During a presentation at the recently concluded MedRebels conference, Dr. Don Buford indicated that there were no “homologus use” indications associated with IV infusion of autologous bone marrow concentrate (BMC). He made this point, in part, because of language the FDA has included in 21 CFR 1271.3 as follows:
The following articles are not considered HCT/Ps:
(4) Minimally manipulated bone marrow for homologous use and not combined with another article (except for water, crystalloids, or a sterilizing, preserving, or storage agent, if the addition of the agent does not raise new clinical safety concerns with respect to the bone marrow);
Part of the problem faced by those in the regenerative medical community is that the FDA hasn’t specified what it means by the phrase “bone marrow for homologous use”, so I will explore aspects of the regulatory environment laid out by the FDA on the use of bone marrow, and what the implications are for those who might want to use it in IV therapy.
As indicated above, Dr. Buford suggested that there was no obvious homologous use for treating a patient with their own bone marrow via the IV route. He was right to urge the audience to be cautious, since the FDA made the following statement in the Minimal Manipulation and Homologous Use (MM/HU) Guidance issued originally on November 16, 2017:
FDA intends to focus enforcement actions on products with higher risk, including based on the route and site of administration. For example, actions related to products with routes of administration associated with a higher risk (e.g., those administered by intravenous injection or infusion, aerosol inhalation, intraocular injection, or injection or infusion into the central nervous system) will be prioritized over those associated with a lower risk (e.g., those administered by intradermal, subcutaneous, or intra-articular injection). HCT/Ps that are intended for non-homologous use, particularly those intended to be used for the prevention or treatment of serious and/or life-threatening diseases and conditions, are also more likely to raise significant safety concerns than HCT/Ps intended for homologous use because there is less basis on which to predict the product’s behavior in the recipient, and use of these unapproved products may cause users to delay or discontinue medical treatments that have been found safe and effective through the New Drug Application or BLA approval processes.
In this statement (from pages 21 and 22 of the MM/HU Guidance), the FDA warns health care providers that there is a priority for enforcement actions that will be taken by the Agency as it polices the wide spectrum of regenerative therapeutic products currently on offer. With respect to delivery of therapy, the FDA takes the following position in terms of regulatory priority and concern:
Higher risk routes:
IV route (injection or infusion)
Injections into the CNS
Lower risk routes:
Of course, the FDA associates a greater risk with therapeutic administration via IV, since there is virtually no data on the use of HCT/Ps via that route. In addition, the FDA actively is pursuing legal injunctions against two clinics, in part, because patients seeking treatment for macular degeneration received intraocular injections of their own fat tissue-derived SVF at those clinics.
I couldn’t agree more with the approach of the FDA when they quite rightly warn the regenerative medical community that they aren’t happy with the cure-all claims made by some physicians and clinics, especially non-homologous uses of HCT/Ps to treat life-threatening and/or serious conditions not normally treated by an injection. For example, MS is a systemic, neurological disease, so a single injection, even IV, is highly unlikely to make a difference and some physicians claim to be able to treat MS in this manner by using amniotic fluid, touting the value of the supposedly viable cells present and, more recently, the presence of exosomes. The FDA hasn’t weighed in specifically on exosomes, but claims made about the alleged therapeutic potential of amniotic fluid-derived exosomes are in the same boat as the claims made for curing neurological diseases with an IV injection.
Clearly, the FDA believes a number of regenerative medical therapies, constituting in my opinion materials like amniotic fluid with viable cells, cord blood-derived anything, SVF (cells from digested fat tissue) and cultured cells, don’t clearly have a precedent or a sufficient basis for providing a therapeutic benefit. The FDA isn’t opposed to a clinic or manufacturer following a pre-market approval approach (e.g., IDE or IND) for any material they might think has a therapeutic benefit, but there are a lot of hoops to jump through when the treatment is intended for a non-orthopedic indication for use (e.g., CNS pathologies), is donor-derived and provided by a route not obviously directly related to the condition to be treated (e.g., IV).
So, the FDA has put on notice the regenerative medical community that routes of administration like IV are red flags, placing the health care professional who provides such therapies at greater risk for regulatory scrutiny. In general, I agree with the sentiments of the FDA as expressed above and in other forums, but I believe there might be some nuances to be considered for use of the IV therapy route. I will explore in the next post possible twists to what the FDA seems to imply is a straight forward concern for all IV-based therapies.