Demonstrating viral clearance of a downstream process is a requirement for drug candidates such as monoclonal antibodies (mAbs) that proceed to phased clinical trials. Due to the specialized nature of viral clearance studies, these studies are often outsourced to dedicated companies, making this a costly process. This expense pushes these studies off until absolutely necessary and thus processes are not optimized for viral clearance during development. Resin manufacturers provide viral clearance data for their resins under “typical” industry conditions. These vendor studies give a rough understanding of the expected viral clearance capability of the resin, but until a complete study modeled to the final process has been performed, the true viral clearance capability remains unknown.

Anion exchange chromatography (AEX) is a well-established downstream processing step in the manufacturing of biologics and known as a good contributor of overall viral clearance of the downstream process. However, it is not clear why some processes do not realize the expected viral clearance levels achieved by other molecules under similar conditions. In this study, Bristol Myers Squibb partnered with Thermo Fisher Scientific to perform a design of experiment (DoE) approach to further probe the understanding of viral clearance during AEX chromatography.

During this webinar a novel DoE approach, using Minute Virus of Mice (MVM) is presented. The study was performed to explore the viral clearance operating space of Thermo Scientific™ POROS™ HQ resin by including design factors such as load pH, conductivity, virus concentration and varying physical and chemical properties of three mAbs. The outcome of the study promotes newly gained awareness on viral clearance during AEX chromatography and will help promote improved effectivity and rigor of viral clearance at this step.

Learning points:

• Discover how a novel DoE approach is valuable in furthering our understanding of viral clearance during AEX chromatography
• Understand how conventional factors of load pH and conductivity and their relationship to a molecule’s net charge and pI are insufficient in predicting the viral clearance performance during AEX chromatography
• Learn more on our proposal of a virus co-elution mechanism based on mAb-virus interactions to explain the strong prediction of viral clearance performance trends shown in this study