Breaking: New FDA Draft Guidance Views Fat Stem Cells As Drugs

FDAWith a new document released today the FDA is more clearly on a path to regulate dubious stem cell clinics in the US.

There are more than 100 such American clinics that are selling stem cell “treatments” to patients and almost all of them use non-FDA approved stem cell products isolated from fat tissue.

The clinics have argued that they do not need FDA approval and just keep on raking in big profits from vulnerable patients.

They have claimed no need for FDA approval because they believe that the stem cells isolated from fat tissue that they use are not “drugs” because they are “not more than minimally manipulated.” In English that means that the clinics are arguing that the purified fat stem cells are basically the same as overall fat tissue.

To me that doesn’t make any sense.

A groundbreaking draft guidance statement today by the FDA for the first time sends the message to the clinics that the clinics are very likely wrong and could be subject to future regulatory action.

It is important to point out that this FDA statement that mentions fat stem cells is “draft guidance” meaning that it is not yet finalized, but make no mistake that this is the clearest snapshot to date on the FDA’s views on fat stem cells and it is unlikely to fundamentally change during the comment period.

The bottom line is that fat stem cells are viewed by the FDA as drugs that must be vetted and approved prior to use by physicians and clinics.  It also reinforces statements from draft guidance issued earlier in October that narrowed exceptions to the same-day surgical procedure guidance for use of biological materials such as stem cells.

In the new document today, the FDA even sets out isolation of fat stem cells as an example of more than minimal manipulation (emphasis mine):

Example 10-1: Original relevant characteristics of adipose tissue, a structural tissue, to pad and cushion against shocks generally include its bulk and lipid storage capacity. A manufacturer recovers adipose tissue by tumescent liposuction and processes the adipose tissue to isolate cellular components, commonly referred to as stromal vascular fraction, which is considered a potential source of adipose-derived stromal/stem cells. The HCT/P generally is considered more than minimally manipulated because the processing breaks down and eliminates the structural components that provide cushioning and support, thereby altering the original relevant characteristics of the HCT/P relating to its utility for reconstruction, repair, or replacement.

A tissue product that is “more than minimally manipulated” again is a biological drug requiring prior FDA approval before use in patients.

I agree with this new FDA draft guidance because again fat stem cells are to my mind (as a cell biologist who has been studying cells for more than two decades) different than fat tissue. Fat stem cells constitute a biological drug that should be approved by the FDA in advance as well as tested in clinical trials before experimental, for-profit use on patients.

Another issue that applies is “homologous use” meaning that a product such as fat stem cells can only be used in a similar fashion or it is automatically a drug. For example, fat stem cells in theory could only be used therapeutically in a manner related to fat tissue-related health problems. The clinics today use fat stem cells to treat pretty much every condition from head-to-toe, which is clearly non-homologous use.

You can make a comment to the FDA on this draft guidance by following the instructions below pasted from the FDA guidance page.

How to make a positive difference? I encourage you to make a quick comment supporting the definition of fat stem cells as more than minimally manipulated and hence biological drugs. It is the safest thing for patients and the best way to go for the stem cell and regenerative medicine field.

Submit one set of either electronic or written comments on this draft guidance by the date provided in the Federal Register notice announcing the availability of the draft guidance. Submit electronic comments to http://www.regulations.gov.  Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. You should identify all comments with the docket number listed in the notice of availability that publishes in the Federal Register.

30 thoughts on “Breaking: New FDA Draft Guidance Views Fat Stem Cells As Drugs


  1. The argument that the “stem cells” become more than minimally manipulated by virtue of being separated from adipose tissue seems logically incomplete or wrong. My understanding of “plain English” is that “separated” is not equivalent to “manipulated”.

    Thus I might be “separated” from my car but that does not mean that my body has been “manipulated” whenever I get out of my car.

    Of course, the objective of separating me from my car might be to change my behaviour (perhaps for the better) by introducing me to a new environment. And so it might be for a stem cell that is separated from fat.

    Heavens forbid that the doctor told me to get out of my car and walk. The exercise might burn fat, that might break down tissue that binds a “stem cell” — the wrath of the FDA be upon me!

    Would it be a crime if such a stem cell were to do something more useful than becoming fat? (No offense to fat, it has its place.)


