Reduction of Lipase Activity in Product Formulation
Downstream processing of monoclonalantibodies (mAbs) hasevolved to allow the specific process for a new product to be developed largelyby empirical specialization of a platform process that enables removal ofimpurities of different kinds. A more complete characterization of impuritiesand the product itself would provide insights into the rational design ofefficient downstream processes. This work identifies and characterizes hostcell protein (HCP) product-associated impurities, i.e., HCP species carriedthrough the downstream processes via direct interactions with the mAb.Interactions between HCP and mAbs are characterized usingcross-interaction chromatography under solution conditions typical of thoseused in downstream processing. The interacting species are then identified bytwo-dimensional gel electrophoresis and mass spectrometry. This methodology hasbeen applied to identify product-associated impurities in one particularpurification step, namely protein A affinity chromatography, for fourtherapeutic mAbs aswell as the Fab and Fc domains of one of these mAbs. The results show both the differencesin HCP-mAbinteractions among different mAbs, and the relative importance of productassociation compared to co-elution in protein A affinity chromatography
United States
Patent Pending
美國
