Modeling and Simulation of Upstream and Downstream Processes for Monoclonal Antibody Production

Abstract

We present a numerical case study for modeling and simulation of upstream and downstream processes for monoclonal antibody (mAb) production. We apply a systematic and intuitive modeling methodology for an existing upstream process and downstream process. The resulting models are based on differential mass balances and kinetic expressions for the reactions and adsorption. Mass balances for the fedbatch reactor yield a model consisting of five ordinary differential equations (ODEs). The downstream process is conducted batchwise in a chromatographic column for capture of mAbs. Mass balances of the chromatographic column yield a system of partial differential equations (PDEs). The chromatographic model applies the nonlinear shrinking core adsorption isotherm model for transition between the mobile phase and the stationary phase. We apply a high-order spectral nodal continuous Galerkin scheme for spatial discretization of the chromatographic column, which result in a semi-discrete ODE formulation. The resulting simulation model, coupling the upstream and downstream processes in batchwise mAb production, can be used as a benchmark for numerical estimation, control and optimization studies.