For the purpose of achieving selective separation of high-molecular weight aggregates, cation-exchange chromatography remains commonly used as an intermediate or final polishing step in most well-established downstream platform processes for mAb purification. Due to wide variation in molecular attributes and aggregation properties of monoclonal antibodies, however, establishing a scaleable cation-exchange unit operation normally requires significant case-by-case bench-scale resource and effort that can expand early-phase development timelines and potentially slow down progression of an asset into clinical manufacturing. In this work, following examples, we present a flexible development workflow that incorporates the use of high-throughput 96-well-plate and conventional chromatography methodologies for rapid step development and characterization of aggregate removal limits, leveraging established linear gradient elution theoretical and experimental approaches. The integration of supporting analytical biochemical characterization methods, as well as the use of accelerated degradation methods for the preparation of process-relevant aggregates suitable for selectivity limit studies will also be discussed.

Accelerating the early-phase portfolio: Platform or first-intent experimental approaches for cation-exchange chromatography and the removal aggregates

247th National Meeting (2014)

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