In recent years, continuous chromatography has emerged as an enabling technology for process intensification, e.g. through increased flexibility, enhanced resin lifetime utilization and decreased buffer consumption. Increased resin capacity usage through overloading is often regarded as a key feature of the technology, but what level of overloading is appropriate in a given situation is not always clear. Here we present a work where the limits for overloading with two columns in the loading zone are explored experimentally in a capture step of monoclonal antibodies. In this study, two columns packed with protein A chromatography resin were connected in series, and loaded with a model mAb until breakthrough was observed on the second column. This was performed for titers of 1.5, 4.0 and 9.0 g/L, and residence times of 2, 3 and 4 minutes. The experimental output was used to predict the available breakthrough levels for different combinations of titer and residence time. Verification runs were subsequently performed on a continuous chromatography system equipped with four columns. The obtained results showed no visible breakthrough on the second column at loading up to the predicted levels, and no loss of material could be measured. In addition, productivity modelling based on the obtained experimental results was performed to investigate the theoretical implications of the available breakthrough levels, and how they can influence the optimal column set-up for different combinations of titer and residence time. We will also share a case study of continuous chromatography being implemented in the Biopharma industry as one approach to achieve increased process efficiency.

Exploring overloading and productivity in continuous chromatography

2019 Spring National Meeting

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