CARA E. BROCKLEHURST, LUIGI LA VECCHIA, HANSJOERG LEHMANN*
*Corresponding author
Novartis Institutes for BioMedical Research, Klybeckstr. 141, CH-4002 Basel, Switzerland

Abstract

Continuous flow chemistry and continuous processes are gaining increasingly importance in pharmaceutical industry, not only for the production of active compounds but also in the R&D processing of new drug candidates. Especially for the early scale-up phase of a drug substance, the utilisation of continuous flow reactors can help to minimize safety risks with respect to the scale-up of hazardous reactions. This article illustrates current developments in this area, showing that problematic reactions, such as nitrations or fluorinations, can be performed and scaled-up safely and efficiently by using commercial continuous flow equipment.

INTRODUCTION

During the past decade, the pharmaceutical industry has had to struggle more and more with increasing costs for the development of new pharmaceuticals. All areas of the development process, from research to production, have been under pressure to improve efficiency. New enabling technologies such as continuous flow processing and manufacturing, have strongly attracted the attention of both pharma industry and academia, since performing organic reactions in continuous flow mode is promising a number of advantages over the traditionally used batch processes. In general, by transferring batch processes to a continuous work-flow, lower costs, greater reliability and safety, better sustainability and novel pathways that are otherwise not accessible, can be expected (1). Despite the fact that continuous processing is nothing new but have been routinely used in other areas of the chemical industry for decades, the pharmaceutical industry interestingly has relied to date on mainly batch or semi-batch processes. And although the potential advantages of continuous processing in pharma industry were discussed already in 2005, it took several years to c ...