Lab-Scale Continuous Biomanufacturing: A Tool for Process Development With Adaptive Strategies for Capture and Virus...

Area of Science:

• Biotechnology and Bioprocessing
• Pharmaceutical Manufacturing
• Process Intensification

Background:

• Monoclonal antibodies (mAbs) are crucial therapeutics for various diseases.
• The growing mAb market necessitates advanced process intensification technologies.
• Current biomanufacturing often relies on batch processes, limiting throughput.

Purpose of the Study:

• To introduce and evaluate a novel lab-scale integrated continuous biomanufacturing (ICB) process.
• To demonstrate adaptive control strategies for process variations.
• To assess the efficiency of continuous downstream processing for mAbs.

Main Methods:

• Development of a lab-scale ICB process combining perfusion upstream cultivation and continuous downstream processing.
• Utilized membrane adsorbers (RC-BioSMB) for continuous chromatography capture.
• Implemented a novel continuous virus inactivation (VI) approach.
• Operated the process continuously for 4 days with adaptive flow rate control.

Main Results:

• Achieved a high overall yield of 88% during the 4-day continuous operation.
• Demonstrated effective removal of host cell proteins (3.4 log) and DNA (2.9 log).
• Successfully adapted flow rates to address upstream process variations (titer, permeate flow rate).

Conclusions:

• The lab-scale ICB process is a viable tool for process development and intensification.
• Continuous downstream processing with adaptive control ensures consistent mAb purification.
• The developed ICB process offers high yield and significant impurity reduction for mAb production.