What happens next with FDA & stem cells: lower your expectations?

FDA stem cell meetingIn the total the FDA has held 3 days of public meetings on stem cells in the last few weeks ranging from science to policy and hearing from many parties including patients and even stem cell clinics so the big question now is, “what happens next?”

The FDA has 4 draft guidances pertaining to investigational stem cell clinical procedures and these were the subject of the second meeting that last a couple of days. Soon the FDA’s online commenting period related to these issues will close (you can still make comments here, but don’t expect the comment to appear quickly as I submitted mine 4-5 days ago and it’s still not up).

Once that is done, can we expect the FDA to finalize those guidances? And if it does, will the guidances change at all due to the meetings or online comments on the docket? My sense is that the FDA will take at a minimum months to consider the comments at the meeting and those submitted online so it’ll be 2017 most likely before they are even close to taking a next step at all.

I do not expect the guidances to change substantially. As a stem cell biologist, I didn’t hear anything at the meetings in terms of science or data that provided a compelling rationale to change the guidances. The FDA should base its decisions on the biomedical science.

There were a variety of ideas presented at the meeting for changes or new elements to the stem cell clinical arena including a “middle ground” that would get stem cell therapies to patients more quickly, but the trade-off there is that there would be far less data to support the potential safety and effectiveness of those stem cell products. On the whole this would simply put more patients at risk in my view.

Several speakers mentioned starting a registry for stem cell clinics, but I don’t see that as having a major positive impact as there are too many unknowns and complexities. Who would run the registry and pay for it? Who would oversee it (the FDA?) and what would happen if commercial entities were noncompliant with participating in the registry? What about the already existing clinicaltrials.gov?

A big meme at the FDA meeting was the idea of very widespread functional homology of fat stem cells throughout the body via paracrine signaling. Yes, the heterogeneous cells within “fat stem cell” products do make many growth factors that could act in a paracrine manner, but I don’t buy the idea that this makes them homologous to many diverse tissues in the body and I don’t expect the FDA will either.

The future

The FDA could never finalize the guidances, resulting in either the status quo continuing of thorough oversight of the good citizens of the field and little-to-no action on the stem cell clinics. Or even without finalizing the guidances, the FDA could step up its oversight of stem cell clinics, which would be helpful given that there are around 600 of them in the U.S. operating without FDA approval and the FDA has been issuing <=1 warning letter per year lately.

If the guidances remain (finalized or not) and are the basis for the FDA’s current thinking moving forward, then most adipose stem cell clinics should be subject to FDA action given that they are using more than minimally manipulated cells and hence drugs in an unapproved manner and they are almost always using the cells in a non-homologous manner.

Perhaps in the short run the most likely thing is that nothing will happen. As my state’s governor Jerry Brown once famously said to voters, “lower your expectations” and perhaps that can be applied to the FDA on stem cells. However, I’m not going to do it. I’m going to keep my expectations high on this.

New paper shows huge American stem cell clinic industry: 570 locations

My colleague Leigh Turner and I today published a new paper in Cell Stem Cell documenting for the first time the American stem cell clinic arena in a comprehensive way, which we found as of February has a remarkable 570 clinic locations via 351 businesses.

These numbers are way beyond the predictions of most researchers and policy makers for stem cell clinics in the U.S., and point to a burgeoning, huge industry from coast to coast (see map below of clinic locations that we found in our research that is Figure 1 of the paper).

Figure 1 Turner Knoepfler Stem Cell Clinics

We focused on those businesses that as best as we could determine do not have FDA approval for marketing stem cell treatments. This means that even if relatively few patients are seen at each of the 570 locations, tens of thousands of Americans each year may be getting stem cell offerings that do not have formal FDA approval.

The businesses in general market fat, bone marrow, and amniotic-related stem cells for a surprisingly wide range of conditions too, pretty much from head to toe and A to Z in a medical dictionary of conditions. It’s not clear scientifically if there are data to concretely support the use of these types of stem cells for such a wide spectrum of conditions.

Our goal was to document this direct-to-consumer marketed industry as fully as possible even as we excluded those businesses that had INDs or operated outside the U.S. A challenge in that regard is that the FDA keeps information about INDs private.

Importantly on the other hand some businesses while having no formal FDA approval may still be compliant because they fall within specific categories of usage. For instance, in some cases with a subset of these clinics such as those that use largely unmodified bone marrow cells for autologous use in homologous orthopedic conditions, no FDA “drug” approval is likely needed.

However, in many other kinds of treatment scenarios that we documented there is a strong likelihood that FDA pre-approval would be needed because of issues such as non-homologous use and/or more than minimal manipulation. Such a large industry with unclear regulatory oversight and pre-approval is a big concern overall.

Still, I do not condone the use of words like “non-compliant” or “shady” to describe all at once this entire clinic marketplace or to characterize the full list of businesses in our database because of a number of reasons including the issue mentioned above with bone marrow being used in a homologous way in some cases as well as the overall complexity of this arena and the lack of clarity from the FDA.

I’ll have more to say about the paper, but I hope you find it a valuable resource.

Woman’s death after “no big deal” fat stem cell therapy: coroner investigating

An elderly woman in Australia reportedly died shortly after receiving a fat stem cell transplant.

Sheila Drysdale passed away hours after getting an adipose stem cell treatment a few days before Christmas in 2013. That death is now being investigated by the coroner there.Macquarie Stem Cells

Not only is this death in Sydney distressing in it of itself, but also it raises broader safety concerns across the globe including here in the U.S. because fat stem cell treatments of this kind are so widely administered. Most have not been approved by the various countries’ regulatory agencies including the FDA here in the U.S.

