JONATHAN KNIGHT, SHAWN CONWAY
Cambrex, Summerfield, North Carolina, USA

Abstract

Batch production has traditionally been – and still is – the mainstay of the pharmaceutical manufacturing sector. However, the economic and technological advantages of continuous flow chemistry are driving many API manufacturers to add it to their toolbox. This article will examine the advantages that continuous flow has for chemical synthesis including safety, efficiency and accelerated development in early-stage drug development, and highlight how the technology can remove uncertainties arising from physical changes in equipment, material quantities and issues during scale up.

Throughout the chemical and pharmaceutical manufacturing sector, the overriding majority of processes are carried out using batch production, with continuous flow chemistry being reserved for reactions that are highly energetic or having specific hazards that can be reduced by the technology. 

The alternative in these cases would be to use small reactors and undertake the chemistry on a scale that, were an uncontrollable event to occur, would not lead to widespread damage or risk to personnel. A few historic chemical sites would house such reactions in process-specific, isolated bunkers that are expensive to both build and maintain, and coupled with the small output volume, makes such processes very cost-inefficient.

Flow chemistry has been prevalent in academia and research for decades, but the transference of a process to manufacturing has been hindered by the lack of suitable, commercially-available equipment that would lead to an economic advantage. This has changed over the last few years, and the industry has seen investment by some of the large pharmaceutical companies, including GSK, Lilly and Joh ...