(67e) Evaluating the Potential of Miniature Scale Chromatography Process Characterization to Support Biomanufacturing Strategies and Regulatory Filings

High throughput downstream chromatography techniques such as resin slurry plates and miniature columns have been well described and implemented for biologics research, discovery, and early process development applications. These techniques have seen relatively little application in late stage development areas, though, mainly due to the necessity of qualified scale-down models and increased precision in this space that is required for regulatory acceptance. However, an automated parallelized scale-down approach could potentially provide much needed reductions in time and resources for activities like formal process characterization where representative data across many conditions is needed to support regulatory filings.

This talk will highlight some of the differences and challenges for utilizing high throughput techniques in late stage development compared to earlier stages of process development and will suggest potential applications in manufacturing space. For miniature columns, theoretical limitations such as transport phenomena and wall effects will be discussed. Practical considerations like pulse testing, pooling strategies, and resin reuse will also be presented. Case study comparisons of formal process characterization strategies for miniature scale and traditional lab scale as well as direct scale-down comparisons across four orders of magnitude will be shown. Finally, recommendations for the ultimate limitations of miniature columns will be provided to suggest future state directions and applications in late stage development spaces.