Ultrafiltration/diafiltration (UF/DF) is the standard unit operation in place in biotechnology industry for the final protein concentration and buffer exchange to produce drug substance. Several researchers have observed and published on the formation of higher order aggregates and particulates during UF/DF as a result of recirculation shear and potential exposure to air-liquid interface. This work examines the effect of screen channel-induced shear on particulate formation during UF/DF. To this end, different types of screened channels were examined for processing of monoclonal antibodies and a fusion protein during UF/DF at a fixed crossflow flux. It was found that channel-induced shear significantly affected the product quality for certain biologics, measured using various techniques, such as size-exclusion chromatography (SEC), Micro-Flow Imaging (MFI), dynamic light scattering (DLS), and filterability through a 0.2 mu m filter. It was demonstrated that cassettes with a more open screened-channel or "lightly suspended" feed screens resulted in consistently better product quality than the corresponding tighter or medium screen cassettes. The mass transfer coefficient for the lightly suspended screened channel was 260% higher than an open non-screened channel and only 22% lower than commercially available medium screen cassettes. The lightly suspended screen channel cassette thus offered the hydraulic advantage of lower differential pressure that an open channel offered, and the process advantage (processing time) that a medium screen channel offered along with consistently better product quality for the different biologics evaluated. The results of this study are useful in UF/DF process development of biologics to produce drug substance (DS) that has a better product quality and potentially lesser particulates. (C) 2016 Elsevier B.V. All rights reserved.