DEEP BIOSIMILARITY ASSESSMENT BY MONITORING MULTIPLE CRITICAL QUALITY ATTRIBUTES OF AN INTACT MONOCLONAL ANTIBODY DRUG USING NATIVE IEC AND SEC COUPLED TO NATIVE ORBITRAP MS

摘要

Manufacturing of innovator biologics can be successfully mimicked to produce generic "biosimilar" drug products. In order to satisfy safety and efficacy requirements, a biosimilar drug must be reasonably comparable to an innovator. Comparability is directly assessed by measuring a panel of critical quality attributes (CQAs). Recently, a multi-attribute method has been demonstrated to measure several CQAs simultaneously using LC-MS peptide mapping data. Additional CQAs, such as charge variants or size variants are conventionally monitored at the intact level using ion exchange (IEC) or size exclusion chromatography (SEC), respectively, coupled to UV detection. Native LC-MS approaches, such as SEC-MS and IEC-MS, can be inclusive with UV detection to combine the traditional gold standard chromatographic assays with accurate mass measurement to allow isoform-specific monitoring of multiple CQAs of intact therapeutic proteins.