Using quality by design and quality risk management principles to aid the development of a high shear wet granulation process

Abstract

This paper presented a combinatorial application of quality by design (QbD) and quality risk management (QRM) tools with the goal of managing process risk and achieving high level of quality control during the development of the high shear wet granulation (HSWG) process. The microcrystalline cellulose and deionized water system was taken as the research object. By defining the critical quality attributes (CQAs) for the granules product, the probabilistic failure modes effects analysis (PFMEA) was innovatively used to assess the potential risks associated with the HSWG process on product quality and prioritize the potential critical process parameters (pCPPs) that must be controlled. Then, the Plackett-Burman design was used to screen critical process parameters (CPPs) from pCPPs. As a result, three operating parameters, i.e. the liquid to solid ratio, the wet massing time and the wet mixing impeller speed were identified as CPPs, and their quantitative relationship with CQAs were further investigated by using the Box-Behnken design. The design space which remained safely away from the edge of failure was built and validated. Retrospective risk analysis results demonstrated that the established process control strategies were efficient to ensure the granules consistently meet the specifications.