Sanford Burnham Prebys physician-scientist advises the FDA on cell-based therapeutics, tissue engineering and gene therapies.
Sanford Burnham Prebys physician-scientist Evan Y. Snyder, MD, PhD, was reappointed to the Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) in the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA). He is serving a four-year term from August 30, 2024, to March 31, 2028.
We sat down with Snyder to learn more about the committee, his advisory role and the importance of safeguards for new therapies.
What are FDA advisory committees?
The FDA advisory committees advise the FDA commissioner in many areas to support the agency’s mission of protecting and promoting public health. This includes advising on whether or not new treatments or other products under the agency’s purview should be approved to enter the marketplace.
There are many committees that focus on topics ranging from food and tobacco products to digital health and veterinary medicine. My committee oversees cell-based therapeutics, tissue engineering and gene therapies.
Who serves on these committees?
Typically, committees have between 12-16 members. Most are academics with complementary sets of expertise. My committee includes individuals proficient in stem cell biology, gene therapy, biomedical engineering, surgery, biostatistics and clinical trial design, among others.
Other members often include a non-voting ex officio industry representative and a voting patient advocate representative. And, for each meeting, you can “roll-in” ad hoc people that have a particular expertise on the topic that’s being discussed.
What is your history on the Cellular, Tissue, and Gene Therapies Advisory Committee?
In the early days of the stem cell field, I was a founding member of the FDA and National Institutes of Health (NIH) Stem Cell Working Group to generate guidelines for human transplantation, and then served on the FDA’s Biological Response Modifiers Advisory Committee which derived from that Working Group, and which ultimately gave rise to the CTGTAC. I served as a recurring ad hoc member of CTGTAC for about eight years. In 2011, I was made acting chair of the committee. And then in 2012, I was appointed as permanent chair.
After my two-year term was complete, I was asked to stay on for a second two-year term. At that point, I hit my term limits and went into my “latency” period. Last year, I was asked to give the committee a lecture on what to look for in reviewing cell-based therapies and cell-based therapy clinical trials. I guess they found my advice useful because I received an invitation to return to the committee.
Can you share a case where you learned a valuable lesson about regulation?
One sobering lesson was learned at my very first session. I was so excited about being on this committee, recognizing that we were the “gatekeepers” of health care for the country and had the power to do such impactful things.
I received the materials to review for my first case — hundreds of pages. They were from a company that wanted to take skin biopsies obtained from the back of a patient’s ear, dissociate the sample into single skin cells and expand them in cell culture, and then send the cells back to a plastic surgeon who would inject them into the nasolabial fold of the donor patient to efface the aging-related furrows there and make the face look younger and pumper.
I confess that I was really having trouble getting invested in the case as I was expecting something more meaningful for us to adjudicate. And then, at lunch, one of the more senior committee members off-handedly remarked how important this case was. Because I could not tell if he was being sarcastic or earnest, I asked him (a bit sheepishly) to elaborate.
He responded that, while the matter may sound trivial, if our committee approved this “therapy”, it would represent only the second autologous cell-based therapy ever approved by the FDA. He added that, if we approve this one, practitioners could start using autologous cells (especially derived from skin) off-label for all kinds of indications whether we had investigated and sanctioned those uses or not.
That changed my perspective immediately. After deliberating, we denied the company approval based on a failure to prove adequate safety. For example, they hadn’t met the required bar for showing that the injected skin cells didn’t continue to proliferate inappropriately under certain common conditions. Also, the company had not followed the patients longitudinally enough to know the long-term outcome. They had not adequately characterized the cells they had expanded artificially in a tissue culture dish and were now transplanting.
How does the committee vote?
We take two votes. First, we vote on whether the applicants have surpassed a threshold for safety. Then we take a second vote on whether they have met their burden for showing efficacy beyond standard-of-care.
When you vote, it’s like “American Idol.” You have a little switch in front of you, and you flip it to vote “yes” (green), “no” (red) or “abstain” (yellow). Your vote then goes up on a tally screen that all (including the public) can see.
At the end of each vote, each committee member has to explain the rationale for why he/she voted that way.
What is the most visible case you have reviewed?
We were asked to review a case related to what is commonly called “human cloning.” The scientific term is somatic cell nuclear transfer (SCNT). One takes a skin cell from a patient, removes the nucleus transfers it to an unfertilized egg (oocyte) whose own nucleus has been removed. Then you “zap” the egg with the donated nucleus, and the egg acts as if it has been fertilized. It begins to divide into 2 cells, then 4 cells, then 6 cells, and form a blastula, and ultimately — if allowed to go to beyond 14 days (which is typically not sanctioned in this country) — into an embryo that will be just like whoever donated that skin cell nucleus. These experiments are exceedingly controversial and actually allowing a human embryo to go to term is outlawed here and in most countries, although SCNT is used routinely for agricultural animals.
There is one indication, however, where SCNT could be therapeutically beneficial in humans. That is in the case of rare mitochondrial diseases which tend to be lethal or incapacitating. Mitochondria are the powerhouses of the cell; when they are diseased, the kids are born with heart, muscle, brain, eye, and/or liver disease — these are tissues that demand high energy.
The mitochondria and the genes encoding mitochondria come only from the mom, not from both parents. A skilled and esteemed reproductive biologist came to the committee with a proposal to perform SCNT for parents at high risk for having kids with mitochondrial disease. The skin cell nucleus from a mom carrying abnormal mitochondria would be placed in the unnucleated egg of a normal woman, which would then be fertilized by the dad in vitro. This was, of course, very contentious. Some members of the press said the procedure would create “three parent” babies and create monsters. There were protests.
Ultimately, our committee had to decide whether to approve a clinical trial or not. And that would help determine whether the U.S. would begin to embrace SCNT. We concluded that the disease represented a critical unmet medical need, requiring new interventions. We determined that the proposed strategy was a reasonable, albeit an arduous, approach if a couple wanted a baby with the genetic inheritance of both parents yet without abnormal mitochondria. However, in our view, the bar for safety had not yet been met (based on the preclinical animal studies). We provided a laundry list of studies that should be pursued before coming back to the committee.
The United Kingdom was considering the same issue. While the UK was holding hearings on the topic, I was summoned (as the committee’s chairman and, hence, the United States representative) to testify before the parliamentary committee, explaining our rationale for not approving a clinical trial for SCNT to treat mitochondrial disease.
Why is it important to you to serve on this committee?
As a physician, I make an impact on each kid I take care of, kid by kid. But there’s a limited number of kids that I can treat during my career. As a scientist, if I get it right, I can make an impact on thousands of patients, but that might not even occur in my lifetime.
On this committee, I can make an impact on potentially thousands of patients in the near term. That comes with a requirement for being incredibly rigorous in assessing the data we are presented with, as well as appreciating the practicalities of what it takes to actually do medicine and improve the lives of real patients in the real world — sometimes needing to make a decision in the face of incomplete and imperfect data. Forestalling a decision can be a decision in itself.
I think as an educator, as a physician, and as a scientist, I have a unique set of skills that might make an impact here.
