Sampling and Analysis in Flow: The Keys to Smarter, More Controllable, and Sustainable Fine-Chemical Manufacturing.

Process analytical technology (PAT) is a system designed to help chemists better understand and control manufacturing processes. PAT systems operate through the combination of analytical devices, reactor control elements, and mathematical models to ensure the quality of the final product through a quality by design (QbD) approach. The expansion of continuous manufacturing in the pharmaceutical and fine-chemical industry requires the development of PAT tools suitable for continuous operation in the environment of flow reactors. This requires innovative approaches to sampling and analysis from flowing media to maintain the integrity of the reactor content and the analyte of interest. The following Review discusses examples of PAT tools implemented in flow chemistry for the preparation of small organic molecules, and applications of self-optimization tools.