Summary: The industrial treatment of waste paper in order to regain valuable fibers from which recovered paper can be produced, involves several steps of preparation. One important step is the separation of stickies that are normally attached to the paper. If not properly separated, remaining stickies reduce the quality of the recovered paper or even disrupt the production process. For the mechanical separation process of fibers from stickies a separator screen is used. This machine has one input feed and two output streams, called the accept and the reject. In the accept the fibers are concentrated, whereas the reject has a higher concentration of stickies. The machine can be controlled by setting its reject rate. But even when the reject rate is set properly, after just a single screening step, the accept still has too many stickies, or the reject too many fibers. To get a better separation, several separators have to be assembled into a network. From a mathematical point of view this problem can be seen as a multi-commodity network flow design problem with a nonlinear, controllable distribution function at each node. We present a nonlinear mixed-integer programming model for the simultaneous selection of the network’s topology and the optimal setting of each separator. Numerical results are obtained via different types of linearization of the nonlinearities and the use of mixed-integer linear solvers, and compared with state-of-the-art global optimization software.