Manufacturers of microfiltration devices typically offer small scale sizing tools for initial evaluation of membrane filtration performance in process streams and for estimating membrane area requirements of the full scale process. Ideally, small scale devices should contain a minimum of membrane area to save valuable bioprocess fluid while also scaling linearly to the corresponding large scale devices. However, differences in flow geometries between small and large scale devices can confound scaling predictions, and variability in membrane and fluid properties can also add uncertainty in scaling estimations, necessitating the use of liberal safety factors that result in increased costs. In this study, the effects of design factors such as underdrain support structure of small scale devices on scalability to large scale devices were investigated. In addition, the impact of membrane variability on scalability was quantified, and a strategy for minimizing scalability uncertainty was assessed. Other contributing factors to filter scalability such as pleating effects and fittings losses were also examined. Successful scale-up was realized with minimal safety factor by: (a) proper small scale device design to maximize performance consistency and minimize non-membrane influences on performance; (b) employing models that simulate the effect of pleating on device performance; and (c) proper accounting of factors such as device variability and hydraulic effects associated with fittings and elevation. (C) 2010 Elsevier B.V. All rights reserved.