While viral safety is a major concern for biologics manufactured using mammalian cells, the numbers of viral contamination events reported in the literature are quite low. During a 10-year period during which biologics derived from a variety of mammalian cell culture processes were evaluated using the in vitro virus screening assay, only reovirus type 2 and Cache Valley virus were detected, and these only in biologics manufactured in Chinese hamster ovary (CHO) cells. From the literature, we know that the murine parvovirus mouse minute virus has also been detected in biologics manufactured using CHO cells. The manifestations of these viral contaminants within the biotech manufacturing processes are discussed, as are the likely sources of the contaminants and some possible approaches for mitigating the risk of future occurrences of these types of contamination.