Downstream purification of mAbs has evolved to allow the specific process for a new product to be developed largely by empirical specialization of a platform process to allow removal of impurities of different kinds. A more fundamental understanding of impurities and the product itself would provide insights into the rational design of efficient downstream processes. This work identifies and characterizes host cell protein (HCP) product-associated impurities, i.e., HCP species carried through the downstream processes via interactions with the mAb. Interactions between HCP and mAbs are characterized using cross-interaction chromatography over a range of conditions typical of those used in downstream processing. The interacting species are then identified by two-dimensional gel electrophoresis and mass spectrometry. This methodology has been applied to identify product-associated impurities in one particular purification step, namely protein A affinity chromatography, for a variety of therapeutic mAbs. The results show both the variation in HCP-mAb interactions with different mAbs, and the relative importance of product-association in protein A affinity chromatography.

Identification and characterization of host cell protein product-associated impurities in monoclonal antibody downstream processing

243rd National Meeting (2012)

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