The present invention provides a method of increasing protein production in a cell culture by growing cells that produce the protein (e.g., the growth phase) in a perfusion cell culture to a high cell density (i.e., at least above about 40×106 cells/N mL) and then switching to a protein production phase, wherein the cells are cultured in a fed-batch cell culture. The present invention further provides a method for clarifying a protein from a cell culture by adjusting the pH of the cell culture to below neutral pH (i.e., below a pH of 7) and settling the cell culture, such that the cell culture separates to form a supernatant layer and a cell-bed layer, wherein the protein is in the supernatant layer.