(541a) Model-Based Investigation of Upstream CHO Cell Culture Process for Production of Monoclonal Antibodies with Desired N-Linked Glycosylation
AIChE Annual Meeting
Wednesday, November 10, 2021 - 3:30pm to 3:53pm
We have investigated the effect of temperature and pH on protein glycosylation for a model Herceptin biosimilar (or Trastuzumab) production using a CHO cell culture cultivation in an upstream fed-batch bioreactor. Mechanistic kinetic model was developed based on the experimental data obtained under different temperature and pH combinations. The mechanistic model contains two parts, including an unstructured cell culture model and a structured intracellular model. For our unstructured cell culture model, viable cell density, glucose, ammonia, and protein concentrations are captured by empirical equations. In the structured model, the intracellular kinetics of biochemical reactions cascade of the N-linked glycosylation process are simulated. The kinetic model is used to understand the effect of temperature and pH on the bioprocess. Finally, feasibility analysis with surrogate-based adaptive sampling is applied to determine a bioreactor operation design space. In this combined experimental and computational study, we have determined how adjusting the bioreactor operating conditions can achieve critical quality attributes of the targeted product. Ongoing work will implement integration with a control system to achieve real-time process control for mAb glycosylation.
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