Abstract
Fed-batch cell culture processes is widely used in biopharmaceutical
industry for monoclonal antibodies (mAbs) manufacturing. As cell culture
platforms continue to evolve, perfusion process stand out an attractive
alternative to fed-batch process due to the high productivity,
manufacturing flexibility and low cost. In this study, the host cell
proteins (HCPs) that accumulated extracellularly in fed-batch and
perfusion process of the antibody (mAb1) were identified and quantified
using liquid chromatography-tandem mass spectrometry (LC-MS/MS),
followed by functional analysis. Due to the high viability and low cell
concentration, less HCPs were detected in steady state (SS) perfusion
process than fed-batch culture and non-steady state (NSS) perfusion. In
perfusion process of mAb1, altered distribution of charged variant
species may provide an opportunity to remove problematic HCPs, including
lipoprotein lipase (LPL). The HCP profile studies could provide guidance
on selecting the appropriate process to maintain good mAb quality for a
therapeutic antibody.
Keyword: perfusion, host cell protein, profiling, downstream process
development, polysorbate degradation