Transfer of a bioprocess into a commercial facility requires packing of Biorad’s CHT™ ceramic hydroxyapetite resin into a one meter Pall Resolute® chromatography column via a pack-in-place method. This presents a unique challenge: a high flow rate (40 L/min) through the column packing nozzle holes is required to achieve the target packing pressure. The impact of these process conditions on resin fine generation and column performance (pressure) for this shear-sensitive resin is not well understood. To understand this risk, a collaborative study among Merck, Biorad, and Pall was completed. A 30% slurry of Type I 40um CHT™ resin prepared in 0.5M NaOH was immediately passed through a Resolute® pack-in-place nozzle five times at 40 L/min. Samples of the prepared slurry and slurry after one, three, and five passes through the Resolute® nozzle were analyzed. Fines and shifts in particle size distribution were evaluated across multiple methods: Micro-Flow Imaging, environmental scanning electron microscopy, and laser diffraction. Optical microscope imaging of the slurry samples was performed for qualitative analysis. Lab scale 2.5cm diameter columns were packed with resin samples and six column volumes of 0.5M NaOH were passed through each column to evaluate the impact of potential fine generation on column pressure profiles. Across all five methods utilized, there was no clear trend in fine generation with respect to nozzle passes. Results from this study indicate that flow rates up to 40 L/min of a 30% CHT™ slurry through a Pall Resolute® column nozzle does not have a discernable impact on CHT™ fine generation and column pressure performance.

Packing CHT™ resin in a one meter pack-in-place Pall Resolute® manual column: Understanding the impact of shear on fine generation and column pressure performance

255th National Meeting (2018)

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