ABSTRACT
An overview of the in vivo assays currently performed to test for the presence of adventitious contaminants is available. Retrospective validation data have been reviewed. Assay problems specifically related to the testing of vaccine viral stocks and cell substrates may be discussed.
Subject(s)
Drug Contamination/prevention & control , Viruses/isolation & purification , Viruses/pathogenicity , Animals , Cell Culture Techniques/methods , Chick Embryo , Guinea Pigs , Humans , Mice , Reproducibility of Results , Yolk SacABSTRACT
The Trasylol manufacturing process was investigated with respect to its capacity for the inactivation/removal of infectivity causing bovine spongiform encephalopathy (BSE). Four process steps were selected for this investigation and scaled down to laboratory scale. Authentic samples of bovine lungs used in the Trasylol manufacturing plant were taken and spiked in laboratory scale experiments with high infectious titres of the rodent adapted scrapie strain ME 7 which served as model for BSE. After performing the respective process steps the output samples collected were tested in C57BL mice carrying the Sinc gene. An overall reduction of the infectious agent in the order of 18 log10 was observed, indicating a very high capacity of the Trasylol process for the inactivation/removal of the BSE/scrapie agent. The discussed safety strategy for the product leads to the conclusion that Trasylol is BSE safe.
Subject(s)
Aprotinin/chemical synthesis , Encephalopathy, Bovine Spongiform/virology , PrPSc Proteins/pathogenicity , Animals , Cattle , Encephalopathy, Bovine Spongiform/pathology , Mice , Mice, Inbred C57BL , Thalamus/pathologyABSTRACT
Sendai virus is one of the more prevalent and serious virus infections of rodents. Infection was found in 66% of the mouse, 63% of the rat, 83% of the hamster, and 44% of the guinea pig colonies examined. Twenty-four inbred and outbred strains of mice were tested for their sensitivity to lethal Sendai virus infection. The 129/J mice tested were approximately 25,000-fold more sensitive than SJL/J mice; however, both mouse strains were similarly permissive in support of viral replication in their lung tissues. Histopathological studies revealed that whereas lesions in both sensitive and resistant mice were qualitatively similar, the lesions in the more sensitive 129/J mice appeared earlier, were much more extensive, and persisted longer than in the resistant SJL/J mice. These results suggest that the observed variance in sensitivity is not the result of a genetic restriction on virus infection and replication but rather is the result of a physiological factor(s) possibly related to some aberration of strain difference in the humoral or cell-mediated immune response.
