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.

达到净净收入需要在英国以环境和财务可持续性的方式快速开发和制造药品。 SUS流的愿景是极大地提高活性药物成分（API）的可持续性，这是小分子药品的环境足迹的主要贡献者。我们将通过实施专门设计的策略来改变未来药物的开发和制造，以最大程度地发挥我们的革命性涡流反应堆的工业影响，该策略刚刚在2023年RSC启用技术竞争中赢得了奖项。SUS-FLOW将创建一个连续，灵活的反应器方法，并通过计算动力学模型，可以使ap的范围内的生产范围内的范围来创建一个持续的反应器方法，该方法可以使范围内的生产范围内的范围，从而可以创造出来，从而可以创造出来的范围。电化学和热化学，只需清洁量最少即可清洁。我们的方法将在很大程度上消除重新设计过程的需求，因为API的生产沿着药品管道进行了扩展。我们将：（i）嵌入光化学和/或电化学，目前尚未在制造中广泛使用，以提供更有选择性的，更高的屈服转换，从而减少了使API和减少废物产生所需的步骤数量。从初始发现到最终制造的整个开发链中都可以使用的技术。我们将将这些反应堆与过程分析（PAT）集成在一起，因为成功的流动过程需要以强大的PAT为基础，这可以加速过程开发并确保产品的持续质量。（iii）应用生命周期评估以量化我们涡流反应器概念的财务，环境和资源利用方面。通过与常规批次的生产过程进行比较，这将有助于确定涡流部署的商业案例，并提供对可以通过部署技术来实现的潜在可持续性增长的全面，基于参数的理解。可持续性。我们最近的反应堆创新是SUS流的起点，利用环形泰勒涡流以实现出色的混合和传质，这些混合和传质反映在非常高的时空产量和高度紧凑的反应器中。使用计算流体动力学和添加剂制造，我们将把这个涡旋概念提高到新的水平。为了确保可制造性和实施，我们正在与主要的制药和CROS.AIM和目标合作：将Vortex反应堆从成功的学术发展转变为在工业环境下制造药物的有吸引力的方法。特定目标将通过五个软件包传递1。为了证明涡流反应堆概念如何消除关键API的可持续性的主要瓶颈2。为连续涡流反应堆创新新功能3。应用有效的PAT来监视，优化和控制涡流反应堆中的连续过程，以量化主要产品和监测低浓度的不需要的副产品。4。通过计算流体动力学优化反应堆性能5。基于生命周期方法，实施可靠的指标，以确定涡流反应堆如何增加特定制造路线的可持续性。