More tough FDA draft guidance on stem cells…still no action

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FDA logoThe FDA released more draft guidance with strong relevance to the stem cell field.

This October 2015 new draft guidance follows about a year after three other previous draft guidances that made it clear the current FDA thinking on various issues including stromal vascular fraction (SVF; fat stem cells) was much more restrictive than generally thought in the for-profit stem cell clinic field.

“Industry” apparently hasn’t been happy about this.

For instance, December 2014 FDA draft guidance very clearly indicated that fat-related stem cell products like SVF are more than minimally manipulated and hence are drugs requiring pre-approval and licensing. Another draft guidance on the same day surgical exemption issued a few months earlier also seemed (appropriately) to point toward more stem cell products being drugs requiring pre-marketing approval.

Still, to my knowledge the FDA has not actually finalized these guidances or taken any action based on them.

The new 2015 draft guidance aims to provide clarity and answer questions on the issue of homologous use. My sense is that this draft guidance, if ever finalized, would limit the unapproved uses of specific human tissues including amnion.

One particularly telling phrase from the new guidance stood out to me:

Generally, 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.

This sure sounds like how hundreds of stem cell clinics are using unapproved adipose and amniotic “stem cells”. Thousands of patients are spending millions of dollars right now on interventions violating multiple FDA perspectives mentioned in the various draft guidances.

Yet despite all this “tough talk” in draft guidances, by all accounts the FDA seems to be doing nothing to back it up in the way of actual actions on stem cell clinics violating these proposed rules or via finalized guidances. For instance, the CBER branch of the FDA suddenly stopped taking actions on stem cell clinics almost 2 years ago and since has done little if anything.  In the same period of time the number of stem cell clinics has roughly doubled. That is an equation for trouble and risks to patients.

What gives with the FDA?

In part I think they are just unbelievably slow in how they take steps on things, but that glacial slowness isn’t working to protect patients in the context of the warp-speed stem cell clinic world. They may also be getting political pushback on what seems to be emerging as a firming up path to regulating adipose stem cell products as drugs.

A big HT to Alexey Bersenev for pointing out the new draft guidance (see #5 in his post and another post). I recommend reading his post for another valuable view on this. He also points out that stocks have dropped for some companies related to this draft guidance and the FDA will hold a public hearing next year on these new draft guidances.

At this snail-like pace from the FDA we can expect these guidances might be finalized (assuming they ever are) in some revised form in…about 2-3 more years. By then there will probably be more than 1,000 stem cell clinics in the US selling unapproved stem cell drugs…

I’m all for public engagement by the FDA and responsiveness to feedback, but the FDA doesn’t have time to move so slowly.

33 Comments


  1. Paul,
    Some of the Parkinson’s patients I talk with are asking why I want to get FDA approval when stem cell therapies do not need to be approved by the FDA. I need a better way to explain than “I want to do this safely and legally”… Any suggestions?
    Jeanne


    • @Jeanne,
      Good point and question. Your answer seems the best to me, although I realize it is not perfect. The FDA does give mixed messages from its words and actions on stem cells. Sometimes I have pointed out that the FDA is paradoxically stricter and harder on the “good guys” who have good intentions than it is with those running predatory stem cell clinics. It’s frustrating at times for patients and scientists too.
      Paul


  2. But who are the “good guys” ?

    ” “good guys” who have good intentions than it is with those running predatory stem cell clinics.”

    Do you have a list or any suggestions how to find a serious stem cell clinic?


    • @Richie, these are good questions. Naively perhaps I view the “good guys” as those primarily focused on helping people rather than just making a buck. If as a company one disagrees with the FDA then I say by all means challenge the FDA’s regs, but in the mean time don’t just go ahead and put patients at risk to make money. Admittedly the FDA needs to be far clearly and more decisive. All this pussyfooting around has created gray areas and doubt.


