Evaluating and modeling the impacts 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
filterability of process solutions on virus removal filters is largely
dependent on preceding downstream process steps, and column
chromatography can have a particularly large impact on the throughput
and flux of virus filtration. Filterability (throughput and flux) on
Planova BioEX was greatly reduced for mAb and plasma IgG spiked with
aggregate, and filterability improvement achieved by processing with
chromatography resins (modified CEX, mixed-mode AEX and normal AEX
column) was specific to protein solution. The various protein solutions
spiked with aggregate showed distinct solution characteristics and by
using the resulting filtration volume and flow rate, experimental and
calculated filtration parameters were compared and evaluated with four
clogging models: cake filtration, intermediate blocking, standard
blocking and complete blocking. Effective purification of feed solutions
by column chromatography has the capability to improve virus filtration
processes. Further, the application of filtration parameters to the
appropriate clogging model makes it possible to extrapolate filtration
behavior to larger processing volumes.