In response to a number of enquiries about companies selling miraculous stem-cell containing therapeutic products who are offering participation in an “IRB-cleared” clinical study, I would urge physicians to be cautious before signing up. In my opinion, there are a number of issues here, including smoke screens by companies that want to make a buck, but who don’t play by the rules. I will review the current smoke screen of using a convenient IRB to approve clinical studies of commercially-available regenerative products that most likely are not compliant with 21 CFR 1271, the controlling regulation for all manner of biological materials (identified as HCT/Ps) removed from living or dead people.
Here’s the setup:
- The company claims to have an incredibly powerful regenerative therapeutic product
- The company claims they have tapped into unique and very powerful stem cells from one or more of the following: umbilical cord tissue; umbilical cord blood; amniotic membranes; and/or amniotic fluid
- The Company indicates that their cell-containing preparations are the “richest” kind, since they have the youngest stem cells (peri-natal, presumably) and secrete the most and best growth factors
- The company has a convenient IRB that can sign up physicians so they can participate in the study while treating their patients with the magic prep
Leaving aside the issue of there not being any clinical study evidence in humans to support any of the claims by these peri-natal tissue product companies, their IRB-based come-on would seem to be pretty straight forward for a physician to make money while treating patients with a miraculous regenerative therapy, with the added advantage of possibly getting a publication out of the effort.
Now, I am all for physicians making money in regenerative medicine, and I am all for physicians participating in clinical studies. The problem with this type of scheme being offered by companies is that it is a dodge of existing rules for working with the materials in question. To fully understand the implications of the schemes being offered, you need to start with the basics (no groaning):
- Donor-derived materials that have viable cells in them, which rely on their metabolic activity to provide a therapeutic benefit, and which are not used in the donor or the donor’s first- and second-degree relatives, are considered to be drugs and biological products by the FDA
- If a material is a drug as outlined in the `351 category of the Public Health Services Act, it must undergo a pre-market approval (PMA) process prior to its sale
- Typically, a PMA will involve controlled clinical studies that are called “Investigational New Drug (IND)” studies
- INDs could be submitted by a company (aka sponsor) and will lay out the intent (what is being treated), scope and clinical study framework in order to establish the safety and efficacy of the donor-derived experimental drug
- The FDA will need to approve a sponsor’s submission, usually with some degree of discussion, after which the sponsor can initiate the IND clinical study
But, you counter, clinical studies are conducted all the time without them rising to the level of an IND. Certainly true, but the devil is in the details. Let’s take the case of a pedicle screw that has just been cleared by the FDA as a Class II device. A physician could engage in an IRB-approved clinical study of the potential therapeutic benefits of using that particular pedicle screw without the need to participate in an IDE (the device equivalent of an IND), since the device is cleared for a particular indication for use, and it will be studied for that indication. On the other hand, if a physician wanted to study the pedicle screw in an off-label use, an IRB should reject the clinical study, since it would lack any clinical support of safety and efficacy in that new indication. There are exceptions, but generally, changing an indication for use, shifting to a different patient population (e.g., adult to pediatric) or changing the dosing of a drug most likely will trigger the need for an IND.
The IRB-study scam has been around a long time in the regenerative medical marketplace. I recall CellTex, a company that cultured autologous-fat derived stem cell preparations, used an IRB-based strategy that enabled physicians to enroll patients in a clinical study, which CellTex claimed would allow physicians to treat patients with their own autologous-derived cultured cell product. The FDA took a dim view of the arrangement and issued a Warning Letter in 2012, which forced a realignment of CellTex’s business model. In addition, they sent a Warning Letter to the CellTex IRB (Texas Applied Biomedical Services) in 2012 that warned them of deficiencies, and finally disqualified them in 2016.
For example, this is how the FDA characterized CellTex’s approach to business in their Warning Letter:
Our investigation of your firm further determined that your firm promotes your process and the use of AdMSC to physicians by encouraging physicians to enroll patients in one of your clinical trials. Your protocols entitled, (b)(4) both explain that patients have an opportunity to be enrolled in these clinical trials if they are presently diagnosed with an (b)(4) for which there is hypothesized or demonstrated clinical benefit for the (b)(4) of the AdMSC product.
The FDA went on to state that
You are promoting the CellTex product in a manner that causes the product to be a drug under section 201(g) of the FDC Act [21 U.S.C. 321(g)] and a biological product as defined in section 351 (i) of the PHS Act [42 U.S.C. 262(i)].
So, companies that think they can offer non-compliant regenerative materials to physicians with the protection of a formalized IRB-approved clinical study simply are delusional.
Which brings me back to companies who are signing up physicians to do clinical studies approved by IRBs with HCT/P product(s). If the products are not compliant with 21 CFR 1271, including 1271.10(a)(iv)—the therapeutic benefit is dependent on the metabolic activity of viable cells present in the preparation—the HCT/P isn’t regulated solely by 1271, but is considered to be a drug and biological product (Section 351 of the PHSA). If it is a drug, then an IRB-approved clinical study isn’t going to provide any cover to the physician participating in the study. So, if a company touts their product because the product contains the best, youngest, highest secreting stem cells ever put in a vial, which means that the product contains viable, donor-derived cells, do not engage with that company. And if the company tries to induce you to sign on to a clinical study with the product, report the company to the FDA.
Furthermore, physicians who believe the hype and regulatory smoke screens offered up by companies in order to get physicians to use products that the FDA considers to be drugs means that physicians are using an unapproved drug, which is a no-no on several levels. For example, the relevant state medical board probably prohibits physicians from using unapproved drugs in patient therapy. Or, the physician’s malpractice insurance may have a clause that limits coverage only to the use of FDA compliant therapies.
An IRB-approved clinical study does not provide a safe harbor for physicians using an FDA non-compliant material, with my favorite group of non-compliant HCT/Ps being most of the products currently obtained from peri-natal tissues and fluids. One variation on this strategy, involvement in an IND clinical trial, presents its own can of worms, which I will deal with in a future post.