Control strategy definition for a drug product continuous wet granulation process: Industrial case study.

This paper describes the specific control strategy of the commercial manufacturing process of an immediate release tablet formulation based on continuous twin-screw wet granulation. This control strategy has been defined by a multidisciplinary team using an enhanced approach, in alignment with the quality by design principles. During process development, experiments have been performed according to multivariate designs first to identify critical material attributes and critical process parameters and then, to define process conditions generating a product having the required quality. Hence, controls have been applied on critical quality attributes and on related critical process parameters and critical material attributes. Due to the specificity of the process that combines batch and continuous unit operations, a specific control strategy has been designed to ensure intermediate and end product quality. Therefore, controls including soft sensor model and in process controls have been developed to continuously monitor granules residual moisture content, assay and dissolution as granules and tablets critical attributes. In addition, process analytical technology implementation enabled increased process understanding and provided support for the development of the control strategy. This study is therefore considered as a real industrial case study of control strategy definition and implementation for an intended commercial continuous manufacturing process.