FDA DRAFT STEM CELL GUIDANCE DOCUMENTS EXPOSED AS IMPROPER RULEMAKING, BAD SCIENCE AND HEARTLESS PUBLIC POLICY

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FDA-NotApprovedStampToday was a good day for people who want continued access stem cells outside of clinic trials, and also for people who want the FDA to allow faster access to this promising technology.

There was a wide spectrum of opinions. Some stem cell companies involved in clinical trials wanted the non-clinical trials clinics shut down. But at least there were representatives from some of these “unproven” clinics and interest groups who made some important points about the rights of patients and how the needs of patients are not being met by the current clinical trials model as it applies to stem cells. I heard a number like 250,000 people are not getting the stem cell treatments they need because of clogged research and regulatory hold-ups. There were numerous calls from very serious, highly credentialed people for the FDA loosen its death grip (my term) restricting access to these therapies, and the thrust of most of these presenters was that these draft guidance documents make thinks much worse.

The guidance documents are really bad and deny access for many

And that was the big takeaway for me; that the guidelines were much, much worse than even I thought. I understood that the guidelines would make illegal the 21 CFR 1271.15 exempt same surgical procedures provided by many of the 600 plus unregulated stem cell clinics.

But what I didn’t understand until Monday’s hearing is that the FDA intends to radically change the rules so that, for example, the most popular form of breast reconstruction surgery post mastectomy (flap something) would become illegal under the new guidelines. Many other popular and widely successful procedures in other areas like orthopedics would be eliminated (outside of clinical trials). We’re not talking unboarded docs with no relevant experience who take a weekend course and starts shooting people up with stem cells. We’re talking about big-time breast reconstructive surgeons, highly regarded orthopedists and other highly skilled and specialized physicians who have successfully worked with tens of thousands of patients. If the FDA gets its way, according to these folks, Poof! These best practices transplant procedures are gone.

Fortunately, there were some very smart professionals making presentations, including an extremely knowledgeable law professor from Boston College, Mary Ann Chirba. She and several other people with regulatory expertise made the case that this whole guidance exercise was an illegitimate attempt to pass new rules without complying with the rulemaking requirements under federal law. Works for me!

They and others honed in on the radical revisions to the two key preexisting terms/concepts used by the FDA to work its illegal magic: homologous use and more than minimal manipulation.

What’s a “main function?”

It was also pointed out that the guidance documents invented a new concept not existing in the statute or rule, namely the “main function” of a cell or HCT/P which is used as a way of forcing stem cell procedures from just registration under 362 into the IND/NDA drug approval path. It was argued persuasively by several regulatory experts that the creation of this new concept and its resulting transfer of many heretofore legal uses of stem cells into illegal new drug products turns the guidance documents into rulemaking without following federal administrative rulemaking procedures.

The FDA doesn’t understand what fat does

Another extremely cogent criticism made by a variety of people including Professor Chirba, other regulators and by both of the two top presenting stem cell researchers, Arnold Caplan and Keith March had to do with the FDA’s view of fat. According to the guidance documents, fat just has a structural function. But these presenters and especially March and Caplan showed that the FDA’s view was biologically unsound. Fat has definite, known and extremely important non-structural uses, starting with energy storage and continuing to assistance in the healing function. The FDA’s unscientific, unsubstantiated restriction on fat allows it to find most of the important uses of fat and fat stem cells illegal as either non-homologous or as a more than minimally manipulated product. The FDA was absolutely and repeatedly pummeled on this point by my count, at least a half dozen very, smart experts. I don’t see how even the FDA, which has a very particular agenda, is going to be able to hold on to its limitations/restrictions on fat/adipose tissue.

The Big Guys say regulations are holding back progress

The two big-time researchers (Caplan and March) also made the point that the regulatory climate is holding back research. Kaplan said that some bone marrow pioneers had observed that if they had the regulatory environment back then as what exists today, bone marrow transplants might never have taken off. Ouch!

Interestingly, Peter Rubin, the plastic surgeon who last Thursday presented the inspiring cases of reconstruction work from fat transfers, presented again. This time he was more critical of the FDA and stated that many of the most successful reconstructive plastic surgery procedures, including breast reconstruction would become illegal under the draft guidance documents. He and many other excoriated the draft homologous document which classifies fat tissue for breast reconstruction as non-homologous because the primary purpose of the breast is lactation. Several of the female presenters had some polite but pointed words to the FDA about that. Most of the day’s presenters agreed that regulation/regulatory expense was delaying bringing this technology to patients.

