The Development of a Simulation to Address the Real Challenges Associated with Industrial Scale Penicillin Production

This paper presents a simulation of an industrial scale filamentous fermentation; the simulation focuses on modeling a 120,000 litre Penicillium chrysogenum batch process. The simulation attempts to address many of the challenges that that are faced by industrial scale filamentous fermentations; these include the control of dissolved oxygen concentration above its critical value and also controlling substrate feed to an optimum trajectory. Previous unstructured models, that didn't consider the changing morphology of Penicillin fermentations, failed to adequately model the historical Penicillin production batch data presented here. This simulation extends previous structured models by including extra process variables such as gas inlet pressure and viscosity, which are shown to have a significant effect on the control strategy of these large-scale fermentations. The accuracy of the model is verified by successfully predicting both the Penicillin and dissolved oxygen concentration using the input data from two industrial 120,000 litre Penicillium chrysogenum batch fermentations. The overall aim of the simulation is to provide an improved test bed for fed-batch Penicillin fermentations that can be used for process monitoring, control and optimization studies.