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Benefits of continuous flow manufacturing in a time of change
Challenges of an efficient continuous flow process and scale-up for azides


*Corresponding author
SAFC, Sigma-Aldrich Inc., 3050 Spruce St., Saint Louis, MO, 63103, US
SAFC, Sigma-Aldrich Production GmbH, Industriestr. 25, 9470, Buchs, CH


Though it has been in practice since the 60’s, continuous flow chemistry has been gaining popularity for application within the fine chemical and pharmaceutical manufacturing sector in the last decade. Synthetic chemists and process engineers are now using continuous flow microreactor technology as a tool for reaction control and process optimization, making it possible to develop and synthesize new chemical entities from small to large scale.

This article explores the increasing interest in continuous manufacturing, input from regulatory bodies, some of the challenges to implementation, and provides a look at how SAFC implemented continuous manufacturing in Buchs, Switzerland for an application to synthesize organic azide compounds.


Though it has been in practice for many decades, continuous flow chemistry, more commonly referred to as continuous manufacturing, is gaining popularity in the fine chemical and pharmaceutical manufacturing sector. In an industry averse to change, where production is still heavily reliant on traditional batch manufacturing, a paradigm shift is looming. The thought behind this trend is reinforced by a long-term vision of leading process engineers and scientists advocating that both industries can benefit significantly from the application of meso- and micro- (flow-) reactor technology, which is expected to lead to increased safety, selectivity and efficiency of reactions and, consequently, higher yields. (1) But, overall, continuous flow chemistry is expected to solve problems that are currently observed in traditional batch technology.

At the 2011 annual meeting of the American Association of Pharmaceutical Scientists (AAPS), Janet Woodcock, M.D., the director of the Center for Drug Evaluation and Research at the U.S. Food and Drug Administration (FDA), said that, “Right now, manufacturing experts from the 1950s would easily recogn ...