Evolving Needs For Viral Safety Strategies in Continuous Monoclonal Antibody Bioproduction

This chapter reviews the techniques developed to limit viral contamination and propagation risk in classical batch monoclonal antibody production processes and how they can be applied to the new and evolving continuous production processes. The specific parameters of continuous/connected processing vary from manufacturer to manufacturer. These differences in processing require developers of biomanufacturing processes to be mindful of the impact of these process modifications on virus safety risk mitigation activities. Biomanufacturers are required to show that their production processes are able to robustly remove significant amounts of virus. Pharmaceutical manufacturers usually target a log reduction value of 12-18 over an entire purification process, through elimination or inactivation steps. With either batch/fed-batch or perfusion modes of bioreactor operation, it is important to know how much endogenous virus impurity is present to ensure that the downstream process is appropriately designed to handle the inactivation and or removal of potential virus to levels required by relevant regulatory agencies.