Quality risk assessment and mitigation of pharmaceutical continuous manufacturing using flowsheet modeling approach

摘要

Integrated flowsheet modeling is an engineering approach that can provide a framework for understanding the impact of process dynamics on drug quality and associated risks during production, thereby facilitating the development of robust continuous processes. In this investigation, flowsheet modeling of continuous direct tablet compression process is exploited to perform sensitivity analysis in the risk assessment and identify potential process parameters and material attributes that affect critical quality attributes of the tablet. In addition, the dynamic response of the model in the presence of a variety of flow disturbances is demonstrated by the use of the residence time distribution analysis for the risk mitigation of the high-risk areas in the continuous direct compression process, which result in out-of-specification products. The outcome of the present work shows the potential of process models in quality risk assessment and mitigation for continuous pharmaceutical manufacturing of drug products and scientific considerations regarding model development. Published by Elsevier Ltd.