September 29, 2020

The Niche

Knoepfler lab stem cell blog

ICMS President Rodriguez interview on adult stem cell regulatory issues

The International Cellular Medicine Society (ICMS) has emerged as an important organization related to stem cell regulatory issues. I think that many people do not understand what ICMS is all about and it certainly evokes strong opinions in the stem cell field.

If you care about stem cells then you need to know about ICMS and its perspectives, no matter whether you agree or disagree. 

Here’s your chance!

I invited the President of ICMS, Dr. Ricardo Luis Rodriguez (see picture below), to participate in an email interview. I thank him for agreeing and providing the very illuminating answers below, which I have posted verbatim.Ricardo Rodriguez

We hear frank answers from Rodriguez about the ICMS view of stem cell regulation, the Texas Medical Board decision on stem cells, the FDA, rogue clinics, physician training, and more.

For convenience, I have also added links to important external resources that Dr. Rodriguez cites. Enjoy this must-read interview and participate in the dialogue via the comments.

1 ) What is your perspective on state versus federal regulation of the stem cell/regenerative medicine/cell therapy field? What are the appropriate roles of, for example, state medical boards and IRBs versus say the FDA?

We think neither state nor federal regulation presently address the needs of the Stem Cell Therapy field. The FDA sees all Stem Cells irrespective of their source (autologous, allogeneic, or IPS) as a drug product. It has a long and expensive pathway to deliver a “safe” product to market. But a product may be deemed “safe” by the FDA, yet present danger in the wrong clinical setting. The Texas Medical Board is the first State Medical board to view autologous stem cell therapy as a procedure, or medical service. But they have not defined a framework in which to bring Stem Cell Therapy to patients in a way that rigorously addresses patients concerns about safety or efficacy.

We feel it is more important to ask: How can we bring innovative therapies to patients, clinics and physicians in a safe and effective manner? How do we ensure that patients who might be desperate for a treatment are appropriately informed and have a clear understanding of the risk-benefit ratio?  Perhaps most importantly for those patients that elect for a given therapy, how do we ensure that the isolation and delivery of the cells is performed as safely as possible? Although there are existing standards for product process, we urgently need standards and protocols for the clinics and facilities where the therapy is rendered. Finally, physicians need guidance for best practices and outcomes monitoring in this young field. The ICMS is addressing these needs through clinical and lab Best Practice Standards, Facility Accreditation programs, and independent data collection in an Outcome and Monitoring Registry.

2 ) Do you believe in self-governance for this field and do you see ICMS playing the central role for the field?

Self-governance does not exist. In medicine, we all practice in a web of organizations that place different strictures in the way we do things. For example, I am a member of my State Medical Society and at the same time belong to the American Society of Plastic Surgeons. Each has its own codes of conduct and expectations. Specialty societies like the ASPS tend to be more effective at creating and enforcing standards because of their focused expertise. For example, in the late 70’s when unregulated Surgery Centers started appearing all over the US, it was Plastic Surgeons who stepped forward to create the American Association for Accreditation of Ambulatory Surgical Facilities (AAAASF). It develops and accredits for standards, procedures and protocols. It has been more effective and comprehensive than the piecemeal legislation that was created by many state legislatures at the time in response to public outcry.

We see the ICMS with its various members focused expertise (physicians, scientists, industry leadership, laboratory specialists, etc) as playing a similar role in the field of stem cell therapy. For example, neither the FDA nor the State legislatures, or for that matter a single specialty society, have the personnel or expertise to look at an entity offering stem cell therapy and evaluate it like the ICMS can. Our team can look at the physician’s credentials to see if he/she has the expertise to treat the conditions with stem cells. We also evaluate the processing facility, the clinic , the surgical suite set up, and finally the treatment registry. We see ourselves fulfilling a very important unmet need in order to maximize patient safety, and fundamentally we achieve this by encouraging transparency and compliance.

3 ) How does the ICMS accreditation program operate? How well do you think it works?

The accreditation process is a 12 to 18 month process that integrates oversight and transparency. The process has multiple steps, including an annual review by an Institutional Review Board, multiple on-site audits and inspections and long-term outcome tracking of patients.  To date, we have 15 clinics in various stages of the process. While this number still represents a modest fraction of the total number of facilities worldwide, it is our belief that having clinics in nearly a dozen countries that are willing to put themselves through this process is statement of both the need for transparency and the power of peer oversight.

