You almost can’t make this stuff up. I know I keep saying that, but it’s been clear for a while now that it was just a matter of time before the FDA came down hard on companies purporting to sell exosome and umbilical cord “stem cell” products. That day was yesterday. Let’s dig in.
What are Exosomes and Umbilical Cord “Stem Cells”?
Exosomes are tiny packets of information that allow cells to communicate. Certain companies have been claiming that they sell an exosome product (as to whether they are or are not that’s not been determined). In fact, since exosomes are found in everything from your own blood to spit, many have been rebranding their amniotic fluid products (derived from the birth sac of newborn babies) as exosome products. Despite all of the buzz and the thousands of patients each day trying these exosome soups, we don’t have a single clinical study that shows that these products will do anything to help any disease.
Umbilical cord “stem cell” products are usually derived from the blood or other tissue (Wharton’s Jelly) found in the “cord” that connects the baby to the mother. When these tissues are fresh, they contain some stem cells, but once they’re collected, processed, frozen, and shock thawed in a doctor’s clinic, they’ll all dead cell products. We recently tested 5 of these products through the CSU Translational Medicine Institute and all were dead on arrival. That included products made by Liveyon, Chara Biologics, and RichSource, the focus of the FDA warning.
Understanding How FDA Works Using Charcoal
A great example of how the FDA works can be illustrated using charcoal. FDA is a claims made process, so the claim that you make defines the regulatory status of your product, whether or not that claim is true. For example, you can sell charcoal for heating homes and it’s not FDA regulated. But selling charcoal to treat poisoning makes that same charcoal an FDA regulated drug.
Realize that in my opinion (and now that of the FDA) all of the companies who received warning letters this week were playing fast and loose with the regulations. They had all registered their products as a donor tissue, a process that takes 45-minutes on-line and has no FDA approval or review. That’s in contrast with persuing a drug approval for their products (which none of these companies have done). That takes many years and millions of dollars for clinical trials for each medical application.
The FDA Exosome Announcement
Many different physicians had instantly figured that what companies selling exosomes were doing wasn’t compliant with FDA regulations. Some (like myself) had even submitted queries to the FDA’s Tissue Reference Group TRIP program, where the agency commits to get back to you quickly. All of those queries from multiple physicians had come back the same. You can’t register an exosome product as a tissue and instead this is a drug product that needs clinical trials and FDA approval. The FDA public safety announcement on exosomes this week says it all:
“There are currently no FDA-approved exosome products. Certain clinics across the country, including some that manufacture or market violative “stem cell” products, are now also offering exosome products to patients. They deceive patients with unsubstantiated claims about the potential for these products to prevent, treat or cure various diseases or conditions. They may claim that they these products do not fall under the regulatory provisions for drugs and biological products – that is simply untrue. As a general matter, exosomes used to treat diseases and conditions in humans are regulated as drugs and biological products under the Public Health Service Act and the Federal Food Drug and Cosmetic Act and are subject to premarket review and approval requirements.”
In addition, the announcement also discusses that the CDC is tracking cases of serious complications of patients treated in Nebraska with exosome products. This again is not surprising, as I have said many times, we have no idea what the safety profile of these products is at this point.
Liveyon is one of the more interesting companies in the stem cell wild west. They are known for their cinematic commercials and the scantily clad women in their ads. They had already been warned by the FDA when their Regen Series product put at least a dozen patients in the ICU. At that point, the company pointed fingers at their supplier, a little company (now defunct) called Genetech (not to be confused with the biopharma known as Genentech). Since then the company has touted the fact that it now makes its own cellular product, known as “Liveyon PURE” and “PURE PRO”. Hence it looks like the FDA showed up to audit it’s new lab and here’s what they had to say:
“An FDA inspection…Because these products are not intended for homologous use only (i.e., to perform the same basic function or functions in the recipient as in the donor)…they are regulated as both drugs and biological products. Therefore, to lawfully market these products, an approved biologics license application is needed…However, no such licenses or INDs exist for the PURE and PURE PRO products marketed by Liveyon Labs and Liveyon LLC.
