This disclosure relates to the use of a hydrophobic hollow fiber filter for the filtration of cell cultures and other biological perfusions, due to its resistance to fouling, as well as the ability to filter solutions with a high solid content. A hydrophobic hollow fiber filter may be used within a filter housing in conjunction with a process vessel and a traditional separation system. When the system is used with alternating tangential flow or tangential flow filtration, the hydrophobic hollow fiber filter results in more effective filtration of the filtrate, leading to greater concentration of the retentate, even in solution containing high levels of solids.