Integrated process consisting of column chromatography followed by virus
filtration for plasma IgG and mAb purification at constant flow rate:
analysis of filtration behavior using clogging models and viral
clearance tests
Abstract
We evaluated filtration behavior and virus removal capability for a mAb
and plasma IgG under constant flow rate directly following flow-through
column chromatography in an integrated process. For mAb solution with
quantified host cell protein (HCP) content processed in flow-through
mode on in-series mixed-mode AEX and modified CEX columns connected to
the Planova BioEX filter (pool-less), HCP logarithmic reduction value
(LRV) of 2.3 and 93.9% protein recovery were achieved for the process.
Filtration behavior for 5 to 15 mg/mL plasma IgG run at flux of 10 to
100 LMH to 100 L/m2 throughput on Planova BioEX filters showed similar
behavior across the protein concentrations tested although filtration
pressure increased with throughput at 50 LMH and above, indicating the
suitability of lower flux processes for continuous processing. Comparing
both plasma IgG and mAb filtration behavior to four clogging models
showed little difference in fit among the models, but with slightly
better fit to the cake filtration model. Viral clearance tested by
in-line spiking X-MuLV or MVM into purified plasma IgG showed robust
removal at low flux. Integrating the Planova BioEX filter into
continuous processes with column chromatography can achieve efficient
downstream processing with reduced footprint and process time.