The inter-chain disulfide bonds of mAbs are crucial to stabilize their three dimensional structures and keep their biological functions. The reduction of mAb disulfide bonds were observed in the cell culture, harvest and subsequent purification processes.1 Addition of cystine or copper sulfate prior to or after harvest has been reported for prevention and remediation of mAb disulfide bond reduction in manufacturing. Recently, we successfully prevented the disulfide bond reduction of mAb-x in manufacturing lots by addition of 200 µM of CuSO4 to the harvest material prior to cell clarification.2 A study was also conducted to evaluate the feasibility of addition of CuSO4 in cell culture to prevent disulfide bond reduction.<br/>Five bioreactors at 1 and 10 L scales were inoculated from a single culture and ran using the same culture conditions. On day 8, 50 µM CuSO4 was added into the 10 L and two 1 L bioreactors while the other two 1 L bioreactors were run as controls without CuSO4. All bioreactors were harvested on day 12. Before clarification, 200 µM of CuSO4 was added to each culture. Clarified harvest was run over a Protein A column for purification and product was analyzed.

Mitigation of monoclonal antibody disulfide bond reduction by copper sulfate: Addition of copper sulfate during cell culture?

2019 Spring National Meeting

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