fdafatstemcell_smRight now the FDA has a big fat stem cell conundrum on its hands. The agency is faced with a tough dilemma as how to deal with fat (adipose) stem cell products and the large number of businesses who sell them.

Are fat/adipose stem cells a drug or not?

If yes, what does the FDA do about the hundreds of clinics currently marketing them without approval?

If not, then how does the agency reconcile that with its past statements and even words this year under new Commissioner Scott Gottlieb indicating that the cells are a drug?

Under Gottlieb’s leadership, the FDA recently took decisive action in two cases related to the use of fat stem cells. There was a “raid” here in California (StemImmune and California Stem Cell Treatment Center, working in collaboration on an anti-cancer approach drew FDA action on a stem cell-vaccine combo drug product) and a strongly worded warning letter to a clinic in Florida, US Stem Cell Clinic, Inc., which is part of the publicly-traded company US Stem Cell, Inc. ($USRM). Gottlieb also issued a very bold, broader public statement on stem cell clinics, indicating the FDA is very active on oversight of this commercial area.

These developments are encouraging to me in the sense that the FDA now both appears to be more active and clearer in its statements. It is addressing a growing stem cell clinic industry that markets what seem to be unapproved biological drugs without any FDA approval. The clinics also most often lack rigorous data from properly controlled studies to back up what they are selling.

In contrast in the recent past the FDA and its CBER branch, the one specifically tasked with regulating biologics like stem cells, hadn’t seemed to be keeping up with the growing stem cell clinic industry. In the past couple years under Obama, the FDA and CBER took near zero apparent action on an industry built selling stem cells without FDA approval and one proliferating at a rapid pace. Now the agency under the new administration seems to be signaling a major change in course on stem cell clinics and a willingness to be bold.

For example, in that warning letter to US Stem Cell Clinic, the FDA indicated unambiguously that a fat stem cell product (similar or identical to that used by many clinics) can be a biological drug that businesses cannot use on patients without prior FDA approval and proper licensing such as a BLA. Presumably this is not a one-time kind of statement about fat stem cells being drugs given consistent past FDA draft guidance.

Where does the FDA go from here?

If the agency wants to be consistent doesn’t it need to do something related to the hundreds of other clinics selling fat stem cell products for a whole medical dictionary’s worth of health problems? On the other hand, does the FDA have the will and the resources to take such large-scale action?  Does anyone recall the agency ever taking action on hundreds of businesses at once in any field of foods or drugs? Even scores or dozens?

Let’s say for the moment that the FDA wants to be consistent on fat stem cell and other stem cell products that are drugs and doesn’t want a huge number of businesses marketing what it views as unapproved drug products, which undermines the agency’s credibility. If so, does it need to inspect every one of those businesses first, issue hundreds of 483 inspection reports, and then potentially draft and issue an equally large number of warning letters? Or can it just issue the potentially hundreds of warning letters without individual inspections, perhaps based on marketing? Each of these scenarios seems relatively unlikely. Also, my understanding is that many if not most warning letters must get cleared by FDA attorneys too before being issued. Overall, this would be a colossal undertaking.

If the FDA cannot do that, does it instead issue a smaller number of letters (warning or untitled) to a smaller number (perhaps 8-12) stem cell clinics, rather than hundreds, picking the specific businesses that it views as the highest risk? If it takes that course of action, do the tons of other clinics take the hint and stop being non-compliant? Or do they instead just keep doing business as usual and hope that being just one lost in a crowd of hundreds of businesses means the FDA won’t take any further steps specifically with them?

In yet another non-mutually exclusive scenario the FDA doesn’t take dramatically more concrete action, but in one of the expected upcoming policy/guidance statements it sends a strong message. For instance, in this scenario perhaps the agency announces unambiguously that fat stem cell products cannot be marketed without approval (perhaps with one or more potentially new exceptions such as for breast reconstruction) and in this way it essentially indirectly signals to the large number of businesses to whom this applies to collectively stop marketing unapproved stem cell drugs. Would such a blanket statement be effective without much action or would the stem cell clinic industry instead just continue to grow fatter at the expense of the bank accounts and potential health of consumers?

Finally, the FDA could back off on the notion of widely classifying adipose stem cells as biological drugs, leaving the big clinic industry largely free to continue business as usual when it comes to adipose stem cell marketing. While this is formally possible, again the recent words and actions from the FDA make it relatively unlikely. What about amniotic stem cell clinics and those businesses marketing bone marrow stem cell treatments that are drugs (e.g. via non-homologous use)?

I asked Patricia Zettler, Associate Professor at Georgia State University College of Law and a former FDA associate chief counsel about the different scenarios for what might happen next with fat stem cell and potentially other noncompliant stem cell commercial outfits. She is one of the most knowledgeable people I know about FDA matters on biologics. Here’s what she said:

Patti-ZettlerProfessor Patricia Zettler

“As you point out, the FDA almost certainly does not have the resources to immediately inspect and issue warning letters to the hundreds of stem cell clinics that may be illegally marketing therapies.  But the hope, I think, would be that sending warning letters to some may bring both the recipients into compliance as well as deter some others from marketing illegal therapies.

Another possibility, I suppose, is sending letters that are not warning letters but that say something like “it appears that the stem cell therapy that you are marketing is an unapproved drug; if you believe that approval is not required, please provide us with the basis for that determination.”  FDA did something similar with some DTC genetic testing companies back in 2010.  This might be a way for the agency to get more information about what products are being offered while at the same time signaling to stem cell clinics that they are at risk of a warning letter or other enforcement action if they do not come into compliance.”

These make good sense to me as possible developments to come.

Several law firms are keeping a close watch on this fat stem cell – FDA situation as well. You can see one example here.

It’s not entirely clear how the FDA will approach the stem cell clinic industry overall or the adipose segment, but there is an expectation in the wider community of more FDA action and clearer guidances to come soon.

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