An Optimisation-based Approach for Biopharmaceutical Manufacturing

This work addresses the integrated optimisation of upstream and downstream processing strategies in the manufacturing processes of monoclonal antibodies (mAbs). In the upstream processing (USP), the bioreactor sizing strategies are considered, while in the downstream processing (DSP), the chromatography sequencing and column sizing strategies are optimised, including the decisions on the resin selection, the number of columns, the column diameter and bed height, and number of cycles per batch. Also, the product's purity requirement is considered, in which the host cell protein level in the final product is examined. A mixed integer linear programming (MILP) model is developed with the objective function to minimise the annual total cost of goods (COG), involving both direct and indirect costs. Finally, an example with different USP and DSP ratios are studied.