To ensure lot-to-lot consistency, the control of raw materials such as chromatographic media is important, since their variation can directly affect both, the final biopharmaceutical product and the process.<br/>Since the final variance is the sum of variation from all steps involved, the process itself has to have “ability…to tolerate variability of materials and changes of the process and equipment without negative impact on quality” (according to ICH Q8/ R2). Thus, the manufacturer needs to understand all critical attributes of raw materials and moreover how to control the variability to ensure consistent supplies.<br/>In this work, the preparative separation of charge variants of a monoclonal antibody by using cation exchange (CIEX) chromatography prove challenging, as the isoform pattern and the yield of the step presumably depends on a combination of properties of the chromatography medium and the process.<br/>Thus, data was collected from different scales by applying different media lots. Afterwards, a statistical model for assessing potential of different CIEX lots to separate the charge variants according to process specifications was developed. On the basis of that, potential critical attributes of the CIEX medium and the process responsible for the observed variations were investigated. The primary rationale is to achieve long term robustness of the CIEX step for separation of charge variants of this monoclonal antibodies by concomitantly optimizing the yield. In addition, a methodology for fast and advanced characterization of different chromatographic media lots to support a robust manufacturing process at large scale is aimed.<br/>

Ensuring long term robustness of a CIEX chromatographic step for separation of charge variants with optimized yield

249th National Meeting (2015)

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