High-throughput bioprocessing system for cell therapy manufacturing

自体细胞和基因疗法(ACGT)已在几个治疗领域显示出治愈潜力，如血癌。仅在免疫肿瘤学方面，据估计，到2030年，ACGT每年可能与多达200万名患者相关，而目前每年接受ACGT治疗的患者只有大约5000人。考虑到其他治疗领域，预计可以从ACGT中受益的患者数量可能会增加几倍。然而，大规模制造是部署的瓶颈之一，因为自体方面(1个生产批次=1个患者剂量)。虽然显然需要更多的生物处理自动化，有几种产品正在开发中，以满足这种需求，但开启细胞疗法的大规模生产也取决于1)制造系统和2)分析自动化的现实足迹。首先，使用当前自动化制造系统容纳预计数量的ACGT批次所需的洁净室足迹，到2030年将需要比目前的产能增长30倍。在这一时间范围内的部署速度构成了很高的风险，并可能成为ACGT可访问性的主要瓶颈。这也将大大增加aCGT的成本，ACGT制造商不得不产生巨额资本支出，使这一行业的吸引力下降。第二，用于ACGT的过程分析技术(PAT)能够控制生物过程和最终细胞产品。由于目前批次不合格率高达10%，因此需要具备PAT功能的生物处理设备。与此同时，在线PAT的部署成本很高，每台仪器的成本高达数万英镑。在几个ACGT批次中安装一套PAT仪器将降低细胞治疗制造商并行运行数百个系统的成本障碍。通过利用MicrofluidX目前的端到端自动化单批次生物处理平台，该项目的目标是构建一个制造系统的原型，该系统可以在较小的占地面积-制造堆栈-中实现多个ACGT批次的生物处理和分析自动化。

Autologous cell and gene therapies (aCGTs) have demonstrated curative potential in several therapeutic areas, such as blood cancers. In immuno-oncology alone, it is estimated that aCGT could be relevant for up to two million patients per year by 2030, compared to only ~5,000 patients per year receiving aCGT today. Taking into account other therapeutics areas, the projected number of patients that could benefit from aCGT could grow several folds higher. However, large-scale manufacturing is one of the bottlenecks to deployment due the autologous aspect (1 manufacturing batch = 1 patient dose). While there is a clear need for more bioprocessing automation, with several products in development targeting this need, unlocking mass-manufacturing of cell therapies also relies on 1) realistic footprint of manufacturing systems and 2) analytics automation.Firstly, the cleanroom footprint required to accommodate the projected volume of aCGT batches using current automated manufacturing systems would need to grow 30-fold by 2030 compared to current capacity. The speed of deployment in this timeframe poses a high risk and could become a major bottleneck to aCGT accessibility. This would also add significant costs to aCGTs, with aCGT manufacturer having to incur significant capital expenditure, making this sector less attractive.Secondly, Process Analytical Technologies (PAT) for aCGT enable control of the bioprocess and the final cell product. With current batch failure rates of up to 10%, there is a need for PAT-enabled bioprocessing equipment. At the same time, online PAT are expensive to deploy, with each instrument costing several tens of thousands of pounds. Fitting a set of PAT instruments across several aCGT batches would lower the cost barrier for cell therapy manufacturers operating several hundreds of systems in parallel.By leveraging MicrofluidX's current end-to-end automated single-batch bioprocessing platform, this project's goal is to build a prototype of a manufacturing system that can automate bioprocessing and analytics for several aCGT batches in a small footprint - The Manufacturing Stack.