Raw materials as a source of contamination in large-scale cell culture.

Large-scale cell culture operations for biotechnology products use millions of litres of complex media and gases as well as huge quantities of organic and inorganic raw materials. These raw materials must always be assumed to contain contamination by adventitious agents such as Minute Virus of Mice (MVM). Genentech has had experience in dealing with two such contaminations. Although the source of these contaminations was not positively identified, there was strong evidence to suggest that the virus entered through a raw material used in cell culture. Analytical methods that can be used to detect the presence of viruses can be used as an early warning system and as part of a strategy to devise barriers against such contamination. Methods such as a polymerase chain reaction (PCR) assay and a cell culture-based infectivity assay have been found to be efficacious in providing early detection of MVM infection. In any contamination, timely interactions with regulatory authorities are vital in minimizing delays in product manufacture.