Process control of biologics manufacturing is critical for ensuring product quality, safety and lot to lot consistency of therapeutic proteins. In this study, we investigate the issue of pink colored antibody product. We show that coloration is a second-order reaction that depends on the concentrations of free sulfhydryl groups from reduced mAb and of the reactive form of B12, hydroxocobalamin. We also provide strong evidence that B12 is covalently bound to mAb protein via a cobalt-sulfur coordinate bond. During culture media preparation and cell culture processing, cyanocobalamin, the chemical form of vitamin B12 added to media, is converted to hydroxocobalamin by low-wavelength visible light (400-550 nm). Cyanocobalamin is stable under red light (wavelength &gt; 600 nm) exposure and does not convert to hydroxocobalamin. We propose a process control strategy to install red lighting (wavelength &gt; 600 nm) in culture media preparation, storage and culture processing areas to provide safe light for biologics and to prevent light-induced variations in product quality.<br/><br/>

Novel control strategy for pink colored IgG4 caused by vitamin B12

253rd National Meeting (2017)

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