Abstract Virus filtration is used extensively in mammalian cell culture derived biopharmaceutical manufacturing processes. This processing step relies on bench scale models that require large volumes of filter load to demonstrate throughput, as well as expensive virus clearance studies to demonstrate clearance of virus spiked into load. A lack of adequate process knowledge about the virus clearance step can result in oversized virus filters and costly reprocessing steps. High throughput process development (HTPD) integrates parallel processing and automated scale-down models to minimize load volumes and process development timelines while maximizing process knowledge. Although a high throughput filter device would be useful for maximizing process knowledge on virus filtration step, a virus filter micro-scale HTPD model is not available. We designed a 96-well filter plate with a single layer of Viresolve® Pro filter media that was produced by MilliporeSigma (Burlington, MA USA). We tested the 96 well filter plate to assess its suitability to be a novel micro-scale HTPD scale-down model. In combination with an automated liquid handling robot, a Tecan EVO, our scale-down model generated flux decay curves for water, buffers and multiple different monoclonal antibodies (mAbs). The experimental setup demonstrated reproducibility and scale-up predictability. Virus filtration optimization is now a viable option using our HTPD scale-down model, enabling rapid process development using a fraction of the load material required for bench scale models while gaining a broader understanding of robustness of this important manufacturing step.

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一种用于病毒过滤的新型高通量工艺开发筛选工具

摘要 病毒过滤广泛用于哺乳动物细胞培养衍生的生物制药制造过程。此处理步骤依赖于需要大量过滤器负载来证明吞吐量的实验室规模模型，以及昂贵的病毒清除研究以证明对负载中掺入的病毒的清除。对病毒清除步骤缺乏足够的工艺知识可能会导致病毒过滤器尺寸过大和成本高昂的再处理步骤。高通量工艺开发 (HTPD) 集成了并行处理和自动缩小模型，以最大限度地减少装载量和工艺开发时间，同时最大限度地提高工艺知识。尽管高通量过滤器设备可用于最大限度地了解病毒过滤步骤的过程知识，但病毒过滤器微型 HTPD 模型不可用。我们设计了一个带有单层 Viresolve® Pro 过滤介质的 96 孔过滤板，该过滤介质由 MilliporeSigma（美国马萨诸塞州伯灵顿市）生产。我们测试了 96 孔滤板，以评估其作为新型微型 HTPD 缩小模型的适用性。结合自动液体处理机器人 Tecan EVO，我们的缩小模型生成了水、缓冲液和多种不同单克隆抗体 (mAb) 的通量衰减曲线。实验设置证明了重现性和放大可预测性。使用我们的 HTPD 缩小模型，病毒过滤优化现在是一个可行的选择，可以使用小规模模型所需的一小部分负载材料进行快速工艺开发，同时更广泛地了解这一重要制造步骤的稳健性。