Fed-Batch Cell Culture Process Development: Implementing a Novel Nutrient Additive for a Robust, High-Titer, Scalable Process

摘要

The fed-batch culture of Chinese hamster ovary (CHO) cells has become well established as the primary method of manufacturing therapeutic recombinant protein products for various disease indications. Fed-batch process-development approaches focus on supporting high-cell-density cultures that are crucial to achieving high product titers but lead to proportionately high nutritional demands. Exhaustion of key nutrients negatively affects cell growth and ability to produce recombinant proteins. To counter that problem, concentrated feeds are added to the culture. Such feeds tend to be difficult to prepare because of limitations in solubility. Often, high or low pH conditions and/or heating steps must be used to dissolve feed components. In many cases, the resulting solutions have a relatively short shelf life (1, 2).