How Scott Gottlieb may transform the FDA’s approach to stem cells

The Trump FDA commissioner nominee Dr. Scott Gottlieb Dr. Scott Gottliebcould dramatically alter how the agency regulates investigational stem cell therapies. How might such changes unfold? There are potential upsides and downsides to  the seismic shift that could be in the offing.

Gottlieb has written in the past about his perception of FDA over-regulation of stem cells such as in this piece in the WSJ. There he made a number of assertions that signal his view at least back then that when it comes to regulation of stem cells by the FDA, less is more.

More recently, a speech he gave at an ISSCR meeting in Berkeley last year is much more balanced in tone than the 2012 WSJ piece. This quote from the Berkeley talk, for example, is balanced and emphasizes standards:

“Expediting the development of these novel and transformative technologies like gene- and cell-based therapies doesn’t necessarily mean lowering the standard for approval, as I believe other countries have done. But it does mean having a framework that’s crafted to deal with the unique hypothetical risks that these products pose.”

Still that WSJ article is concerning.

For instance, he and his co-author Coleen Klasmeier, both former employees of the FDA, strongly criticized a federal court ruling in 2012 that the FDA could regulate laboratory-proliferated stem cells as a biological drug. Oddly, much of the basis for their criticism was far broader than the reality of the court ruling. They suggested, for instance, that the ruling opened a veritable Pandora’s box of FDA over-reach potential that extended to all autologous uses of stem cells (lab-grown or not) and beyond, but that was not the case as the ruling was focused on lab-grown stem cells. Even so they made largely unsupported generalizations such as the following:

“If the FDA’s victory is upheld on appeal, then conceivably nothing done as part of clinical practice is beyond the agency’s reach.”

In the intervening years since the 2012 court ruling and the WSJ article, we have seen that the sky hasn’t fallen from the FDA having obtained the defined authority to regulate lab-expanded stem cells as drugs. In fact, oddly enough if anything the more time that has passed, the less inclined FDA’s CBER biologics branch that oversees stem cells has been to take action on stem cell biologics. It’s hard to view the FDA issuing less than one warning letter per year to stem cell clinics even as there are upwards of 600 of these clinics as a form of overreach.

From a scientific and medical perspective, there are good reasons to regulate lab-grown stem cells as drugs. The cells are known to change their differentiation properties, accumulate mutations and epigenetic changes, and undergo other significant alterations in the dish in the lab. There is also, perhaps more directly related to the FDA’s mandate on biologics, substantial potential for contamination of cells in a lab during proliferation.

Since 2012, another big change has been the explosion of adipose stem cell clinics onto the scene, which use more than minimally manipulated liposuctioned material to make a biological drug product via enzymatic and other steps. However, the clinics argue their products aren’t drugs and they generally do not have any FDA approval to market stem cells. Nonetheless such offerings are being sold at hundreds of clinics around the country. How would a newly minted FDA commish Gottlieb view these clinics? Through the same lens as the autologous, homologous bone marrow-based approaches? What about the clinics using bone marrow and amniotic cells in non-homologous manners that make such products drugs? Continue reading

Poll: How will Trump’s FDA handle stem cells?

Cell Surgical Network, largest group of US clinics, using lab-expanded stem cells in patients?

Elliot Lander Mark BermanIs the largest affiliated group of stem cell clinics in America, Cell Surgical Network, now using laboratory-proliferated stem cells in patients?

Do they already have some kind of final FDA approval for this clinical approach given that lab-grown stem cells are generally viewed as drugs requiring premarket approval?

Over the years I’ve reached out to interview many members of our diverse community in the stem cell arena including those operating stem cell clinics. One past such past interview (here and here) was with the leaders of Cell Surgical Network, Drs. Mark Berman and Elliot Lander.

Even though more broadly those operating stem cell clinics across the U.S. and I don’t see eye to eye on many things, the interviews are valuable to the community, providing insights generally not otherwise found in the public domain.

