A new framework for calibration of DEM models of cohesive materials is presented. DEM simulations are a widespread numerical tool for modelling granular assemblies and related processes, but require careful calibration to give realistic predictive results. To this aim routine small-scale laboratory tests are used to investigate powders rheology while limiting resource investment, in conjunction with a rational approach to reduce computational costs as well. A specific order in numerical tests and calibrated variables is defined, enabling the implementation of an automatic iterative routine to calibrate material parameters from a given dataset. This method is successfully applied to calibrate four common increasingly cohesive powders of pharmaceutical relevance. Our framework saves an important amount of computational expense when compared to traditional parameters design space approaches, and proved to be able to calibrate very cohesive powder exhibiting plastic bulk volume loss of up to 25% (after uniaxial consolidation up to 10kPa).