Model-based Optimization for Laboratory-Scale Upstream Processing in Monoclonal Antibody Production

The production of monoclonal antibodies (mAbs) is a complex pharmacological process involving upstream and downstream chains, focusing on mAbs production and purification, respectively. This paper presents a process optimization based on an end-to-end mechanistic model for the upstream process chain to enhance the production of mAbs. Upstream processing considers cell expansion, cell production, and primary harvesting steps by filtration. The optimization results offer users the optimal initial concentrations of the medium in the bioreactors, the duration of the cultures, the feed flow rate profiles, and the permeate flow profile in the filtration operation. Simulations incorporating interconnected reactors and process constraints led to optimized initial media concentrations and feed flow profiles, resulting in a 25% increase in mAb production compared to baseline conditions.