The combined approach of quality by design (QbD) framework and discrete element method (DEM) is applied to force feeding process within the tableting machine to assess the influence of potential critical process conditions (CPPs) and critical material attributes (CMAs) on tablet quality. The numerical model considers the three paddled force feeder of a FETTE 1200i tableting machine. The influence of the selected potential CPPs: turret speed and paddle wheels speed and CMAs: API dose strength, inter-particle cohesion, and particle-wall friction on the critical quality attributes (CQAs) tablet mass, tablet mass variation, and content uniformity are evaluated by using a fractional-factorial screening design. In addition to the CQAs, the DEM provides the opportunity to shed light on the powder flow phenomena within the force feeder thus an understanding on the impact of the paddle wheels on powder over-lubrication and particle attrition is provided. Such a combined approach of QbD and DEM helps in identifying the significance of selected CPPs and CMAs and thereby to generate the design space providing an optimal tablet quality. (C) 2019 Elsevier B.V. All rights reserved.