Of the previous five posts in this series, there were two posts (Part One and Part Two) on the Warning Letter received by Ms. Kristin Comella, which the FDA issued on August 24th, followed by three more posts (Part Three, Part Four, Part Five) on the questions Ms. Comella included in a stunningly blunt diatribe against the FDA that she issued on August 29th. I promised in Part Five that I would return to the Warning Letter to review the issues the FDA had with Ms. Comella’s clinic (US Stem Cell Clinic; USSCC), which were uncovered during the audits they conducted earlier this year.
One common sentiment expressed on the Internet is that the reason the FDA issued all of their adverse findings is that they have determined that the stromal vascular fraction (SVF) obtained from a patient’s fat tissue is a drug. However, Ms. Comella and other SVFers contend that SVF isn’t a drug, since it is just a material produced as a practice of medicine (see Parts 1 and 2 for my dim view of this position). More importantly, the impression she wants to give everyone is that her clinic’s internal procedures ensured that their enzymatic digestion of autologous fat tissue to produce SVF was performed at the highest standards for medical clinics, and those meanies at the FDA were just picking on her and her clinic. It is a nice story, but a careful review of the comments made in the FDA’s Warning Letter would indicate that the clinic wasn’t operating optimally, whether it was making just SVF or a drug called SVF.
But you might be thinking: What does this guy know about generating SVF with enzymes? As it happens, I know quite a bit. The reason is that I created, optimized, validated and commercialized an enzyme-based, fat tissue digestion technology platform in 2002/2003 for Vet-Stem, Inc. (Poway, CA; now known as Vet-Stem Biopharma), which has continued to this day to produce autologous SVF preparations for veterinarians to use in treating dogs, cats and horses. Keep in mind this service was offered publicly in the veterinary market years before an effort emerged to do SVFing in the human world. Furthermore, the fact that Vet-Stem successfully commercialized its SVF service probably encouraged physicians to adopt SVFing in their clinics, and subsequently, going boldly where they shouldn’t have gone. Before I get accused of being two-faced by calling out the human clinics offering SVF therapy, but not condemning what I did at Vet-Stem, you should know that back in 2002 the founders of Vet-Stem sent an enquiry to the FDA’s Center for Veterinary Medicine (CVM) about their proposed activities and received a response that was not negative. As a result, the founders hired me and the rest is SVFing history. So, to all of the human SVFing clinics, show us the FDA letters supporting your activities!
Now back to the first item the FDA outlined in their Warning Letter:
1. Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, namely, your SVF product, including procedures for validation of all aseptic and sterilization processes [21 CFR 211.113(b)]. For example:
a. Your firm recovers adipose tissue and manufactures autologous SVF from this adipose tissue. During the period December 8, 2015 –April 17, 2017, your firm manufactured at least (b)(4) batches of SVF product. Your firm failed to validate and document your aseptic manufacturing process or to establish written procedures to prevent microbiological contamination of the SVF product. Your firm administers the SVF product by various methods, including intravenously and intrathecally. By the nature of its method of administration, the SVF product purports to be sterile and is expected to be sterile.
b. (b)(4) testing of the (b)(4) used in the manufacture of the SVF product is not performed.
c. On May 3, 2017, our investigators observed an accumulation of dust on two air vents in the room where the SVF product is manufactured.
d. Your firm failed to use disinfectant agents that are appropriate for use for cleaning the (b)(4), the (b)(4), and the (b)(4), which are located inside the aseptic processing area. For example, you use non-sterile (b)(4) and non-sterile wipes and do not use a sporicidal agent.
The approach the FDA takes in this observation obviously embraces their drug manufacturing rules (based in large part on current Good Manufacturing Practice, cGMP). But keep in mind that USSCC produces SVF that is injected back into a patient. So, the points the FDA made about a lack of documentation with respect to how the material is to be kept sterile are valid and this type of documentation should have been in place especially given that the clinic was injecting SVF preparations via IV and intrathecal (within the spinal cord sac) routes. Now, the FDA’s citing a lack of validation of protocols falls squarely into the cGMP arena, but anyone producing SVF should have, at a minimum, written documentation covering all aspects of the protocol itself.
Item 1c references an observation by the auditors of the presence of dust on air vents in the SVF processing area. You don’t need to be following cGMP guidelines to know you should avoid having dust in the processing area, which means this is evidence of bad physical plant maintenance that clearly makes it harder to keep a patient’s SVF sterile. The issue cited in Item 1d concerning the use of non-sterile wipes in a supposedly aseptic area also is just a lapse of common sense and has nothing to do with not operating by cGMP rules.
I will continue reviewing non-cGMP related issues the FDA cited in the Warning Letter to Ms. Comella in the next post.