FDA admonishes Regenerative Therapies Manufacturer in Untitled Letter

Recommendation

7/8 May 2024

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Regulatory Requirements and Practical Implementation

The use of human cellular or tissue-based products (HCTP/S) continues to gain in importance, which is also reflected in the increasing number of companies active in this field and also in the form of regulatory activity. Frequently, applications and therapeutic approaches arise here from the medical research environment or from existing medical activities. Those responsible are often not aware, though, that they fall under the corresponding drug regulations for the development and marketing of such therapies. This is also evident in the following letter from the Office of Compliance and Biologics Quality in the Center for Biologics Evaluation and Research (CBER) of the United States Food and Drug Administration (FDA). It refers to the website of the Regen Center, which offers cellular products derived from human umbilical cord blood, umbilical cord tissue, amniotic membrane or adipose tissue as "regenerative medicine therapy" to treat various diseases such as chronic obstructive pulmonary disease, leukemia, diabetes, heart failure, and lung and kidney diseases and disorders.

On the website the center offers stem cell injections for the treatment of autoimmune diseases such as rheumatoid arthritis, lupus, psoriasis and Lyme disease, but also for neurological diseases such as ALS, multiple sclerosis, dementia, stroke, Parkinson's and Alzheimer's disease and many more.The FDA notes that these cellular products appear to be human cells, tissues, or cellular or tissue-based products (HCT/Ps) as defined in 21 CFR 1271.3(d). These would then be subject to regulation under 21 CFR Part 1271 enacted under Section 361 of the Public Health Service Act (PHS Act) [42 U.S.C. 264].  HCT/Ps that do not meet all of the criteria in 21 CFR 1271.10(a), and where there is no exemption under 21 CFR 1271.15, are not regulated exclusively under section 361 of the PHS Act [42 U.S.C. 264] and the regulations in 21 CFR part 1271. Accordingly, such products are covered by the requirements for drugs, devices, and/or biological products under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and/or the PHS Act. Therefore, they are subject to extensive pre-market testing.

Since the Regen Center's products are not likely to be subject to 21 CFR 1271.15, and since these cellular products are intended for non-homologous uses, it appears that the products would have to be regulated as drugs under the definition in section 201(g) of the FD&C Act [21 U.S.C. 321(g)] and as biological products under the definition in section 351(i) of the PHS Act [42 U.S.C. 262(i)]. That means, for marketing for human use, a valid biologics licence must accordingly be in force. This is only issued after proof that the product is safe, pure and effective. Alternatively, in the development stage, an Investigational New Drug (IND) application would be required for human use in clinical phases. Therefore, the FDA refers to the comprehensive existing set of regulations on regenerative medicine and their regulations for HCT/Ps. This is described in a series of four guidance documents that can be found on the FDA website with information about the relevant regulatory framework for such products.

Similarly, the Regen Center also describes the use of exosomes in conjunction with the regenerative therapies. Exosomes for human clinical use also count as drugs and biological products under Section 351 of the PHS Act and the FD&C Act and are subject to premarket review and approval requirements. Accordingly, the FDA requires the Regen Center to respond within 30 days that the company is responsible for compliance.

For more deteilaed information, please see the  "Untitled Letter der FDA".