You can read Part 1 here, which is an interesting look inside the Network. The final portion of this blog post series, Part 3, is my take on their answers and you might not be surprised that I often disagree with them.
Today, the questions are focused on some very critical issues for the Cell Surgical Network including potential FDA regulatory factors for the Network, the definition of their SVF product (biological drug or not a drug), and whether homologous use (see more on homologous use here) applies to their clinical interventions. In addition, I questioned them about why patients have to pay to be part of the Network clinical trial. I also asked for their vision of the future.
1. There seem to be some divergent views on SVF. On occasion the FDA has indicated that in certain circumstances that SVF is a 351 biological drug not strictly regulated by 361 HCT/P regs, but it seems this is on a case by case basis. On the Cell Surgical Network websites it is stated unambiguously that the Network clinics do not need FDA approval for use of SVF. Why do you hold that view? Have you received guidance from the FDA that your SVF product is not a drug? Have you met with the FDA to talk about these kind of issues and if so, how’d that go?
Lander/Berman: I asked Dr. Berman to weigh in on this and here are some of his comments…It seems everyone seems to ignore or forget the PURPOSE of 21 CFR part 1271 – namely to prevent the transmission of communicable disease. The only reason the FDA can claim that HCT/Ps are a drug is if they are being processed in a laboratory manner or have the potential of transmitting communicable disease. Once you use a laboratory to process the cells you are under FDA jurisdiction and they have a list of validation procedures they require all facilities to meet. It’s rare that a physician with a laminar flow hood or a laboratory actually meets these validation standards. If they don’t meet these standards, then the FDA asserts that there is risk of disease transmission and as such claims authority and requires an IND.
California Stem Cell Treatment Center and all members of the Network use a completely closed sterile surgical procedure to isolate SVF (not pure stem cells). There is no laboratory processing of the cells. All supplies, devices and drugs are already FDA approved though not specifically for SVF / stem cell production. As is typical of many surgical devices and drugs, it is completely legal, ethical and appropriate to use approved products “off-label.” While we have followed the FDA exemptions listed in part 1271, we are not really under the FDA jurisdiction as they have NO jurisdiction or ability to approve surgical procedures – just devices and drugs. Since we do not use a laboratory method to produce SVF, only a surgical method, then there is nothing for the FDA to validate in our process. There is simply no risk of transmission of communicable disease. Arguably, Ceteno (sic), Celltex, Intellicell and others all have laboratory involvement that didn’t meet FDA standards for GMP production of HCT/Ps. The FDA mandates are based on the Congressional desire to prevent organ donors from transmitting disease – so it isn’t a question of mass numbers (as one sees with most drug productions), just a question of validating one’s laboratory procedures.
We produce SVF (over 40 ingredients and can’t be characterized) in a surgical procedure (can’t be approved by the FDA – they’ve never approved a surgical procedure). If the FDA can’t approve a surgical procedure, why would we possibly request them to approve this procedure? Also, since the FDA is concerned that they could be responsible for any drug they approve, it’s unlikely they would approve anyone by written request as it would leave them liable without having done their “due diligence.”
Finally, the FDA has audited our IRB approved protocol and there was never any communication indicating that it wasn’t appropriate. Out of the 29 protocols from the ICMS IRB reviewed, only one was rejected by the FDA (not ours). That, in itself, is an indication that we are not in any violation of FDA regulations.
2. Your website & clinical trial page indicate that the Network treats perhaps as many as a few dozen different conditions with SVF (http://www.stemcellrevolution.com/currently-studying/). What is the evidence to support such diverse, seemingly in many cases non-homologous use of SVF?
Lander: We do have many conditions that we are looking at and in choosing them we have attempted to exploit either the regenerative, immuno-modulatory, or anti-inflammatory properties of SVF. Although SVF is used in all of our protocols, our deployment techniques vary considerably. I think the term homologous has been used rather loosely and in the field of regenerative medicine, a new paradigm defies simplistic categorizations of cell types. After all, what type of tissue is an undifferentiated progenitor cell? Can it be homologous? Isn’t it potentially everything? For example, if it forms cartilage then could it have ever been anything other than a cartilage precursor? Our comfort zone is that we are surgeons performing a type of surgical tissue transfer procedure. There is no difference than when we replace a bladder with ileum or a coronary artery with a saphenous vein from an extremity. At the end of the day, the ability to use various tissues to treat human disease is within the realm of a surgeon’s domain.
3. In terms of mechanism, how do you believe the SVF therapy works to help patients with specific conditions? Is the mechanism more of a “cell therapy” approach where the cells engraft and help heal a tissue or is it more of a trophic/growth factor mechanism where SVF stimulates existing tissue and cells to become healthier? Both? Depends on the condition?
Lander: Our SVF is essentially uncharacterized but we do know that it contains a rich broth of cells and growth factors. Although there may be conditions of engraftment and transdifferentiation of cells, the autocrine and paracrine effects of the growth factors play a major role in the healing effects we are seeing. This may explain, for example, why it is possible to treat neurologic diseases by mitigating nerve damage using cells that may not easily form nerve tissue.
4. In the Network clinical trial (http://clinicaltrials.gov/ct2/show/NCT01953523?term=cell+surgical+network&rank=1) do the participants have to pay to participate and if so why and how much?
Lander: Our project relies on patient funded research. We are very transparent about the fact that we are a research organization but also a business entity. Treatments are generally 6 to 9 thousand dollars but that can vary. We set fair prices back when we started in 2010 and thereby provided an alternative for patients who at that time were going overseas and paying 30-90 thousand dollars for nebulous treatments. Most government grants mandate that we apply for an IND investigational new drug application with the FDA. Pharmaceutical companies may not perceive value in our research because it is hard to monetize and commercialize autologous cells. Charitable sources are difficult to obtain and so we have turned to our patients. This is a reasonable approach yet we are always reminded that our consent process for paid investigational procedures must be very specific and comprehensive.
5. How did you first get interested in stem cells and what excites you the most about stem cells looking to the future?
Lander: The serendipitous identification of large numbers of readily accessible adult mesenchymal cells in fat has offered a unique opportunity for physicians to help their patients treat disease. Physicians take the Hippocratic Oath which mandates that we must do everything in our power that is safe to help our patients. Clinicians need to collaborate closer with basic science researchers to move the translational ball along farther. Our safety data is excellent so far. We hope to provide placebo controlled trials using cryo-preservation of SVF in the near future. Physicians from different specialties will be bringing their expertise to our organization and we are watching our database grow. The future has so much potential as we learn to define which cell types, deployment methods, and combination of growth factors work best for specific diseases enabling us to distinguish optimal treatments.