This work presents a novel strategy for primary recovery of a monoclonal antibody from CHO cell culture, allowing for a robust 2-column process. This strategy includes harvest treatment followed by weakly charged depth filtration. The results demonstrate that the strategy is not only very effective in reducing impurities including host cell protein, DNA, and product aggregates, but also significantly improves the depth filter throughput. Additionally, the recovery step has a profound impact on the subsequent downstream process, with process impurity levels in the Protein A / viral inactivated pool already meeting target bulk drug substance acceptance criteria, and the reduction in product aggregates allowing for a cation exchange polishing step instead other options undesirable from a manufacturability viewpoint. Results from a full factorial DOE study (N≥3) demonstrate that the process is consistent and robust across a range of harvest treatment and depth filtration operating conditions. An additional study with different harvest feed streams further demonstrates process robustness, while successful pilot-scale (50L, 500L) runs demonstrate the scalability of the process.

Strategy for primary recovery of a mAb employing harvest treatment and depth filtration

249th National Meeting (2015)

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