In case you haven’t heard, Ms. Kristin Comella, Chief Scientific Officer of the US Stem Cell Clinic (USSCC) was the recipient of a Warning Letter from the FDA concerning her clinic’s use of collagenase to digest fat tissue from patients to produce a stem cell-containing preparation known as stromal vascular fraction (SVF). I reviewed the Warning Letter itself in Parts One and Two in this series, but shifted over in Part Three to reviewing an incredibly in-your-face rebuttal letter Ms. Comella published on August 29th addressing various issues in the Warning Letter. I will continue with my answers to the 12 questions Ms. Comella posed to the FDA at the end of her diatribe. I have presented her questions exactly as she wrote them:
Comella Question Four: “Will you restrict the type of patients who are being treated using in-clinic protocols with bone marrow?”
My Response: The FDA focuses on what physicians use in treating patients. They don’t determine which patients receive what therapy, since that would mean they are regulating the practice of medicine. Thus, physicians are the ones who need to be selective when using autologous tissue-derived preparations; preferably just the ones that are FDA-compliant. In the case of your clinic’s wide-ranging list of pathologies, I suspect the FDA took one look and decided that there wasn’t a solid rationale supporting the use of the SVF-based therapies being provided and came a-knockin’. As for bone marrow-derived treatments, using BMC to treat pathologies that would constitute a non-homologous use will land you, and your clinic, back in the same position you’re in now.
Comella Question Five: “Will you restrict the discretion of physicians on patient selection to treat using their own body tissue?”
My Response: Again, I think the simple answer is the FDA doesn’t restrict the discretion of physicians in practicing medicine. On the one hand, if physicians want to make stuff from a patient’s tissue that is included in 1271 (by definition), they become manufacturers of that autologous therapeutic preparation, which means that they need to meet all of the requirements of 1271.10(a). If they can’t satisfy 1271.10(a), they are non-compliant with the FDA’s rule. On the other hand, if the physician wants to work with a patient’s bone marrow or blood in treating skeletal pathologies, more power to them, since a patient’s blood and bone marrow aren’t included in 1271, but there are some restrictions (see my answer to Q4). So, it just depends on the nature of the tissue being used and the pathology being treated.
Comella Question Six: “Are you intending to limit surgical procedures which have been in practice for decades that involve more than minimal manipulation?”
My Response: This is a bit of a puzzler, Ms. Comella. The whole point of subpart 1271.15 is to provide physicians with the opportunity to practice medicine, since the FDA isn’t allowed to intervene with a physician’s approach to treating a patient. So, I would guess that the FDA isn’t interested in invading surgical suites to police what is going on. I am curious though why you think you have a good understanding of what is and isn’t compliant with respect to minimal manipulation. I read the draft guidance on minimal manipulation the FDA issued in 2014 and thought it was pretty obvious you couldn’t digest fat tissue to produce SVF and still meet this requirement. Apparently, you thought differently.
Comella Question Seven: “Are you intending to limit surgical procedures which have been in practice for decades that involve non-homologous use?”
My Response: The points I made in response to Q6 above also apply to this question. Including the fact that I read the draft guidance the FDA issued in 2015 on homologous use and understood perfectly why using SVF from fat tissue wasn’t homologous use. Again, you seem to have a different interpretation.
Comella Question Eight: “Are clinics using fat tissue but not using enzyme permitted to operate?”
My Response: Kristin, Kristin, Kristin, what a poorly formulated question. It all comes down to the degree of manipulation of the fat tissue and what its intended use is—as in 1271.10(a)(1) and 1271.10(a)(2). Not to put too fine a point on it, but if someone wanted to create SVF via an enzymatic digestion protocol and did so within a clinical trial format (probably an IDE), a company eventually might get approval to market their enzyme-digested fat tissue system. And the FDA would be smiling, since that company played by the rules. The problem for the FDA is that hundreds of clinics have decided they didn’t want to spend tens of millions of dollars and wait 5-7 years to get approval, so they just opened their own SVFing clinics, like you did. In contrast to the Warning Letter you received from the FDA that highlighted your non-compliant use of a patient’s fat tissue, fat grafting is widely used for cushioning or supporting subcutaneous layers, like in the face or the hand, and it is FDA-compliant. Clearly, some fat tissue preparations currently are being used in clinics without an issue with the FDA.
I will finish my review of the Comella 12 (questions) in the next post.