This invention relates to methods for rationally designing cell culture media for use in cell cultures, e.g., cell cultures employed in polypeptide production cell culture media designed with the disclosed methods methods of producing a polypeptide of interest, e.g., an antibody, using such media polypeptides produced using the methods and media disclosed herein and pharmaceuticals compositions containing such polypeptides. The rationally designed media contain a concentration of an amino acid that is calculated for use in cell mass, a concentration of the amino acid that is calculated for use in cell maintenance, and a concentration of the amino acid that is calculated for incorporation into the polypeptide of interest.