In the previous post, I covered a material I call Fuzz Balls produced in the Lipogems System. My contention is that the Fuzz Balls can’t be used to treat orthopedic pathologies for regulatory reasons, which definitely is a minority position. I also mentioned that I had been taken to task for the somewhat tongue-in-cheek use of the term “Fuzz Balls”. I would like to cover in this post a very important issue that was revealed in a recent publication by van Dongen, et al. (2016), since it relates to producing Fuzz Balls. They describe a process to make their own version of Fuzz Balls, which they identified as FAT-stromal vascular fraction (SVF) or “fractionation of adipose tissue-stromal vascular fraction”. It is the use of “SVF” when referring to Fuzz Ball-like preparations that gives me heartburn.
Fuzz Balls from the van Dongen, et al. process contain extracellular matrix derived from the adipose tissue, which is similar to the material obtained with the Lipogems System. The key point is that FAT-SVF should in no way, shape or form be considered as equivalent to SVF produced by enzymatic digestion. The FAT-SVF contains a mixture of fat tissue and cells, albeit mechanically rearranged, which definitely is not a single cell preparation. SVF produced by enzymatic digestion is a single cell preparation.
Consequently, FAT-SVF can’t be injected IV, which can be done with true SVF preparations, with a couple of precautions. At least that is what my ex-boss, Dr. Bob Harman, reported at a TOBI conference a few years ago, when he indicated that Vet-Stem (now VetStem Biopharma, Poway, CA) provided autologous SVF preparations to veterinarians that had been used for more than 3,000 IV infusions. Dr. Harman clarified that was treatments not patients. I really doubt that it was one patient with 3,000 treatments, so it probably is safe to use an IV route to administer true SVF. In contrast, as best I can tell, there is no safe way to provide Fuzz Ball therapy intravenously, especially since one likely outcome could be a patient that blips out due to a fat embolism. And that would be a serious downer for the Fuzz Ballers out there. While I feel strongly about not injecting Fuzz Balls via IV, I am the other kind of doc, so I am not trying to tell physicians how to practice medicine—but don’t do this.
So, in the world of fat tissue-derived therapeutic preparations, you can use enzymes to produce SVF, or you can use a mechanical method like Lipogems to produce Fuzz Balls. And, as mentioned above, van Dongen, et al. used their own mechanical method to produce what they unfortunately refer to as FAT-SVF. But not all mechanical methods end up in Fuzz Balls, since there are ways to generate true SVF preparations with mechanical methods.
Condé-Green, et al. (2016) reviewed the literature in which a variety of mechanically-based systems have been described to “separate cells from the adipose matrix.” Thus, by using these mechanical methods it is possible to produce a single cell preparation, similar to the enzymatic-produced SVF preparations. In their evaluation of published reports (with a couple of clinical studies, but mostly in vitro research), they indicated that overall the yield of single cells through mechanical action was greatly reduced compared to the yield achieved by enzymatic digestion.
The Condé-Green, et al. authors believe there has been a shift over to mechanical methods for isolating cells from fat tissue, since they believe that the use of non-enzymatic methods meets the requirement for minimal manipulation contained in 21 CFR 1271, which covers the manufacturing of HCT/Ps (i.e, processing fat tissue). I hesitate to burst this bubble, but there is a phrase that the FDA used in their draft Guidance on Same Surgical Procedure Exception that refers to the state of the HCT/P that is removed from the patient. The FDA mentions “such HCT/P” in the language covering how a physician can qualify for an exception from a requirement to register with the FDA [1271.15(b)].
Why is the phrase “such HCT/P” a problem? If I am reading the regulatory tea leaves correctly, the implication is that what you, as a manufacturer, obtain from a patient is what you, as a physician, need to return to the patient. Thus, if you take fat tissue out of the patient, you need to return to the patient something that resembles fat tissue. The mechanical methods reviewed in Condé-Green, et al. all yield SVF, which the FDA has indicated is not the same as the original fat tissue. Consequently, however you make SVF, it isn’t the same as the original material, so it isn’t compliant with 21 CFR 1271.
Don’t be fooled: Fuzz Balls aren’t the same as SVF. And if you don’t want to use the term Fuzz Balls, call the new fad material FB2, which stands for “fat-based fuzz balls”. Much more scientific, don’t you think?