The FDA’s CBER branch recently issued a warning letter to Amniotic Therapies, LLC.
The warning letter pertains to both AlphaGEMS-related products that are used by a number of stem cell clinics as well as problems determined at the manufacturing facility.
I went to the Amniotic Therapies website, but perhaps not coincidentally it is down, which could be due to the FDA warning. An archive of the site (screenshot above) provides information on their products.
Notably, CBER described the company’s products as unapproved biological drugs that do not meet minimal manipulation and homologous use criteria.
Given the numerous amniotic stem cell clinics out there in the US using apparently similar products, one wonders if further FDA action could be pending.
It is also interesting to speculate how this might impact the amniotic stem cell clinics since for many this was a probable supplier of amniotic material. In addition, I’ve also often wondered how amniotic suppliers and clinics get the material to begin with and do the mothers who gave birth realize where this material has gone?
FDA Barred from Shutting Down Tissue Therapy Company
“…the infections all occurred because one physician at an Ohio hospital repeated failed to follow package instructions meant to ensure sterility.”
http://www.kendalllawgroup.com/wp-content/uploads/2016/08/Article-from-Law360-about-TRO.pdf
Thanks Bill. Very important development there.
Paul
While an important fact, I find it rather curious that the bacterial infections were found to be from Mycoplasma Hominis, which is typically associated with the female reproductive tract.
However, it would be nice if the FDA was more transparent with the details of their independent lab testing…wishful thinking.
@Dustin, thanks for raising some really important points including the vaginal/birth canal home for this bacteria, which could suggest the microbes origin. More on this microbe: https://en.wikipedia.org/wiki/Mycoplasma_hominis_infection.
While the risk of infection is a big deal overall, in this case my sense at this early point in this situation is that the FDA invoking non-homologous use and more than minimal manipulation are a much bigger deal for this and other businesses.
Paul
Mycoplasma testing is also not specifically required per GTP. Part of the big issue here is transparency. GTP is not explicit as to what sterility testing needs to be done, how frequently, what organisms, etc. A firm does not know the FDA considers their sterility testing insufficient until an inspection. Even when asked for GTP clarifications at the FDA San Antonio convention, they waffled and refused to give straight answers. This isn’t just for amnion, blood, bone, eye, and skin are all subject to GTP’s vague guidelines.
There are a number of research and other major hospitals, which, I believe, allow third parties to collect the material directly in the OB wards. I’ve been told this is becoming more standard. They offer storage services, which are not often purchased, but I’m not sure if they still collect the material.
Not only does the FDA view these products as more than minimally manipulated and their advertised use as non-homologous, but the manufacturing facility appears to have lacked formal SOPs, proper QA/QC, and basic sterility testing!
Marketing these products as a form of “Stem Cell Therapy” is shady as is. Now they’re being distributed with mycoplasma hominis…wonderful!
“Two unopened vials from the same lot were tested by an outside laboratory and confirmed positive for M. hominis.”
@Dustin – Their web site does not market any products as stem cell therapy.
Bill is right, but a number of stem cell clinics do say they use the products: https://www.google.com/search?q=AlphaGEMS
Paul
I only see one clinic in that list and they don’t claim the products contain stem cells either.
But wouldn’t that mean the product is now a biologic and must be regulated as such? Lack of clear stem cell therapy guidelines is used by dubious clinics to sneak under the radar, but if this is not a stem cell therapy and is the product of a living cell, then it must be a biologic drug product – right?
A few companies are getting around this by calling it a dietary supplement but that’s another kettle of fish.
Thanks Bill…I agree, the Amniotic Therapies website, when operational did not make these specific claims. However, the clinics using them often do. They also appear to be more than happy to sidestep the viable stem cell controversy, as opposed to other companies whom are more forthcoming regarding their product’s contents.
http://www.rmiclinic.com/there-seems-to-be-a-lot-of-controversy-about-amniotic-stem-cell-injections-as-to-whether-they-even-contain-any-live-cells/
Also, here’s a glimpse of AT’s website in the past… the inclusion of this page appears to be misleading to me, specifically the portion covering regenerative cells found in human amniotic tissue.
https://web.archive.org/web/20160322071632/http://amniotictherapies.com/science/science-research/
Yet, you are correct. There is no mention of viable stem cells on the product’s page. Likely because, if they were included, the product would no longer be solely regulated as a 361 HCTP.
https://web.archive.org/web/20160322065120/http://amniotictherapies.com/products-main/alphagems-micro-sterile-flowable-amniotic-adhesion-barrier/
I wouldn’t say this is an accurate account of the situation. The facility does have proper SOP, QA/QC, and sterility testing. I wouldn’t say the “unopened vials” (lacking any chain of custody) were truly confirmed. The products are not marketed as stem cell therapy and while some doctors use amniotic products in conjunction with stem cells, this is not how they are marketed. Several amniotic injectable manufacturers have gotten almost identical warning letters (BioD, MiMedix, etc.).
This update elaborated some findings: http://www.massdevice.com/judge-blocks-fdas-move-shutter-amniotic-therapies/
BioDLogics, Pinnacle Transplant Technologies, Castle Surgical, etc. have all been recipients of FDA untitled letters. This is a warning letter…
“An Untitled Letter is an initial correspondence with regulated industry that cites violations that do not meet the threshold of regulatory significance for a Warning Letter.”
“Warning Letters are issued only for violations of regulatory significance.”
Regardless, I was merely commenting on what was included in the FDA warning letter. In the letter, the FDA claims that upon inspection, Amniotic Therapies LLC…
1) Failed to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile
2) Failed to establish and follow written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess
and
3) Failed to establish and follow written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures
…among others. Again, these are the FDA’s words, not mine.
Finally, regarding marketing of similar products as a form of “Stem Cell Therapy”, here is one of many examples you may find using a quick Google search.
http://www.hedleyortho.com/services/sports-medicine/stem-cell-injections/
You do understand how vague FDA letters are, right? A “failed to provide written procedure” can mean many things. It can mean that there was not a procedure, that there was one but it was not documented, that there was one but the FDA didn’t like the procedure, that one was provided but the FDA lost it, that there was one but the FDA didn’t specifically ask for it… this is in court (and winning) for a reason. You can’t take FDA letters completely at face value. They are written in a different verbiage and do not state the depth of breadth of an issue.