In August, the U.S. Food and Drug Administration (FDA) issued a stern warning letter to a California-based company for manufacturing and distributing unapproved products derived from umbilical cord blood and for failure to comply with current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements. Because these products were derived from human cells, tissues, or cellular or tissue-based products (HCT/Ps), they are subject to specific FDA regulations, which the company purportedly failed to follow.
Products such as these are part of a larger, growing market for regenerative medicine products, which includes products involving HCT/Ps and other genetic material used to treat and manage diseases. The global regenerative medicine market is estimated to reach $48.97 billion by 2025. With the rise in popularity of regenerative medicine products, this recent warning letter serves as a reminder to the industry of the importance of understanding FDA’s requirements in this area.
FDA issued the warning letter after an inspection resulted in a Form 483 noting significant deviations from CGMPs and CGTPs. Although the company responded to these concerns, the FDA issued the warning letter noting the company’s failure to have an investigational new drug (IND) application in effect to study the products or an approved biologics license application (BLA) to lawfully market such products. The warning letter noted that the company described itself as "specializing in the harvesting and isolation of stem cells to manufacture and commercialize innovative products," and distributed the products directly to physicians throughout the United States.
Specifically, the FDA’s inspection revealed that the company’s umbilical cord blood-derived products were being manufactured for use in recipients unrelated to the donors of the products. Accordingly, because these products were not intended for homologous use only (i.e., to perform the same basic function or functions in the recipient as in the donor), FDA considered these products as both drugs and biological products requiring both an IND and a BLA.
The FDA’s still-evolving framework for regulating regenerative medicine products currently includes four significant guidance documents that discuss FDA’s risk-based approach to regulating such products. Such an approach includes considerations about how products are being administered as well as what diseases and conditions they are intended to treat. Notably, FDA’s Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use, issued in 2017, outlines the criteria for HCT/P products to avoid regulation as a drug, device or biological product under the Food, Drug, and Cosmetic Act (FDCA).
In a press release following the warning letter, the director of FDA’s Center for Biologics Evaluation and Research noted that “[t]he FDA remains highly committed to facilitating the development and availability of safe and effective cellular therapy products” but warned that the FDA “will not hesitate to take appropriate action to protect people from being harmed by products with potential significant safety concerns.” In addition to the warning letter highlighted here, the FDA sent another 20 letters to manufacturers and providers that FDA suspects are offering unapproved stem cell products.
Manufacturers of these products, and providers using such products, should take careful note of FDA’s approach to regulating HCT/Ps and other regenerative medicine products.