  3. Paul, to me it all sounds like the powerful drug companies are slowly getting their way in stopping all of us who want stem cell treatments to ONLY have FDA approved stem cell therapies. The powerful drug companies in collaboration with the FDA just want to play God over our own mind and bodies and want to stop us being able to decide what treatment we may wish to have. I’m happy for guidelines and the pros and cons on treatments offered but the final decision regarding if a stem cell treatment should proceed should be our decision. Of course any stem cell treatment would require many tests and the signing of an informed consent by patient before proceeding.


  4. The FDA is responsible for assuring the safety and quality of foods and drugs in order to protect the public from harm, and whilst their decisions are often used to inform the wider public on the usefulness of therapeutics, their guidances are not helpful for the general public seeking information on “good and bad” clinics. But there is a new document that can provide qualified guidance for patients and the community.

    Some time ago I posted regarding studies we conducted to assess the merit of claims made by stem cell clinics carrying out unregulated treatments. http://www.ipscell.com/2015/07/neighborstem/#comment-32003

    These results are considered in, “The Guide on Unproven Cellular Therapy for Patients and Community” published recently by The Presidential Task Force of the International Society for Cellular Therapy (ISCT).

    You can read about it here: http://www.celltherapysociety.org/news/255511/ISCT-launches-the-first-guide-on-unproven-cellular-therapy-for-patients-and-community.htm
    and download it free here: http://www.celltherapysociety.org/?page=PTF2015

    I hope some will find it helpful and informative.
    Wolf ([email protected]).


  5. @Paul, that’s true, but the problem for any potential stem cell patient is to get to know, which clinic / stem cell physician belongs to the good guys?
    Do you have an idea how to judge this?


  6. Wolfram Mardin I still don’t see or believe people like Ritchie or myself are getting the answers we are looking for. We are just getting the politician type answer of nothing. I am now looking at Bangkok for heart treatment and have also looked at the Texas Heart Institute trial but if I was accepted I can’t afford to live in the USA for 18 months and apart from the cost of airfares from New Zealand there is also the chance of being one of the 25% getting the placebo treatment. This is why many of us go elsewhere, pay the money and take the risk. There needs to be some common ground here where we can have paid treatment at approved clinics but also agree for the treatments to be used as a trial. At least they will be controlled treatments with proper records kept. Yes I understand that they will not be blind treatments but so what. I can state that the 2 IV treatments I have had over the last 6 years have helped both my LVEF and eGFR more so on the 1st treatment.


  7. @David Shear @Wolfram Mardin

    Yes, that’s true, I have read much now, it is an very interesting report and I learned a lot, but the answers we were looking for, are not included.

    The crucial question is still …

    how to differ the good guys from the others, the good clinics from the others and how to recognize/find a serious stem cell clinic…?

    Of course many stem cell therapies are not backed by big clinical studies, but there are already some of these new therapy options which could help people.

    For example the PRP-therapy. Insurances still don`t pay for PRP, because there are still not enough double blind clinical trials. But many physicians have already observed how good PRP could work in practice. By the way I saw it myself.

    So this is just one example, but I am sure, there are already more stem cell therapies with good results, but not enough studies.


  8. @Richie and David – thanks for the interesting comments and questions. The answer to the question of how to differ “the good guys from the others” is simple, but also disappointing for patients – drug therapies are demonstrated to be effective and safe only in controlled studies – anything else is at best a potential therapy, but may also not work in man and at worse, may be dangerous. That’s as brief as I can put it, and I I can see you know this already.

    “There needs to be some common ground here where we can have paid treatment at approved clinics but also agree for treatments to be used as a trial.”

    When treatments are available you should get them, but for many diseases there are no approved therapies. And non-approved treatments offered by some clinics simply do not work. Again, disappointing to hear. There are however, many trials being run (see clinicaltrials.gov for your illness) – find the ones that are “recruiting” and call the responsible institute – maybe you can get on one. If you need help with this just drop me an email.
    Of course, it is your decision to pay for therapy abroad in a non-approved clinic, but I can guarantee that for heart disease it will not work, as research has not yet been demonstrated to work in the clinic – but the area is very hot and I think a breakthrough (or several from different directions) is likely soon.

