OPTIMIZATION OF NUTRIENT CONCENTRATION LEVELS IN FEED MEDIA FORMULATION FOR CHINESE HAMSTER OVARY CELLS

Chinese hamster ovary cells (CHO) are the most commonly used host for production of therapeutic proteins in the last few decades. Pharmaceutical industries have invested a lot of money in process optimization and process intensification of production of therapeutic proteins from CHO cells. One of the challenges faced in process optimization and process intensification is the manufacturing of CHO cell culture media. CHO cells need large amounts of nutrients such as sugars, amino acids and other organic molecules to grow and produce therapeutic proteins. Packing the feed media with maximum possible concentrations of nutrients is needed to have a desirable impact on downstream processing and increased growth of cells. However, the average CHO cell culture media has about a hundred compounds. This leads to precipitation of some compounds. Precipitation is not desirable as it leads to production of a media that is not well defined and affect process reproducibility. The primary approach used to date is to evaluate a large number of media alternatives in experimental solubility and stability tests. This requires manpower, is time consuming and costly in creating and evaluating the many media alternatives. This project applies thermodynamic principles to predict phase boundaries of amino acids in cell culture media. The solubility of amino acids in the media can be maximized by studying the phase boundary predictions. A group contribution based approach is used to develop interaction parameters between the functional groups of the amino acids. Previous attempts to do this in the literature are not very good in terms of predictions and number of amino acids modeled. This project aims to model phase boundaries of the 20 amino acids