Modern day monitoring and control challenges outlined on an industrial-scale benchmark fermentation process

This paper outlines real-world control challenges faced by modern-day biopharmaceutical facilities through the extension of a previously developed industrial-scale penicillin fermentation simulation ( Ind- PenSim ). The extensions include the addition of a simulated Raman spectroscopy device for the purpose of developing, evaluating and implementation of advanced and innovative control solutions applicable to biotechnology facilities. IndPenSim can be operated in fixed or operator controlled mode and gener- ates all the available on-line, off-line and Raman spectra for each batch. The capabilities of IndPenSim were initially demonstrated through the implementation of a QbD methodology utilising the three stages of the PAT framework. Furthermore, IndPenSim evaluated a fault detection algorithm to detect process faults occurring on different batches recorded throughout a yearly campaign. The simulator and all data presented here are available to download at www.industrialpenicillinsimulation.com and acts as a bench- mark for researchers to analyse, improve and optimise the current control strategy implemented on this facility. Additionally, a highly valuable data resource containing 100 batches with all available process and Raman spectroscopy measurements is freely available to download. This data is highly suitable for the de- velopment of big data analytics, machine learning (ML) or artificial intelligence (AI) algorithms applicable to the biopharmaceutical industry.