The previous post provided an introduction into what’s happening in the world of fat tissue-based therapeutic preparations in the USA. I focused on the situation in which physicians use enzymatic digestion of a patient’s fat tissue to manufacture stromal vascular fraction (SVF), which is a single cell suspension containing mesenchymal stem cells (MSCs). I ended the post by commenting on an apparent transition from enzymatic digestion to mechanical approaches to produce SVF, but there is a mechanical system that produces a type of fat tissue-derived preparation I will refer to as Fuzz Balls, which are not SVF.
I had used the term Fuzz Ball previously in a post for my ex-employer’s blog, for which I was criticized for not treating the noble profession of caregivers of the regenerative kind with the reverence they deserved. In order to forestall any complaints this time around, I will point out that those among you who are mainlining amniotic fluid-based products into your patients, with no obvious proof of therapeutic benefit, have done far more to demean the medical professionals in the regenerative world than I have.
The mechanical system to produce one type of Fuzz Ball preparation is sold by Lipogems. Essentially, the Lipogems System involves lipoaspiration into a closed system consisting of a cylinder, valves, filters, bags of fluid and waste collection bags. The Fuzz Balls are produced by physically shaking the cylinder, which is filled with washed lipoaspirate tissue and some ball bearings, for a few minutes and then forcing the busted-up fat tissue through filters, resulting in Fuzz Balls.
One of the reasons I wanted to cover Fuzz Balls is their growing popularity in the USA, despite being non-compliant with 21 CFR 1271. My assessment represents a minority opinion, since there appears to be a widely-held impression that autologous, Fuzz Ball preparations made with the Lipogems System are FDA-compliant. After all, the process is claimed to meet the requirement of minimal manipulation and the Lipogems System was cleared twice as a 510(k) device by the FDA. The second clearance (K161632) was received from the FDA in 2016. The original FDA clearance letter limited the indications to “lipofilling”-type procedures in a variety of different kinds of surgeries. But why a second letter? I have no doubt clever people pointed out to the FDA that autologous fat had uses in surgical procedures that technically aren’t “lipofilling”, so the FDA acknowledged the distinction and changed the language as follows:
“The device is intended for use in the following surgical specialties when the transfer of harvested adipose tissue is desired: orthopedic surgery, arthroscopic surgery, neurosurgery, gastrointestinal and affiliated organ surgery, urological surgery, general surgery, gynecological surgery, thoracic surgery, laparoscopic surgery, and plastic and reconstructive surgery when aesthetic body contouring is desired.”
Somehow, that statement has been used to open the floodgates of Fuzz Ball treatments for all manner of ailments including knee OA, which makes no sense to me. Bear in mind, the FDA could have written “…when the transfer of harvested adipose tissue for treating bone, joint and other pathologies is desired…”, but they didn’t. Also, notice the scope of the language provided by the FDA includes “surgery” in every instance. Non-surgically trained strip mall docs probably are on thin ice with their state medical boards if they engage in treating patients with Lipogems-derived preparations for non-surgical pathologies.
All of which, in my opinion, means that the FDA is unwilling to sanction a free-for-all in the use of Fuzz Balls for whatever ails a patient. This is especially obvious if you recall that the FDA has issued a draft Guidance on working with adipose which contains the following example:
Example B-2: Adipose tissue is recovered and processed for use, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent, to treat bone and joint disease. Because adipose tissue does not perform this function in the donor, using HCT/Ps from adipose tissue to treat bone and joint disease is generally considered a non-homologous use.
It seems to me that the language “Adipose tissue is recovered and processed for use…to treat bone and joint disease…is generally considered [to be] a non-homologous use…” can be understood without too much trouble. Notice that the FDA didn’t cite an exception for fat preparations processed with the Lipogems System.
Ah, you might think, the physician simply is using the Lipogems System for an off-label treatment indication. Unfortunately, it isn’t so simple to claim an “off-label” use, just because a cleared device is available to process fat tissue. The material being produced in the cleared technology is an HCT/P, which means that the manufacturer of the HCT/P—the physician—needs to meet all of the requirements of 21 CFR 1271.10(a) in order to be able to invoke the exception from registration with the FDA, as stated in 1271.15(b).
In view of the example I provided above, using Fuzz Balls for non-surgical, bone and joint disease treatments is non-homologous, so the physician/manufacturer can’t invoke the 1271.15(b) exception, which means the physician isn’t compliant with the registration requirement of 1271. Until the FDA explicitly endorses the use of Fuzz Ball-type products for treating OA via intra-articular delivery, it isn’t a compliant use in my opinion.
And don’t bother pointing out that the draft adipose Guidance hasn’t been finalized. Guidances aren’t legally enforceable documents, but serve to provide additional information about existing regulations. So, the FDA issued the draft guidance on adipose tissue to inform stakeholders about how the Agency views the existing statutory language known as 21 CFR 1271. And that doesn’t allow for using adipose tissue to treat patients intra-articularly for OA—minimally manipulated or not, as indicated in Example B-2 shown above. I also will point out that the FDA was aware of the Lipogems System during the period they were writing the draft guidance on adipose tissue, which might mean that they didn’t think physicians would use the Lipogems’ Fuzz Balls for non-lipofilling purposes. Silly Agency.
To be fair, the FDA always leaves themselves some wiggle room—the “generally considered” language shown above—that lets them decide on a case-by-case basis to allow something or not. So, who knows? The FDA might come to embrace the use of adipose tissue-derived Fuzz Balls as a therapeutic option for use at point-of-care, but I am betting they won’t.