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

Mathieu A Morin; Wenyao Peter Zhang; Debasis Mallik; Michael G Organ

doi:10.1002/anie.202102009

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

Angew Chem Int Ed Engl. 2021 Sep 13;60(38):20606-20626. doi: 10.1002/anie.202102009. Epub 2021 May 6.

Authors

Mathieu A Morin^{1

2}, Wenyao Peter Zhang³, Debasis Mallik¹, Michael G Organ^{1

3}

Affiliations

¹ Department of Chemistry and Biomolecular Sciences, Centre for Catalysis Research and Innovation (CCRI), University of Ottawa, 10 Marie Curie, Ottawa, ON, K1N 6N5, Canada.
² Department of Chemistry, Carleton University, 203 Steacie Building, 1125 Colonel By Drive, Ottawa, ON, K1S 5B6, Canada.
³ Department of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada.

PMID: 33811800
DOI: 10.1002/anie.202102009

Abstract

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.

Keywords: analytical methods; continuous manufacturing; flow chemistry; process analytical technology (PAT).

Publication types

Review
Research Support, Non-U.S. Gov't