Process intensification has become an important strategy to lower production costs and increase manufacturing capacities for biopharmaceutical products. In particular for the production of viral vectors like lentiviruses (LVs), the transition from (fed‐)batch to perfusion processes is a key strategy to meet the increasing demands for cell and gene therapy applications. However, perfusion processes are associated with higher medium consumption. Therefore, it is necessary to develop appropriate small‐scale models to reduce development costs. In this work, we present the use of the acoustic wave separation technology in combination with the Ambr 250 high throughput bioreactor system for intensified perfusion process development using stable LV producer cells. The intensified perfusion process developed in the Ambr 250 model, performed at a harvest rate of 3 vessel volumes per day (VVD) and high cell densities, resulted in a 1.4‐fold higher cell‐specific functional virus yield and 2.8‐fold higher volumetric virus yield compared to the control process at a harvest rate of 1 VVD. The findings were verified at bench scale after optimizing the bioreactor set‐up, resulting in a 1.4‐fold higher cell‐specific functional virus yield and 3.1‐fold higher volumetric virus yield.

中文翻译：

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使用新型按比例缩小模型进行慢病毒生产的灌流工艺强化


工艺强化已成为降低生物制药产品生产成本和提高生产能力的重要策略。特别是对于慢病毒 （LV） 等病毒载体的生产，从（补料）分批过渡到灌流工艺是满足细胞和基因治疗应用日益增长的需求的关键策略。然而，灌流过程与较高的培养基消耗量有关。因此，有必要开发合适的小规模模型以降低开发成本。在这项工作中，我们介绍了将声波分离技术与 Ambr 250 高通量生物反应器系统结合使用，以使用稳定的 LV 产生细胞进行强化灌注工艺开发。在 Ambr 250 模型中开发的强化灌流过程，以每天 3 个容器体积 （VVD） 的收获速率和高细胞密度进行，与收获速率为 1 VVD 的对照过程相比，细胞特异性功能性病毒产量高 1.4 倍，体积病毒产量高 2.8 倍。在优化生物反应器设置后，这些发现在实验室规模上得到了验证，导致细胞特异性功能性病毒产量高出 1.4 倍，体积病毒产量高出 3.1 倍。