Model predictive control for steady-state performance in integrated continuous bioprocesses.

Perfusion bioreactors are commonly used for the continuous production of monoclonal antibodies (mAb). One potential benefit of continuous bioprocessing is the ability to operate under steady-state conditions for an extended process time. However, the process performance is often limited by the feedback control of feed, harvest, and bleed flow rates. If the future behavior of a bioprocess can be adequately described, predictive control can reduce set point deviations and thereby maximize process stability. In this study, we investigated the predictive control of biomass in a perfusion bioreactor integrated to a non-chromatographic capture step, in a series of Monte-Carlo simulations. A simple algorithm was developed to estimate the current and predict the future viable cell concentrations (VCC) of the bioprocess. This feature enabled the single prediction controller (SPC) to compensate for process variations that would normally be transported to adjacent units in integrated continuous bioprocesses (ICB). Use of this SPC strategy significantly reduced biomass, product concentration, and harvest flow variability and stabilized the operation over long periods of time compared to simulations using feedback control strategies. Additionally, we demonstrated the possibility of maximizing product yields simply by adjusting perfusion control strategies. This method could be used to prevent savings in total product losses of 4.5-10% over 30 days of protein production.