    “Of course many stem cell therapies are not backed by big clinical studies, but there are already some of these new therapy options which could help people.”

    “could” is the operative word here and when trials are completed, we will know more about patient stratification, dose, efficacy and safety. As for David (see above) if patients can get on a trial then this will help speed the path to approval, but it is still a long road.

    Best wishes, Wolf ([email protected])


  9. Wolfram thank you for your reply but I do not agree with your comments “but I can guarantee that for heart disease it will not work,” I have heard of a number of heart function improvements with stem cell treatment and I can state that the 2 treatments I had did give me improvement.

    As I have said before if we wish to spend the money that is our choice, then would it not be better for people like yourself to help us spend it at an approved clinic for a specific type of stem cell treatment that may give us a chance of some improvement. There are so many reports and complaints by businesses, researchers and people involved in the stem cell field on how much money is being spent (wasted some say) in non approved treatments at clinics by people like myself. Maybe some of this lost money could be transferred into assessing some of these more experimental treatments through approved clinics if there was more assistance and guided from the people involved rather than just keep being so negative. Over the years many advances have been made in many areas by mistakes or people thinking and doing outside the box and if we wish to take the risk then that is our right.


  10. @Wolf, David
    Thanks for your reply, I agree with you, the most stem cell therapies are not backed by double blind clinical studies. And so there is no evidence.

    But there are already stem cell therapies with a good outcome – not backed by studies, only backed by the experience of physicians who use these therapies. One example is the PRP-Therapy. Physicians who use PRP know that PRP could heal avascular necrosis (see my last post). The alternative for avascular-necrosis-patients is often a big surgery with often no good outcome. So in this case I think it could be advisable to use/try PRP instead of a big surgery.
    And I think there are already more therapies which work, in spite of the missing double blind clinical studies.

    For example regenexx seems to my an example for a serious stem cell clinic. They use PRP and publish much about their experiences.

    Please consider there are many potential stem cell patients who are in a serious situation. For some of them sometimes a new stem cell therapy ist their only chance. In this case these patients must decide, if the offered stem cell therapy could may help – (may has helped already other patients), or if the offered therapy is absolutely experimental and the only aim of the clinic is to get the money of the patients. This is the crucial question for them – and they try to differ between the “good guys” and the others


  11. concerning heart-treatment

    some month ago I collected the following article:

    http://www.dailymail.co.uk/health/article-3005476/How-stem-cells-fix-broken-heart-just-one-jab.html

    “‘We are not exactly sure why it works,’ said Professor Anthony Mathur, the trial’s chief co-ordinator at Barts and Queen Mary University of London.
    ‘It may be that the stem cells repair the partially damaged tissue, rather than regenerate new tissue. But whatever the process, we have had very positive results from the patients who have had the treatment so far.’”


  12. @David – this is where wishful thinking and scientific proof do not align.

    You say your stem cell treatments gave you an improvement but I can guarantee that the clinic cannot show any data to support this nor how the therapeutic was responsible for improvement.

    In analogy, there are claims that visiting the weeping Madonna in Naples can cure cancer and several people claim they were cured – but I think you would agree that without an evidence-based demonstration for how this works, it could also be spontaneous recovery or other treatments they were taking.

    Improvements can come from less stress, diet, exercise etc. So unless one can prove with statistically sound means that the stem cells were responsible, your hypothesis that the stem cell treatment itself improved your condition is speculation. In our study of hundreds of patients taking unproven stem cell therapies, several claimed improvements, but clinical data did not support this and others having the same treatment actually got worse.

    “assessing some of these more experimental treatments through approved clinics” I agree with you and this assessment is called clinical trials. But trials are dependent on patient volunteers to contribute to the data – unfortunately those taking unproven therapies will not be eligible for real studies.

