title: The development of an industrial-scale fed-batch fermentation simulation.
abstract: This paper describes a simulation of an industrial-scale fed-batch fermentation that can be used as a benchmark in process systems analysis and control studies. The simulation was developed using a mechanistic model and validated using historical data collected from an industrial-scale penicillin fermentation process. Each batch was carried out in a 100,000 L bioreactor that used an industrial strain of Penicillium chrysogenum. The manipulated variables recorded during each batch were used as inputs to the simulator and the predicted outputs were then compared with the on-line and off-line measurements recorded in the real process. The simulator adapted a previously published structured model to describe the penicillin fermentation and extended it to include the main environmental effects of dissolved oxygen, viscosity, temperature, pH and dissolved carbon dioxide. In addition the effects of nitrogen and phenylacetic acid concentrations on the biomass and penicillin production rates were also included. The simulated model predictions of all the on-line and off-line process measurements, including the off-gas analysis, were in good agreement with the batch records. The simulator and industrial process data are available to download at www.industrialpenicillinsimulation.com and can be used to evaluate, study and improve on the current control strategy implemented on this facility.
authors.affiliation: Biopharmaceutical Bioprocess Technology Centre, Merz Court, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Control Systems Group, School of Electrical and Electronic Engineering, University of Manchester, Manchester, United Kingdom; Perceptive Engineering Limited, Vanguard House, Keckwick Lane, Daresbury, Cheshire, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Goldrick
authors.affiliation: Control Systems Group, School of Electrical and Electronic Engineering, University of Manchester, Manchester, United Kingdom.
authors.forename: Andrei
authors.initials: A
authors.lastname: Ştefan
authors.affiliation: Perceptive Engineering Limited, Vanguard House, Keckwick Lane, Daresbury, Cheshire, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Lovett
authors.affiliation: Biopharmaceutical Bioprocess Technology Centre, Merz Court, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Gary
authors.initials: G
authors.lastname: Montague
authors.affiliation: Control Systems Group, School of Electrical and Electronic Engineering, University of Manchester, Manchester, United Kingdom. Electronic address: barry.lennox@manchester.ac.uk.
authors.forename: Barry
authors.initials: B
authors.lastname: Lennox
mesh_terms: D061249:Batch Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D018533:Biomass; D019149:Bioreactors; D003198:Computer Simulation; D005285:Fermentation; D007218:Industrial Microbiology / Q000295:instrumentation / Q000379:methods*; D007700:Kinetics; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D010406:Penicillins / Q000032:analysis / Q000378:metabolism; D010408:Penicillium chrysogenum / Q000378:metabolism
chemical_list: D010406:Penicillins; D010100:Oxygen
keywords: Industrial fermentation; Kinetic modelling; Penicillin production; Simulation; Structured model