The high cost of Protein A chromatography resins drives the need to improve the current process to achieve maximum productivity while maintaining high resin utilization. Two strategies were employed for a monoclonal antibody on MabSelect SuRe resin in this work. The first Strategy is “super batch”, which we utilize a single short bed column with rapid cycling to increase productivity, combined with variable load flow rates to enhance resin capacity utilization. The second strategy is continuous multi-column chromatography process. In this mode, as multiple columns are connected in loading zone, high resin utilization can be achieved with a relatively short load residence time, therefore leading to both higher resin utilization and higher productivity.<br/>To optimize the Protein A chromatography process with the two strategies, chromatography general rate model coupled with Langmuir adsorption isotherm was used to simulate protein breakthrough curves for batch mode with dual or triple flow rates, as well as for continuous mode where columns are connected in series. In batch mode, the optimized variables include flow rates in different load phases and switch time in between. In continuous mode, the optimized variables include protein load amount, load residence time, column number in the loading zone and non-loading zone. The model results with optimized variables were verified by experiments. Overall, both manufacturing strategies result in greatly enhanced productivity compared to traditional batch process. The productivity and performance comparison of the above two strategies will be discussed in detail in the context of different upstream manufacturing scenarios.<br/>

Optimization of batch and continuous multi-column protein A chromatography with mechanistic model and experiments

2019 Spring National Meeting

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