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

新的疾病治疗方法越来越多地使用生物材料，而不是传统药物中的化学物质。这些治疗中最先进的是使用人类细胞来治疗严重和无法治愈的疾病。最近的成功包括以前无法治疗的血癌的显著长期缓解。然而，与传统药物相比，这种产品的制造非常复杂。产品必须“生长”，有时需要几周或几个月的时间，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。特别是制造环境有很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剂来相互交流，并从周围的环境中消耗物质。这创建了一个复杂的系统，随着时间的推移而发展，并且对于制造商来说，这可能是一个非常昂贵的系统。由于对这些问题的理解不足，目前这些新疗法的许多制造工艺效率极低，风险很高。我们建议建立这些关系的数学模型，以便制造商能够以更低的成本和更低的工艺失败风险来生产产品。我们建议使用不同类型的建模以获得最佳效率。第一种方法将有效地筛选影响正在生长的细胞的东西。第二种是一种特定类型的建模，它根据其组件的变化率来描述系统，因此对于随时间发展的系统建模是很好的。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细胞，其中一些产品可能是危险的。此外，如果病人自己的细胞是用来培养治疗的，如果生产失败，就没有替代产品可用。如果我们取得成功，它将帮助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，为英国的经济增长做出贡献。

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.