Pharmaceutical Roundtable Study Demonstrates the Value of Continuous Manufacturing in the Design of Greener Processes

Abstract

The American Chemical Society (ACS) Green Chemistry Institute (GCI) Pharmaceutical Roundtable conducted a study to elucidate the value of continuous processing, which had been defined as a key research area for green engineering. In the course of defining the business case for continuous processing, individual cases were collected and evaluated to determine specific drivers to implement continuous processing and to find key success factors. The magnitude and timing of effects and the relation to the principles of green chemistry were investigated.

Continuous Suzuki-Miyaura Reactions with Novel Ce-Sn-Pd Oxides and Integrated Crystallization as Continuous Downstream Protocol

“…Several examples for continuous multistep API syntheses or even end-to-end manufacturing plants have been reported [3][4][5][6][7][8][9] and reflect the great effort which has been done to establish suitable continuous protocols for the primary and secondary manufacturing of APIs. Although the advantages of continuous processes are well-known [10,11] (e.g., increased throughput, reduced waste, simplified scale-up or improved safety, especially when hazardous reagents are used [12]), the application of continuous processes is not yet standard practice in pharmaceutical manufacturing, despite the effort of the Federal Drug Administration (FDA) [13,14]. Economic concerns and the lack of adequately educated personnel, technical challenges (insufficient reliability, leaking), and equipment for production at larger scales are hurdles for the implementation of continuous processes in industry [11].…”

Development of an Intermittent-Flow Enantioselective Aza-Henry Reaction Using an Arylnitromethane and Homogeneous Brønsted Acid–Base Catalyst with Recycle

“…10 These methodologies are also easily aligned with the majority of the highest standards of quality and green chemistry principles recommended by the FDA and EPA. 11 By relying less on process-tailored infrastructure and more on flexible continuous process equipment, chemists can benefit from shorter optimization campaigns, improved and simplified synthetic strategies, timely delivery of the desired quantities of APIs, and reduced risk and cost associated with the development and production of APIs.…”

Microscale technology and biocatalytic processes: opportunities and challenges for synthesis

“…Multiphase flow conditions, where flow instabilities, fast biocatalyst inactivation, and low conversion rates are often encountered [26,27], provide opportunities for process intensification. Continuous processes will constitute a key research area for the engineering of green and sustainable processes [28]. Microscale technology and flow chemistry is not yet used as much for manufacturing as is batch reactor technology and myths of it not being useful for production persist.…”

“…Continuous processing and bioprocesses have been recognized as the most important key green engineering research areas by pharmaceutical and fine chemicals manufacturers alike [13,28]. Continuous operations have major benefits in reduced costs, equipment size, energy consumption, solvent utilization, and waste.…”