Development and fine-tuning of a scale down model for process characterization studies of a monoclonal antibody upstream production process

Abstract

Background It has always been an objective of process development and more recently it has also become a regulatory expectation to build robustness into and demonstrate proper control of a manufacturing process, thus ensuring that the biological product meets consistently its quality attributes and specifications. This is achieved mainly through systematic process development and understanding. Once a process is locked and ahead of consistency runs at the intended commercial scale, process characterization studies (PCS hereafter) further contribute to the demonstration of process robustness and the justification of process control ranges. These studies characterize the relationship between process parameters and process performance as well as product quality attributes. For practical reasons PCS are performed in a scale down model (SDM hereafter) of the manufacturing process studied. Therefore, it is essential to establish a SDM that is representative of the commercial scale. Here we describe a road map for developing a scale down model of a cell culture process for recombinant protein production. The cell culture process modeled was a 12,000 L scale fed batch process producing a monoclonal antibody.