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An integrated continuous downstream process with real-time control: A case study with periodic countercurrent
Anton Löfgren1, Joaquín Gomis-Fons1,2, Niklas Andersson1
1Department of Chemical Engineering, Lund University, Lund, Sweden.
Biotechnology and Bioengineering
|January 18, 2021
Summary
This study demonstrates how integrated continuous downstream processing with real-time control enhances recombinant protein purification. The advanced system boosts productivity and yield while reducing costs and buffer consumption.
Area of Science:
- Biotechnology and bioprocessing
- Chemical engineering
- Pharmaceutical manufacturing
Background:
- Integrated continuous downstream processing offers significant advantages in reducing costs and increasing flexibility for biopharmaceutical manufacturing.
- Process analytical technology (PAT) is crucial for real-time monitoring and control of complex bioprocesses.
- Current batch processes often face limitations in productivity and efficiency.
Purpose of the Study:
- To evaluate an integrated continuous downstream process for recombinant protein purification at laboratory scale.
- To assess the effectiveness of a real-time controller in adapting to process disturbances.
- To compare the performance of the integrated continuous process against a traditional batch process.
Main Methods:
- A two-system setup featuring continuous solvent/detergent virus inactivation, periodic countercurrent chromatography, and a final polishing step was employed.
- A real-time controller was implemented to dynamically adjust the process parameters.
- A concentration disturbance was introduced to validate the controller's performance.
Main Results:
- The real-time controller enabled the process to recover from a concentration disturbance within 6 hours.
- Compared to a process without a controller, the controller improved product output per cycle by 27%, resin utilization by 16.5%, and decreased specific buffer consumption by 21%.
- The integrated continuous process demonstrated a 95% increase in productivity and a 28% increase in yield compared to the batch process, while maintaining high purity and yield.
Conclusions:
- Integrated continuous downstream processing, augmented by real-time control, significantly enhances efficiency and adaptability in recombinant protein purification.
- The implemented controller effectively manages process variations, leading to improved resource utilization and consistent product quality.
- This approach represents a substantial advancement over traditional batch methods, paving the way for more efficient and flexible biopharmaceutical manufacturing.
