LAUSR

Abstract Virus filtration is a critical process in the production of biotherapeutics and drug products derived by plasma fractionation. The processing steps upstream of virus removal filtration impact the filterability (throughput and flux) of process solutions. We processed mAb and plasma IgG spiked with aggregate and plasma IgG spiked with IgM by chromatography resins and examined the filterability of the output on a virus filter (Planova BioEX). The greatly reduced filterability for protein solutions with aggregate was improved by processing with specific chromatography resins, but residual amounts of high molecular weight aggregates had a marked impact on filterability. For mAb, mixed-mode AEX effectively reduced aggregate content and significantly improved filterability. Mixed-mode AEX was also effective for reducing aggregates in plasma IgG but modified CEX showed even greater improvement in filterability. The results clearly show that virus filter performance can be optimized by careful choice of column chromatography. Finally, applying the throughput and flux from the virus filter to four classical clogging models showed that mAb with aggregate and plasma IgG with IgM were best fit to the standard blocking model and plasma IgG with aggregate was best fit to the complete blocking model, suggesting that differences in solution properties result in different clogging mechanisms.