During the inspection, the FDA documented evidence of significant deviations from CGTP and CGMP requirements in the manufacture of the PURE and PURE PRO products, including deficient donor eligibility practices, such as failing to screen donors’ relevant medical records for risk factors for communicable diseases; inadequate aseptic practices, such as failing to follow procedures to prevent microbiological contamination; and deficient environmental monitoring, such as failing to establish a system for cleaning and disinfecting the processing room and equipment. These deviations pose a significant risk that the products may be contaminated with viruses or other microorganisms or have other serious product quality defects, which could potentially lead to patient harm.”
What was amazing about Liveyon is that despite the fact that it was involved in a huge contamination scandal and being warned that they couldn’t claim that they were selling a stem cell product, they doubled down. Liveyon continued to claim that their product had mesenchymal stem cells and they brought the manufacturing in house.
CharaCore and RichSource
I have blogged on these companies/products before (see CharaCore blog and RichSource blog). Both also claim to be selling stem cell products and both had no mesenchymal stem cells per the CSU tests. In addition, I can now reveal that I received nasty grams from their respective attorneys claiming that I was wrong that both companies were violating FDA regulations by claiming to sell stem cell products. Given that both companies were just called on the carpet by the FDA for offering unapproved stem cell products, I guess it’s now clear that both companies were incorrect.
The FDA is getting more serious month over month. What’s also unique here is that they’re being proactive on exosomes. For example, umbilical cord “stem cell” products have been blowing up over the last 24-36 months and it took at least 1-2 years for the FDA to come out publically on the issue. Exosomes have only been blowing up for 6-12 months and already the FDA clearly understands that they are the newest and latest crazy product that is rapidly replacing umbilical cord scams. The agency is clearly stopping exosomes before the wave begins to crest rather than waiting for it to get there.
From the chatter on Linkedin, most physicians who are involved in regen med and attend conferences now recognize that they shouldn’t be using these products. Why? Not only are there serious safety concerns, but also it’s illegal for these physicians to be advertising unapproved drug products. What could happen? Look no further than this Las Vegas couple who ended up in federal prison for promoting unapproved Botox via local ads.
However, I also see die-hards on Linkedin who are now digging in their heels. Even though the FDA couldn’t have been more clear, these are physicians are claiming that we don’t yet know enough about what’s happening with exosome products. To these physicians and the companies they work for, I would read the history of the unapproved Botox debacle. Meaning it’s my guess that come November 2020 we will see some perp walks by federal agents escorting people out of their homes and into black SUVs.
What Should Patients Do?
While the CEO for the company that makes the exosome or umbilical cord product you are injected with or the doctor administering it may end up getting in serious trouble, why should you care? First, we have no clinical data that show that these products work to help treat the clinical conditions for which they are being marketed. Even if you wanted to take a chance there, there’s another huge issue. By trying to deliver live exosomes or cells, these companies are avoiding what’s called terminal sterilization. Why is that a big deal?
A terminally sterilized product is one that has been irradiated before use to kill bacteria and viruses. This also kills all the human cells as well. This is by far the safest way to use someone else’s tissue or cells. However, many of the companies selling these products skip this step, because they want to claim that they’re selling something that’s still alive. However, doing that right using a drug manufacturing standard is very hard and very expensive. Meaning that you need to extensively screen donors and make sure that no contamination gets introduced into the manufacturing process. Given the CDC warnings that we have been consistently seeing, many of these companies are placing patients at risk
The upshot? The FDA is getting more and more serious about companies and medical providers who make, distribute, or use these products. If you’re a patient, we’ve seen countless examples now of serious injuries caused by the allogeneic products. So stick with using your own tissues until we start to see FDA approved and blessed exosome and umbilical cord stem cell products.