A Perspective on Continuous Flow Chemistry in the Pharmaceutical Industry

Abstract

Continuous flow manufacture is an innovative technology platform, which is gaining momentum within the pharmaceutical industry. The key advantages of continuous flow include faster and safer reactions, which can be more environmentally friendly, smaller footprint, better quality product, and critically, the ability to perform chemistry that is difficult or impossible to do in batch mode. Globally, significant efforts have been made to develop the manufacturing flexibility and robustness of processes used to produce chemicals in a continuous way, yet despite these scientific developments, a major challenge for industry is the established application of flow technology to commercially relevant examples. The identification of opportunities to apply flow solutions to current processes is also critical to the success of this new technology for pharmaceutical and fine chemical companies. This review highlights industrial hurdles and the importance of education and showcases recent (2018−2019) and relevant industrial examples where utilization of flow technology has been successfully performed.

The evolution of Tamiflu synthesis, 20 years on: Advent of enabling technologies the last piece of the puzzle?

“…Having solved the shikimic acid availability concerns over the years by developing more efficient extraction and purification processes or alternatively by fermentation using genetically engineered E.coli bacteria, [ 25 , [28] , [29] , [30] ] the use of hazardous azide chemistry needs more attention. The application of continuous flow technology in Tamiflu synthesis proved to be a potential enabling tool for safe handling of the hazardous azide chemistry as well as improving efficiency [ 32 , 53 , 92 ] Continuous flow synthesis has attracted considerable attention in synthetic chemistry and pharmaceutical industry in the last decade owing to its well-documented advantages, [ [55] , [56] , [57] , [58] , [59] , 65 , 67 , 79 , [96] , [97] , [98] , [99] , [100] ] resulting in numerous pharmaceutical drugs approaches being redesigned into continuous flow synthesis [ 56 , 58 , [60] , [61] , [62] , [63] , [64] , [65] , 106 ] In this light, we envisage that Tamiflu synthesis can hugely benefit from continuous flow technology application to afford truly efficient synthetic procedures. Furthermore, the promising Tamiflu synthetic approaches which were previously ruled out for large scale synthesis in batch based on either safety concerns or poor efficiency can be reconsidered in flow.…”

The rise of continuous flow biocatalysis – fundamentals, very recent developments and future perspectives

“…[37][38][39][40][41][42] Additionally, a very recent review article was published by Hughes dealing with applications of flow chemistry in the pharmaceutical industry focusing in the patent literature, 43 whereas Lee et al emphasized on the translation of the pharmaceutical manufacturing from batch to flow, 44 and Baumann et al concentrate on the perspectives of continuous flow chemistry in the pharmaceutical industry. 45 Monbaliu and co-workers summarize the impact of continuous flow on platform-chemicals derived from biomass. 46 Also the continuous synthesis of polymers have been reviewed by Zaquen et al very recently.…”

Flow chemistry experiments in the undergraduate teaching laboratory: synthesis of diazo dyes and disulfides

“…Notable examples where flow has made an undeniable impact are photochemistry [3][4][5], electrochemistry [6][7][8], multiphase reactions [9][10][11][12] and handling of toxic, explosive or other hazardous reagents and intermediates [13-15, 16, 17]. Its value has been recognized by the industry as well and many companies are establishing small expert groups specialized in flow chemistry [18,19]. Hence, there is a high demand for skilled personnel with at least a notion of flow chemistry.…”