    • The analogy of you being in your car and then being “separated” is not applicable to the fat stem cells and fat tissue issue at hand.
      Within intact fat tissue the fat cells are literally part of the fat tissue.
      They are completed integrated into the fat and are woven into it with probably billions of connections between each fat cell and the surrounding other parts of the fat tissue. They are a unified whole.
      To get the stem cells out the tissue has been treated with enzymes and run through a column.
      The fat tissue has to be destroyed as well to achieve this goal.
      In contrast you and your car are not only easily separated but also are unrelated, modular things.


  2. “There are more than 100 such American clinics that are selling stem cell “treatments” to patients and almost all of them use non-FDA approved stem cell products isolated from fat tissue.” Can you be more specific? What is the exact number and what are the names of the clinics that would not fall into your “dubious” category? I am assuming there are some since you stated “almost all”.


      • This is not a question for me. You made the statement and I would like to know which ones you consider to be not dubious. I have had treatment in the US and have experienced many improvements to my health. I don’t consider the clinics where I went dubious, but I’m sure you might, hence my question to you. Since your intent is to safeguard patients it would seem, then please print a list of those you consider not to be in the “dubious” category. I know many patients who would like this information. I also do not know where your 100+ figure came from as to the number of clinics that are selling stem cell “treatments”, Is there a reference you can give where that information was obtained? Thank you.


  3. Hello.
    Help me find a contact (email address) Shinya Yamanaka, Sir John Gurdon, please?
    You own more detailed information.
    I read about the treatment of the cells (restore neural connections in the brain).
    I am looking for a cure for his daughter with the help of stem cells.
    I need some advice, since I received offers.

    It’s about life.

    Kind regards,
    Liudmyla.


  4. Dubious must be in the eye of the beholder.Peyton Manning,R.G. 3,and how about 86 year old Gordie Howe’s amazing recovery from a series of strokes.I suppose patients like Gordie don’t have time to wait for the FDA and Evangelical NIH director Collins to acknowledge that this amazing technology is pretty much safe, when done properly, as compared to drugs,and from what I read from around the world,seems to be delivering positive results where none existed before.
    When I read about patients positive results with diseases for which we have no real treatment for, and then read that clinical trials will start in 3 years,I get a little frustrated.The trials will last for years and people like myself who have one of the said diseases with no real treatment,don’t have a decade There needs to be more consideration about compassionate use and people like myself should be able to take the only chance we really have.When you can’t sit for more than a few minutes or find sleep extremely difficult and your doctor is more worried about the Florida Attorney general’s interest in what he’s prescribing,one can get a feeling of hopelessness.
    If I want to try this technology on myself I should be able to make an informed decision for myself.It’s my life,it’s my pain and it should be my decision.If it helps me that’s great,if it helps someone in the future that’s great too.
    The funny thing is we are talking about adult stem cells, which are inferior to HESC’s.We as a Nation are spending a lot of time and treasure trying to make a silk purse out of a sows ear.Everyone calls HESC’s the gold standard yet most are trying to appease the Luddittes by using these less effective cells.Hopefully soon we will come to our senses and begin to appreciate what the gold standard can do,and seize upon it.
    NIH director Collin”s tabling of Robert Lanza’s NED cell lines is just another attempt at obstruction.He’s running off the NIH’s stem cell researchers when he should be expanding research.

    More science and less ideology would suit me just fine!


      • Dear Paul K., I believe you are getting trolled? Please don’t allow those who would “pose questions” in the name of causing dissent invade this wonderful, informative blog. HAPPY HOLIDAYS!!!


    • Adult stem cells are not necessarily “inferior” to embryonic stem cells or “less effective.” Comparing them is like comparing apples and oranges. They have different capabilities, different mechanisms, and different uses/applications.


      • Adult cells are harder to grow.They need to be created for each patient.(very expensive) There is more chance of a problem with all these cells being grown probably without good manf. process.They have their place but they are still inferior.
        I noticed a new patent for HeMSC’s application # 13905526.Two or three days ago.Claim to be several magnitudes better than adult cells.There was also 70 disease application included..

        Great reading!


