During production of concentrated monoclonal antibody formulations by tangential flow ultrafiltration (TFF), high viscosities and aggregation often cause extensive membrane fouling, flux decay and low product yields. To address these challenges, the co-solutes histidine or imidazole were added at high concentrations from 250 to 320 mM to reduce the viscosity by up to ten-fold relative to conventional low co-solute formulations, to as low as 40 cP at 250 mg/mL. At high mAb concentrations of up to 280 mg/mL, the transmembrane flux was increased threefold by adding high concentrations of co-solutes that also lowered the viscosity. Furthermore, the co-solutes also increased the mAb gel point concentration c(g) by up to 100 mg/mL mAb and thus enhanced concentration polarization-driven back-diffusion of the mAb at the membrane wall, which led to increased fluxes. The low viscosity and hollow fiber filter modules with straight flow paths enabled more uniform TMP and wall shear stress tau(w) profiles, which mitigated the reversible flux decay that results from an axial decline in the local TMP. The concentrated mAb was stable by SEC before and after extended storage at 4 degrees C and 37 degrees C. (C) 2016 Elsevier B.V. All rights reserved.