In the previous post When Fat Hits the Regulatory Fan: Mechanical Disruption of Adipose Tissue with the Lipogems System Part One, I introduced what I think is a curious situation that has resulted from instructions the FDA provided to physicians on how to review the standards outlined in 1271.15(b) to see if they can invoke the exception to register with the FDA. When a physician makes an HCT/P the FDA wants them to consider if it is “such HCT/P”, as defined in the regulation, as well as explained in the Guidance on the same surgical procedure exception they issued on November 16th (Winners and Losers Emerge at Long Last After the FDA Issues Two Guidances—post dated 111617 for links and background information), and if they qualify they don’t need to consider if their HCT/P meets the minimal manipulation or homologous use criteria listed in 1271.10(a). The question of the moment in the regenerative medical world is does this allow a physician to use a 510(k)-cleared kit (i.e., Lipogems System) to mechanically disrupt a patient’s adipose tissue (making what I refer to as fuzz balls) and subsequently use that HCT/P to treat musculoskeletal pathologies? If I were a betting man, I would say no, but how the FDA gets to no is going to be interesting.
There are two aspects to using a kit that mechanically disrupts adipose tissue that physicians might feel provides them cover to use the fuzz balls as a practice of regenerative medicine without limitation:
- Since the Lipogems System is cleared for processing adipose tissue, a physician can use the fuzz balls on an off-label basis to treat even non-homologous pathologies in orthopedics.
- From the language in the 510(k) letter, I infer that the FDA considers the product produced after the processing (the device is loaded with lipoaspirate, washed, shaken—subsonically—for a while in the presence of ball bearings, washed again and forced through frits to yield fuzz balls) to be substantially equivalent to standard fat grafts obtained by predicate liposuction systems.
The second point mentioned above will be seized upon by some physicians to rationalize their satisfying the “such HCT/P” standard in 1271.15(b), meaning that, by being substantially equivalent to lipoaspirate, the fuzz balls essentially are the same as the “original” HCT/P. Thus, I am sure there are physicians who will contend that since they meet the “such HCT/P” standard, and since the FDA has told them to stop contemplating other elements of 1271 if they can invoke the exception to registration, therefore they are free to inject adipose tissue-derived fuzz balls into orthopedic pathologies as a part of their practice of medicine when using a cleared kit to produce this type of HCT/P.
Normally, at this point in my recitation of a situation like this, I would quote something pithy the FDA wrote in one or the other Guidances to show the error of the physicians’ thinking that using a cleared device will allow them to evade the very tight restrictions of 1271.15(b). Unfortunately, I don’t have anything pithy to offer. What I can offer are the following scenarios that I believe the FDA might use to blunt the enthusiasm of physicians in this situation:
- Just because the fuzz ball preparation obtained from the cleared device has been declared by the FDA to be substantially equivalent to a liposuction system for the specified indications for use, it doesn’t mean that the FDA considers the fuzz balls to meet the standard of being equivalent to the original HCT/P, which is a necessary condition to meeting the “such HCT/P” requirement in 1271.15(b). If fuzz balls aren’t the same as the original HCT/P within the intent of 1271.15(b), at a minimum, it seems to me that physicians will have to register with the FDA when they use a cleared kit to make fuzz balls in order to treat patients outside of the indications for use.
- The FDA stated a long time ago that in order to determine if an HCT/P meets the homologous use standard it would consider the objective intent of the manufacturer. In the case of making fuzz ball preparations at point-of-care (POC), the physician is the manufacturer. But a manufacturer isn’t allowed to ignore the elements of 1271.10(a)(1 and 2), so the physician as manufacturer would have to acknowledge that the FDA says that adipose tissue-derived preparations can’t be used for treating orthopedic pathologies, since they have stated that such use would be non-homologous. But, if the objective intent of the manufacturer is to create a preparation that will be used in a non-homologous manner, the manufacturer will not be working with an HCT/P that is covered by 1271, so the manufacturer will need to follow a pre-market application approach involving clinical studies. Which means that the physician won’t be able to invoke the exception in 1271.15(b), because the HCT/P being made isn’t eligible for regulation by 1271, but rather is a biologic drug and physicians can’t treat patients with an unapproved biologic drug.
- The cleared kit doesn’t contain an autologous POC fuzz ball preparation, since it is just a kit. So, it isn’t obvious that a physician could decide to use the kit in an off-label fashion, since fuzz balls are the therapeutic preparation and the kit just lets the manufacturer make the autologous preparation at POC.
Handicapping these three scenarios from the FDA’s point-of-view is hard, because they get to define the language and set the parameters related to elements in 1271. However, of the three approaches, the first approach in which they could declare that fuzz balls don’t meet the standard of being “such HCT/P”, despite the language in the Lipogems’ 510(k), is my odds-on favorite strategy for the FDA to use to tamp down the swelling enthusiasm for fuzz balling. I think it is the most pertinent, especially in view of a footnote (number 27 on page 19) they included in the minimal manipulation and homologous use Guidance, as follows:
“27 Some breast reconstruction or augmentation procedures involving re-implantation of autologous adipose tissue that is only rinsed or cleansed may meet the exception in 21 CFR 1271.15(b).”
Notice how the FDA has associated the processing of autologous adipose tissue with the words “…only rinsed or cleansed…” in the context of meeting the “such HCT/P” requirement in 1271.15(b). Since the Lipogems’ process involves more than just rinsing and cleansing in my opinion, it is possible that the FDA is indicating that it won’t allow physicians to invoke the exception when using mechanically disrupted adipose tissue (i.e., fuzz balls in the Lipogems System) even with an obvious fat grafting indication for use. It is interesting that the FDA didn’t include the other two processing actions (i.e., sizing and shaping) that they mentioned in the Same Surgical Procedure Exception Guidance (see AABBCC for links to the Guidance) in the footnote, so perhaps the Agency doesn’t think too many processing protocols will meet the strict requirements of “such HCT/Ps”.
More importantly, if subsonic shaking of adipose tissue isn’t what the FDA had in mind when it wrote the phrase “…only rinsed or cleansed…”, I don’t understand how the Agency is going to square the apparent intent of the footnote to limit what physicians can do to process lipoaspirates and still allow them to invoke the same surgical procedure exception when they use the Lipogems System to make fat grafts for implanting into subcutaneous tissue depots. It seems to me there is an obvious conflict between Footnote 27, shown above, and the 510(k)-cleared indications for use of the Lipogems System for body contouring in the fields of plastics and reconstructive surgery and other fat grafting uses in a wide spectrum of surgical disciplines. Thus, will the FDA allow a physician to invoke the exception to register if they use the Lipogems System as indicated?
In my opinion, one way out is for the FDA to point to language they frequently use to give them wiggle room: “would generally be considered”. In which case, the Agency just would state that physicians using fuzz balls made by a cleared kit for fat grafting are eligible to invoke the exception to register as long as physicians use the fat grafting preparations as indicated. Of course, physicians trying to use fuzz balls for treating other conditions would be squashed summarily, or so we could hope.
My views of the regulatory challenges presented by the Lipogems System 510(k) clearance that I have shared in this and the previous post (When Fat Hits the Regulatory Fan: Mechanical Disruption of Adipose Tissue with the Lipogems System Part One) are somewhat theoretical, but I will review some of the practical aspects of fuzz balling and how they might fit into the regulatory landscape that is emerging in the USA.