High-throughput bioprocessing system for cell therapy manufacturing

自体细胞和基因疗法（acgt）已在许多治疗领域显示出治疗潜力，如血癌。据估计，仅在免疫肿瘤学领域，到2030年，每年有多达200万名患者接受aCGT治疗，而目前每年只有约5000名患者接受aCGT治疗。考虑到其他治疗领域，预计从aCGT中受益的患者数量可能会增加几倍。然而，由于自身的原因，大规模生产是部署的瓶颈之一（一个生产批次=一个患者剂量）。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，以满足这一需求，但开启细胞疗法的大规模生产也依赖于1)制造系统的实际足迹和2)分析自动化。首先，与目前的产能相比，到2030年，使用当前自动化制造系统来容纳aCGT批次的预计数量所需的洁净室占地面积需要增长30倍。在这个时间范围内的部署速度带来了很高的风险，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，因为aCGT制造商不得不承担大量的资本支出，从而降低了该行业的吸引力。其次，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物。由于目前的批次故障率高达10%，因此需要pat支持的生物处理设备。同时，在线PAT的部署成本很高，每台仪器都要花费数万英镑。在几个aCGT批次中安装一套PAT仪器将降低同时操作数百个系统的细胞治疗制造商的成本障碍。通过利用MicrofluidX目前的端到端自动化单批生物处理平台，该项目的目标是构建一个制造系统的原型，该系统可以在小范围内自动进行几个aCGT批次的生物处理和分析。

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.