According to Process Analytical Technology perspective, drug product quality should be ensured by manufacturing process design. Initial step of the process analysis is investigation of critical process parameters (CPPs). It is generally accepted to type the CPPs based on project team knowledge and experience [5]. This paper describes the use of Design of Experiments tool for selection of the CPPs. Seven factors of wet granulation process were investigated for criticality. Low and high levels of each factor represented maximal and minimal settings of wide operational ranges. Granulates were produced in line with Plackett-Burman experimental matrix, blended with extra-granular excipients and compressed into tablets. Semi-products and final products were tested. Out of specification result of any critical quality attribute was treated as critical failure. The high-shear granulation factors, i.e. quantity of binding solution, rotational speed of impeller and wet massing time were considered of critical importance. Operational ranges of the parameters were optimized. The process performance was confirmed in qualification trials.