Authorities and procedures for licensing veterinary biological products in the United States.

The licensing procedures reviewed above provide a framework for the production of pure, safe, potent, and efficacious veterinary biological products. The licensing, inspection, and testing activities of the Veterinary Biologics program provide the oversight necessary to ensure the continued availability of high-quality veterinary biological products in the United States.

Risk analysis for the importation of veterinary biologicals into the United States of America.

International trade in veterinary biological products has been restricted by the following factors: a) concerns that contaminated products could result in the introduction of foreign animal disease agents into the importing country b) differences between countries in the technical requirements for product registration. The provisions of the North American Free Trade Agreement (NAFTA) and the General Agreement on Tariffs and Trade (GATT: now the World Trade Organisation [WTO]) require importation decisions to be science-based and transparent. This requires regulatory agencies to implement valid, credible, and science-based risk analysis models for decision-making. The Veterinary Biologics section of the United States Department of Agriculture, Animal and Plant Health Inspection Service, currently uses a formalized risk analysis model to evaluate the safety risks associated with proposals to field test and license new and biotechnology-derived veterinary biological products. This model for evaluating field tests has been modified to evaluate proposals to import veterinary biological products into the United States of America. The authors describe this risk analysis model, which was specifically designed to evaluate the risks of importing veterinary biological products potentially contaminated with foreign animal disease agents.

Present systems and future needs for risk assessment of biologicals in the United States of America: the perspective of the regulator.

The authority for regulating veterinary biologicals in the United States of America (USA) is provided in the Virus-Serum-Toxin Act, enacted in 1913 and amended in 1995. The Act authorizes the Secretary of Agriculture to prescribe regulations governing the preparation and marketing of veterinary biologicals shipped into, within or from the USA. The mandate of the United States Veterinary Biologics Program is to ensure that all veterinary biological products under Government jurisdiction in the USA are pure, safe, potent and effective. The Program is based on licensing, inspection and testing. Risk assessment techniques, and effective strategies for risk management and risk communication, are essential tools for regulatory officials charged with the responsibility of developing requirements for licensing veterinary biological products and production facilities. To accommodate scientific advances, heightened consumer awareness and the international harmonization of requirements, regulatory agencies must continually review and update programme requirements. The author discusses programme updates initiated to address future needs of the United States Veterinary Biologics Program.

A computerized system to store and retrieve data on biological and biotechnological veterinary products of the American continent.

The Veterinary Biologics Information System is a project the main goal of which is to collect, analyze and manage data concerning registered veterinary biologics and biotechnological products employed to control animal diseases by the countries of the Americas. Data from each country was gathered by cataloguing each biological product on a questionnaire form. The collected data was then fed into an electronic data base system. A retrieval program was subsequently developed, allowing the user quick access to all data stored in the system. The system operates in English and Spanish and includes such information as the product name, registration number, ingredients, species for which the product is approved for use, the disease against which the product is used, names of manufacturers and distributors and other distinguishing characteristics of the product including expiry dates and withdrawal times. This computerized system, with on-line data bases which can be quickly updated, provides a dynamic answer to the question of timely information concerning veterinary biological products.

Licensing veterinary biologics in the United States.

The authority for the regulation of veterinary biologics in the United States is provided in the Virus-Serum-Toxin Act, enacted in 1913 and amended in 1985. The Act authorizes the Secretary of Agriculture to prescribe regulations governing the preparation and marketing of veterinary biologics shipped into, within, or from the United States. The veterinary biologics program carries out the mandate to ensure that all veterinary biological products under the U.S. jurisdiction are pure, safe, potent, and efficacious. The program is based on licensing, inspection, and testing. Establishment licensing defines the production facilities, manufacturing practices, and the responsible person. Product licensing defines the product, the method of production, and testing requirements; it also assures product purity, safety, potency, and efficacy. Biologics production is based on the Master Seed concept, in which a master parental stock is the source of all seed materials for production. The final product may not be more than five serial passages removed from the Master Seed. Host animal immunogenicity is demonstrated by statistically valid host animal vaccination and challenge studies using the minimum level of antigen at the highest level of passage. Potency tests are correlated to host animal immunogenicity and are conducted on each serial of product prior to release for marketing to assure efficacy. Conditional licensing procedures that assure purity, safety and a reasonable expectation of efficacy are used to provide products for emergency conditions, limited markets, local situations, or other special circumstances. Licensing for further manufacturing permits two or more licensees to work together in the production of a product.(ABSTRACT TRUNCATED AT 250 WORDS)

USDA licensing policy for biologicals produced by R-DNA.

The advent of recombinant DNA technology has prompted a review of current Standard Requirements used in licensing Veterinary Biological Products. Unique problems associated with the production and testing of biologics derived from the new biotechnology are reviewed to insure compliance with the United States Department of Agriculture's requirement for purity, safety, potency and efficacy. Requirements for plasmid/vector characterization and stability will be discussed and correlated with the Master Seed concept. Practical methodology used to monitor antigenic expression, concentration, purification and stability during production and recovery is considered. Bulk and/or final container testing will meet established criteria for biologicals produced by conventional procedures. Experience in preparation and regulation of recombinant-derived biologicals may require revision of current Standard Requirements or special additional requirements. This flexible approach will facilitate licensing of these new products.

Effect of formaldehyde on the immunochemical and biological activity of staphylococcal enterotoxin B.

Staphylococcal enterotoxin B was treated with 0.15 or 0.3% formaldehyde at 37 C and pH 7.3. As early as 8 hr after addition of HCHO, the toxin was unable to precipitate as much antibody from antiserum as untreated toxin; greater amounts of treated toxin were required to reach equivalence and to inhibit precipitation. With increasing time, its reactivity decreased so that at 32 weeks it could precipitate only 20% as much antibody as untreated toxin. When other factors were kept constant, the degree of inactivation increased as the HCHO concentration increased from 0.6 to 1.4%. Treated toxin gave a "reaction of partial identity" by the Ouchterlony double-immunodiffusion technique. The emetic effect of the toxin for the monkey remained essentially unchanged for about 48 hr of treatment, but the amount required to cause death by the intravenous route increased from 25 to over 1,000 mug/kg of body weight. HCHO destroyed the pyrogenic effect for rabbits. The treated toxin remained immunogenic for rabbits even after 4 to 5 weeks of exposure to 0.3% HCHO at 37 C.