Application of a Statistical Approach to the Process Development of Futibatinib by Employing Quality-by-Design Principles. Part 2: Development of Design Space for Impurities Using the Response Surface Methodology

This study aims to construct a design space of impurities for risk assessment based on the quality-by-design concept through focusing on the design of experiment and statistical analysis. First, we identify multiple regression equations for critical process parameters of impurities using face-centered composite design, which is a type of response surface methodology. Next, a design space is constructed by these prediction models for analyzing the risk of the impurities. Finally, this risk is evaluated by process understanding and control ranges in the construction of a control strategy. This study proves that the commercial manufacturing method is a robust process and futibatinib can be stably produced.