Digital Chemical Engineering (Mar 2024)
Predictive models for upstream mammalian cell culture development - A review
Abstract
The production of therapeutic proteins in mammalian cell culture is an essential unit operation in biopharmaceutical manufacture that can benefit from the predictive insights of effective process models, leading to accelerated process development and improved process control. This review outlines and evaluates current approaches to predictive model development for mammalian cell culture and protein production. Classical mechanistic and data driven approaches are analysed, together with potential challenges in model development and application, including the experimental requirements for parameter estimation. Hybrid models, which may offer greater robustness, are then explored along with hybrid model architecture and the steps involved in model development. Successful examples from other cell fermentation processes are also considered, for application to the development, monitoring and control of mammalian processes.
