Genentech has had direct experience with two contaminations of large-scale cell cultures by Minute Virus of Mice (MVM). No definitive source of either contamination has been identified, although the conclusions of the investigation were consistent with a raw material used in cell culture as the source. Effective analytical barriers were developed following the first contamination using polymerase chain reaction (PCR) and cell culture-based methodology for MVM, and these were employed on a routine basis. This approach was effectively used to detect and contain the second contamination, thus dramatically minimizing its impact. Close interactions with regulatory authorities were critical in the positive management of these situations.