US Animal Biologics Regulated by USDA Under Distinct Framework From Animal Drugs
Animal biologics in the U.S. are regulated by USDA, not FDA. Licensure requires proof of purity, safety, potency, and efficacy. Unlike the UK and EU, no approval pathway for animal biosimilars exists.
Biological veterinary medicinal products (biologics) are an innovative and fast-growing component of the veterinary pharmaceutical market. In the U.S., animal biologics are subject to the regulatory oversight of the U.S. Department of Agriculture (USDA) rather than the U.S. Food and Drug Administration (FDA), which regulates other therapeutic products, including animal drugs. In contrast, in the UK and EU, biologics do not have separate regulatory frameworks or regulators, and there are clear approval routes for biosimilars.
In the United States, animal biologics and animal drugs are distinct categories. The definition of animal drug is very broad under the Federal Food, Drug, and Cosmetic Act (FDCA) and includes any substance "intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals." In contrast, animal biologic is a much narrower category — in addition to a general intended use requirement "for treatment of animals," an animal biologic must fit certain subject matter and mechanism-of-action criteria. If a therapeutic product does not meet both of these additional criteria, it is not regulated as an animal biologic and generally, by default, will be considered an animal drug. Both product categories require premarket authorization — licensure for biologics, and approval for drugs — but they are regulated under different statutory frameworks implemented by different agencies.
U.S. animal biologics are regulated under the Vaccine-Serum-Toxin Act (VSTA) by the Center for Veterinary Biologics (CVB) in the USDA Animal Plant Health and Inspection Service (APHIS) Veterinary Services. This distinct jurisdiction grew out of early 20th-century concerns about tainted vaccines for livestock, a category not then regulated by the precursor to the FDA, and has remained with USDA ever since. The regulatory requirements for licensure of an animal biologic by CVB are generally determined between CVB and the sponsor, in a manner distinct from the FDA approval pathway for animal drugs.
Under USDA regulations, an animal biologic includes "all viruses, serums toxins (excluding substances that are selectively toxic to microorganisms), or analogous products" at any stage of production, shipment, distribution, or sale, for use in the treatment of animals. In addition to this subject matter requirement, the definition also requires that the substance "act primarily through the direct stimulation, supplementation, enhancement, or modulation of the immune system or immune response." The regulations include examples of the types of products that may be included in this definition, among them vaccines, bacterins, allergens, antibodies, antitoxins, toxoids, immunostimulants, certain cytokines, antigenic or immunizing components of live organisms, and diagnostic components, that are of natural or synthetic origin, or that are derived from synthesizing or altering various substances or components of substances such as microorganisms, genes or genetic sequences, carbohydrates, proteins, antigens, allergens, or antibodies.
Elsewhere, APHIS explained what it means for a product to act primarily through the direct stimulation, supplementation, enhancement, or modulation of the immune system. Specifically, it stated that "stimulation" refers to active immunization, "supplementation" refers to passive immunization (such as through blood or other components), and "enhancement" or "modulation" refers to the upregulation or fine-tuning, respectively, of the immune system to generate an effective immune response.
The VSTA authorizes USDA to ensure that veterinary biologics are pure, safe, potent, and efficacious. Today, licensure for a new animal biologic by USDA requires preclinical and clinical studies demonstrating purity, safety, potency, and efficacy in target species, facility and product licenses, including facility inspections, and labelling review to ensure claims are supported by product data and license conditions. USDA has also issued guidance that describes a case-by-case basis by which it determines the scope of regulatory requirements.
Notably, under the VSTA, there are no user fees for animal biologics licensure, no fixed timeline for review, and no pathway for approval of animal biosimilars.