Dynamic optimisation and comparative analysis of fed-batch and perfusion bioreactor performance for monoclonal antibody (mAb) manufacturing

Abstract

Integrated continuous bioprocessing (ICB) holds great promise towards achieving higher efficiency, a critical target for ensuring the advent of biopharmaceutical manufacturing. Culture productivity must be drastically improved to reduce production cost projections, especially in comparison to traditional fed-batch process platforms (Pollock et al., 2017). The present paper explores the benefits of continuous bioprocessing, employing dynamic optimisation of upstream fermentation for production of monoclonal antibodies (mAb). Industry-standard cultures of hybridoma cells have been used to develop models of mAb bioreactor operation. These models track several state variable trajectories of interest, including profiles for viable cells, substrates, by-products and the target mAbs product. Dynamic optimisation of both operation modes (fed-batch and perfusion bioreactors) has been undertaken, with the objective function of maximizing the final mAb product titers through optimal feeding strategies in two reactor types for improved culture proliferation. The clear differences in terms of reactor space (capital costs) and time (operating costs) are highlighted, and a fair comparison basis is established so as to evaluate performance. For both modes of operation, a technoeconomic analysis illustrates the implications of optimal bioreactor designs, with a view to systematic decision-making in mAb ventures.