    Best wishes, Wolf ([email protected])


  13. @ Wolf,
    thank you for interesting answers, please take a look at my 2 last posts above, concerning the results of the University of London


  14. @Richie – none of these reports show any statistically significant data to prove that any improvement seen is not simply spontaneous or due to other effects (exercise, other therapies) and they do not show how stem cells are purported to achieve a recovery.

    “‘We are not exactly sure why it works” he says so logically he cannot be sure it is due to stem cells.

    It needs to be rigorously proven and until it is, I as a clinician and scientist cannot offer patients such treatments, as I don’t see demonstration of safety, evidence of efficacy (dose-response) or a rationale for why the cells have worked.


  15. @ Wolf,
    but what would you recommend a patient who has no other chance? Till today I think there is no evidence for the stroke-therapy Gordie Howe received in Mexico – Gordie Howe has shown an amazing recovery as you can read here on this site.
    So the question is, should a stroke patient try this therapy, too, although there is no evidence (just the case reports of Gordie Howe and maybe Bart Star)?

    I really think about this question. My aunt has suffered a serious stroke about two years ago, now she is handicapped and in a really unhappy situation without any chance to get much better with conventional treatments. A new therapy would be her only small chance to get really back in life. I don´t really believe in the stem cell therapy for stroke patients. But I think nobody knows exactly, and maybe these therapies will work??? And maybe I should go with her to Mexico?
    I really don´t know, what is the right decision? … and I think nobody knows.

    By now I decided to wait till May 2016, in May 2016 ends a small study by Stemedica about stem cell based stroke treatments, and I will wait for these results … but it is a small study … and the results may help me, but of course there will no big evidence even after this study …

    This example shows how difficult it is to make a decision for potential stem cell patients and sometimes new stem cell treatments are the only hope. The “good guys” are clinics who really try to heal you, the others don´t and it is very difficult or not possible to differ.

    .


    • Richie and Wolf, my feeling is even if the treatment can’t be proven to work but the person shows and feels better then is this not better than feeling unwell or sick??? This is why there needs to be some sort of agreements between approve and experimental treatments and I think any should have proper logged results kept for at least 6 months..


  16. @David – is feeling better not better than feeling sick? Good question! Another question is whether “feeling” is a suitable measure of long term clinical success. As a clinician, my aim is to improve patients’ quality of life (QoL) and therapies are considered according to a balance between QoL and clinical benefit – i.e. between patient well-being and disease management.

    In the long term, these factors correlate – if disease is not well managed, patients will not feel good. But in the short term, “feeling better” can also result from external events, especially the knowledge that a treatment is being given.

    Patients receiving stem cell therapies that don’t actually work, may “feel better” because they are happy just to be treated in an otherwise seemingly hopeless situation – but if there is no clinical correlate and disease burden has not been reduced, the “feeling better” gives way to the disease symptoms again and QoL goes down.

    Can I advise a patient to take a therapy for which I have not seen any scientific evidence of efficacy just so they may “feel better”? No – especially when there are increased risks involved (such as cardiac disorders where operative stress may actually increase existing damage).

    Which leads to Richie’s question – should a stroke patient try this therapy although there is no evidence? From a clinical perspective, no, not until there is clear clinical trial evidence that is works and is safe.

    Richie, you say that “maybe these therapies will work”, but existing therapies already work – they are not ideal and we are waiting for improvements – but they are cardioprotective and reduce further damage. To abandon these and place a patient under further stress because they “may work” would be irresponsible to me.


  17. @Wolfram
    I agree with you but if anybody is in a more or less hopeless situation – maybe after a big stroke, more than two year after this event there is no more hope for a significant improvement, I can understand all patients, who try an experimental application which is only “backed” by “case reports” in media like Gordie Howe.

    But of course I know this is a big danger and a good chance for unseroius clinics to raise much money. The “good guys”, as we discussed above, are in my opinion clinics who offer indeed experimental stem cell applications and know at once about real success in some cases. So they would know that their therapy could may really help their patients.
    I think it will take many, many years until some of these experimental stem cell applications will really be approved by enough double blind clinical studies.

