The impact of typical anion-exchange flowthrough conditions on the IgG mass loading of an anion-exchange membrane scale-down unit (Mustang (R) Q coin) was investigated. High performance size-exclusion chromatography and multiangle laser light scattering results suggested the presence of a small fraction of IgG aggregates with average radius >100 nm under anion-exchange flowthrough conditions. The small filtration area presented by the 0.35 mL membrane volume Mustang (R) Q coin limited the membrane throughput due to fouling from the aggregates at higher antibody loading. Data in this report indicated that a 0.2 mu m hybrid polyethersulfone and polyvinylidene fluoride membrane in-line prefilter with a minimum filtration area of 20 sq cm alleviated the Mustang (R) Q coin fouling. The combined cake filtration and intermediate blocking model was proposed as the most likely membrane pore blocking mechanism. Increasing the filtration area in the in-line prefilter resulted in higher IgG mass throughput. Thus, using an appropriately sized in-line prefilter could provide more robust antibody throughput performance on scale-down membrane anion-exchange units. (C) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 26: 1654-1661, 2010