Operator training in recombinant protein production using a structured simulator model

• An operator training simulator based on a structured compartmentalized model is presented.
• The simulator virtually trains plant operators and other process personnel in running fed-batch protein production bioprocesses.
• The transfer of process understanding, skills and performance from the simulator to the real process is shown.

Model-based operator training simulators (OTS) could be powerful tools for virtual training of operational procedures and skills of production personnel in recombinant protein processes. The applied model should describe critical events in the bioprocess so accurately that the operators’ ability to observe and alertly act upon these events is trained with a high degree of efficiency. In this work is shown how this is accomplished in a structured multi-compartment model for the production of a recombinant protein in an Escherichia coli fed-batch process where in particular the induction procedure, the stress effects and overflow metabolism were highlighted. The structured model was applied on the OTS platform that virtually simulated the operational bioreactor procedures in real or accelerated time.Evaluation of training using the model-based OTS showed that trained groups of operators exhibited improved capability compared with the untrained groups when subsequently performing real laboratory scale cultivations. The results suggest that this model-based OTS may provide a valuable resource for enhancing operator skills in large scale recombinant protein manufacturing.