Evaluation of process simulation as a decisional tool for biopharmaceutical contract development and manufacturing organizations

Reduction in process time due to continuous bioprocessing is appealing to biopharmaceutical contract development and manufacturing organizations (CDMOs) as it translates to an increased number of batches per year. While continuous bioprocessing can benefit clients by reducing cost of goods, end-to-end continuous bioprocessing is not practical as CDMOs must accommodate a wide range of molecules and processes. Hence, it is imperative to evaluate and customize continuous production based on client needs. This paper evaluates the application of process simulation as a decisional tool to select an appropriate downstream processing strategy. Fully continuous and hybrid (continuous Protein A operation only) downstream processing were assessed for a 2000 L fed-batch bioreactor producing 1, 5, and 10 g/L of monoclonal antibody at 40 and 200 kg production demands. Hybrid and continuous processing decreased batch duration by 20% and 60%, respectively. The largest cost reductions were observed for 5 and 10 g/L titer processes during 40 kg production. A range of factors will influence the selection of a processing method and the impact can be readily assessed using process simulation. Therefore, it is recommended that CDMOs use process simulation to ensure the most favorable processing strategy is selected.