Today’s post is a new, striking interview with Lander and Berman (pictured above). I invited them to do this short Q&A because there have been indications that their group of clinics may be gearing up to or already has been taking a different approach (at least compared to what I knew about in the past) to using stem cells in patients with the possible new approach involving laboratory-amplified stem cells.

For instance, on their website FAQ page they refer to using seemingly laboratory expanded cells (emphasis mine):

“Autologous lipo-aspirate can be frozen as SVF Stromal Vascular Fraction (contains mesenchymal and hematopoetic stem cells). SVF can be deployed for repeated treatments and also expanded under IRB approval as part of a safety trial providing vast quantities of autologous stem cells that could be used throughout that patient’s life.”

The question of lab expansion is such a crucial point because to my knowledge lab-expanded stem cells are considered a biological drug by the FDA requiring pre-market approval steps such as an IND, IDE, and/or BLA. Also, typically a safety trial of the type mentioned would be an FDA-approved, Phase I clinical trial based on an IND and I’m not aware of Cell Surgical Network having that.

To my knowledge, IRB approval alone is not a sufficient basis for doing a clinical trial on a biologic. Am I missing something here? Is Cell Surgical Network’s apparent IDE application with the FDA going to encompass data usually found in an IND as well? Why not do an IND and an IDE In this case?

The point of this interview was to try to clarify this situation. Thanks, to Berman and Lander  of CSN for doing it.

PK: I’m hearing that you are apparently growing adipose stem cells in the lab these days for clinical use (transplantation) in patients. Is that correct?

CSN: Yes – Our patients receive re-implantation (not transplantation) of their own cells under this protocol. 

Continue reading

Good stem cell news on trials, FDA, cool new papers & more

pericyte-paper

Guimarães-Camboa, et al, Cell Stem Cell figure

In the whirlwind that is the stem cell and regenerative medicine world, there are many concerning things that need attention, but also good stuff happens too and this post focuses on the positive.

The Asterias spinal cord injury clinical trial, a phase 1/2a trial called SCiStar, continues to make encouraging news with a clean safety profile and additional hints at possible positive indicators of efficacy. With the usual, important caveats such as that this is early and it is not an RCT, the SCiStar momentum is positive. I’m excited to see what the future holds for this one including from an RCT. You can read my interview from last month with Asterias leadership here.

I remain very enthusiastic about ViaCyte’s trial as well using a stem cell capsule product for treatment of Diabetes. Their joining forces with BetaLogics a year ago just made their position even stronger.

I’m going to do a post soon on an analysis on the total number of stem cell and regenerative medicine trials compared to historical data I collected. Stay tuned on that. I’m guessing it’ll be good news.

Recently, we also saw evidence of fast action from FDA in response to the 21st Century Cures Act in terms of providing a clear document on Regenerative Advanced Therapy designations and applications. It’s still unclear how the Cures stem cell provisions will play out, but I consider quick, clear action from the FDA to be a positive. I wish they were this fast on other stuff like dealing with stem cell clinics marketing unapproved drug products.

There have been a number of cool papers recently that I recommend reading:

FDA Regenerative Advanced Therapy Designation Rules Are Up in Response to Cures Act

The 21st Century Cures Act specifies some new FDA rules about investigational stem cell-based regenerative medicine therapies and perhaps most importantly defined a new class of product called a “Regenerative Advanced Therapy” or RAT, which is entitled to an expedited review.

The FDA already has a new page up on RATs, which specifies the specifics of RAT designation and how an entity may submit an application for RAT designation. This was remarkably fast of the FDA.fda-rat-designation

Some things on the RATs page stand out including that a request for a RAT depends on an IND. The IND must either be existing or submitted along with the RAT request. This is a major point as obtaining an IND requires rigorous, controlled data.

Stem cell businesses out to make a quick buck off of patients and potentially hypothetically interested in get RATs are going to be out of luck unless they change their world view to be data-centric and also go for INDs.

Also, the FDA is emphasizing that the condition in question must be “serious of life-threatening” and the FDA decides on what meets this criteria.

Oddly, the FDA will not require data be part of the RAT itself. I don’t quite get this, although perhaps their thinking is that the data requirement of the IND will suffice.