Optimization of a Mammalian Cell Bioprocess using a Semi-Mechanistic Model

点击翻译按钮获取中文摘要

Chinese hamster ovary (CHO) cells are used extensively in the pharmaceutical industry to produce recombinantproteins to treat an array of diseases. The productivity and the therapeutic effectiveness of these proteins arehighly influenced by the chemical composition of the chemical medium and the bioreactor operating conditionsthat are used to grow the cells.Optimizing the media composition is very challenging due to its complex nature involving tens of differentcomponents such as aminoacids and non-aminoacid species (salts, vitamins, metals etc.).Our industrial collaborator (Sigma-Aldrich), a main manufacturer of cell culture media, is currentlyexperimenting with an advanced system of 48 micro-reactors (Sartorius-AMBR 15, 15 ml volume each), that itis not available in our lab, to develop new cell lines and growth media. Although industrial antibodymanufacturing involves either fed-batch or perfusion operations, the AMBR micro-bioreactor system iscomparatively much easier, quicker and cheaper to run for the purpose of media development.The work of my group in modeling of mammalian cells (Nikdel and Budman, 2016) can be directly applied totwo aspects that are of interest for Sigma for the purpose of media development with the AMBR system:i- To expand the validity of the model developed at Waterloo under the first Engage project for describing bothAMBR and perfusion operations using different media formulations andii- To develop a novel hybrid modeling approach, where the metabolic model describing the dynamics ofaminoacids is combined with an empirical model to describe non-aminoacid components (salts, vitamins,metals, etc.). This model will be later used for media and process optimization.