Integrated design of biopharmaceutical manufacturing processes: Operation modes and process configurations for monoclonal antibody production

Abstract

Monoclonal antibodies are leading the growing biopharmaceutical markets. To sustain the increasing demand, manufacturing processes should be optimized to increase efficiency and flexibility. This work investigates the impacts of the application of single-use equipment in batch, continuous, and hybrid scenarios. Operating costs and time are compared at different production scales from clinical to commercial manufacturing for individual unit operations and for the final integrated scenarios. A modified kinetic model is presented for the main cultivation unit. The model is validated using experimental data from literature and from a pilot facility using Chinese hamster ovary cells. Integrated scenarios with fed-batch cultivation and continuous capture have the lowest operating costs. The selection of operating modes across production scales is discussed along with further considerations for the design of integrated processes. The presented models could be used for the development of process design, control, and scheduling efforts for achieving sustainable biopharmaceutical manufacturing.