Human lives have been lost when quality control has not been sufficient. For example, thirteen children died in 1901 from tetanus, after receiving doses of diphtheria antitoxin which had been prepared from horse serum contaminated with the tetanus bacilli. The experimental animal is still the main indicator in the detection of desirable and undesirable activities of newly produced vaccine batches. Mice are injected with concentrated crude or purified product and observed for clinical symptoms. Many can be detected by in vitro testing, but some still require animal testing.
Cell culture is used in many cases.
Rabies virus causes clinical symptoms or death in mice when administered intracerebrally. The two groups are then compared for the development of tumors. Multiple doses of the product are administered to two animals of the intended species, with observation for development of symptoms during a specified period. Usually it is possible to use in vitro techniques. When it is necessary to use in vivo techniques, the specific antibodies must be demonstrated in the animal after immunization, either by challenging the animal with the virulent microorganism or by a serum-antibody assay.