Part One of my review of the speakers’ comments at the two-day stakeholder workshop the FDA held on September 12 and 13 to review four draft Guidances the Agency wants to finalize can be found here(opens in a new tab). The theme I had started with was the irony associated with certain speakers of large corporations wishing to cut their costs of product development for obvious reasons, that from my perspective, don’t have a lot to do with supporting the FDA’s primary mission of maintaining the safety of the American people.
In a similar vein, I would like to highlight the comments of the CEO of MiMedx, a several hundred-million-dollar corporation working in the field of placental-derived materials. By way of background, you should know that MiMedx had received an Untitled Letter from the FDA back in August, 2013 concerning their “AmnioFix” product. What prompted the FDA to send MiMedx the Untitled Letter? AmnioFix, it turns out, contains micronized placental tissue, which the FDA pointed out in their letter didn’t meet the requirement of minimal manipulation. So, I wasn’t surprised when the MiMedx CEO spoke against the draft Guidances on Minimal Manipulation and, for good measure, Homologous Use (for links to all of the draft Guidances, visit this post(opens in a new tab)). The CEO prefaced his comments by stating that the industry wants “…rules and regulations that are clearly delineated, easily interpreted and uniformly enforced.” Which is what I thought the FDA was attempting to do with the draft Guidances, since they are written in relatively plain English.
But I suspect the real issue that MiMedx has with 21 CFR 1271, the law that spawned the draft Guidances, is the CEO’s statement to the effect that the FDA has changed the law—1271—without following the correct process. This contention of illegal rule making is another theme of the Workshop, a position that was stated very bluntly by the speaker for Navigant Consulting, who claimed that the concept of “main function” is a new one and was adopted without proper rule making. This is a very technical point of regulatory law. However, I suspect the FDA uses words and phrases in draft Guidances that don’t directly appear in 21 CFR 1271 in order to provide a different perspective on the actual language used in 1271. The FDA probably figured out a long time ago that just repeating the same words in a different order wasn’t helpful.
This situation reminds me of a Markman hearing in a patent infringement lawsuit that sometimes is used by a court to try to get the two parties to agree to what the specific language in a patent claim means by using other words. The language of the claim isn’t changed at the conclusion of the Markman hearing, but now there are different words to aid the judge and/or jury when the infringement case goes to trial. In all probability, the same situation happens at the FDA when they try to use other words beside the exact words and phrases that appear in 1271. So, I think the folks who claim that the FDA had by-passed appropriate rule-making procedures because the Agency used different words don’t have a Thesaurus to stand on.
The last theme I will cover in this post is the one promoted by a number of speakers in which a patient’s own cells shouldn’t be considered by the FDA as drugs. Perhaps the best advocate of this position was Kristen Comella, of U.S. Stem Cell, Inc. Ms. Comella stated that she was the Chief Scientific Officer of her company, which provides physicians with training and the supplies to digest a patient’s fat tissue to produce a single cell suspension known as stromal vascular fraction (SVF). Of course, a plain reading of 1271 language would immediately clue you in that taking a structural tissue, which the FDA considers adipose tissue to be, digesting it with enzymes, which Ms. Comella’s company would be happy to sell you, and then recovering the SVF preparation to treat patients is a process that rises above minimal manipulation, and probably also could be considered as non-homologous use. In fact, if after reading the 1271 regulation, you didn’t understand that creating autologous SVF wasn’t permitted, you could consult the draft Guidance on working with fat tissue and read the following:
Example A-1: Adipose tissue is recovered by tumescent liposuction. The adipose tissue undergoes processing or manipulation (e.g., enzymatic digestion, mechanical disruption, etc.) to isolate cellular components, commonly referred to as stromal vascular fraction, which is considered a potential source of adipose-derived stromal/stem cells for clinical therapeutic uses. This processing breaks down and eliminates the structural components that function to provide cushioning and support, thereby altering the original relevant characteristics of the HCT/P relating to its utility for reconstruction, repair, or replacement. Therefore, based on the definition of minimal manipulation for structural tissue, this processing would generally be considered more than minimal manipulation.
Pretty obvious to me that producing SVF at point-of-care is not compliant with 1271. But according to Ms. Comella, SVF should have the same status as bone marrow aspirate, since she states that fat aspiration is a less invasive procedure compared to a bone marrow aspiration and has fewer adverse events. I strongly beg to differ, but the main point she makes is that, hey, you take cells from fat and you take cells from bone marrow, so the two sources of cells should be treated the same. Enough said! What Ms. Comella conveniently doesn’t address is that the process to separate the cells from bone marrow involves centrifugation and a few minutes, whereas the separation of cells from fat involves, in her company’s case, the use of enzymatic digestion and about an hour of multi-step processing in a tissue culture hood. Hardly equivalent.
If the material being obtained from a patient is governed by 1271, then that material can be classified as a biologic drug if it doesn’t meet standards outlined in 1271, which is explained with different words and examples in the four draft Guidances. Consequently, what Ms. Comella is asking is that the FDA change 1271 to accommodate companies that want to make money by providing physicians with access to a patient’s own cells. Nice try, but the FDA needs to maintain a safe medical environment in the US and enforcing 1271 is part of that effort. So, the score now is FDA 4 and speakers 0.
I will review in the next post suggestions from Workshop speakers concerning how the FDA can be more responsive to the needs of the regenerative medicine community, which involves the FDA changing the rules, but in a scientific way.
