Commercial process development for biopharmaceuticals often involves process characterization (PC) studies to gain process knowledge and understanding in preparation for process validation. One common approach to conduct PC activities is by using design-of-experiment, which can help determine the impact process parameter deviations may have on product quality attributes. Qualified scale-down systems are typically used to conduct these studies. For an ultrafiltration/diafiltration (UF/DF) application, however, a traditional scale-down still requires hundreds of milliliters of material per run and can only conduct one experiment at a time. This poses a challenge in resources as there could be 20+ experiments required for a typical UF/DF PC study. One solution to circumvent this is the use of high-throughput systems, which enable parallel experimentation by only using a fraction of the resources. Sartorius Stedim Biotech has recently commercialized the ambr® crossflow high-throughput system to meet this need. In this study, the performance of this system during a monoclonal antibody UF/DF step was first compared with a pilot- and a manufacturing-scale tangential flow filtration (TFF) system at a single operating condition. Due to material limitations, it was then compared to only the pilot-scale TFF system across wider ranges of transmembrane pressure; crossflow rate; and diafiltration concentration in a PC study. Permeate flux, aggregate content, process yield, pH/conductivity traces, retentate concentration, axial pressure drop, and turbidity values were measured at both scales. A good agreement was attained across scales, further supporting its potential use as a scale-down system.

中文翻译：

---

使用高通量 ambr® 交叉流系统对单克隆抗体进行超滤和渗滤处理，简化工艺表征工作

生物制药的商业工艺开发通常涉及工艺表征 (PC) 研究，以获得工艺知识和理解，为工艺验证做准备。进行 PC 活动的一种常见方法是使用实​​验设计，这可以帮助确定过程参数偏差可能对产品质量属性产生的影响。合格的按比例缩小系统通常用于进行这些研究。然而，对于超滤/渗滤 (UF/DF) 应用，传统的按比例缩小每次运行仍需要数百毫升材料，并且一次只能进行一个实验。这对资源提出了挑战，因为典型的 UF/DF PC 研究可能需要 20 多个实验。避免这种情况的一种解决方案是使用高通量系统，仅使用一小部分资源即可实现并行实验。Sartorius Stedim Biotech 最近将 ambr® 交叉流高通量系统商业化，以满足这一需求。在这项研究中，首先将该系统在单克隆抗体 UF/DF 步骤中的性能与单一操作条件下的中试和制造规模的切向流过滤 (TFF) 系统进行了比较。由于材料限制，随后将其与跨膜压力范围更广的中试规模 TFF 系统进行了比较；横流率；和 PC 研究中的渗滤浓度。在两个尺度上测量渗透通量、聚集体含量、工艺产量、pH/电导率迹线、截留物浓度、轴向压降和浊度值。在各个尺度上达成了良好的一致性，