Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical Modelling

Fed-batch and perfusion bioreactors are commonly used in biopharmaceutical production. This study applies mathematical models to investigate the influence of substrate concentration in the media added (Sm), operating substrate concentration in the bioreactor (S), and bioreaction time on the performance of both bioreactors. The performance parameters are titer, productivity, product yield, wasted substrate, and mean product residence time. The difference between the substrate concentration in the media and the operating substrate concentration has a major impact on performance parameters. For a fixed S, operating at higher values of Sm is more beneficial to both fed-batch and perfusion performance. Higher productivities are obtained in perfusion, and mean product residence times are shorter. Furthermore, perfusion can obtain titers comparable to fed-batch when operated at similar substrate concentrations. All this suggests that perfusion is more advantageous. It is advantageous to operate the bioreactors over a longer bioreaction time. However, for fed-batch bioreactors, there exists an optimal time after which there is a major progressive reduction in productivity.