Intro to the Center for Veterinary Biologics (CVB)

What U.S. government agency regulates and inspects biologics products for animals—for example, the rabies and distemper vaccines administered to dogs? FDA’s Center for Veterinary Medicine (CVM)? The answer is “No.” Veterinary biologics are regulated and inspected by the Center for Veterinary Biologics (CVB), an agency of the U.S. Department of Agriculture (USDA) under its Animal and Plant Health Inspection Services (APHIS) agency.

While the FDA gets its statutory authority from the 1938 Food, Drug, and Cosmetic Act (FDC Act) as codified in the Code of Federal Regulations (CFR) Title 21, CVB’s authority comes from the 1913 Virus-Serum-Toxin Act as codified in CFR Title 9. Initially, the Virus-Serum-Toxin Act was created due to significant losses from unregulated manufacture and distribution of anti-hog cholera serum.

At the International GMP Conference held virtually in March 2021 co-sponsored by the University of Georgia at Athens and FDA, USDA CVB Senior Biologics Specialist Kendall Graber introduced the principles of good manufacturing as required by the Virus-Serum-Toxin Act and discussed how the USDA manages compliance to the Title 9 regulations for animal biologics.

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Graber noted that the USDA is made up of multiple agencies and offices. APHIS—the Animal and Plant Health Inspection Service—was established in 1972. But much of the work of protecting animal and plant health has been conducted under USDA for more than 100 years, including the regulation of veterinary biologics since 1913.

His presentation included:

An introduction to CVB, including its history and what it regulates, including how many sites and species
Specifics regarding the standards outlined in 9 CFR and the similarities with 21 CFR
How the agency manages compliance through actions such as inspections and product release
Insight into risk assessment and prevention of extraneous agents
Efforts aimed at harmonization of standards for veterinary biologics and animal health regulations

This article is presented in four parts. Specifically, Part 1 covers:

History and background of APHIS/CVB
What the agency regulates and how
The number of sites, products, and species regulated
How it supports the health of the U.S. herd

History and Background of CVB

The CVB is located in Ames, Iowa, as part of the National Centers for Animal Health and is responsible for regulation of veterinary biological products. By contrast, the FDA Center for Veterinary Medicine regulates veterinary pharmaceuticals.

In 1906, Upton Sinclair’s novel, The Jungle, exposed health violations and unsanitary practices in the American meat packing industry, which contributed to the public outcry leading to reforms in the industry. Around that same time, Hog Cholera was sweeping through the country causing devastating losses.

An anti-Hog Cholera serum was successfully tested in 1907 by the Bureau of Animal Industry’s field station near Ames, Iowa. However, not all products were effective. Significant losses from unregulated manufacture and distribution of anti-Hog Cholera serum demonstrated a need to ensure the safe and effective supply of animal vaccines and other biological products.

As a result, Congress passed the Virus-Serum-Toxin Act of 1913 to ensure safe and effective animal vaccines and other biological products. The Act requires that anyone who prepares, sells, barters, exchanges, or ships veterinary biological products must do so in compliance with U. S. Code (USC) regulations. Here, the term “serum” is used to reference serum for which immunological claims are made and does not include the other uses of serum or serum products.

What Does CVB Regulate?

CVB’s mission is to implement the provisions of the Virus-Serum-Toxin Act to ensure that veterinary biologics are not “worthless, dangerous, contaminated, or harmful,” Graber explained. Rather, they should be pure, safe, potent, and efficacious. Another important facet is these products should be available for use.

The regulation of veterinary biological products includes several significant procedures established and enforced by the CVB. These include:

Licensing or registration of veterinary biological products based on safety and efficacy data submitted to and reviewed by CVB
Inspection of facilities, equipment, personnel, processes, and documentation both pre- and post-licensure
Testing both pre- and post-licensure
Serial release, or market release of individual serials (a serial is a manufacturing batch)
Compliance actions taken on an establishment, product, or serial, when violations are determined
Monitoring of product after release through pharmacovigilance

The agency regulates biological products, which, by definition, are all viruses, serums, toxins, or analogous products which are intended for use in the treatment of animals, and which act primarily through the immune system or the immune system response.

Treatment includes prevention, diagnosis, or management of animal disease by-products, which act primarily through the direct stimulation, supplementation, enhancement, or modulation of the immune system or immune response.

What Sites, Products, and Species Are Under CVB’s Purview?

The scope of products under the agency’s purview is wide, as the definition of veterinary biologic product is based on immune response and treatment. CVB works cooperatively with the Center for Veterinary Medicine on regulatory jurisdiction for newer technologies and treatments such as cancer treatments. This allows the manufacturer to have a clear path to registration of these products and technologies from the start of registration.

The scope of its regulation covers the diagnosis, prevention, and control or treatment of diseases of pets, livestock, wildlife, and exotic animal species. They include zoonotic agents, such as brucellosis and rabies.

The list of species for which veterinary biologics are currently authorized for use includes companion animals, like dogs, cats, and horses; production animals like cattle, swine, and chickens; and exotic animals, like alligators, elephants, raccoons, and non-human primates.

CVB’s mission is to implement the provisions of the Virus-Serum-Toxin Act

The agency works with state and federal animal health control programs dealing with emerging agents. And they also have issued licenses for products necessary for preharvest food safety, such as vaccines for salmonella in poultry, and E. coli in beef.

“Veterinary biological products are regulated with the customer in mind,” Graber said. “The most obvious are animal owners and veterinarians. But the tools regulated by CVB also assist in health programs such as diagnostic test kits and vaccines used in eradication programs. We work with other laboratories, universities, and foreign regulators, and we also work with the biologics manufacturers as partners in animal health.”

CVB Regulates Nearly 100 Product Licensees

At the end of fiscal year 2020, there were 86 licenses and permittees regulated by the CVB. These establishments ranged from one or two people operating at one site to large corporations with thousands of people and multiple sites.

There were 96 domestic and 28 foreign manufacturing sites, as well as 33 domestic quarantine sites, for a total of 1,579 active products in fiscal year (FY) 2020. As a result, in FY 2020 the CVB authorized market release of approximately 16,600 serials amounting to over 121 billion doses released into the market.

Its authority covers a wide spectrum of products, including over 527 unique products for at least 223 animal diseases. CVB is responsible for ensuring that appropriate and adequate standards are used.

Support of the U.S. Herd

CVB supports the animal health industry and the general health of the U.S. herd by providing quality deliverables as part of the regulatory process. Prior to veterinary biological products being registered through CVB, a thorough evaluation of data submitted by the biologics manufacturer is conducted to support the use, safety, and efficacy of a vaccine. This is augmented with critical testing conducted by the CVB laboratory.

Once a product is licensed, CVB continues to regulate and monitor the product throughout the product lifecycle. This occurs daily with granting market authorizations and monitoring pharmacovigilance reports.

Compliance inspections are performed at regular intervals and noncompliance is addressed. CVB also provides services to support the marketing and international distribution of products made in the United States by developing tests and reagents to standardize testing outcomes, export certification of products, inspection of facilities, and annual training of domestic and international manufacturers and international regulators via the Institute for International Cooperation in Animal Biologics.

[Author’s Note: Part II will cover comparison of GMPs in 21 CFR and requirements in 9 CFR—the similarities, and differences and CVB’s compliance program.]