Selective protein precipitation is widely used in the production of biopharmaceuticals. Butantan Institute’s hepatitis B vaccine is composed by the virus recombinant surface S-antigen (HBsAg). Continuous centrifugation is currently used to remove host cell proteins precipitates in the virus-like particles purification process. Clarisolve® depth filter is presented as an efficient tool to clarify high-density cell cultures. We evaluated 20MS, 40MS and 60HX Clarisolve® units against centrifugation (control) in order to verify its feasibility as an alternative technique to precipitates removal. They presented similar and satisfactory performance in terms of pressure, filtrate turbidity, OD280, total/specific protein and DNA content, as well as electrophoretic profile. The 40MS media was selected for a 180 L/m2 flux challenge (volume in proportion to the industrial scale). Resistance increased exponentially at the end, even though far from the limit pressure, with no impact in quality (turbidity). Therefore, 40MS was considered the ideal candidate to replace HCP clearance by centrifugation.