Recently, I received an ad from Apex Biologix sent via email. Their ad focused on a product made from amniotic fluid collected from donors in the USA. The ad covered the composition of their product, how it was produced and what it might be used for. Since the ad made a number of statements that I can’t really argue with, but others that I think are misleading, I will share my take on the ad touting their amniotic fluid product. My focus will be on the statements made in the ad, how they are meant to lull the reader into thinking happy thoughts about amniotic fluid products, and the continued hyping of the next shiny therapeutic agent—exosomes. I will leave aside a discussion about the clinical merits of a product composed of amniotic fluid, since I can’t find any publications in which amniotic fluid products have been evaluated in any kind of a clinical trial format.
In what I find to be an interesting twist, the FDA made the following statement about amniotic fluid in the final Guidance it issued last November on Minimal Manipulation and Homologous Use (“Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-based Products: Minimal Manipulation and Homologous Use”; p. 14):
Secreted body fluids (e.g., amniotic fluid) are generally not considered HCT/Ps… Cells from secreted body fluids are generally considered HCT/Ps, and the definition of minimal manipulation for cells or nonstructural tissues would apply.
Notice that the FDA indicates that cell-free amniotic fluid is not considered to be regulated by 21 CFR 1271, the rule that describes the dos and don’ts for working with Human Cells, Tissues and Cellular and Tissue-Based products (HCT/Ps). In view of this clarification, if you read my posts regularly, you might wonder why I have celebrated the demise of companies like BioD, which was once a fertile source of amniotic fluid/micronized tissue products. But amniotic fluid with micronized tissue has never been FDA-compliant due to the micronization of placental tissue, and it clearly is not the same type of product as plain old amniotic fluid.
In view of the non-HCT/P status of amniotic fluid, what is there to discuss with respect to the Apex ad for their product? There is quite a bit to discuss, especially in view of the mostly unsupported statements Apex has made in promoting the alleged virtues of amniotic fluid. Apex does point out that their product is “Sterile filtered 100% pure liquid allogeneic tissue with no cryoprotectant or dilution”. Since they indicate that the raw material is sterile-filtered (meaning with a pore size no larger than 0.2 µm), this precludes the presence of maternal or fetal-derived cells, live or dead, while the lack of a cryoprotectant further supports the impression that there are no nucleated cells present, and certainly none that are viable.
So far, so good. They also inform us that each lot of the product is tested for endotoxin and for the presence of microbial contamination (USP <71>, which refers to the US Pharmacopeia, a compendium of validated protocols for manufacturing drugs for human use). This type of testing is mandated by the FDA, so meeting these standards is something the sellers of amniotic fluid products are required to do.
They provide a list of biochemicals present in amniotic fluid, with bar charts in the ad showing levels of selected growth factors. Their list includes the usual suspects, like hyaluronic acid, lipids, proteins, electrolytes and everyone’s favorite therapeutic agent of the moment, exosomes. Nothing in the list is especially unique to amniotic fluid, but of course we are supposed to be impressed. I will leave a discussion of exosomes to the next post. Their bar charts don’t indicate that there are more cytokines of value in amniotic fluid versus, say, plasma, so I don’t really know why a physician would be attracted to using amniotic fluid. It very well may be that amniotic fluid has a special profile of valuable cytokines, but I am not sure why physicians should be encouraged to think of biologics like they might think about coffee—that the ones from amniotic fluid are the richest kind in the absence of any clinical proof of efficacy.
There is a puzzling statement touting the level of hyaluronic acid (HA) present in Apex’s amniotic fluid product, in which they indicate that HA is present at “…<150ng/ml”. Not to put too fine a point on it, but 0 ng/mL also is possible with the way they stated the HA level, which would mean that there is no HA in the amniotic fluid product. Along the same vein, they mention that their amniotic fluid provides something they call “maximum bioavailabilty of protein secretome”. I have been in the science business for more than 40 years and I can’t fathom what that phrase means. The protein secretome is just a fancy way of referring to proteins found in biological fluids or tissues. I guess “maximum bioavailability” just refers to the fact that the proteins are in a fluid state, as opposed to being in a solid form (like in amniotic tissue), so they can be digested by the body more quickly. Why the proteins in amniotic fluid are so special eludes me, and apparently the Apex folks as well, since they don’t clarify their comment.
I will move on in the next post to a couple of other issues I have with the Apex ad. One issue concerns the presence of fetal fecal matter (meconium) in amniotic fluid products. The other involves Apex’s puffery surrounding exosomes that, miracle of miracles, are found in amniotic fluid, which it seems Apex considers to be the richest kind.
Prevalence of meconium-stained amniotic fluid was reported recently to be approximately 9.2% of pregnancies.