Cells may have latent or persistent virus infection (e.g., herpesvirus) or endogenous retrovirus which may be transmitted vertically from one cell generation to the next, since the viral genome persists within the cell. Such viruses may be constitutively expressed or may unexpectedly become expressed as an infectious virus. Viruses can be introduced into the MCB by several routes such as: (1) Derivation of cell lines from infected animals; (2) use of virus to establish the cell line; (3) use of contaminated biological reagents such as animal serum components; (4) contamination during cell handling.

Adventitious viruses can be introduced into the final product by several routes including, but not limited to, the following: (1) Use of contaminated biological reagents such as animal serum components; (2) use of a virus for the induction of expression of specific genes encoding a desired protein; (3) use of a contaminated reagent, such as a monoclonal antibody affinity column; (4) use of a contaminated excipient during formulation; and (5) contamination during cell and medium handling. Monitoring of cell culture parameters can be helpful in the early detection of potential adventitious viral contamination.