Development of a Control Strategy for Hydrogenation of Aryl Nitro Analogs by Kinetic Justification

This article describes the development of a control strategy for controlling potentially mutagenic impurities that result from the hydrogenation of aryl nitro analogs, utilizing concepts outlined in the International Conference on Harmonisation guidelines (ICH M7, Option 4). A kinetic model was developed in conjunction with a detailed understanding of gas–liquid mixing principles and heterogeneous catalyst properties to provide a process for commercial manufacturing control included in the manufacturing of pibrentasvir.