Biosimilars and biologics are manufactured in bioreactors by means of a complex bioprocess with producing cells. In our case these were mAb producing CHO cells. Successful bioprocess control requires not only continuous monitoring of many parameters but also optimization of cell culture conditions. Due to the high development costs and relatively low performance of clinical trials and competition in the market, the goal of bioprocess developement is to increase productivity, speed up the process and improve product quality with respect to the specifications for biosimilarity. Our goal was targeted bioprocess development with optimized supplementation and culture conditions for IgG-producing CHO cells. By combining bioprocess parameters and altered composition of supplemental media, we monitored their effect on four clones of two CHO cell lines. We studied the effect of different feeding strategies, supplementation of medium with putrescine and cultivation temperature on IgG glycosylation and culture productivity of CHO in fed-batch. We found that putrescine supplementation in combination with higher cultivation temperature significantly improved product yield in addition to achieving sufficient product quality although the quality of the product varied considerably between the clones used. With optimized bioprocess conditions, we also detected higher viable cell density, an increase in glucose and glutamine uptake and lower specific productivity. In spite of lower specific productivities, the final volumetric productivities were however higher in three out of four tested clones. Depending on the type of bioprocess, differences in specific glutamine and glucose consumption and lactate accumulation were also observed. The target values of mAb fucosylation were closer to target in the optimized type of bioprocess. Our data shows that it is possible to find bioprocess conditions for optimization of IgG N-glycosylation profile without sacrificing product titers, if the right clone is selected beforehand.
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