In the ever dynamic biotherapeutics landscape, process development teams have an increasingly challenging task of developing, over shorter timelines, robust cell culture processes that achieve desired productivity targets and product quality profiles. To meet this challenge, new technologies such as metabolic modeling can be employed to identify changes that can enable process improvements and optimization. A variety of cell-based models exist and have been used to provide insight into changes in cell metabolism, and to predict how variations in process inputs (e.g., raw materials, process parameters, etc.) will affect culture performance and/or product quality. Here, we present how two different Chinese Hamster Ovary (CHO) cell models can be applied to aid the development of a therapeutic antibody. The two models were designed with different purposes in mind for their use within an industrial cell culture process development organization. The first, a multiscale, mathematical model describing CHO cell growth, antibody production, and glycosylation, was developed in MATLAB to provide a quantitative understanding of how to manipulate a cell culture process to improve antibody titer and control glycosylation effectively. A user interface (UI) was designed to accompany the model to facilitate the ease with which process scientists can use the multiscale model to make predictions and determine process parameter values that would lead to a specified production target. The second is a genome-based Chinese Hamster Ovary (CHO) cell model capable of predicting cell culture metabolite trends and product glycosylation patterns. It provides the ability to make amino acid feed concentration predictions to improve cell culture performance and product glycan distribution, making it an ideal tool for process optimization. We describe how these two models can be applied to early and late phase clinical development to meet timeline demands.

Applications of metabolic models during large molecule development life cycle

2019 Spring National Meeting

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