This kind of “liposuction stem-cell therapy” procedure is often marketed by stem cell clinics as safe and effective for a host of conditions.

The AAP article that reported the death provides more details:

“… in July 2013, Mr Drysdale heard an advertisement for Macquarie Stem Cells, whose celebrity patients included the late model Charlotte Dawson and cricket legend Geoff Lawson, and began investigating the possibility that stem-cell therapy could help his wife after reading about encouraging US case studies online.”

This part of the report also highlights how what goes on in the U.S. has global implications for patients and the stem cell field.

Continue reading

More on Nervana Stem Cell Clinic in Sacramento

I blogged recently about how Sacramento has a new stem cell clinic using amniotic stem cells called Nervana Stem Cell Center. Its website currently offers no details on the people behind the company that I could find.

Nervana Stem Cell Center

Google Image

I sent Nervana a message on their website to try to learn more based in part on a commenter on this blog having suggested that a Dr. Tushar Goradia may be the main physician at the clinic:

Hi,
I noticed your ad in the Sac Bee and was checking out your website. Who is the physician at Nervana? Is it Dr. Tushar Goradia? Does Dr. Goradia have experience and training with stem cells? Are other doctors part of this team and do they have stem cell experience and training?
Thanks,
Paul

No reply.

I have called Nervana several times and only got a recording over a period of weeks, but then last week I got an actual person on the phone. This representative couldn’t say who the main doctor was, but said in a few months that would become known.

The rep did mention there is a second doctor there named Clarence Lee and a nurse practitioner named Robin Jackson. I read Dr. Goradia’s profile on LinkedIn and it does list Nervana with him as the owner. I also was able to find Jackson’s LinkedIn profile, where her employment at Nervana is listed. Her role there is described this way:

FNP-C
Nervana Stem Centers
– Present (3 months)Fair Oaks, California
Injection of Stem Cells into joints and IV therapy

No luck on finding out about Dr. Lee yet.

I hope the community can learn more about Nervana, get information on who the doctors are and their backgrounds in stem cells, and what they are doing in the way of stem cell interventions. From what I understand this clinic is already administering amniotic stem cells to patients for a variety of conditions including pain and arthritis here in Sacramento so there’s somewhat of a pressing need for information.

FDA warning points to tougher regulation of fat stem cells & clinics

FDA logoLast week I blogged about how the FDA had issued a warning letter to a series of three co-owned fat stem cell clinics across the US.

What does this FDA action mean on the broader stem cell clinic arena, particularly to those selling fat stem cells?

The FDA is still in the process of getting public comment and finalizing draft guidelines related to stem cell clinical products including fat stem cells aka adipose stem cells and stromal vascular fraction or SVF.

Even so, the FDA just issued this new warning letter at least partially related to SVF to a series of co-owned clinics in CA, FL and NY here in the US going under the names Irvine Stem Cell Treatment Center, Miami Stem Cell Treatment Center, and Manhattan Regenerative Medicine Medical Group.

In the letter the FDA explicitly calls SVF a biological drug in this context and mentions that there’s no IND and no BLA (for more on these key acronyms see here) at the clinics.

As discussed in the comments on my first post on this warning letter, the FDA language is a bit puzzling in the language used in the part calling the SVF a drug. The letter first mentions several target conditions as an implied possible reason for the definition as a drug and then only later indirectly mentions more than minimal manipulation as possibly involved. Non-homologous use is also mentioned. Overall this letter is not very clear. A helpful FDA reform would be a commitment to clear writing in its public communication.

Still the relatively unambiguous wording in the letter calling SVF a drug here is striking given that the FDA again has not to my knowledge finalized its guidance on SVF. It’s hard not to read the letter as meaning the FDA has every intention of defining SVF as a drug in many if not all cases.

This is a big deal because scores of stem cell clinics in the US are injecting SVF into patients on a daily basis without any FDA approval, licensing, etc. It’s not clear why these three co-owned clinics got the first FDA warning letter in the last few years on stem cells when there are all these other clinics doing very much the same thing. That’s also puzzling and leaves an important open question. More broadly as far as I know there’s no public information on how the FDA assesses which entities to focus its limited resources upon at any one given time.

What does this mean for all those other fat stem cell clinics out there? It’s bad news for them as the FDA could and really should be taking a close look at them too. The FDA is slow at times to take action as I’ve been critical of them about in the past, but once they get going, those not following the rules have reason to be concerned.

What about those recent still only draft FDA guidances (e.g. see a nice piece by Alexey on the situation with fat stem cells here)? I suppose they could change or take a long time to be finalized, but this warning letter can be viewed as a strong signal that the guidances are unlikely to change in their core points.

One of the largest collective users of SVF in the stem cell clinic world is Cell Surgical Network (CSN), with whom Irvine was previously affiliated. I contacted CSN more than a week ago by email for comment on the warning letter and to get their perspective on this development, but have not received a reply. To my knowledge, CSN has not been subject directly to FDA action, but I do not know when the apparent split with the Irvine clinics occurred.

Until more information about what the FDA is doing & thinking (at least as expressed by their written words) hits the  public domain, the key puzzles mentioned above will remain open for speculation. However, this letter possibly signals a major turning point for regulation of clinical use of adipose stem cells, particularly in the clinic realm.