This paper describes a simulation based approach applied to control design with the current challenging and promising technology of two-stage turbocharged diesel engine. One of the main aspects of this study is that the target engine was not available during the first year of control development. Therefore, a specific simulation methodology using LMS Imagine.Lab AMESim and Matlab/Simulink, has been set up in order to be able to take the maximum benefit of the engine simulator as a virtual bench while limiting the model inaccuracy risks for the control application.