Membrane chromatography has already proven to be a powerful alternative to polishing columns in flow-through mode for contaminant removal. As flow-through utilization has expanded, membrane chromatography applications have included the capturing of large molecules, including proteins such as IgGs. Such bind-and-elute applications imply the demand for high binding capacity and larger membrane Surface areas as compared to flow-through applications. Given these considerations, a new Sartobind Phenyl (TM) membrane adsorber was developed for large-scale purification of biomolecules based on hydrophobic interaction chromatography (HIC) principles. The new hydrophobic membrane adsorber combines the advantages of membrane chromatography-virtually no diffusion limitation and shorter processing time-with high binding capacity for proteins comparable to that of conventional HIC resins as well as excellent resolution. Results from these studies confirmed the capability of HIC membrane adsorber to purify therapeutic proteins with high dynamic binding capacities in the range of 20 mg-MAb/cm(3)-membrane and excellent impurity reduction. In addition the HIC phenyl membrane adsorber can operate at five- to ten-fold lower residence time when compared to column chromatography. A bind/elute purification step using the HIC membrane adsorber was developed for a recombinant monoclonal antibody produced using the PER.C60 (R) cell line. Loading and elution conditions were optimized using statistical design of experiments. Scale-up is further discussed, and the performance of the membrane adsorber is compared to a traditional HIC resin used in column chromatography. Biotechnol. Bioeng. 2010;105: 296-305. (C) 2009 Wiley Periodicals, Inc.