Virus Testing (Adventitious Agents)

Viruses are generally not removed by filtration. BVDV exists and a common adventitious agent in bovine serum. Tests for animal viruses such as IBR that produce a cytopathic effect in the host cell. Evidence of cytopathic effect include: inclusion bodies, abnormal number of giant cells, or other cytopathology indicative of cell abnormalities attributable to an extraneous agent. Test detections hemagglutinin producing virus such as PI3. Hemagglutinin is dependent upon selective attachment of erythrocytes onto the monolayer surface of tissue cultured cells. Test to detect and quantify antibodies specific for BVDV type 1 and type 2. Gamma irradiation provides good log reduction of most viruses while maintaining serum functionality.

Reference	Title	Description
9CFR 113.46	Detection of cytopathogenic and/or hemadsorbing agents	If specific cytopathology or hemadsorption attributable to an extraneous agent is found, the material under test is unsatisfactory and shall not be used to prepare biologicals products.
9CFR 113.53	Requirements for ingredients of animal origin used for production of biologics.	Serum used to prepare a biological product shall be tested as prescribed in 113.53. A lot of ingredient found unsatisfactory by any prescribed test shall not be used to prepare a biological product.
9CFR 113.47	Detection of extraneous viruses by the fluorescent antibody technique	Test for detection of extraneous viruses by the fluorescent antibody technique. Cells shall be tested for Bovine virus diarrhea virus (BVDV), Reovirus, rabies virus, bluetongue virus, bovine adenoviruses (group A and group B), bovine parvovirus, bovine respiratory syncytial virus.
9CFR 113.215	Supplemental Assay method for titration of bovine viral diarrhea virus neutralizing antibody.	In vitro assay method that determines the serum neutralizing (SN) antibody titer to bovine viral diarrhea virus (BVDV) in serum as part of potency requirements for veterinary vaccines. Applies to cytopatic strains of either genotype 1 or genotype 2. Terminology of 1:10, 1:20 etc. specifies 1 part plus 9 parts (liquid).
CHMP/BWP/457920	Guidelines on the use of bovine serum in the manufacture of human biological medicinal products	Test for viral contaminants should be carried out prior to any steps taken to inactivate or remove viruses. Specific test for the following viruses should be considered: Bluetongue and related orbiviruses, bovine adenovirus, bovine parvovirus, bovine respiratory syncytial virus, bovine viral diarrhea virus, rabies virus, reovirus 3.
CVMP/743	Requirements and controls applied to bovine serum used in the production of immunological veterinary medicinal products	Combination of general and specific test to be carried out should be capable of detecting viruses inducing viraemia and transplacental infection such as Bovine Adenovirus, Bovine viral diarrhea virus, parvovirus, bovine respiratory syncytial virus, reovirus, parainfluenza 3, IBR and those responsible for diseases exotic to Europe such as Bluetongue. Test should be carried out before any inactivation treatments. Secondary test should be performed after the inactivation treatment at which time no virus should be detected in the final serum batch. These tests could be omitted if no virus is detected before inactivation treatment.
EP 5.2.4	Cell Cultures for the production of veterinary vaccines
EP 5.2.5	Substances of animal origin for the production of immunological veterinary medicinal products
Serum Neutralization (SN)	Serum virus neutralization is a serological test to detect the presence and magnitude of functional systemic antibodies that prevent infectivity of a virus.