Optimal control of a hybridoma bioreactor. Changes induced by considering by-products in the objective function

The main target in the production of monoclonal antibodies (MAbs) is reduction of operating costs. One of the pertinent challenges is improving the yield of MAbs through the reduction of secondary metabolic products. Therefore searching for an optimal nutrients supplying strategy becomes mandatory. This study is about the influence of by-products together with the dead cell concentration upon the performance of a bioreactor for MAbs production. The byproducts and the dead cell concentration are considered in the objective function for optimal control of the system. Three cases were studied: fed batch, continuous and the sequence fed batch – continuous. The optimization procedure was based upon genetic algorithms, which are applied either for the optimal glutamine set point computation for the fed batch operating mode, or the determination of the time inlet flow profile for the continuous mode, both guaranteeing the optimum monoclonal antibody production.