Systems and methods of controlling fouling during a filtration procedure are described. A plasmapheresis method includes accepting a selection of a plasma flow rate and predicting an estimated procedure end time based at least partially on a plasma collection target volume. The method also includes flowing blood past a membrane and changing a plasma flow rate until the selected plasma flow rate through the membrane is achieved. The method also includes determining an acceptable rate of pressure change with time for respective times to the estimated procedure end time, the acceptable fouling rate limit being associated with a system pressure and adjusting the plasma flow rate based on the determined acceptable rate of pressure change with time.