Miniaturized chromatography columns are now commercially available and designed for use with automated robotic liquid handling systems. These technologies allow for parallel processing of chromatographic conditions, saving time and reducing material demands. This work investigates whether miniaturized chromatography columns can be used as a high-throughput strategy for downstream process characterization. Downstream process characterization encompasses the studies that support delivery of a robust process with a better understanding of the impact of process parameters upon product quality. Typically process characterization studies utilize well established milliliter-scale chromatography scale-down models that maintain a constant column bed-height and superficial fluid linear velocity across scales, maintaining constant residence time. A proof-of-concept case study for the suitability of miniaturized columns to support process characterization evaluated a mixed-mode polishing chromatography step for a monoclonal antibody product. A Quality by Design (QbD) approach was implemented for process characterization which included a systematic risk assessment that informed experimental planning. Experiments were performed using both the miniaturized and more conventional bench scale chromatography columns. Results were evaluated by comparing chromatographic performance (step yield, elution volume, and chromatographic profile), product quality (aggregate and product host cell protein), time, and material demands. Statistical analysis indicated that both chromatography scale-down model systems were affected by the same parameters (similar trend direction and magnitude) with regards to process performance and product quality. The use of this miniaturized system resulted in eight-fold increase in experimental throughput and up to 90-fold in material savings. Verification that these miniaturized chromatography columns provide an accurate representation of manufacturing scale columns is needed. Successfully verification can potentially allow performance of process characterization on additional parameters (or combinations of parameters) that conventional scale-down model systems may not be able to as a result of resource and time constraints.

Evaluation of an automated, high-throughput, micro-scale chromatography system for process characterization

247th National Meeting (2014)

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