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

Sus-Flow：利用下一代反应器通过光化学、电化学和热化学加速可持续连续药物制造

• 批准号: EP/Z53299X/1
• 负责人: Mike George
• 金额: $ 252.1万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FZ53299X%2F1
• 关键词: Sus; Flow; Accelerating; Sustainable; Continuous

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.

实现净零需要在英国以环境和财务可持续的方式快速开发和制造药物。Sus-Flow的愿景是大大提高活性药物成分（API）生产的可持续性，这是小分子药物产品环境足迹的主要贡献者。我们将通过实施一项专门设计的战略来改变未来药物的开发和制造，该战略旨在最大限度地发挥我们革命性的Vortex反应器的工业影响力，该反应器刚刚在2023年RSC使能技术竞赛中获奖。Sus-Flow将创建一种以计算流体动力学建模为基础的连续灵活的反应器方法，可以提高一系列API生产的可持续性，通过提供单程光化学、电化学和热化学以及通过仅需要最少量的溶剂来清洁。我们的方法将在很大程度上消除重新设计流程的需要，因为API生产将沿着药品管道扩大。我们将：（i）嵌入光化学和/或电化学（目前在制造中尚未广泛使用），以提供更具选择性、更高产率的转化，从而减少制造API所需的步骤数量并减少废物的产生。(ii)通过简单的反应器提供光化学和电化学，这些反应器可以部署在多步连续工艺中，可从毫克扩展到吨，从而提供一种可沿着从最初发现到最终制造的整个开发链的单一技术。我们将把这些反应器与过程分析（PAT）集成在一起，因为成功的流程需要强大的PAT来支撑，这可以加速工艺开发并确保产品的持续质量。(iii)应用生命周期评估来量化我们Vortex反应器概念的财务、环境和资源利用方面。通过与传统的间歇式生产工艺的比较，这将有助于确定涡旋反应器部署的商业案例，并提供全面的，基于参数的理解，通过部署该技术可以实现的潜在可持续性收益。我们的团队是高度跨学科的，包括具有有机化学，反应器设计和创新过程分析专业知识的化学家，以及在流体建模、生命周期评估和可持续性方面具有技能的工程师。我们最近的反应器创新是Sus-Flow的起点，利用环形泰勒涡流实现出色的混合和传质，这反映在非常高的时空产率和高度紧凑的反应器中。利用计算流体动力学和增材制造，我们将把Vortex概念提升到新的水平。为了确保可制造性和实施，我们正在与主要的制药公司和CRO合作。目的和目标：将Vortex反应器从一个成功的学术开发转化为一种有吸引力的工业化制药方法。具体目标将通过五个一揽子计划实现。展示涡旋反应器概念如何消除关键原料药生产可持续性的主要瓶颈。2.为连续涡旋反应器创新新的能力。3.应用有效的PAT来监测、优化和控制涡旋反应器中的连续过程，以量化主要产物并监测低浓度的不需要的副产物。通过计算流体动力学优化反应堆性能。基于生命周期方法实施可靠的指标，以确定Vortex反应器如何提高特定制造路线的可持续性。