        • Adult stem cells are harder to grow? Have you ever actually grown them? ES cells require more skill to culture. Also, culture media are usually more expensive for ES cells and they require more expansion in culture in addition to differentiation protocols to obtain the desired lineage. Good manufacturing processes are required for both cell types. Again, comparing them is like comparing apples and oranges because they are used to do different things; they each have advantages for different applications. ESCs are pluripotent and used to differentiate into various cell types for cell replacement. Adult stem cells are multipotent and used largely to modulate the lesion environment through factor secretion and physical effects, not cell replacement. Also, there are many patents for improving MSCs. Indeed, even Stemedica as discussed here has a patent for improving MSCs by culture in low oxygen tension. However, please note that 13/905526 that you mentioned does not actually describe isolation of adult stem cells. It describes differentiation of ESCs and iPSCs into MSCs; 13/905526 is actually an ESC patent. The stem cell field is a lot broader than the work done by just one company.


  5. History will tell if the people ridiculing these “dubious” clinics serve the interest of patients vs pharmaceutical companies or universities trying to get stem cell isolation processes patented. Being safe is one thing, being blind to the benefits of an “FDA non-approved” procedure is another thing. If myself or a loved one (or any human being) can be saved or improved from the “anecdotal” report or even from the “placebo” effect, I am all for it. Wouldn’t you?.


    • vs. these for-profit clinics (who are also trying to get stem cell isolation and treatment process patented) charging exorbitant fees and burning through the savings of the patients and their families for something not proven to work (and making the patients pay to participate in their own “clinical trials”), where the people running the clinics typically do not even have backgrounds in stem cell research? I would think that in this case the companies and the universities are more likely to serve the interest of the patients. Also remember that FDA-approved does not only mean that it is efficacious; it also means that it is safe. Without running a carefully reviewed clinical trial or treating patients in a regulated environment, patients could potentially be subjected to unsafe procedures that could even lead to disability or death for the sake of pursuing the “anecdotal” or “placebo” effects that you describe. I am not saying that all such clinics are necessarily like this or that seeking a profit is bad; I just think that when you take a lot of money from someone and potentially put their life/livelihood at risk, you should at least be able to convincingly deliver a result that can clearly be attributed to your treatment (which is why in this country clinical trials are performed to seek FDA approval). Granted, depending on the disease and the procedure, if there were a couple of really convincing anecdotal recovery stories and if the clinic had a good safety record and their people really seemed to know what they are talking about when it comes to stem cells and their effects, I would probably recommend it to my loved ones even without FDA approval if we were really desperate. However, I haven’t really seen much of that yet, which is why when a loved one recently did ask me for advice about using one of these clinics I told her not to (after careful investigation).


      • “Also remember that FDA-approved does not only mean that it is efficacious; it also means that it is safe.”

        An article written by investigative reporter Jon Rappoport in May, 2012 says much to the contrary. It states, “The discovery of a page, on the FDA’s own website, proves the FDA is fully aware that the drugs it certifies as safe have been killing Americans, at the rate of 100,000 per year.”

        I also wonder how many of those in the industry believe that patients are being charged outrageous sums for treatment because that’s what others would like them to believe. Has anyone done any research as to what patients are paying on average? My treatments were certainly affordable. Many clinical trials have costs associated with them for patients and there are always risks, but patients should be able to make their own choices especially when all other options have been exhausted. The new FDA guidelines will only add to the cost for patients as they will be forced to go offshore for treatment.

        It seems very strange that the FDA is now trying to implement these guidelines after years of not doing so. I have seen no data to support the need for them. This essentially means that patients will be waiting at least another decade for accessible treatment outside of exclusionary FDA approved clinical trials. How many doctors could afford the millions needed to do this anyway? That will further limit the field and the innovation that doctors bring to it. However, I’m sure that is a desirable outcome for those who have their own interests to protect.


        • Hi Barbara,
          While it is true that nothing is for sure safe or effective, everything is relative and FDA-approved drugs have better odds of being safe and effective than something that has not been studied and is not approved.
          Happy Holidays,
          Paul


          • I don’t agree that approval makes something safer. Many approved drugs come with black box warnings. There are already thousands of studies done on adult stem cells and safety is not an issue. As many in the industry have recommended, efficacy can be established as patients are treated.

