Towards the Optimisation of the Production of Monoclonal Antibodies

Abstract A systematic research strategy is proposed for the control and optimisation of monoclonal antibody (MAb) production from mammalian cell cultures. This approach consists of a novel model-based methodology for the design of dynamic experiments to minimise the required experimentation and to improve parameter precision, as well as model-based control and optimisation techniques. This framework is to be applied to a novel integrated, unstructured, dynamic model, which incorporates growth kinetics, cell death, cell metabolism, cell cycle, and MAb synthesis, glycosylation, and production; the simulation results of which demonstrate its satisfactory predictive capability. For the purpose of unique parameter estimation, global sensitivity analysis is performed on the proposed model, through which the parameters with significant impact on the model output, i.e. MAb concentration, are identified