Developing Efficient Models to Define Economic and Low Risk High Value Manufacture of Cell Based Products

开发有效的模型来定义细胞产品的经济且低风险的高价值制造

• 批准号: EP/R031649/1
• 负责人: Robert Thomas
• 金额: $ 51.76万
• 依托单位: Loughborough University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FR031649%2F1
• 关键词: Developing; Efficient; Models; Define; Economic

New treatments for disease are increasingly made from biological materials rather than the chemicals in conventional drugs. The most advanced of these treatments use humans cells as treatments for serious and incurable diseases. Recent successes include dramatic long term remission of previously untreatable blood cancers. However, the manufacturing of such products is highly complex compared to a conventional drug. Products have to be 'grown', sometime over weeks or months, rather than quickly synthesised in a chemical reactor. This creates many challenges for manufacture. In particular there are many opportunities for the manufacturing environment to move outside an acceptable range. This can mean the product grows into the wrong number or type of cells. Further, cells talk to each other through the release of small signalling agents and deplete things from the environment around them. This creates a complex system that evolves over time, and a potentially very expensive system to handle for a manufacturer. Many current manufacturing processes for these new treatments are exceedingly inefficient and high risk due to a poor understanding of these issues.We propose to create mathematical models of these relationships so that manufacturers can create their products at lower cost and with lower risk of process failure. We propose to use different types of modelling for optimum efficiency. The first will efficiently screen for things that affect the cells being grown. The second is a specific type of modelling that describes a system in terms of the rate of change of its components and is therefore good for modelling systems that evolve with time. These models will help us understand how to control manufacture for maximum efficiency and acceptable risk.Avoiding process failure is very important because some of these products could be dangerous if the wrong cells are produced. Furthermore if a patient's own cells are being grown to treat them there is no replacement product available if manufacture fails. If we succeed it will help the UK see more ground breaking therapies at market as well as supporting a high value manufacturing industry contributing to UK economic growth.

新的疾病治疗方法越来越多地由生物材料而不是传统药物中的化学物质制成。这些治疗方法中最先进的是使用人类细胞治疗严重和不可治愈的疾病。最近的成功包括戏剧性的长期缓解以前无法治疗的血癌。然而，与传统药物相比，此类产品的制造非常复杂。产品必须“生长”，有时需要数周或数月，而不是在化学反应器中快速合成。这给制造业带来了许多挑战。特别是，制造环境有许多机会超出可接受的范围。这可能意味着产品生长成错误数量或类型的细胞。此外，细胞通过释放小的信号物质和消耗周围环境中的物质来相互交谈。这就产生了一个复杂的系统，随着时间的推移而发展，并且对于制造商来说，处理这个系统可能非常昂贵。由于对这些问题的认识不足，目前许多用于这些新治疗的制造工艺效率极低且风险很高，我们建议建立这些关系的数学模型，以便制造商能够以较低的成本和较低的工艺故障风险来制造产品。我们建议使用不同类型的建模以获得最佳效率。第一个将有效地筛选影响细胞生长的因素。第二种是一种特定类型的建模，它根据系统组成部分的变化率来描述系统，因此适用于建模随时间演变的系统。这些模型将帮助我们了解如何控制生产以获得最大的效率和可接受的风险。避免过程失败非常重要，因为如果生产错误的电池，其中一些产品可能是危险的。此外，如果患者自己的细胞正在生长以治疗它们，则如果制造失败则没有替代产品可用。如果我们成功了，这将有助于英国在市场上看到更多突破性的疗法，并支持高价值的制造业，为英国经济增长做出贡献。

项目成果

Understanding cell culture dynamics: a tool for defining protocol parameters for improved processes and efficient manufacturing using human embryonic stem cells.

• DOI: 10.1080/21655979.2021.1902696
• 发表时间: 2021-12
• 期刊: Bioengineered
• 影响因子: 4.9
• 作者: Kusena JWT;Shariatzadeh M;Thomas RJ;Wilson SL
• 通讯作者: Wilson SL

Assessment of Automated Flow Cytometry Data Analysis Tools within Cell and Gene Therapy Manufacturing.

• DOI: 10.3390/ijms23063224
• 发表时间: 2022-03-17
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Cheung M;Campbell JJ;Thomas RJ;Braybrook J;Petzing J
• 通讯作者: Petzing J

The importance of cell culture parameter standardization: an assessment of the robustness of the 2102Ep reference cell line.

• DOI: 10.1080/21655979.2020.1870074
• 发表时间: 2021-12
• 期刊: Bioengineered
• 影响因子: 4.9
• 作者: Kusena JWT;Shariatzadeh M;Studd AJ;James JR;Thomas RJ;Wilson SL
• 通讯作者: Wilson SL

Application of a simple unstructured kinetic and cost of goods models to support T-cell therapy manufacture.

应用简单的非结构化动力学和商品成本模型来支持 T 细胞疗法的生产。

• DOI: 10.1002/btpr.3205
• 发表时间: 2021
• 期刊: Biotechnology progress
• 影响因子: 2.9
• 作者: Shariatzadeh M

Modeling the selective growth advantage of genetically variant human pluripotent stem cells to identify opportunities for manufacturing process control

• DOI: 10.1016/j.jcyt.2024.01.010
• 发表时间: 2024-04-03
• 期刊: CYTOTHERAPY
• 影响因子: 4.5
• 作者: Beltran-Rendon，Catherine;Price，Christopher J.;Thomas，Robert J.
• 通讯作者: Thomas，Robert J.