4 ) To me it seems that balancing risk and innovation is a difficult challenge for regulators such as IRBs. Can you tell me more about your IRB?  How do you choose its members? How does it function?

An IRB’s main purpose is to evaluate the safety of treatments for patients, and determine whether or not the therapy conforms to the tenets of the Belmont Report. By its definition, the IRB has to review therapies that are investigational in nature. The approach of the IRB is based upon a risk assessment, and evaluates whether the treatment puts patients at undue risk. The IRB review is built upon several key elements:

1) proof of professional qualification for primary investigator and other key individuals engaged in the study

2) scientific support for the safe use and application of the materials utilized in the study

3) the specific inclusion and exclusion criteria for study participants

4) methodology, including measures and collection and evaluation processes for the tracking of all outcomes and the reporting of potential complications for all study participants

5) the informed consent specific to the study

The ICMS IRB works from a published set of processes and protocols, which is available at our site, and is governed by a volunteer executive council. We have a very strong conflict of interest policy, and have specifically detached the IRB from the leadership of the ICMS. We have a written policy that a member of the ICMS board of directors cannot serve on the IRB. Membership in the IRB is open to ICMS members, and our goal is to bring together a board that has specific knowledge on the scientific and medical elements of stem cells and cell-based therapies with community members. Members of the IRB are elected by the board and serve a two-year term.

5 ) Via its accreditation program and its IRB, ICMS gives legitimacy, sort of a stamp of approval if you will, to physicians and clinics offering cellular therapies. In that regard, does ICMS have any liability should there be negative outcomes at clinics and/or related to the practice of physicians who have received the ICMS stamp of approval?

We do not offer a “stamp of approval” or confer legitimacy; rather we engage the clinics in a process that includes various quality systems elements (Standards, Accreditation). These are designed to ensure safe isolation and delivery of cell products. Informed consent practices ensure that patients are properly aware of the scientific credibility of the treatment and the associated risk-benefit ratio. The maintenance of data registries to track adverse events in the field and eventually collect outcomes data help develop safer and more effective practices.

 As for negative outcomes, nobody can guarantee results in stem cell therapy or medicine in general. Just like a scalpel blade manufacturer cannot guarantee the safe and effective outcome of a surgical procedure, ICMS cannot guarantee the outcome of a stem cell treatment.  Our aim, of course, is to minimize the likelihood of poor outcomes by having clinics adopt the stringent systems and procedures that are necessary for accreditation.  In this regard, we are simply following the precedent set by other accreditation agencies such as the AABB, which sets guidelines and treatment standards for blood therapies.

6 ) Just in 2012 alone it seems that stem cell-related cosmetic procedures and sports medicine are going more mainstream, however some of the practitioners do not get IRB approval nor ICMS accreditation, which seems to me to be a legitimate concern. We even see some of these places getting FDA warning letters. Do you have concerns about the field or certain groups within the field in a way getting ahead of itself/themselves because of all the excitement and potential of stem cells?

It is very hard not to be swept up by the excitement and potential of stem cells. Three years ago I asked the FDA an opinion as to whether SVF (Stromal Vascular Fraction) was considered a “drug” or autologous tissue. It took over 2 years to get an answer. Although I did not do clinical SVF therapy, I cannot blame those who for one reason or another thought that SVF would be considered to be outside the purview of the FDA. What is clear with the warning letters is that the FDA perceives any type of autologous therapy as a drug and not a tissue.  Thus, autologous therapy is subject to the same FDA regulations imposed for mass manufacturing of drugs for distribution.   At the moment, anyone trying to jump ahead of the FDA will face serious consequences.

The problem as I see it is that adult autologous cell therapy is a highly individualized therapy. As such, the cost of going through an IND and BLA process will make it prohibitively expensive to bring to market, as the cost of developing the therapy is not amortized by mass production. Sadly, I believe the practical outcome of the FDA position is that IPS and allogeneic therapies, which are mass-produced and pose risk to many patients, will come to market before autologous therapies. This is ironic because autologous cells have a lower risk profile than allogeneic or IPS cells and they pose a risk only to the owner of the cells.

