The shift from empirical to science-based process development is considered to be a key
factor to increase bioprocess performance and to reduce time to market for biopharmaceutical products
in the near future. In the last decade, expanding knowledge in systems biology and bioprocess technology
has delivered the foundation of the scientific understanding of relationships between process input parameters and
process output features. Based on this knowledge, advanced process development approaches can be applied to maximize
process performance and to generate process understanding. This review focuses on tools which enable the integration of
physiological knowledge into cell culture process development. As a structured approach, the availability and the proposed
benefit of the application of these tools are discussed for the subsequent stages of process development. The ultimate
aim is to deliver a comprehensive overview of the current role of physiological understanding during cell culture
process development from clone selection to the scale-up of advanced control strategies for ensuring process robustness.
Keywords: Biopharmaceuticals, cell physiology, mammalian cell culture, Process Analytical Technology, process development,
quality by design.
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