The simulated moving bed (SMB) is a type of continuous chromatographic separation, formed by a train of chromatographic columns. Operating a SMB unit is a complex task due to its low operating range and its sensitivity to any change. In order to control the system in an efficient way, a rigorous model with a suitable computational strategy was employed in this work. The polynomial approximation method in finite element was used to discretize the spatial variable of the internal model of a NMPC controller. The satisfactory performance of the controller, when applied to separate the enantiomers of praziquantel subject to equipment failures, was achieved within an acceptable computational effort for real-time application.