(106c) Improving the Accuracy of Scale-up of Membrane Filters for Microfiltration of Biological Fluids

Small scale sizing tools are commonly used for initial screening of microporous membrane filtration performance and for estimating filtration area requirements for full scale processing. Ideally, these small scale devices contain a minimum of membrane area to minimize the consumption of valuable bioprocess fluid and will predictably scale to the corresponding larger devices. However, scaling predictions can be confounded by a number of factors, including differences in flow geometries between small and large scale devices, non-membrane flow resistances, and variability in membrane and fluid properties. In this study, the effects of design factors such as membrane 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 associated with membrane variability was assessed. Other contributing factors to filter scalability such as fittings losses and variability in process conditions were also examined. It was found that successful scale-up could be realized 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; c) implementing a methodology in which only membranes within a specified narrow performance range are installed into small scale devices, and d) proper accounting for process variability and hydraulic effects associated with fittings and elevation.