The development of an industrial-scale fed-batch fermentation simulation.

Area of Science:

• Biotechnology
• Chemical Engineering
• Process Systems Engineering

Background:

• Industrial-scale fed-batch fermentation is crucial for producing pharmaceuticals like penicillin.
• Accurate process simulation is essential for optimizing bioreactor performance and control.
• Existing models may not fully capture the complex environmental and chemical dynamics of large-scale penicillin production.

Purpose of the Study:

• To develop and validate a mechanistic simulation of industrial-scale penicillin fermentation.
• To create a benchmark for process systems analysis and control studies.
• To provide a downloadable resource for evaluating and improving fermentation control strategies.

Main Methods:

• Developed a mechanistic simulation based on a structured model of Penicillium chrysogenum fermentation.
• Extended the model to incorporate key environmental factors (dissolved oxygen, viscosity, temperature, pH, CO2).
• Included the impact of nitrogen and phenylacetic acid concentrations on biomass and penicillin production rates.
• Validated the simulation using historical data from a 100,000 L industrial bioreactor, comparing predicted outputs with on-line and off-line measurements.

Main Results:

• The simulation accurately predicted on-line and off-line process measurements, including off-gas analysis.
• Model predictions showed good agreement with industrial batch records.
• The developed simulator serves as a reliable tool for analyzing and controlling penicillin fermentation.

Conclusions:

• The validated mechanistic simulation provides a robust benchmark for industrial penicillin fermentation.
• The simulator and associated data are available for research and development to improve process control.
• This work facilitates the evaluation and enhancement of control strategies in large-scale biopharmaceutical manufacturing.