FDA Warning Letter: Unauthorized Drugs and Biological Products

The U.S. Food and Drug Administration (FDA) has reviewed Evolutionary Biologics' website and other available information and has determined that the company is distributing several unapproved new drugs and unlicensed biological products in the United States. The products in question are EXO RNA™, EVO JEL™ and EVO HYBRID™, which are derived from exosomes, umbilical cord tissue, placental tissue and amniotic membrane.

According to the FDA, the sale of these products falls under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the Public Health Service Act (PHS Act), which prohibits their distribution without prior approval. The products are advertised on the company website with health claims that indicate that they are intended to diagnose, cure, treat, or prevent disease. Examples of these claims include:

• EVO JEL™: Promoted as anti-inflammatory, regenerative and supportive for orthopaedic applications, e.g. for joint diseases, muscle damage and tendon injuries.
• EVO HYBRID™: Claimed to have a regenerative effect through growth factors that reduce inflammation, stimulate neuron growth and promote longevity.
• EXO RNA™: Promoted with claims to treat neurodegenerative diseases by stimulating neuron growth and inhibiting inflammation in the brain.

Under 21 U.S.C. § 321(g)(1) of the FD&C Act and 42 U.S.C. § 262(i) of the PHS Act, these products are classified as drugs and biological products. To be approved for the market, a Biologics License Application (BLA) would be required, which has not been issued for any of these products.

Violations of the HCT/P regulatory process

Some of the products are made from human tissue and therefore fall under the Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) rules under 21 CFR 1271. To be regulated only under Section 361 of the PHS Act, the products would have to be intended for so-called "homologous use," meaning they could only be used for the same function in the recipient as in the donor.

• One product is offered in liquid form and intended to be used for anti-inflammatory and regenerative purposes, which goes beyond the natural function of umbilical cord tissue. This is a non-homologous use and is subject to additional regulations.
• Another product contains tissue from the umbilical cord, placenta and amniotic membrane, which act as a barrier in their natural state. However, processing it into a "flowable" form changes the original structural properties and makes it a minimally manipulated tissue subject to additional regulation.

The exosome-based product advertised for neurodegenerative diseases is of particular concern. In its Warning Letter, the FDA refers to a Public Safety Notification on exosome products, which warns of grave side effects. Patients treated with unapproved exosome products have reported severe health problems.

The FDA is ordering the company to immediately cease distribution of these products and provide a written explanation of corrective actions taken within 15 business days. If Evolutionary Biologics does not take appropriate action, it may face legal proceedings, including product seizures or cease and desist orders. In addition to the products mentioned, the FDA is also investigating other products advertised on the company's other websites. Here, too, health-related statements are being made that indicate that these products are being sold as drugs without FDA approval.

A missing or incorrect classification of products has often led to a Warning Letter, as in this case. Read the full Warning Letter on the FDA website.