Creation of a process understanding of chromatographic performance loss during biotherapeutic manufacture: A UK-India partnership

创建生物治疗药物生产过程中色谱性能损失的流程理解：英国-印度合作伙伴关系

基本信息

批准号：
EP/K029053/1
负责人：
Daniel Bracewell
金额：
$ 60.09万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FK029053%2F1
关键词：
Creation process understanding chromatographic performance

项目摘要

The importance of international collaborations in research is recognised both by individual researchers and by institutions and government, with studies showing that the average impact of publications resulting from these collaborations is significantly higher than that of papers with national co-authorship. This collaborative project between leading academic groups in the UK and India addresses the purification operations used to manufacture biopharmaceuticals e.g. antibodies and hormones such as insulin. They are supported in this activity by four industrial partners selected to provide support to the analytical and manufacturing aspects (being leading companies in their respective areas) as well as to provide a route to transfer the findings of the research to practice. Many of the latest drugs are based upon proteins rather than traditional small molecules (e.g. antibiotics). These protein drugs are produced for the treatment of diseases such as cancer. Antibodies such as Herceptin dominate this market. The research collaboration described here is focused on the study of the performance of the core purification method used for the manufacture of biopharmaceuticals - chromatography. Specifically we seek understand the mechanisms which determine the manufacturing lifetime of this operation and can lead to changes in performance. This issue presents a major hurdle to manufacturers. They must establish a robust purification process with acceptable costs for production before seeking approval for such medicines from the regulatory agencies. Clearly problems leading to delays can lengthen the times before medicines can made available to patients. This can affect both manufacturers of new products and those seeking to compete at reduced costs and widen the availability of this class of medicines (products often termed biosimilars).In comparison to other areas of manufacturing, bioprocessing is unusual in several respects. Typical product quantities are small (~250 kg/year), but are manufactured to extremely high purity and quality specifications (impurities < 0.001%). The variability typically seen in these processes has led to extremely regulated manufacturing, whose dictum is that "the process is the product". No significant change can be made to a licensed manufacturing process without detailed and time-consuming review by the international regulatory authorities. Developing and validating a bioprocess for manufacture takes ~10 years at a cost of £800M. Development is often empirical, with little use of modelling compared to other manufacturing sectors. These unusual features emphasise the need for a more fundamental understanding of the bioprocess. This research programme is structured towards building mechanistic understanding of the events that lead to changes in chromatographic performance in the manufacturing setting. There is evidence for several mechanisms the first stage is to structure these into a series of proposed mechanisms. Following consultation and study of historical data from our industrial partners we will embark upon experimental studies. Here detailed analytical measurements are required to identify specific critical species that are associated with the root cause of the mechanism.The project is to be led by UCL in London and IIT in Delhi in collaboration with IIT Bombay and the University of Kent. These academic groups are supported by industrial partners; ABB, Dr Reddy's Labs, GE Healthcare, Genzyme, PerkinElmer and Regeneron.

个人研究人员和机构和政府都认可了国际合作在研究中的重要性，研究表明，这些合作产生的出版物的平均影响大大高于国家共同撰文的论文。英国和印度领先的学术团体之间的这个合作项目介绍了用于生产生物制药的净化操作，例如抗体和激素，例如胰岛素。他们在这项活动中的支持下，四个工业合作伙伴被选为为分析和制造方面（作为其各自领域的领先公司）提供支持，并提供了将研究结果转化为实践的途径。许多最新的药物基于蛋白质，而不是传统的小分子（例如抗生素）。这些蛋白质药物是用于治疗癌症等疾病的。诸如Herceptin之类的抗体主导了这个市场。此处描述的研究合作侧重于研究用于生产生物制药的核心纯化方法的性能 - 色谱。具体而言，我们寻求理解确定此操作制造寿命的机制，并可能导致性能变化。这个问题给制造商带来了重大障碍。在寻求监管机构的此类药物批准之前，他们必须建立一个可接受的生产成本的强大净化过程。显然，导致延迟的问题可能会延长患者可以使用药物之前的时间。这可能会影响新产品的制造商，以及试图以降低成本竞争并扩大此类药物的可用性（通常称为生物仿制药）的产品。在与其他制造业的其他领域相比，生物处理在几个方面都是不寻常的。典型的产品数量很小（〜250 kg/年），但制造至极高的纯度和质量规格（杂质<0.001％）。在这些过程中通常看到的可变性导致了极为监管的制造业，其要求是“该过程是产品”。没有国际监管机构的详细且耗时的审查，无法对获得许可的制造过程进行重大更改。开发和验证生产的生物处理费用约为10年，成本为8亿英镑。与其他制造业相比，开发通常是经验的，几乎没有建模。这些不寻常的特征强调需要对生物程序有更基本的理解。该研究计划旨在建立对事件的机械理解，从而导致制造环境中色谱性能的变化。有几种机制有证据表明，第一阶段是将这些机制构造成一系列提出的机制。经过咨询和研究我们工业伙伴的历史数据，我们将进行实验研究。这里需要进行详细的分析测量，以确定与该机制根本原因相关的特定关键物种。该项目将由UCL在伦敦和IIT与IIT孟买和肯特大学合作。这些学术团体得到了工业伙伴的支持； ABB，Reddy博士实验室，GE Healthcare，Genzyme，Perkinelmer和Regeneron。