Rogue facilities and treatment paradigms with little scientific justification have made a lot of headlines, but it is important to look at the overall situation more objectively.  In the 10 years since the first injection of stem cells into the heart, just fewer than 5,000 patients have been treated under the jurisdiction of the FDA and EMEA.  During that time, millions have died from acute MI or congestive heart failure.  We know quite clearly that autologous cell therapies for these patients are overwhelmingly safe.  We see clear trends of efficacy.  Should these millions of patients have been given the choice of autologous stem cell therapy?  While we are adamantly against the field ‘getting ahead of itself’, the FDA’s current interpretation of it’s jurisdiction over autologous stem cell therapies is having the unintended effect of favoring treatments in offshore markets, not always done under appropriate regulatory oversight.  One of the ICMS’ priorities is to reach out to these international clinics and physicians to offer improved standards, guidelines, and accreditation.

7 ) Can you tell me about your recent conference? Who attended and how did it go?

This was the 4th conference that the ICMS has hosted. It has grown from about 75 people in 2009 to over 200 this year. The quality of the speakers has increased dramatically as well. We have always intended to have a conference that was based on the clinical experiences of physicians treating patients, rather than the review of new bench research. We have always been pleased that our conference has had such an international following. Starting from the first year we had speakers from all around the world bringing their experiences to their peers. The audience for our conference has always been predominantly physicians, but we have seen a marked increase in the number of researchers and scientists in attendance.

 I think some of the highpoints of this year’s conference were the presentations by Dr. Saud Sadiq from the MS Research Center of New York and the panel discussion by Todd McAllister, Francesca Vitelli and Warren Sherman MD, from Columbia Univ., on issues revolving around clinical translations.

8 ) Do you offer training to physicians who are interested in conducting stem cell-related procedures? If not, is there some other official organization that provides such training? Do you see med schools or health systems/hospitals in the future beginning to offer residency or specialist training in cellular therapy or stem cell-related therapies? How do we insure that all those practicing in these areas have the appropriate training?

At this point we do not offer training to physicians interested in stem cell related procedures. We are a young organization and must remain focused on our task, which is the accreditation program and treatment registry. In any case, thinking about appropriate specialist training in Stem Cell Therapy is putting the cart before the horse.  Diagnosis always comes before therapy.  Stem Cell Therapy should be administered by physicians who have expertise in the diagnosis and therapy of the diseases they are treating. There is nothing new or unique about the procedures used to harvest or deliver stem cells. This training is best acquired in a residency program or within your own specialty society.

For example, no amount of stem cell training will turn a Family Practitioner with limited exposure to surgical training into a Neurosurgeon capable of treating traumatic brain injury after effects with stem cells. A “stem cell specialist” brings to mind the old adage “when your only tool is a hammer, the rest of the world looks like a nail”. In its early days, Radiation Therapy was also considered a magical cure. I am old enough to remember patients who were radiated in the face to treat acne!  A physician who is not trained in the specialty he is treating and acting as a ‘stem cell specialist’ poses more danger to his patient through misdiagnosis and procedural mishaps than from malignant transformation of an adult autologous cell.

9 ) What do you see as the future for the ICMS? Are there any changes you’d like to make or new goals to achieve? 

The focus of the ICMS remains patient safety and the development of global standards for the translation of point-of-care therapies. Our accreditation program, truly the first in the world to look at whole of the treatment, from patient recruitment to post treatment follow up, is built upon the foundation of peer oversight and transparency embedded in our guidelines. We are very proud of the work being done: we have 15 clinics in the program from nearly a dozen countries.  Over the next year, the greatest change with the ICMS will be in how we manage this accreditation program. In October of last year, the ICMS announced an alliance with AABB to would explore working together to establish a global accreditation program for clinics and facilities providing cell-based medical therapies. The accreditation, based on the standards established by ICMS and the processes developed by the AABB, significantly expands the existing scope of peer review in cellular therapies. This collaboration, which was announced at the AABB Annual Meeting in San Diego, seeks to increase the transparency of facilities and of treatments being offered to empower patients to make an informed healthcare decision. While this relationship is new, it is built on our established mission of peer oversight and transparency.

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