In a nutshell, what does all of this week’s big FDA developments on stem cells and regenerative medicine mean for stem cell clinics?
There’s much to be upbeat about so overall I’d say it’s good news, but I see three significant potential problems too. Dang.
The good news is that the FDA seems determined to deal with the highest risk stem cell clinics, but unfortunately the FDA sent mixed messages on clinics in a broader sense and in some ways left the door open to certain clinics still being predatory with for-profit risky procedures on patients. After a few days of mulling it over and talking to various stakeholders as well as the FDA itself, I’m thinking we folks concerned about stem cell clinics should probably somewhat lower our expectations on what’s to come.
In my first post I went through the two finalized guidances in depth and already found a potential loophole in one area for some stem cell clinics related to the issue of homologous use (i.e. using like cellular product to treat only like health condition such as skin cells for skin, blood for blood, etc.). Clinics selling bone marrow stem cell “treatments” for non-blood or immune related conditions, which is non-homologous use, may unfortunately still qualify for the same surgical exception. This is what I see as potential problem #1.
I was hoping I was wrong on that possible loophole related to the homologous use standard, but when I asked the FDA about this and some other issues by email, it seems like the answer suggests the loophole exists. Here was one of my questions to the FDA:
“…it would seem that the issue of homologous use only comes into play further downstream in the flow chart/decision making process and perhaps is not involved in the “such HCT/P” determination…Is that correct? Or instead, could non-homologous use nullify a potential same-day surgical exception?”
An FDA spokesperson responded to it this way:
“With regard to your question on homologous use, you are correct – as described in the same surgical procedure exception (SSPE) guidance, homologous use is independent of the SSPE determination. See specifically the response to question 1:
“The assessment of whether the exception in 21 CFR 1271.15(b) applies is independent from the determination of whether the HCT/P meets the criteria in 21 CFR 1271.10(a) (e.g., the criteria of minimal manipulation in 21 CFR 1271.10(a)(1) and homologous use in 21 CFR 1271.10(a)(2) are not considered when determining whether an HCT/P meets the exception in 21 CFR.1271.15(b)).”
I have to admit to still not being crystal clear on this, but my reading of it all is that the FDA may allow minimally manipulated bone marrow stem cells to be used in a non-homologous fashion and yet still qualify for the same surgical exemption, and hence not be regulated as a drug on that level. That would be a big problem. For instance, it would seem risky to me to inject bone marrow (even if it’s minimally manipulated) into someone’s lungs, brain, etc. and hence that should go through drug review.
I asked Patricia Zettler, Associate Professor at Georgia State College of Law and an expert on FDA matters, about this non-homologous use issue and she seemed to have a similar take:
“I think you’re right—what FDA is saying here in question 3 is that even minimal manipulation that is something other than rinsing, cleansing, sizing, and shaping will cause a HCT/P to fall outside of the same surgical procedure exemption. But, so long as the HCT/P is not processed beyond rinsing, cleansing, sizing, and shaping, it does seem like homologous use is not required to fall within the same surgical procedure exemption.”
Interestingly, there’s sort of a fork in the road here for fat versus bone marrow stem cells, as it appears other language in the final guidances make fat stem cells unable to qualify for same surgical exception no matter what if I read things right.
In the media the FDA leadership also seems to be indicating not a ton may happen practically speaking relative to the nearly 600 clinics out there in total, which highlights potential problem #2. In an article in the NY Times by Sheila Kaplan and Denise Grady on the FDA development, the notion of mixed messages from the FDA came up (emphasis mine):
“But the message seemed mixed. Dr. Gottlieb and Dr. Marks also said that orthopedic procedures — injecting the fat-derived cells into joints — were of lower priority than treatments that involved injecting or infusing the cells into the central nervous system or bloodstream.
“There are hundreds and hundreds of these clinics,” Dr. Marks said. “We simply don’t have the bandwidth to go after all of them at once.”
Agh! That last part is disappointing, but I get it on the resource side. I understand that the FDA has a great number of responsibilities and limited resources so a risk-based approach to stem cell clinics makes sense practically speaking, but on the other hand knowingly letting potentially hundreds of non-compliant stem cell businesses operate has risks too including to patients, the stem cell field, and to the agency itself.
Potential problem #3 is that the FDA is generally giving stem cell clinics and other firms 3 years to come into compliance. This is not out of the ordinary from what I understand in terms of the FDA giving industries time to adapt to newly finalized guidances, but in the stem cell clinic arena we already know there are many predatory firms out there putting patients at risk to try to make big profits. They shouldn’t get a 3-year free pass so I hope the FDA acts basically now on the highest risk non-compliant firms. There are some indications they might do this.
Even if the FDA “only” goes after the highest risk two dozen or so stem cell clinics out there, it could have major, positive impact. In my view, there are scores of particularly high risk clinics operating in the US so even in just this area, the FDA will have a lot of work to do. For instance, there are probably at least a few dozen clinics marketing unproven and now arguably non-compliant offerings to children, which I see as particularly ethically dicey and very high risk to the children. The FDA can’t let these kids down by standing on the sidelines as stem cell clinics experiment on them for profit.
Overall, we’ll have to wait and see what actual actions the FDA takes and how those compare to its statements and guidances. It’s going to be a mixed bag, but so far I like how the agency is moving on stem cells with Dr. Scott Gottlieb at the helm.