In the past, viruses were cultured in vivo, as in the production of smallpox virus on the brains of mice. Since 1949, primary cell cultures have largely been produced using in vitro methods. In vaccine production, mice are used most extensively for quality control. Vaccine formulations include constituents such as living tissues, viruses and bacteria. Thus, since all vaccine batches are not the same, their content and effects must be tested regularly at selected stages of production to monitor safety, as required by federal regulations.
Quality control is the most essential aspect of vaccine production.
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.