Advanced process control of AAV manufacture: digitalisation, PAT and automation to improve productivity, quality and consistency

基因疗法的治疗潜力是变革性的，许多基本上难以治愈的疾病将得到安全、有效和持久的治疗。治疗方法现在开始获得批准(例如Roctavian、Zolgensma和Luxturna)，但成本仍然是进入市场和广泛获得患者的一大障碍，部分原因是制造工艺不够优化。如果基因疗法要用于治疗高度流行的疾病，那么需要在制造上取得突破。一个需要改进的领域是过程分析技术(PAT)和连续过程监测。目前的方法依赖于训练有素的操作员在离散的时间点进行费力的离线分析，这带来了显著的成本、延误和增加了污染的机会。该项目将使用下一代自动化和新颖的PAT技术，以实现对制造过程的实时表征和控制。

The therapeutic potential for gene therapies is transformative, where many largely intractable diseases will be treated safely, effectively and durably. Therapies are now starting to get approved (e.g. Roctavian, Zolgensma, and Luxturna), but cost remains a large barrier to entry and widespread patient access, partly due to suboptimal manufacturing processes. If gene therapies are ever going to be used to treat highly prevalent diseases, then breakthroughs need to be made in manufacturing.One area in need of improvement is process analytical technology (PAT) and continuous process monitoring. Current methods rely on laborious off-line analysis performed by highly trained operators at discrete time-points which introduces significant costs, delays and increases the chances of contamination. This project will use next-generation automation and novel PAT technologies to enable real-time characterisation and control of the manufacturing process.