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