Monoclonal antibodies (mAbs) comprise a large group of marketed biologics. This means that, for each mAb therapeutic, many more have entered process development. They are, therefore, a frequent modality being tested and developed in biotech industry. With the large body of knowledge gathered on mAbs, purification platforms aiming to speed up and streamline their process development have been developed and successfully applied. However, with many mAbs entering the development, there are always challenging molecules that do not fit the platforms and require more development time and resources; they present unique issues that need to be resolved. There are different types of challenges, including limited operating space for product stability and peak splitting on the cation exchange (CEX) resins. This work describes such challenges and the ways to find solutions. First, we assessed the Protein A pool stability with respect to pH and salt in the platform operating range. We found that our mAb was stable only in the narrow range of both parameters. Next, we evaluated the CEX performance within the stable range but observed significant peak splitting phenomenon. We then investigated the impact of several factors through single variable testing and design of experiments (DOE) approach while our goal was to minimize peak splitting and maximize yield. The solutions we propose could become part of the platform approach for mAbs with limited pH and salt stability profile.<br/>

Challenging antibody purification process development: solving CEX peak splitting phenomenon

2019 Spring National Meeting

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