Novel spiking methods developed for anion exchange chromatography operating in a continuous process

Area of Science:

• Biopharmaceutical Manufacturing
• Process Engineering
• Virology

Background:

• Transitioning from batch to continuous processing in biopharmaceuticals offers advantages but complicates viral clearance demonstration.
• Continuous processing generates fluctuating column outputs, requiring careful consideration for viral clearance study design.
• Traditional viral clearance studies using in-line spiking in downscaled continuous systems are complex and require specialized expertise.

Purpose of the Study:

• To develop and evaluate an alternative method for assessing viral clearance in continuous biopharmaceutical manufacturing.
• To investigate the impact of different virus introduction methods on viral clearance in a continuous chromatography step.
• To demonstrate the robustness of anion exchange chromatography in continuous processing for viral clearance.

Main Methods:

• Evaluated a flow-through anion exchange chromatography step in a monoclonal antibody (mAb) manufacturing process.
• Utilized a standard chromatography system and five distinct methods for introducing mouse minute virus.
• Compared viral clearance under conditions mimicking continuous processing variability (concentrated peaks) versus traditional batch loading.

Main Results:

• Viral clearance of mouse minute virus was consistently similar across all five tested introduction methods.
• Both concentrated peak loading (simulating continuous flow) and homogeneous batch loading yielded comparable viral clearance results.
• Anion exchange chromatography demonstrated robust viral clearance performance under evaluated conditions.

Conclusions:

• An alternative, simplified approach for evaluating viral clearance in continuous biopharmaceutical processes was successfully demonstrated.
• Anion exchange chromatography is a robust unit operation for viral clearance in continuous manufacturing, irrespective of loading pattern.
• The findings facilitate more practical viral clearance studies for continuous biopharmaceutical production.