FDA survived a legal challenge to its authority to regulate stem cells as drugs, in a landmark decision by the U.S. District Court of Appeals for the DC Circuit. FDA had cited Regenerative Sciences, a Colorado-based company, in a 2008 warning letter, for violating FDA’s human cell, tissue and tissue-products (HCT/P regulation), and stated that Regenerative was promoting “mesenchymal stem cells under conditions that cause these celsl to be drugs … and biological products.”
Regenerative sued FDA, and the trial-level federal court agreed with FDA.
The District Court did not find that the stem cell mixture fell within HCT/P regulations, as it was more than “minimally manipulated,” because culturing the stem cells affected their characteristics.
On appeal, Regenerative made the familiar argument that FDA has authority over interstate introduction of foods, drugs, cosmetics, and biologics, but no authority over the practice of medicine, which the Tenth Amendment to the U.S. Constitution delegates to the states.
In the opinion, U.S. v. Regenerative Sciences, LLC, the DC District Court of Appeals found that Regenerative’s procedure results in a product that is a “drug,” not an HCT/P under 21 CFR 1271. According to the Court, FDA was not regulating the procedure, but the product – i.e., the mixture containing stem cells and the antibiotic, doxycycline. FDA could regulate the mixture as a drug (as it was intended to treat orthopedic diseases), and therefore Regenerative was subject to current Good Manufacturing Practices (cGMPs) applicable to all drugs.
This decision is a clear win for the FDA, and it constricts the ability of companies marketing stem-cell treatments to argue that their therapies are part of the practice of medicine and therefore beyond FDA reach, or, that their therapies are “minimally manipulated” and therefore within the HCT/P regulations.
As a result, as well, FDA is likely to send out more warning letters for those violating the HCT/P regulations. For example, FDA has issued a warning letter in the past to a medical spa that injected stem cells for “natural breast augmentation.”
FDA noted that the procedure did not fall within the regulations: “Specifically, your processing alters the relevant characteristics of the adipose tissue relating to the tissue’s utility for reconstruction, repair or replacement. Therefore, the processing would not meet the definition of minimal manipulation for structural tissue such as adipose tissue.” (FDA also argued that the treatments did not meet the definition of homologous use in 21 CFR 1271.3(c); and repeated that “in order to lawfully market such a biological drug product, a valid biologics license must be in effect,” or, the sponsor has an investigational new drug (IND) application in effect.
A thorough review of the HCT/P regulations is necessary before promoting stem cell therapies. The purpose of the regulation is to create a unified registration and listing system for establishments that manufacture human cells, tissues, and tissue-based products…..
Among other things, these regulations provide foundational definitions for stem cell practice, including:
1271.3 (c)Homologous use means the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor….
(e) Manufacture means, but is not limited to, any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any human cell or tissue, and the screening or testing of the cell or tissue donor.
(f)Minimal manipulation means:
(1) For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement; and
(2) For cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells or tissues.
These definitions are important, because stem cell therapies outside the definitions are prohibited.
As the Regenerative case shows, it’s not always easy to determine whether a given procedure or treatment falls within or outside the regulations — i.e., is homologous and minimal manipulation, or not. Also note the broad test of “manufacture,” which includes all steps in the recovery, processing, storage, labeling, packaging or distribution of any human cell or tissue.
To seek legal counsel regarding stem cell therapy products and services, contact our FDA legal team.