    .


  18. … and futhermore I think the “good guys” are clinics who are interested in the outcome of thei application and offer some follow up appointments after the application. If the don’t do so, they will never know, if their therapy is working


  19. Richie – it’s not correct to say cardiac patients have no hope of significant improvement. The cardioprotective field aims to improve quality of life and for many patients it is successful – although these patients do not recover fully, they certainly don’t have a “hopeless situation”.

    I wonder what you’re expecting from fat stem cells (MSCs) – a cure? No clinic has ever cured stroke damage using MSCs and fat stem cell clinics don’t even look for repair of damage (for obvious reasons). Why don’t you use this as your criterion for selection – ask the clinic to show clear evidence of repaired heart tissue and then get an independent clinician to review it.

    Where scar tissue has developed, it is unlikely that current drugs or stem cells can directly repair tissue, so even if the patient receives MSC, they will still need support from beta-blockers and other protective agents. And like I said before, you expose the patient to physical stress, one of the worse things you can do for a cardiac patient.


  20. @Wolf you say “The cardioprotective field aims to improve quality of life and for many patients it is successful – although these patients do not recover fully, they certainly don’t have a “hopeless situation”. If you believe this, then what is the difference if a person having a stem cell treatment who actually feels better and can physically do more, is this not an improved quality of life. For me it has been and many other people seem to be saying the same thing. I think most of us have open minds in this fields and know that any treatment may not repair the damage or problem but if it does give us hope then that is a move in the right direction. Hope is all we get from what many doctors and hospitals offer us now by giving us drugs that we have to take which quite often give us other side effects. Many drugs only camouflage the problem and we still slowly decline in health and I hear you say so this is what happens with people getting stem cell treatment. To me both responses are similar but stem cell does not fill your body with a lot of potentially harmful chemical elements, it gives you something to help the body to try and repair itself the best it can.

    You finish off by saying “And like I said before, you expose the patient to physical stress, one of the worse things you can do for a cardiac patient.” OK if is this is correct statement, then surely a patient being blocked by FDA or some other regulating body or a doctor of not being able to have the treatment they wish, does this not put a lot of physical stress on a patient. If the patient is of sound mind and it has been well documented that they understand the risks, then it should be their choice to decide if they want to have stem cell treatment that has not been proven to be unsafe. To me it is no different to somebody being prescribe a mixture of different prescription drugs that have not been proven to be safe when taken by a particular individual person. Yes each drug has had rigorous testing but there have been many that have cause people to die or become seriously ill even with all this testing. Every person is different and many react differently to various drugs or combinations of drugs. Is this not a risk and a potential physical stress by not knowing how you will react to what has been prescribed?


  21. @David – please excuse the Q&A style here but I wanted to address your questions specifically

    “what is the difference if a person having stem cell treatment feels better and can physically do more, is this not an improved quality of life” Yes indeed – show me the clinical data that proves “he can physically do more”. I have not seen any fat stem cell clinic present this for cardiac disease, type I diabetes, multiple sclerosis, HIV, or other diseases with a clear tissue degeneration or pathology. Only in some arthritic indications is data convincing, although not yet better that existing drugs.

    “but if it does give us hope” Like I said, hope and “feeling better” is good – but short-term and ultimately if no clinically relevant improvement is seen, then the patient may be worse off that staying on the same medication.

    “stem cell does not fill your body with a lot of potentially harmful chemical elements” But fills your body with potentially harmful stem cells – and these have yet to undergo safety testing. At least approved drugs have passed this point.

    “it gives you something to help the body to try and repair itself” That’s also the aim of many drugs, and others prevent further damage too. The data for their success is proven and available to all – for stem cells it’s unproven speculation at best. Let’s see what clinical trials report.