            You and I will never agree on this issue because I have experienced a much better quality of life after having stem cell treatment than I could ever have expected from prescription medications and conventional treatment. For me, the risks of autologous stem cell treatment are minute as compared to the risk of repeated steroid and drug use. The FDA guidelines will simply force more patients offshore which will actually up the cost and risks for patients from the U.S. There is theory and then there is reality and that’s the reality.

            Natural News posted an article on Dec. 23. Here’s an excerpt: “Last year, GlaxoSmithKline finally had to admit its executives were running a criminal bribery scheme in China, and Novartis was discovered to have faked clinical trial results and committed yet more scientific fraud while running hospital kickback schemes to push its drugs.

            Merck, for its part, is home to two virologists who filed a False Claims Act against the company with the federal government, describing how Merck would spike post-vaccine blood samples with animal antibodies in order to commit scientific fraud and fool the FDA.

            Pfizer ran vaccine experiments in Nigeria that killed children, causing Nigerian authorities to issue arrest warrants for Pfizer executives. Price fixing crimes are so common among drug companies that numerous U.S. states have threatened to level criminal charges against those companies if they didn’t refund the money they stole from state coffers. Read my detailed investigative article entitled Big Pharma criminality no longer a conspiracy theory: Bribery, fraud, price fixing now a matter of public record for even more examples.” (You can find his article online).


            • Spot on Barbara. Saying that a drug is “safer” just because it’s approved by the FDA, is absolutely non-sense and ignorant.


            • Big pharma has its share of misdeeds. No argument here on that. But how does that make unproven stem cell interventions acceptable?
              If not for the FDA, wouldn’t risks from drugs produced by Big pharma be even worse? You truly think that no regulation is better? That’s like throwing the baby out with the bathwater.
              For example, would Big pharma industry self-regulation be acceptable to you? I doubt it. So why should stem cell clinic self-regulation be acceptable?
              And, yes, for any given drug having it be FDA-approved makes it more likely to be safe and effective. It’s not an iron clad guarantee, but it’s got to be better than unregulated medical anarchy.


              • I don’t consider my own stem cells a drug. I believe the FDA is crossing the line trying to impose more regulations on what should be considered a medical procedure. I don’t care to get on the merry-go-round with that discussion however. Again, please let your readers know which clinics you believe are not “dubious”. You would be doing patients a great service.


        • If you look past the secondary source (the article written by the “investigative reporter”), the mentioned page on the FDA website is a single page on adverse drug reactions (ADRs) that is part of an overall learning module on drug interactions and labeling. It cites two studies, one (Lazarou et al., JAMA) that was a meta-analysis of 39 prospective studies over 32 years in hospitals and one (Gurwitz et al., Am J Med) that was a study of adverse drug events in 18 nursing homes. The first study found that fatal adverse drug reactions occurred in 0.32% of hospitalized patients and thus estimated that 106,000 deaths in hospitals in 1994 resulted from adverse drug reactions among approximately 33,100,000 hospitalized patients. Of note, they conclude that “It has been shown that careful drug monitoring in hospitals leads to a reduction of many of these ADRs, suggesting that some type A and type B ADRs may be due to inadequate monitoring of therapies and doses.” They also note that “While recognizing the benefits of drug therapy, we chose not to compare benefits of drugs to the side effects of drugs.” The other study found that over a 1-year period in nursing homes, 1 fatality occurred among 28,839 residents. It is quite a leap to go from the data from these two studies to saying that drugs approved by the FDA are unsafe and that the FDA is killing patients. At most, one could say that adverse drug reactions are problematic, which is exactly what these studies and the FDA web page actually say. Beyond that I still submit that risks associated with a carefully studied treatment that had to go through an evaluation process are bound to be lower than the risks associated with an unregulated treatment that did not have to be evaluated.

          As for an example of pricing, see the review by Lau et al. Cell Stem Cell (Dec 4 , 2008). They found an average cost of $21,500 for stem cell therapies administered by online clinics, not including travel and accommodation, and that was in 2008. The person who recently asked me for advice about receiving treatment at one of these clinics was quoted about $26k. I think that this is a lot of money for something that is not proven to work and may be associated with risks. I am not sure what your costs were, but this seems to be fairly standard.

