Sus-Flow: Accelerating Sustainable Continuous Medicine Manufacture via Photo-, Electro-and Thermo-chemistry with Next-Generation Reactors

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Achieving Net Zero requires the rapid development and manufacture of medicines in the UK in ways that are both environmentally and financially sustainable. The vision of Sus-Flow, is to greatly increase the sustainability of the manufacture of active pharmaceutical ingredients (APIs) which is a major contributor to environmental footprints of small molecule pharmaceutical products. We will transform the development and manufacture of future medicines by implementing a strategy specifically designed to maximize the industrial impact of our revolutionary Vortex reactor, which has just won a prize in the 2023 RSC Enabling Technologies Competition.Sus-Flow will create a continuous, flexible reactor methodology, underpinned by computational fluid dynamics modelling, that can increase the sustainability of production for a range of APIs, by delivering single pass photochemistry, electrochemistry, and thermal chemistry and by requiring only a minimum amount of solvent for cleaning. Our methodology will largely eliminate the need to redesign processes, as API production is scaled-up along the medicine pipeline. We will:(i) Embed photochemistry and/or electrochemistry, which is currently not widely employed in manufacture to deliver more selective, higher yielding transformations, thereby reducing the number of steps needed to make an API and decreasing generation of the waste.(ii) Deliver photo- and electro-chemistry with simple reactors that can be deployed in multi-step continuous processes, scalable from milligrams to tonnes, thereby providing a single technology that can be used along the whole of development chain from initial discovery to final manufacture. We will integrate these reactors with process analytics (PAT) because successful flow processes need to be underpinned by robust PAT, which can accelerate process development and ensure the continuing quality of the product.(iii) Apply Life Cycle Assessment to quantify the financial, environmental, and resource utilisation aspects of our Vortex reactor concepts. Through a comparison with conventional batch-based production processes, this will help to identify both the commercial case for vortex reactor deployment, as well as providing a comprehensive, parameter-based understanding of the potential sustainability gains that can be achieved by deploying the technology.Our team is highly interdisciplinary comprising chemists with expertise in organic chemistry, reactor design and innovative process analytics, and engineers with skills in fluid modelling, Life Cycle Assessment and sustainability. Our recent reactor innovations are the starting point of Sus-Flow, exploiting toroidal Taylor vortices to achieve excellent mixing and mass transfer that are reflected in very high space-time yields and highly compact reactors. Using computational fluid dynamics and additive manufacture, we will take this Vortex concept to new levels. To ensure manufacturability and implementation, we are partnering with both major pharma and CROs.Aims and Objectives: To transform the Vortex reactor from a successful academic development into an attractive methodology for manufacturing medicines in an industrial context. Specific objectives will be delivered via five packages.1. To demonstrate how the Vortex reactor concept can eliminate major bottlenecks to sustainability in manufacture of key APIs.2. To innovate new capabilities for continuous Vortex reactors.3. To apply effective PAT to monitor, optimise and control continuous processes in Vortex reactors, both to quantify major products and to monitor low concentrations of unwanted by-products.4. To optimise reactor performance via Computational Fluid Dynamics.5. To implement reliable metrics, based on Life Cycle approaches, to identify how Vortex reactors can increase the sustainability of a particular manufacturing route.