The 3 Billion Dollar Player Weighs-in

The biggest dollar player was the California Stem Cell Institute which has a 3 billion dollar budget and 12 research centers. Its director spoke, and his message was clear, concise and right on the money (and with 3 billion, it should be). The FDA has to loosen-up its grip and find an intermediate path between unregulated stem cell clinics and full-on clinical trials, because there is a desperate unsatisfied need and that need will be satisfied – just as water flowing down a hill will find a path – with or without the FDA’s help. He was very persuasive. Reminds me of an old TV ad: “When EF Hutton talks, people listen.”

Interestingly, no one picked up on what I though was the most egregious over reach in the draft guidelines, namely that the FDA tacitly incorporated or read the homologous and more than minimally manipulated requirements from registration facilities (1270.10) into the exemption for same surgical procedures (1271.15). Under the actual rule (1271.15) same day surgical procedures can do non-homologous and more than minimally manipulation. At least those two terms are not in that rule. Legal Method 101 says that if terms are in 1271.10 but not in 1271.15, then they’re in in 1271.15. (Maybe too technical. I’ll have more to say about that another time.)

Maybe there is a viable lawsuit

Something else I realized as a result of a couple of the astute presentations. I said in the last post that you can’t sue on a guidance document because it’s just the agency’s “current thinking.” However, if a guidance document is really disguised rulemaking without meeting the rule changing requirements, then maybe there is a lawsuit. Many presenters were clear about the fact that these guidance documents are disguised rule changes, so I’m now more optimistic about the chances of a legal challenge.

People are Mad and are going to do something about it

And speaking of possible legal challenges, while all of the presenters were very professional, very cordial, ostensibly courteous and complimentary to the FDA panel members on the dais, I sensed that quite a few, many in fact, were pretty upset by what the FDA is trying to do with the draft guidance documents.

So here is my prediction/wish/what I hope to make happen. There won’t be one lawsuit filed if the draft guidelines go into effect. There will many lawsuits. I don’t think these folks are going to go quietly. My sense is that the big players, sophisticated players, like Rubin, the fellow who started a society and has 5800 members, the guy with dozens of clinics, they have seen too many good results to give up their most effective tools. All these guys either run or are closely connected to prestigious professional societies and I predict that many of them are going to try to stop these guidance documents, in court or in Congress.

I hope for everyone’s sake the FDA really listened today, because people are mad as hell and there not going to take it. They want better and quicker access to this new technology, and my hope is they will get it.

Rick Jaffe, Esq.

www.rickjaffe.com

Autologous Cell Therapies Do Not Represent a Public Health Risk and Should Not Be Regulated Like Drugs

SevOne Founder and Stem Cell Institute patient, Michael Phelan discusses what’s financially at stake for scientists, universities, drug companies, and the FDA who oppose autologous stem cell therapy and lobby for patients’ own stem cells to be regulated as drugs.

VIEW FULL ARTICLE

Forbes interview with Michael Phelan from Feb 2013: One Man’s Reluctant Tour for Adult Stem Cells by John Farrell

Excerpt:

“I chose the Stem Cell Institute because they published their research in Translational Medicine. In addition, I corresponded with physicians and researchers experienced in Autologous Stem Cell treatments, including Roger Nocera, author of Healing Cells – Cells that heal us from cradle to grave, and I also listened to Arnold Caplan of Case Western.

So, at a Johns Hopkins managed hospital in Panama I had a mini-liposuction procedure. From my adipose-fat tissue they separated and expanded my cells, which took about a week then they gave to me in an IV.

I had visual problems for over a year before treatment, including double vision. After my first treatment in May of 2012, my vision problems resolved and I was able to continue driving. My mental and physical energy improved dramatically. A number of other problems improved. So, I was pleased with the outcome.”

Professor Arnold Caplan discusses mesenchymal stem cell therapy for multiple sclerosis

Professor Caplan is “The father of the mesenchymal stem cell (MSC)”. In this clip, he describes a mouse experiment using human MSCs in a mouse model of MS. The experiment shows that it’s possible to place human cells in mice that have normal immune systems. He continues to discuss the astounding results.