          It is not strange at all for the FDA to be trying to implement regulation now, as these clinics are becoming increasingly popular and now present enough of an issue to get onto the FDA radar. Such treatments can be associated with side effects even when there is no benefit. See Dobkin et al. (Neurorehabil. Neural Repair 2006), who found that 5 cases of complications occurred among 400 patients who received fetal brain implants for spinal cord injury, even though no clinically useful improvements were found in any of the 400 patients. I myself was a reviewer on a case report where several individuals with ALS died after receiving cell transplants with no clinical benefit.

          I would argue that it is actually doctors who don’t know much about stem cells but sell treatments to patients who limit the field and potential innovation more than any FDA regulation would. Lau et al. said it well: “This finding might suggest that providers are making inaccurate claims in
          their direct-to-consumer promotional materials.
          Patients may not be receiving sufficient and appropriate information and may be shouldering inordinate risks. Clinics may also be contributing to public expectations that exceed what the field
          can reasonably achieve.”

          I agree that patients should be able to make their own choices, but it is up to those working in the field and the government to help ensure that those choices are educated choices

          I agree with you that regulations will provide a desirable outcome for those who have their own interests to protect: the patients.


  6. Perhaps another way of asking this to to ask about bone marrow transplants which the FDA has clearly said are not a FDA approved product (see however cord blood stem cells). In that case they are isolated/separated from the individual and transplanted into the same or unrelated individual and are processed or shipped. All of this has been considered minimal manipulation that does not change the characteristic of the cells or their function.
    It seems to me that the FDA should apply the same logic to adipose tissue. It is separated from the tissue like bone marrow. It is minimally processed like bone marrow and as long as the processing does not change the functional characteristic of the cells it should be not a biological product.

    If however the fat cells were selected by a process or expanded or combined with a device (think silicone breast implants) then it would be a product. If it was for non homologous use (critical limb ischemia, osteoarthritis etc) just like CD34+ cells are used for non homologous purposes then t would be a product.

    So while I agree that the FDA could regulated adipose derived stem cells as a biologic under their definitions on use, manipulation etc. I don’t think their argument that separation from intact structural tissue is a reasonable justification for calling it more than minimal manipulation and if that was the criteria than any surgical procedure is more than minimal manipulation. Use a vein as a artery in graft is non homologous use etc. Th FDA should be extremely cautious in trying to reach via regulations into the practice of medicine.


    • You make a good point, bone marrow transplants and the isolation of fat stem cells are analogous and are minimally manipulated so in that respect they could be considered to be transplants.

      What worries me is that while I can dig out thousands of peer-reviewed publications on the medical benefits and mechanism of action for bone marrow stem cells – I can find no similar scientific and clinical reports for the benefits of fat stem cells. Isn’t there such a thing as evidence-based medicine these days.

      On the other hand, if folks insist on paying thousands for what may be snake oil, should be care?


    • Hi Mahendra,
      Thanks for the comment. I can see your points in the comparison to marrow transplant, but there are some complications related to the current use of stromal vascular fraction by stem cell clinics.

      The fat is treated with collagenase and more often than not it is processed through a column that is not an FDA-approved device for purification/concentration of adipose stem cells.

      Also, I’m not at all sure that the resulting product is less than minimally manipulated. Are there solid data out there to show that the resulting product has not changed the functional character of the cells?

      Another issue is that although fat stem cells are used for some cosmetic procedures where adipose tissue is the target tissue to address medically (i.e. homologous use), most current uses of fat stem cells are indeed non-homologous use. For example, neurological disorders are one of the most commonly “treated” with stromal vascular fraction by stem cell clinics.

      Finally, I don’t see a vein used as an artery graft as necessarily non-homologous use. They are both blood vessels.


  7. Barbara,I love the way you tell it like it is.The more I read about what you say gives me hope,now if I can find a good doctor here in the good ol USA that does stem cells for copd maybe I could enjoy life a little better what is left of it. I am 75 good shape but can’t breathe,On inhalers and oxygen 24/7 my grand kids keep me from doing stupid,because it is just to hard some days to go on.I have written to you this past day or two,I like to read every thing you have to say and believe you are truly a hero for trying to get as much out about copd and stem cells.As far as clinical trials go,you have to get off your meds to get into one and than you do not know if you are getting the meds in the trial or a sugar pill.Keep up your good work.
    Dee Geardino

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