Effect of mixed-mode and surface-modified column chromatography on virus
filtration performance
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 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. 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
was 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.