Monoclonal antibodies are the most successful and prominent products in the pharmaceutical industry today. Increases in cell densities and improved expression of the target protein have significantly boosted productivity. With these achievements, new challenges of higher levels of process-related impurities such as HCP and HCDNA have arisen. The downstream purification process, which is aimed at reducing these impurity levels to acceptable levels, has now become a very costly and time-consuming operation. With the rise of biosimilars, the demand for affordable treatments and the increased pressure on time-to-market for new therapeutics, the need for robust and compact downstream process trains has never been more relevant. Conventional mAb production processes use traditional technologies of centrifugation and depth filtration for the removal of cells and cell debris. The main target of these steps is to provide a low turbidity clarified fluid, free of insoluble particles. In most current processes, controlled reduction of insoluble impurities such as DNA is not a decisive goal of the clarification stage. Yet multiple studies have shown that the efficiency of the protein A capture step is correlated with the presence of these components. 3M Emphaze AEX Hybrid Purifier is aimed at removing DNA-related impurities in the clarification stage. The current study proposes two simple methods for detecting breakthrough and control of these impurities. By removing DNA before the critical protein A step, drastically reduced levels of both DNA and HCP can be obtained in the protein A elution pool. The robustness of this approach was proven by showing consistent results for different mAbs. The study shows that the proposed solution offers a robust and effective strategy for dealing with the main impurity challenges and allows further process simplification based on the obtained achievements.

DNA impurity removal in the clarification stage is key to mAb process efficiency improvement

2019 Spring National Meeting

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