VIDEO – The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (Part 7 of 7)

In this final segment, Prof. Caplan discusses: Mesenchymal stem cells make anti-bacterial molecules, How retro-orbital injections of human MSCs cure mice with cystic fibrosis infected by pneumonia aeruginosa 70% of the time, The process by which MSCs kill bacteria in the body, Clinical trial for using MSCs to treat sepsis, “MSCs are drug stores for sites of injury or inflammation. They are site regulated, multi-drug delivery vehicles”, MSC transitions: ostegenic, trophic and immunomodulatory, MSCs are not stromal cells. They are not part of the connective tissue, The name of the MSC has changed. It is a “Medicinal Signaling Cell” and has nothing whatsoever to do with “stem-ness”, Cell plasticity, transdifferentiation in the mesengenic process.

VIDEO – The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (Part 6)

In part 6, Prof. Caplan discusses Trophic properties of mesenchymal stem cells; MSCs for heart disease; MSCs homing to heart injury site and also to skin incision site; MSCs limit left ventricular thinning following infarction; Trophic properties of MSCs: anti-apoptotic, anti-fibrotic, anti-scarring, angiogenic, mitotic; phase 1 data for allogeneic MSCs show fewer arrhythmias, prompt heart rate recovery, and improved lung function; autologous adipose tissue-derived stromal vascular fraction for treatment of chronic heart disease; Active mesenchymal stem cell clinical trials around the world; Induction therapy with autologous MSCs in kidney transplants; MSCs can coax neural stem cells to become oligodendrocytes, curing mice with MS using allogeneic human MSCs.

VIDEO – The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (Part 5)

In part 5, Prof. Caplan discusses: Mesenchymal stem cells produce huge quantities of bio-molecules, some of which are immunosuppressive; MSCs put up a curtain of molecules around themselves that allows donor (allogeneic) MSCs to be transplanted into a recipient free from immune response; The bio-chemical mechanism of how MSCs shield themselves from host T Cells; Allogeneic hematopoietic stem cell business model; Treatment of graft vs. host disease in children and adults; Treatment of Crohn’s disease with allogeneic mesenchymal stem cells.

VIDEO – The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (Part 4)

In part 4, Prof. Caplan talks about isolating mesenchymal stem cells from bone marrow using specialized; calf serum choosing different assays to prove multipotency – osteogenesis, chondrogenesis, adipogenesis; point of care with autologous bone marrow in orthopedic surgery; tissue engineering bone with lineage restricted MSCs; banking bone discarded bone marrow from orthopedic surgeries for future use;

The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (VIDEO Part 3)

In part 3, Professor Caplan discusses the science behind mesenchymal stem cells: sources of mesenchymal stem cells (MSCs), because all MSCs are pericytes one can find them in any tissue that has blood vessels, pericytes express markers of MSCs, frequency of pericytes in human tissue, most abundant source of pericytes is adipose (fat) tissue, adipose-derived stem cells, how MSCs are separated from fat, chemistries MSCs from different tissues are not the same, MSCs function at sites of injury, mesenchymal stem cell homing in mice, MSCs don’t make fat, they don’t make muscle. They come back as pericytes, and not all pericytes are MSCs.

The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (VIDEO Part 2)

In Part 2, Prof. Caplan discusses the two types of regenerative medicine: tissue engineering and in vivo tissue regeneration, hematapoietic and mesenchymal stem cells. All mesenchymal stem cells are pericytes and have immuno-modulatory and trophic properties

Prof. Caplan was speaking in Panama City, Panama at “La Medicina Del Futuro En El Presente”, an event organized by the honarable Ruben Berrocal MD, Minister of Science, Technology and Innovation SENACYT (National Secretariat of Science, Technology and Innovation) and Prof. K. S. Jagannatha Rao, Ph.D., FNASc, FABAP, FASB, FLS (Reino Unido) Director INDICASAT-AIP (Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia — Institute for Scientific Research and High Technology Services).

The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (VIDEO Part 1)

Professor Arnold Caplan of Case Western Reserve University is widely regarded as “The Father of the Mesenchymal Stem Cell”. This lecture is a “must see” for anyone interested in stem cell therapy. In Part 1, Prof. Caplan proposes a new regulatory pathway for approval of cell-based therapies and regenerative medicine called “Progressive Approval” to replace the current US FDA system that is now in place.

Prof. Caplan was speaking in Panama City, Panama at “La Medicina Del Futuro En El Presente”, an event organized by the honarable Ruben Berrocal MD, Minister of Science, Technology and Innovation SENACYT (National Secretariat of Science, Technology and Innovation) and Prof. K. S. Jagannatha Rao, Ph.D., FNASc, FABAP, FASB, FLS (Reino Unido) Director INDICASAT-AIP (Instituto de Investigaciones Cientificas y Servicios de Alta Tecnologia — Institute for Scientific Research and High Technology Services).