Converting a mAb downstream process from batch to continuous using process modeling and process analytical...

Area of Science:

• Biopharmaceutical Manufacturing
• Chemical Engineering
• Process Intensification

Background:

• The biopharmaceutical industry is shifting from traditional batch manufacturing to continuous processes to boost productivity and reduce costs.
• Monoclonal antibody (mAb) production relies heavily on downstream processing, which traditionally uses batch methods.

Purpose of the Study:

• To convert a batch mAb downstream process into an integrated continuous process.
• To achieve process intensification and automation for improved efficiency.

Main Methods:

• Integrated continuous downstream processing combining protein A chromatography and ultrafiltration/diafiltration.
• Implementation of surge tanks for continuity and automated control systems for pH, conductivity, and load mass using Process Analytical Technology (PAT).
• Model-based simulation for optimizing continuous capture loading conditions and in-line protein quantity monitoring for cation exchange chromatography (CEX).

Main Results:

• Achieved 21% resin capacity utilization and 28% productivity improvement in the continuous capture process compared to batch.
• Demonstrated automatic load mass control for CEX with <1.3% deviation from off-line analysis.
• Reduced total process time from 4 days to under 24 hours, with an overall productivity of 23.8 g mAb/day.

Conclusions:

• Successfully converted a batch mAb downstream process to a continuous one, maintaining comparable yield and quality.
• The developed continuous process offers significant improvements in productivity and processing time.
• This work provides a valuable reference for implementing continuous manufacturing in similar biopharmaceutical processes.