Typically performed in later stages of the drug development cycle and after process scale-up to the commercial scale, scale-down studies validate the extended reuse of chromatography resins and form the basis for establishing a recommended resin lifetime. However, to expand process knowledge and avoid late process changes, gaining an understanding of factors that may limit or impact resin life-time earlier in the development cycle, well ahead of process scale-up is highly desirable. In this work, we develop high-throughput 96-well plate and on-column methodologies to mechanistically explore factors that can impact column degradation and resin lifetime. Using commercially available Protein A chromatography media together with a well-characterized monoclonal antibody expressed in CHO as a model system, we simulate extended cycling through batch exposure to high-alkali and cell culture broth fouling conditions. Equilibrium adsorption behavior and mass transport properties of cycled and treated resin are studied. Based on these measurements, the development of a predictive mechanistic model of chromatographic behavior as a function of cycle number is discussed and tested against results obtained from a conventional 50-cycle scale-down resin lifetime study.

High-throughput approaches for early assessment of chromatography resin lifetime

247th National Meeting (2014)

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