Are Your Stem Cells Too Old? The FDA’s Position on Umbilical Cord Blood: Don’t Be Misled!
August 28, 2018
These companies are quick to tell unassuming physicians that there are many live viable cells in their products. This is where things get murky. If there are live cells in their products that will actually have some type of biologic effect, than this appears to be a violation of FDA guidelines.
FDA guidelines state that if a product has live cells with metabolic activity, than this product requires significant testing before it can be released to the public. So, there are two avenues that these companies can pursue. They either have to say that there are no live cells and register the product as a tissue product. This is a relatively easy process. If they claim live cells, than they have to apply for a biologics license. This is a process which requires a few years of testing and a biologics license which is a very arduous process.
In order to make sure that my thinking was correct, I sent an inquiry to the FDA on Aug 23,2018 and here is my answer from them. I took the liberty of highlighting certain portions in yellow highlight:
Dear Dr. Purita:
Thank you for your email to the Center for Biologics Evaluation and Research (CBER). CBER, one of seven centers within the Food and Drug Administration (FDA), is responsible for the regulation of many biologically derived products, including blood intended for transfusion, blood components and derivatives, vaccines, allergenic extracts, and cell, tissue and gene therapy products.
Cellular therapies are regulated by CBER as human cells, tissues and cellular and tissue-based products (HCT/Ps). FDA has a risk-based approach to the regulation of HCTP/s. Under the authority of Section 361 of the Public Health Service (PHS) Act, FDA established regulations for all HCT/Ps to prevent the transmission of communicable disease.
The regulations in 21 CFR Part 1271 identify the criteria for regulation solely under Section 361. HCT/Ps that meet all of the criteria in 21 CFR Section 1271.10(a) are regulated solely under Section 361 of the PHS Act. If all of the criteria in 21 CFR Section 1271.10 are met then no pre- market review (application to FDA) is required.
To satisfy these criteria, an HCT/P must be: No more than minimally manipulated (relates to the nature and degree of processing); intended for homologous use only (the product performs the same basic function in the donor as in the recipient); not combined with another article (with some limited exceptions); and the HCT/P does not have a systemic effect and is not dependent on the metabolic activity of living cells for its primary function, or if it does, the HCT/P is intended for autologous use or use by a first-or second-degree blood relative.
HCT/Ps that do not meet all of the criteria of 21 CFR Section 1271.10 are also regulated under Section 351 of the PHS Act and/or the Federal Food, Drug and Cosmetic Act as drugs, devices and/or biological products and would require pre-market approval.
Stem cell products have many different sources and potential biological activities and therefore need to be evaluated individually with respect to the 21 CFR Section 1271.10(a) criteria. Many experimental stem cell therapies do not meet at least one of these criteria.
For a stem cell product that does not meet the criteria for regulation solely under Section 361, a Biologics License Application (BLA) would need to be approved before commercial marketing.
The recently issued guidance documents titled “Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use” and “Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception” were provided to assist sponsors of HCT/P products in determining whether their products meet the first two criteria listed above. Even if a product meets both of those criteria, it must still meet the last two in order to be regulated solely under Section 361, and not require pre-market approval. Please know that guidance documents represent FDA’s current thinking on how sponsors of FDA regulated products can comply with current FDA requirements. Sponsors may adopt an alternative approach; however, that approach must still comply with FDA’s regulations, and in the case of cellular therapies, the regulations outlined in 21 CFR 1271.
With the issuance of the guidance documents mentioned above, FDA is adopting a risk-based and science-based approach that builds upon existing regulations to support innovative product development while clarifying the FDA’s authorities and enforcement priorities. This risk-based approach allows product developers time to engage with the FDA, to determine if they need to submit a marketing authorization application and, if so, submit their application to the FDA for approval. For the first 36 months following issuance of guidance documents above, the FDA intends to exercise enforcement discretion for certain products with respect to the FDA’s premarket review under the existing regulations. This policy will allow for a more orderly transition and limit the impact on available resources within the FDA.
A recent article published in The New England Journal of Medicine by Peter Marks, M.D., Ph.D., CBER Center Director and Scott Gottlieb, M.D., FDA Commissioner, provide further insight into FDA’s regenerative medicine policies: http://www.nejm.org/doi/full/10.1056/ NEJMsr1715626
We hope this information has been helpful. If you need further assistance, you may contact our office at [email protected] or 1-800-835-4709.
Consumer Safety Officer
Center for Biologics Evaluation and Research
Office of Communications, Outreach and Development U.S. Food and Drug Administration
This informal communication represents my best judgment at this time. It does not constitute an advisory opinion in accordance with 21 CFR 10.85, and does not necessarily represent the formal position of FDA or otherwise obligate the agency to the views expressed.
From: joseph purita]
Sent: Thursday, August 23, 2018 1:58 PM
To: CBER OCOD Consumer Account <[email protected]> Subject: opinion from FDA concerning certain products
I am writing this email to obtain an opinion from the FDA concerning certain products that that are being marketed to various specialties. In particular, I am wondering about umbilical cord blood derived mesenchymal stem cell products. My understanding is that these products are registered as a 361 with the FDA. Yet, these products state in some of their advertising material that they contain live mesenchymal stem cells which have metabolic activity. My understanding is if a 361 registered product has live stem cells with metabolic activity than it becomes a 351 requiring an IND license. I would like some guidance from the FDA on these products. If indeed these products registered as a 361 contain live cells with metabolic activity is that a violation of FDA regulations if they are used to treat patients for a variety of conditions? Do they actually require a 351 classification and IND application?
Dr. Joseph Purita
In the above letter, at the end, you can see my initial inquiry and subsequent answer from the FDA. On the surface this seems like a complicated letter. However, when you analyze it, it is fairly straight forward. As we can see the FDA is very specific that if a product has live cells with metabolic activity than this qualifies as a 351 product. A 351 product requires what is called an IND (Investigational New Drug application). This requires a few years of clinical testing and a few million dollars before the product is released for general use. It is fairly clear cut that these cord blood products fall into one of two categories. Either they do not have live cells with metabolic activity and thus they are essentially a growth factor tissue product or they have live cells with metabolic activity which is currently not allowed by the FDA regulations.
I am sure the dance by these companies will continue for a while longer.
The public needs to be aware that the chances are if a physician is utilizing these products you may not be getting what you were promised.
– Dr. P
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