Our new paper in the journal Cell Stem Cell on the large stem cell clinic marketplace in the U.S. documented a wide range of different kinds of clinics, stem cells used, and conditions claimed to be treated, but here I want to focus on the fat stem cell clinics in this post. I’m going to try to address one of the major questions I’ve been getting in the last few days since our paper came out:
Are some fat stem cell clinics selling unapproved drugs?
Fat stem cell clinics typically sell therapies based on a product extracted from their customers’ fat tissue, even though there’s no conclusive data that these are safe or effective.
Sometimes this liposuction product after further processing is simply called “fat stem cells” or “adipose stem cells”, while other times it goes by the name “stromal vascular fraction” or SVF.
Regardless of what anyone calls it, the adipose cellular product (for simplicity from here on out in this post I’ll call it SVF) is substantially different than the original fat. The FDA calls this kind of significant processing by the name “more than minimal manipulation” and it means that the resulting “stuff” is almost certainly a drug requiring FDA approval before use.
In fact in one of its draft guidances in 2015, the FDA used SVF as an example of what they often are going to define as a more than minimally manipulated drug. Definition of SVF as a drug makes sense to me as a scientist because the process to make it is fairly involved including in most cases an enzymatic treatment (see my illustration above). I’m not aware of fat stem cell clinics having FDA approval to sell SVF. Therefore, in that sense it seems likely the answer to the reporters’ question about the selling of unapproved drugs is often, but not always “yes”.
Here is the actual FDA guidance language, which is as clear as the FDA has ever been on this particular point on SVF as a drug (emphasis mine):
“Example 10-1: Original relevant characteristics of adipose tissue, a structural tissue, to pad and cushion against shocks generally include its bulk and lipid storage capacity. A manufacturer recovers adipose tissue by tumescent liposuction and processes the adipose tissue to isolate cellular components, commonly referred to as stromal vascular fraction, which is considered a potential source of adipose-derived stromal/stem cells. The HCT/P generally is considered more than minimally manipulated because the processing breaks down and eliminates the structural components that provide cushioning and support, thereby altering the original relevant characteristics of the HCT/P relating to its utility for reconstruction, repair, or replacement.”
As I’ve written before, a “more than minimally manipulated” human cell/tissue product is usually going to be a biological drug requiring prior FDA approval before use in patients.
Further, in a warning letter sent to three jointly owned fat stem cell clinics, the FDA also seemed to refer to those clinics’ version of fat stem cells as a drug product too in December 2015. Some owners of fat stem cell clinics, however, have argued that their products are not drugs because in their view in each case it is minimally manipulated.
In the context of our paper showing such a large overall stem cell clinic industry, what this all means is that the fat stem cell clinics (a large slice of the general stem cell clinic pie) in the US are very likely in many cases administering unapproved biological drugs to large numbers of American patients each year. However, the FDA has been slow to act leaving arguably some room for debate. Absent action or more finalized guidances, there’s an uncomfortable gray zone. A big fat one in fact.
Another major issue that could lead to defining SVF as used by many clinics as a drug is something called “homologous use” (a primer on that term here). By this the FDA is thought to mean that for any given biological product, its origin is homologous (substantially similar to) the target tissue. For instance, if you use bone marrow stem cells as a treatment, the organ you are treating should have some similarity to that product such as a joint, a bone, etc. That often does not need FDA drug approval. This is using apples for apples if you will by analogy, rather than apples for oranges, which would be non-homologous use.
What the homologous use rule means for fat stem cell clinics is a potential big regulatory challenge because to qualify for homologous use they could in principle only treat fat-related medical conditions (again, by analogy using apples for apples). Most offer fat stem cells for conditions having nothing to do with fat (apples for oranges). This sure raises questions about non-homologous use. There may be some instances where fat stem cells are used for fat-related cosmetics conditions, making that homologous use, but these are not as common as other uses that are marketed.
Again with just the one exception of the warning letter mentioned above, there has been no apparent recent FDA action on fat stem cell clinics. It’s possible the FDA is waiting to do more until after its public meeting on stem cells in September or maybe it will never take any large-scale substantive action. Some of the clinics have told me essentially that absent FDA action they think they’re right to view their clinical practices with fat stem cells as outside the scope of FDA regulation. Could they be right? Why did the FDA issue that one warning letter, but not other ones for all those other clinics? Why hasn’t the FDA done more in this area to make things clearer? Has FDA inaction contributed to the mushrooming of the US stem cell clinic industry?
In future posts I’m going to discuss the bone marrow stem cell and amniotic stem cell businesses. Some of the same issues arise there, but also some interesting, unique ones as well.