Ensuring Compliance: Regulatory Guidance for Virus Clearance Validation

The concern over virus contamination in the manufacture of biological therapeutics is related to viruses endogenous to the cell line (e.g., murine retrovirus) and adventitious viruses, which can be introduced during manufacturing (e.g., parvovirus). To date, biological therapeutics derived from cell lines have not been implicated in the transmission of viruses to humans. Nevertheless, to assure product safety, steps that can be shown to remove or “clear” virus should be a part of the manufacturing process for all biologics. Biopharmaceutical manufacturers are required to test and validate the effectiveness of the manufacturing process to achieve an appropriate level of virus safety. The validation approach is generally modeled after the current regulatory guidance. This application note summarizes the broad principles for assessing virus clearance of biological therapeutics.