In biopharmaceutical process development, resin‐based high throughput screening (HTS) is well known for overcoming experimental limitations by permitting automated parallel processing at miniaturized scale, which results in fast data generation and reduced feed consumption. For membrane adsorber (MA), HTS solutions have so far only been available to a partial extent. Three case studies were performed with the aim of aligning HTS applications for MAs with those established for column chromatography: Process parameter range determination, mechanistic modeling (MM), and scalability. In order to exploit the MA typically features, such as high mass transfer and easy scalability, for scalable high throughput process development, a scale‐down device (SDD) for MA was developed. Its applicability is confirmed for a monoclonal antibody aggregate removal step. The first case study explores the experimental application of the SDD developed. It uses bind and elute mode and variations of pH and salt concentration to obtain process operation windows for ion‐exchange MAs Sartobind® S and Q. In the second case study, we successfully developed a mechanistic model based on parameters obtained from the SDD–HTS setup. The results proved to validate the use of the SDD developed for parameter estimation and thus model‐based process development. The third case study shows the transferability and scalability of data from the SDD–HTS setup using both a direct scale factor and MM. Both approaches show good applicability with a deviation below 20% in the prediction of 10% dynamic breakthrough capacity and reliable scale‐up from 0.42 to 800 ml.

中文翻译：

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用于膜层析聚集物去除单克隆抗体的按比例缩小装置的高通量筛选设置。

在生物制药工艺开发中，基于树脂的高通量筛选 (HTS) 以通过允许在小型化规模下进行自动化并行处理来克服实验限制而闻名，从而可以快速生成数据并减少进料消耗。对于膜吸附器 (MA)，HTS 解决方案迄今仅部分可用。进行了三个案例研究，目的是使 MA 的 HTS 应用与柱色谱的 HTS 应用保持一致：过程参数范围确定、机械建模 (MM) 和可扩展性。为了利用 MA 的典型特征，例如高传质和易于扩展，用于可扩展的高通量工艺开发，开发了用于 MA 的按比例缩小设备（SDD）。它适用于单克隆抗体聚集物去除步骤。第一个案例研究探讨了所开发的 SDD 的实验应用。它使用结合和洗脱模式以及 pH 和盐浓度的变化来获得离子交换 MA Sartobind® S 和 Q 的工艺操作窗口。在第二个案例研究中，我们成功地开发了基于从 SDD–HTS 获得的参数的机械模型设置。结果证明验证了开发用于参数估计的 SDD 的使用，从而验证了基于模型的过程开发。第三个案例研究使用直接比例因子和 MM 显示了来自 SDD-HTS 设置的数据的可传输性和可扩展性。两种方法都显示出良好的适用性，在预测 10% 动态突破容量和从 0 开始可靠放大方面的偏差低于 20%。