Packing of large-scale chromatography columns with irregularly shaped glass based resins using a stop-flow method

Rigid chromatography resins, such as controlled pore glass based adsorbents, offer the advantage of high permeability and a linear pressure-flow relationship irrespective of column diameter which improves process time and maximizes productivity. However, the rigidity and irregularly shaped nature of these resins often present challenges in achieving consistent and uniform packed beds as formation of bridges between resin particles can hinder bed consolidation. The standard flow-pack method when applied to irregularly shaped particles does not yield well-consolidated packed beds, resulting in formation of a head space and increased band broadening during operation. Vibration packing methods requiring the use of pneumatically driven vibrators are recommended to achieve full packed bed consolidation but limitations in manufacturing facilities and equipment may prevent the implementation of such devices. The stop-flow packing method was developed as an improvement over the flow-pack method to overcome these limitations and to improve bed consolidation without the use of vibrating devices. Transition analysis of large-scale columns packed using the stop-flow method over multiple cycles has shown a two- to three-fold reduction of change in bed integrity values as compared to a flow-packed bed demonstrating an improvement in packed bed stability in terms of the height equivalent to a theoretical plate (HETP) and peak asymmetry (A(s)).