPD, diabetes, Parkinson’s disease, and, well, you get the picture—a veritable kitchen sink of illnesses and diseases. The problem is that for her clinical program to hang together SVF must be used in a homologous way. Not surprisingly, the FDA quite clearly indicated their unhappiness:"

"Comella claimed her company’s activities were beyond the jurisdiction of the FDA, since she believes SVFing is a part of the practice of medicine. The FDA was having none of this nonsense:"

"Comella Question Six: “Are you intending to limit surgical procedures which have been in practice for decades that involve more than minimal manipulation?”

My Response: This is a bit of a puzzler, Ms. Comella. The whole point of subpart 1271.15 is to provide physicians with the opportunity to practice medicine, since the FDA isn’t allowed to intervene with a physician’s approach to treating a patient. So, I would guess that the FDA isn’t interested in invading surgical suites to police what is going on. I am curious though why you think you have a good understanding of what is and isn’t compliant with respect to minimal manipulation. I read the draft guidance on minimal manipulation the FDA issued in 2014 and thought it was pretty obvious you couldn’t digest fat tissue to produce SVF and still meet this requirement. Apparently, you thought differently."

"Comella Question Eight: “Are clinics using fat tissue but not using enzyme permitted to operate?”

My Response: Kristin, Kristin, Kristin, what a poorly formulated question. It all comes down to the degree of manipulation of the fat tissue and what its intended use is—as in 1271.10(a)(1) and 1271.10(a)(2). Not to put too fine a point on it, but if someone wanted to create SVF via an enzymatic digestion protocol and did so within a clinical trial format (probably an IDE), a company eventually might get approval to market their enzyme-digested fat tissue system. And the FDA would be smiling, since that company played by the rules. The problem for the FDA is that hundreds of clinics have decided they didn’t want to spend tens of millions of dollars and wait 5-7 years to get approval, so they just opened their own SVFing clinics, like you did. In contrast to the Warning Letter you received from the FDA that highlighted your non-compliant use of a patient’s fat tissue, fat grafting is widely used for cushioning or supporting subcutaneous layers, like in the face or the hand, and it is FDA-compliant. Clearly, some fat tissue preparations currently are being used in clinics without an issue with the FDA."

SHREDS like he just surfed a winter pounding at Mavericks...the guy is a great writer....LOL.....those are just mini slices...the guy CLEARLY KNOWS FDA REGULATIONS and how to properly comply and operate in FDA REGULATED ENVIRONMENTS and his resume, again, I'd say makes him a "qualified expert", so the blogs are just brilliant IMO. He's gonna write another part, addressing the specific violations the FDA WARNING LETTER CITES and how serious they are, in PART SIX. I think he publishes once a week- something like that. GOOD STUFF, fascinating to me.