This article describes a systematic miniplant-based approach to rapid development of simulated moving bed (SMB) chromatography applications. The methodology involves analysis of single-column pulse tests to screen adsorbents and operating conditions and to determine initial values of profile advancement factors used to specify flow rates for an initial SMB miniplant experiment. A lumped-parameter linear driving force rate-based model is developed by fitting process data from a single miniplant run. The data are fit in a two-step procedure involving initial determination of effective adsorption isotherm constants as best-fit parameters with subsequent adjustment of calculated mass transfer coefficients to refine the data fit. The resulting simulation is used to guide further miniplant work and minimize experimental effort. The methodology is illustrated with miniplant data for a binary protein separation showing excellent agreement between model results and process data generated over a wide range of operating conditions. (C) 2009 American Institute of Chemical Engineers AIChE J, 55: 2848-2860,2009