Automated Online-Sampling Multidimensional Liquid Chromatography with Feedback-Control Capability as a Framework for...

Area of Science:

• Biopharmaceutical manufacturing
• Analytical chemistry
• Process analytical technology (PAT)

Background:

• Continuous manufacturing of monoclonal antibodies (mAbs) requires robust real-time monitoring.
• Traditional offline sampling for liquid chromatography (LC) is time-consuming and infrequent.
• Characterizing mAb quality attributes like aggregation and charge variants is crucial.

Purpose of the Study:

• To develop an automated online multidimensional LC workflow for real-time bioprocess monitoring.
• To streamline measurements of mAb concentration and critical quality attributes.
• To enable automated data export and feedback control for multiple bioreactors.

Main Methods:

• Implementation of an automated online sampling system integrated with multidimensional LC.
• Development of a streamlined analytical framework for automated data processing.
• Utilizing readily available LC technology for real-time analysis and control.

Main Results:

• Significant reduction in data turnaround time from weeks to hours.
• Increased data points per bioreactor, enhancing process understanding.
• Demonstrated accurate results for mAb concentration, aggregation, and charge variants.
• Minimized labor and manual intervention through automation.

Conclusions:

• The developed automated online LC workflow effectively enables real-time monitoring of biopharmaceutical processes.
• This approach significantly improves throughput and data turnaround time for mAb production.
• The framework supports enhanced process understanding, control, and quality assurance.