High throughput screening (HTS) is a proven way to quickly evaluate multiple operating conditions for early development work, and is now increasingly being applied to late-stage process characterization activities. Resin lifetime studies require intensive material and labor resources at bench scale and there has not yet been a robust alternative at the high throughput scale due to limitations in the column hardware. By nature HTS chromatography columns are only intended for a minimal number of reuses. The columns typically fail due to leakage near the inlet adapter after about 10 reuses. In this study, a method of removing and replacing the inlet adapter of HTS columns without altering column integrity was developed. Column integrity was evaluated by connecting the HTS column to an AKTA system and measuring HETP and asymmetry by injecting a salt spike and measuring conductivity profiles. This method has allowed for lifetime studies to be performed at the high throughput scale. Using a TECAN robotic liquid handler, evaluation of up to 8 cleaning regimens can be evaluated in parallel to the end of resin lifetime. This allows determination of resin lifetime under optimal regeneration conditions before moving to bench and manufacturing scale, saving an extensive amount of operator time and materials, as well as building a robust design space. Additionally, by qualifying high throughput columns as small scale models, it may be possible to eliminate bench scale lifetime studies altogether.

Overcoming limitations of high throughput scale chromatography columns to facilitate the evaluation of extended resin lifetime

253rd National Meeting (2017)

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