Optimization of a pH-shift control strategy for producing monoclonal antibodies in Chinese hamster ovary cell cultures using a pH-dependent dynamic model

• Published in: Journal of bioscience and bioengineering Vol. 125; no. 2; pp. 245 - 250
• Main Authors: Hogiri, Tomoharu, Tamashima, Hiroshi, Nishizawa, Akitoshi, Okamoto, Masahiro
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.02.2018
• Subjects: Animals; Antibodies, Monoclonal - biosynthesis; Cell culture; Cell Culture Techniques; Chinese hamster ovary; CHO Cells; Cricetulus; Dynamic simulation; Hydrogen-Ion Concentration; Mathematical model; Monoclonal antibody; Optimization; Cell culture; Dynamic simulation; Chinese hamster ovary; Monoclonal antibody; Mathematical model; Optimization
• ISSN: 1389-1723; 1347-4421
• DOI: 10.1016/j.jbiosc.2017.08.015

To optimize monoclonal antibody (mAb) production in Chinese hamster ovary cell cultures, culture pH should be temporally controlled with high resolution. In this study, we propose a new pH-dependent dynamic model represented by simultaneous differential equations including a minimum of six system component, depending on pH value. All kinetic parameters in the dynamic model were estimated using an evolutionary numerical optimization (real-coded genetic algorithm) method based on experimental time-course data obtained at different pH values ranging from 6.6 to 7.2. We determined an optimal pH-shift schedule theoretically. We validated this optimal pH-shift schedule experimentally and mAb production increased by approximately 40% with this schedule. Throughout this study, it was suggested that the culture pH-shift optimization strategy using a pH-dependent dynamic model is suitable to optimize any pH-shift schedule for CHO cell lines used in mAb production projects.