i-PREDICT: Integrated adaPtive pRocEss DesIgn and ConTrol

i-PREDICT：集成自适应过程设计和控制

• 批准号: EP/W035006/1
• 负责人: Maria Papathanasiou
• 金额: $ 53.94万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW035006%2F1
• 关键词: PREDICT; Integrated; adaPtive; pRocEss; DesIgn

The UK holds a leading position in the global life sciences scene. In this sector, biopharmaceuticals play a dominant role with almost £81bn in annual turnover (Life Sciences Competitiveness Indicators 2020, published: February 2021). Through the Life Sciences Vision 2021, the government is highlighting manufacturing innovation and ramp up as the UK's central aims. For the first time, Transition to Net Zero s brought at the centre of Life Sciences targets. For the UK to remain at the forefront of biopharmaceutical manufacturing, the Government is also encouraging digital innovation leading to time-/cost- efficient processes (Made Smarter, Review 2017). The crucial, positive health impact of (bio-) pharmaceutical processes may outweigh the environmental footprint of the sector that works with considerably lower volumes compared to other industries. Cumulatively, however, this remains to be an imminent challenge. Making those processes environmentally and economically sustainable is a complex task, involving conflicting objectives. For example, one would need to decide on the optimal number of separation cycles that meet both the target purity of the drug and create the least possible environmental footprint.Computer modelling tools can be of great help, lending themselves to the design and solution of multifactorial problems for the identification of the most suitable process setup and operating mode. In this respect, the research question this project aims to answer is: "How can we use computer modelling tools to embed environmental and economical sustainability in bioprocesses, while meeting the purity constraints?". In essence, the goal is to employ Engineering thinking and tools for the development of a systematic framework and software platform that will assist: (a) quantification of the impurity content on the downstream separation performance, (b) identification of a feasible and optimal design space, within which process performance is deemed satisfactory with respect to the tracked key performance indicators (KPIs) and (c) design of optimisation and control policies to ensure optimal operation. The novelty of the proposed work lies in two main aspects. Firstly, environmental sustainability KPIs, such as buffer and energy consumption will be considered for the first time systematically in the design of a bioprocess. Secondly, Engineering innovation will be deployed through the development of a computer modelling framework and software platform (i-PREDICT), harnessing the power of different modelling methodologies. In the junction of Engineering, Manufacturing, Digitalisation and Bioprocessing, i-PREDICT will enable bioprocess digitalisation and integration via continuous monitoring. This is one of the first computational attempts realising "Pharma 4.0" through the development and experimental validation of Industry 4.0-aligned frameworks for upstream in-process monitoring, optimisation and control. This work will create a roadmap towards the integration of product quality in the design of the bioprocess. Endorsing process intensification, this project proposes to consider upstream/downstream interplay through the quantification of the impact that impurity propagation in downstream. This novel concept will allow the design of variability-robust separation processes, enabling seamless unit integration and downstream scale-up. The digital and mathematical tools developed here will be validated experimentally, closing the loop from in silico to in vitro. This highly ambitious, multi-disciplinary project will create a step change towards a revolutionary research area of integrated design, optimisation and control in (bio-) pharmaceutical processes.

英国在全球生命科学领域处于领先地位。在这一领域，生物制药发挥着主导作用，年营业额近810亿英镑（生命科学竞争力指标2020，发布：2021年2月）。通过2021年生命科学愿景，政府将制造业创新和发展作为英国的核心目标。“向净零排放过渡”首次将生命科学目标置于中心位置。为了保持英国在生物制药制造领域的领先地位，政府还鼓励数字化创新，从而实现时间/成本效益的流程（Made Smarter, Review 2017）。与其他行业相比，（生物）制药工艺对健康的关键积极影响可能超过该行业的环境足迹，而该行业的工作量要小得多。然而，累积起来，这仍然是一个迫在眉睫的挑战。使这些过程在环境和经济上可持续是一项复杂的任务，涉及相互冲突的目标。例如，人们需要决定分离循环的最佳次数，既要满足药物的目标纯度，又要创造尽可能少的环境足迹。计算机建模工具可以提供很大的帮助，有助于设计和解决多因素问题，以确定最合适的过程设置和操作模式。在这方面，该项目旨在回答的研究问题是：“我们如何使用计算机建模工具将环境和经济可持续性嵌入生物过程，同时满足纯度限制？”本质上，目标是采用工程思维和工具来开发系统框架和软件平台，这将有助于：(a)对下游分离性能的杂质含量进行量化，(b)确定可行和优化的设计空间，在该空间内，工艺性能被认为与跟踪的关键绩效指标（kpi）相关，并且(c)设计优化和控制策略以确保最佳操作。这项工作的新颖性主要体现在两个方面。首先，环境可持续性kpi，如缓冲液和能源消耗将首次在生物工艺设计中被系统地考虑。其次，工程创新将通过开发计算机建模框架和软件平台（i-PREDICT）来部署，利用不同建模方法的力量。在工程、制造、数字化和生物加工的交汇处，i-PREDICT将通过持续监测实现生物过程的数字化和集成。这是通过开发和实验验证与工业4.0相一致的上游过程监控、优化和控制框架，实现“制药4.0”的首批计算尝试之一。这项工作将为在生物工艺设计中整合产品质量创建一个路线图。赞同工艺强化，本项目建议通过量化杂质在下游传播的影响来考虑上游/下游的相互作用。这种新颖的概念将允许设计变异性-稳健的分离过程，实现无缝单元集成和下游规模扩大。这里开发的数字和数学工具将通过实验验证，关闭从计算机到体外的循环。这个雄心勃勃的多学科项目将在（生物）制药工艺的集成设计、优化和控制方面创造一个革命性的研究领域。

项目成果

A model-based approach towards accelerated process development: A case study on chromatography

• DOI: 10.1016/j.cherd.2023.08.016
• 发表时间: 2022-12
• 期刊: Chemical Engineering Research and Design
• 影响因子: 3.9
• 作者: Steven Sachio;C. Kontoravdi;M. Papathanasiou