Computer modelling and simulation for the design of integrated downstream bioprocesses

Simulation is a powerful tool for accelerating bioprocess design. This paper demonstrates the use of simulation to explore the nature and impact of the interactions that exist in a typical bioprocess for the recovery of a labile intracellular protein. In order to achieve acceptable process designs an integrated approach must be adopted. Data from a continuous fermentation, with proven models for cell harvesting, cell disruption, cell debris removal, and precipitation have been integrated and used to demonstrate the consequences of different process designs and operating decisions on the resulting process performance. The trade-off between product recovery and purity for a range of operating conditions has been represented through a window of operation, showing how process conditions must be modified in order to maintain process performance. This ability to predict process performance, including the impact of the various interactions is essential before embarking on rigorous bioprocess sequence design and optimisation for industrial application.