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Continuous flow processing in the pharma industry – an unstoppable trend?
22 October 2015 • Author(s): Bernhard Gutmann and Christian Oliver Kappe, University of Graz
Continuous flow processes have many distinct advantages over discontinuous batch production and therefore, in the last century, continuous operation has become by far the most dominant form of production for high-volume and low-cost materials such as petrochemical and commodity chemicals. The first applications of continuous processes in the pharmaceutical industry emerged only comparatively recently and the vast majority of production is still undertaken in batch reactors. Herein, we highlight some of the advantages that continuous flow processing offers for the synthesis of pharmaceuticals and fine chemicals.
Drivers for the pharmaceutical industry to move production from batch to flow are much weaker than for the commodity chemical industry. The production volumes of pharmaceuticals are considerably less than those of bulk chemicals and product lifecycles are often short. Furthermore,
pharmaceuticals are significantly more complex than commodity chemicals and their production usually requires many – often widely diverse – synthesis steps in addition to multiple rounds of isolation and purification. The complexity and diversity of these molecules, and the consequently involved and diverse process conditions required for their synthesis and isolation demand flexible, multipurpose reaction vessels for their production. Stirred tank-reactors are easy to handle and can be employed for a range of different operations. However, despite their long history and prevalence in synthesis laboratories, batch-type reactors have some severe, well-recognised limitations. Most importantly, chemical reactions which release large amounts of energy or proceed via unstable, highly toxic or explosive intermediates are difficult or impossible to implement in tank reactors.
In the past few decades, technologies for continuous synthesis have advanced tremendously and a plethora of discrete flow components and modules, including pumps, mixers, reactors and separation units, along with an increasing number of integrated standalone flow reactors, have become commercially available. The emergence of various reactor designs, addressing the diverse physicochemical requirements of chemical reactions, along with the emergence of technologies for feed delivery, flow metering, continuous separation, etc., enables the assembly of specialised, high-performance flow systems by combining these operation units.
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