Systems biotechnology of animal cells: the road to prediction

A central concern of biopharmaceutical R&D is the production of sufficient quantities of recombinant products from manufacturing processes based on animal cell culture. The way in which bioprocess researchers have addressed this question experienced a tremendous shift over the years, progressing from almost empirical to more rational approaches. A step further is the application of systems biotechnology: recent technological advances for large-scale cell state characterization and creative methods for host cell modeling are becoming crucial for next-generation bioprocess optimization. Here we provide an overview of the main trends towards this goal, with a focus on metabolic models as central scaffolds for data integration and prediction of bioprocess outcomes.