Abstract
Representative cultivation models are needed for designing efficient monoclonal antibody (mAb) production processes. Simple Monod-type kinetic models could fail to capture changes at different phases and conditions. Current models rarely account for process-related impurities, which hinders optimizing integrated processes. A three-module hybrid approach is thus introduced here. Module 1 is a kinetic metabolism model until cell death based on Monod-type equations. Module 2 is a data-driven module for updating parameters based on system dynamics and changes in cultivation conditions. Module 3 proposes a kinetic model for the generation of host cell proteins and DNA. The model is applied to newly established high-performance CHO cell lines and is validated with experiments at different operating conditions. The adopted modular approach helps identify weak model links, which can be corrected via the data-driven module. The proposed model combines accuracy and simplicity for design and control applications of cultivation processes considering quality aspects.
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