    “a patient being blocked by FDA or some other regulating body…does this not put a lot of physical stress on a patient.” No – that’s mental stress. A patient undergoing a clinical procedure experiences a whole different type of stress, as I know you are aware. Imagine going through that pain with a weak heart, and no demonstrable benefit. That is a real life-threatening situation and balanced against short-term hope, my decision would be clear.

    “If the patient is of sound mind and it has been well documented that they understand the risks, then it should be their choice to decide if they want to have stem cell treatment that has not been proven to be unsafe.” Of course – people have been choosing alternatives for centuries. It’s no different to choosing acupuncture or herbal medicine – you might “feel better” for a while with those too.

    “each drug has had rigorous testing but there have been many that have cause people to die or become seriously ill even with all this testing.” Unfortunately true, and this also applies to unproven stem cell therapies, where individuals have already died. At least with approved medications, patients have the knowledge that extensive testing on efficacy and safety has been performed.


  22. @Wolf
    “I wonder what you’re expecting from fat stem cells (MSCs) – a cure? No clinic has ever cured stroke damage using MSCs and fat stem cell clinics don’t even look for repair of damage (for obvious reasons).”

    But there are some clinics with supposed cures (like Gordie Howe).

    I really hope that MSCs could repair the damage after a stroke in the brain. I know there is no evidence for this hope – only arguable case reports. Futhermore It is disappointing that many fat stem cell clinics don´t look after their results.

    “Why don’t you use this as your criterion for selection – ask the clinic to show clear evidence of repaired heart tissue and then get an independent clinician to review it.”
    That´s a crucial question – most clinics don´t have results, otherwise there are some clinics who have results, for example Regenexx in the orthopedics.
    Every clinic without clear results seems to be unserious in my opinion.

    In most points i agree with you, and i don`t really believe that my aunt (can only speak a little after a big stroke) could be healed by a stem cell therapy, but I hope I am not rigth, and i hope the first study of Stemedica (who treated Gordie Howe) will show some encouraging results. If these results are good, I will think of trying this therapy, because my aunt is in a very poor situation and so she is willing to take some risk – not every risk, but some risk.

    This first study of Stemedica ends in May and I hope Paul will comment it here…


  23. @Wolf
    Thanks for your very informative response and I understand why you make such comments. I think we both look at things differently because of our different situations and maybe we both are right or wrong – who knows. I my be blind or obsessed by the potential of stem cell treatment and I fully understand it still has a long way to go. However with this in mind, I think we need researchers who do push the boundary’s so long as any treatment or research is well documented. Enough said from my side on the pros and cons.


  24. @David – I truly believe researchers are pushing the boundaries every day, not only in the stem cell area but also in new small molecule, protein and nucleic acid therapies. However, the hype around stem cells has lead many to believe that they are the long sought magic bullet and that they are ready to go.

    We had the same hype when antibodies and antisense RNA were the magic bullets – now we have some great therapeutic antibodies but the lag between hype and reality was at least 15 years of R&D – it will be the same with stem cells.

    Until then I think we will see some crucial breakthoughs every year and that will fuel confidence we are on the right path. Whatever you decide to do I hope you can share your experience with the larger community.


  25. @Wolf Thanks and yes agree. When I find someone that will help with the stem cell treatment I seek I will most certainly be more than willing to share with the larger community. I hope that I can have the treatment as a proper trial or at least as a non blind trial so that records and results are kept. I have a personal copy of my health history and will keep that up as well. I wish you the best for your future research.


  26. Nov 11, 2015 – Japanese Times News

    Gene therapy helps teens with rare genetic disorder

    Gene therapy has dramatically improved the conditions of two bedridden teens suffering from a rare disease, Jichi Medical University said Tuesday.
    ……………………………………………………………………………………………

    Not sure if anyone has read this but have posted web site just in case you may be interested.

    http://www.japantimes.co.jp/news/2015/11/11/national/science-health/gene-therapy-helps-teens-rare-genetic-disorder/#.VkUHr-K2HYg

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