Viral safety and clearance evaluation--implications for process change and comparability

A key component in the development of safe cell-based biologicals is the incorporation of procedures to ensure virological safety using a three-pronged approach--raw material testing, including testing of the cell banks; incorporation of virus clearance steps in the production process; and lot-by-lot virus testing of culture harvests. During the development of a biological, changes are made to improve product quality, purity, yield, and consistency and to meet other production requirements. It is important to evaluate process changes in view of virus safety. Changes to the cell culture and purification processes may necessitate the repeat of virus testing and clearance steps to ensure that they have not been adversely affected by the changes. It is also important to evaluate the effect that column re-use has on virus clearance. The impact of process change and column re-use are described and the importance of these at various stages in development and post license is discussed.