In the previous post: When the Fat Hits the Regulatory Fan: Processing Adipose Tissue in the “Such HCT/P” Era Part One, I started reviewing relevant statements that I think might apply to adipose tissue in the two final Guidances the FDA issued on November 16, 2017 (see my views and the link below):
I have focused on adipose tissue in this series, since so much of the current free-for-all in the regenerative medical arena is due to physicians, clinics and networks of clinics not following the rules on adipose tissue outlined in 21 CFR 1271 —the primary regulatory law the FDA established to ensure the safety of patients receiving HCT/P therapies. Many physicians have ignored the prohibition against doing whatever they want with a patient’s adipose tissue, so I thought I would help the healthcare providers understand just how much the FDA isn’t going to allow this abuse to continue. I will focus in this post on the second set of adipose-related comments I found in the two Guidances (with edits):
Minimal Manipulation and Homologous Use (con’t):
“Example 11-1: …A manufacturer processes adipose tissue by removing the cells, which leaves the decellularized extracellular matrix portion of the HCT/P. The HCT/P generally is considered more than minimally manipulated because the processing alters the original relevant characteristics of the HCT/P relating to its utility to provide cushioning and support [by eliminating the adipocytes, which are the cells that provide the bulk in adipose tissue].”
“Example 14-1: …A manufacturer recovers adipose tissue…and processes (e.g., enzymatically digests, mechanically disrupts, etc.) the adipose tissue to isolate cellular components…, commonly referred to as stromal vascular fraction…In this example, the HCT/P generally is considered more than minimally manipulated because the processing breaks down and eliminates the adipocytes and the surrounding structural components that provide cushioning and support…”
“If an HCT/P is intended for use as an unproven treatment for a myriad of diseases or conditions, the HCT/P is likely not intended for homologous use only.”
“[With regard to homologous use]…the same basic function or functions of HCT/Ps are considered to be those basic functions the HCT/P performs in the body of the donor, which…the HCT/P would be expected to perform in the recipient. It is not necessary for the HCT/P in the recipient to perform all of the basic functions it performed in the donor in order to meet the definition of homologous use.”
“Example 19-3(a): Adipose tissue is used to fill voids in the face or hands…This is homologous use because providing cushioning and support, (sic) is a basic function of adipose tissue.”
“Example 19-3(b): An HCT/P from adipose tissue is used to treat musculoskeletal conditions such as arthritis or tendonitis by regenerating or promoting the regeneration of articular cartilage or tendon. This is generally not considered a homologous use because regenerating or promoting the regeneration of cartilage or tendon is not a basic function of adipose tissue.”
“Example 19-3(c): An HCT/P from adipose tissue is used to treat neurological disorders such as multiple sclerosis by limiting the autoimmune reaction and promoting remyelinization. This is generally not considered a homologous use because limiting the autoimmune reaction and promoting remyelinization are not basic functions of adipose tissue.”
“Example 19-3(d): Adipose tissue is used for transplantation into the subcutaneous areas of breast for reconstruction or augmentation procedures. This is homologous use because providing cushioning and support is a basic function of adipose tissue.27”
“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) .” [The exception is to not register with the FDA when a physician minimally handles (“rinsed or cleansed”) the fat tissue in a lipoaspirate so that the tissue meets the “such HCT/P” standard contained in 1271.15(b) .]
“…the use of an HCT/P from adipose tissue for the treatment of a degenerative, inflammatory, or demyelinating disorder would generally be considered a non-homologous use.”
Based on the statements I have listed in this post and the previous one When the Fat Hits the Regulatory Fan: Processing Adipose Tissue in the “Such HCT/P” Era Part One, I offer up the following points for what a physician can and can’t do with a patient’s adipose tissue:
- No enzymatic digestion of adipose tissue is allowed, and the resulting single cell suspension (known as stromal vascular fraction or SVF) can’t be used to treat a patient.
- Collecting single cells released by mechanical action in the process of obtaining a lipoaspirate, concentrating those cells and using that preparation to treat patients isn’t allowed. The reason is that the FDA defines the relevant form of an HCT/P as the tissue being collected from the patient, so the physician needs to return that same type of sample for it to meet the 1271.15(b) exception of “such HCT/P”. Cells obtained from adipose tissue by whatever means can’t provide cushioning or support when returned to the patient, therefore the physician can’t invoke the same surgical procedure exception and must register with the FDA. Furthermore, since cells aren’t the same as the original HCT/P collected, there also is an issue with homologous use.
- An HCT/P from adipose tissue in any form can’t be used to treat autoimmune diseases, musculoskeletal diseases, and just in case someone thinks they see a crack to try to wiggle through, the FDA classifies the use of “…adipose tissue for the treatment of a degenerative, inflammatory, or demyelinating disorder…” as non-homologous.
- Autologous treatment of subcutaneous depots with fat grafting preparations are allowed, including those in the face and hands, as well as for reconstructive or augmentative treatment of breast tissue.
None of the conclusions I just summarized are new, except the one in which the FDA now allows breast reconstruction and augmentation with autologous adipose tissue. They all were apparent (to me, at least) after the publication of the draft Guidance on adipose tissue back in December 2014. In fact, I questioned the FDA’s determination that breast augmentation/reconstruction with adipose tissue was non-homologous in the draft Guidance and predicted they would retreat from such a silly position. They have.
What the FDA won’t retreat from is enforcing 1271 rules with healthcare providers. We know this because the FDA provided a handicapping of offenses committed by 1271-non-compliant physicians toward the end of the minimal manipulation/homologus use Guidance. For example, the FDA indicated that healthcare providers who administer HCT/Ps by routes with a higher risk (e.g., IV, aerosol, intraocular, and intrathecal/CNS) and HCT/Ps intended for non-homologous use (especially in treating “…serious and/or life-threatening diseases and conditions…”) are providing treatments with “significant safety risk”. As a consequence, they would receive priority scrutiny and appropriate enforcement by the FDA.
I think any physician or network of clinics providing SVF or FB (fuzz balls, obtained from mechanically disrupted adipose tissue) treatments of a laundry list of indications or conditions will stand a good chance of getting a Warning Letter from the FDA. So, my advice is to focus on bone marrow and whole blood as starting materials, skip the maybe viable cell-containing amniotic fluid-derived products and anything adipose tissue-related, except for fat grafting options in subcutaneous tissues. I know it is going to be hard for physicians to wean themselves from using non-compliant amniotic fluid products and to severely restrict fat in their treatment diet, but better to start now and not wait until your name gets associated with the likes of Thomas Young, MD, Steven Victor, MD, Thomas Gionis, MD and Kristin Comella, PhD, who, while not an MD, still makes this Hall of the Shamed list by having received a blistering Warning Letter from the FDA on August 24th (see my views and the link below):
- FDA Hammers A Flaunter of the Rules Against Making and Treating Patients with Fat Tissue-derived Stem Cells – Part One
In the next post, I will work through the special case of adipose tissue being used to create fuzz balls, since a 510(k)-cleared kit (Lipogems System) exists for that purpose. Most likely, physicians will cling to that kit as a way to get their fat fix. However, based on what I have read in the Guidances, they will need to enter a rehab program since I suspect the FDA will not tolerate non-homologus use of fuzz balls.