Chara Biologics fancies itself the premier source of alleged therapeutic peri-natal donor-derived products. They claim to be “…the forefront of regenerative medicine” and “The Medicine of the Future”. Imagine that, a company being the medicine of the future. Sorry to disappoint anyone taken in by the bombast, but the reality is much less than the hype. For example, a review of the company’s website (performed on March 31, 2019) showed the following description of one of their products (with edits):
Rich in scaffolding, with a significant amount of extracellular matrix, including elements such as growth factors, collagen, lipids, proteins, carbohydrate and other nutrients. These elements help to protect, cushion, lubricate, and reduce inflammation. Offered at 1cc & 2cc vials for local joint injections.
As indicated elsewhere on the website, it would appear that this product is obtained from donor-derived peri-natal tissue (some combination of amniotic tissue, Wharton’s Jelly/umbilical cord tissue and cord blood) and is being sold to healthcare providers for use in treating patients with no relationship to donors of the raw material. This can be a big no-no if a product contains viable cells. In the case of CharaFlex™, they don’t hype viable cells as far as I can tell, so it looks like that isn’t one of its problems.
However, from the description of the CharaFlex™ product, it would seem the manufacturer’s stated objective intent is to have physicians inject the contents of a vial in order “…to protect, cushion, lubricate, and reduce inflammation.” Unfortunately, though brief, there are a couple of issues with the product as described:
- The only way to inject a hunk of peri-natal tissue through a tolerably-sized needle (say 19g) is if the tissue is micronized.
- Chara Biologics indicates that the product is useful for reducing inflammation.
The very first time, but certainly not the last, that I became aware of the issue of micronization was in an Untitled Letter to Osiris, way back in August, 2013. This is one statement the FDA made about Osiris’ injectable, amniotic membrane-derived product:
Your Ovation® product does not meet the minimal manipulation criterion set forth in 21 CFR 1271.3(f)(1) because your manufacturing process alters the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement.
I would think it should be evident to anyone paying attention to what the FDA said about Osiris’ Ovation product that you can’t take hunks of tissue and micronize them to create an injectable material, since this process rises above minimal manipulation [21 CFR 1271.10(a)(1)]. Osiris acknowledged their faux pas and agreed to stop selling the product by the end of 2014. On the other hand, MiMedx chose to fight the FDA on its Untitled Letter concerning their injectable, placental tissue-derived product, until last year, when MiMedx was granted RMAT status for AmnioFix, allowing them to conduct a pre-market approval IND with an expedited timeframe.
Oh, and then there is an example in the final version of the Minimal Manipulation and Homologous Use Guidance the FDA issued in November 2017 (corrected in December, 2017) that specifically addresses the problem with micronization of structural tissues (with edits):
Example 10-2: Original relevant characteristics of amniotic membrane relating to its utility to serve as a barrier generally include the tissue’s physical integrity, tensile strength, and elasticity.
b. A manufacturer grinds and lyophilizes amniotic membrane and packages it as particles. 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 serve as a barrier.
Consequently, as was the case with a number of micronized peri-natal tissue-derived products previously called out by the FDA, I suspect CharaFlex™ also will be found to be non-compliant.
The second point I made above involves a statement by Chara Biologics that includes a health-related claim, namely that the product is able to reduce inflammation. Reducing inflammation clearly implies that the product is able to mitigate the badness everyone knows is associated with inflammation, including painful inflammatory conditions, which includes just about all inflammatory conditions.
It might be helpful to consider language the FDA issued in a Warning Letter to a company selling umbilical cord-derived products called “Cord for Life” on March 29, 2019. The FDA identified how the umbilical cord blood-derived products they sell are used (with edits):
Information and records gathered during and following the inspection, reflect that your products, which your firm refers to as “regenerative products” or “regenerative medicine” products, are intended for “therapeutic uses” to treat, for example, orthopedic conditions. Therefore, your products are drugs as defined in section 201(g) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) [21 U.S.C. 321(g)] and biological products as defined in section 351(i) of the Public Health Service Act (PHS Act) [42 U.S.C. 262(i)].
Notice that the FDA uses the company’s statements concerning “therapeutic uses…to treat…orthopedic conditions…” to determine that those products are drugs. Chara Biologics never specifically indicates how their products are to be used, since I couldn’t find any statements on the website in which are listed conditions healthcare providers are encouraged to think about treating with Chara’s products, so the owners of Chara might think they have skated on this issue.
While someone might argue that “inflammation” isn’t an orthopedic condition, per se, nonetheless, Chara Biologics indicates that CharaFlex™ can reduce inflammation. Inflammation is a medical condition, usually associated with pain, that is treated by all kinds of drugs, which is what I believe the FDA will say about Chara’s product—that it is intended for treating, mitigating, etc. a medical condition and hasn’t undergone the proper pre-marketing approval clinical studies required of experimental drugs.
Thus, CharaFlex™ has all of the characteristics of a 1271 non-compliant HCT/P, including processing above minimal manipulation and Chara’s objective intent to treat a medical condition—inflammation—which means the product is an unapproved drug. Any healthcare provider purchasing this product might want to ask their state medical board if they are allowed to treat patients with unapproved drugs.
There is another product listed on the Chara Biologics website called CharaCore™, which I will address in the next post, along with some quibbles about scientifically unfounded statements, and a lack of published human clinical studies on the peri-natal tissue-derived materials Chara Biologics hawks to an apparently uncritical group of healthcare providers.