Integration of academic perspective into the scale-up of CHO cell bioprocessing: Manufacturing understanding

这项灵活交换计划（FLIP）的申请将把曼彻斯特大学的高级学者（Alan Dickson教授）带入眼镜蛇生物制剂的世界，眼镜蛇生物制剂是一家生产生物制药和蛋白质药物的公司，它彻底改变了以前无法治愈的疾病的治疗方法。在他们的制造过程中，Cobra Biologics开发了一种小规模的工艺（少量培养细胞-茶杯大小），并将其扩展到20,000多倍，以达到能够制造足够的商业成功所需产品的规模。扩大规模有多个步骤，尽管已经开发并遵循了标准流程，但未来十年可能产生的生物制药的性质意味着需要对用于扩大规模的流程进行更大的控制。由于需要更大的控制，需要更多的工艺基础知识（即，在小规模生产中有效的不一定适用于大规模生产），这些信息只能在关键的生产时间内收集到有限的数量。虽然未来的生物制药生产将在缺乏基本知识的情况下继续进行，但工艺的效率和成功的确定性将通过在工艺设计和控制中应用更大的合理性的能力而得到提高。这种蛋白质药物具有巨大的潜力，可以改变生活，但成本和日益增长的经济状况意味着成功（对患者和英国plc）需要该部门朝着更大的确定性努力快速生产。虽然FLIP是针对Dickson教授和Cobra Biologics撰写的，但整个工业基础都对生产确定性感兴趣，这项工作的结果将被沟通，并对其他生物制药制造商产生影响。迪克森教授将与Cobra Biologics合作，审查不同生物制药产品和工艺的生产放大过程的历史数据，并定义与特别成功或更麻烦的例子相关的事件（从过程或产品质量中读出）。根据这些评估，将进行实验，以测试“现场”制造过程中的工艺质量指标。测试将在曼彻斯特大学和眼镜蛇生物制剂公司进行（每个地点的优势都集中在提供广泛、全面的工艺质量分析）。这项技术交流将使Cobra Biologics获得一个非常强大的学术团体的专业知识，而Dickson教授将获得数据，并有可能在“真正的”制造过程中测试工艺质量指标，这些机会在其他情况下不会出现。这是一次跨越工业/学术界面的真正的愿景交流，双方将从彼此的观点中学习，这些学习将转化为后续的研究项目和商业活动。总体而言，长期目标是产生手段和技术，以确保通过对系统的详细了解来指导扩大生产规模，从而在有价值药物的质量和数量方面受益。

This Flexible Interchange Programme (FLIP) application will bring a senior academic (Prof Alan Dickson) from the University of Manchester into the world of Cobra Biologics, a company that manufactures biopharmaceuticals, protein medicines that have revolutionized the treatment of previously untreatable diseases. In their manufacturing processes, Cobra Biologics develop a process at small scale (cultured cells in small volumes - tea cup size) and scale this up 20,000+ times, to a scale that enables the manufacture of sufficient of the required product for commercial success. There are multiple steps of increasing scale and, although standard processes have been developed, and are followed, the nature of the biopharmaceuticals that are likely to be generated in the coming decade means that there will need to be much greater control of the processes used to increase the scale. With the need for greater control comes a need for greater basic knowledge of the processes (i.e. what works well at small-scale does not necessarily work at large-scale), information that can only be collected in limited amounts under the critical timelines of manufacturing. Whilst manufacture of tomorrows biopharmaceuticals would continue in the absence of the basic knowledge, the efficiency of processes, and the certainty of success, will be enhanced by the ability to apply greater rationality to process design and control. Such protein medicines have great potential and can be life-changing but the cost, and increasingly the economic situation, means that success (for patients and UK plc) requires the sector to work towards greater certainty in rapid manufacture. Whilst the FLIP is written in relation to Prof Dickson and Cobra Biologics, interest in certainty of production is shared across the entire industrial base and the outcome of this work will be communicated and have implications for other manufacturers of biopharmaceuticals..To address these issues, Prof Dickson will work with Cobra Biologics to review historical data on manufacturing scale-up processes for different biopharmaceutical products and processes and define events (in read-outs from the process or the quality of the product) associated with particularly successful or more troublesome examples. From these assessments, experiments will be undertaken to test indicators of process quality in "live" manufacturing processes. The tests will be undertaken at the University of Manchester and Cobra Biologics (with the strengths of each site focused on providing a extensive, comprehensive profiling of the process quality). This technology exchange will give Cobra Biologics access to the expertise of a very strong academic group whilst Prof Dickson will have access to data, and the potential to test indicators of process quality across "real" manufacturing processes, opportunities that would not arise under other circumstances. This is a true exchange of vision across the industrial/academic interface, in which both partners will learn from each other's perspectives, learnings that will be translated to subsequent research projects and commercial activities. Overall, the long-term objective is to generate the means and techniques to ensure that scale-up to manufacturing scale is guided by detailed understanding of the system with benefit in terms of quality and amount of valuable medicines.