Sartorius Stedim Biotech GmbH, August-Spindler-Str. 11, 37079 Göttingen, Germany.
PDA J Pharm Sci Technol. 2020 Nov-Dec;74(6):644-659. doi: 10.5731/pdajpst.2019.011254. Epub 2020 Jul 16.
Scalability of filter throughput in normal flow filtration runs is an important consideration in the development of biopharmaceutical downstream processes. Depending on the filtration mode used, filter device geometry can significantly affect scalability. In this study, scaling of different polyethersulfone sterilizing-grade filters was performed in two filtration modes-at constant flow and at constant pressure-using a particulate model solution as well as a cell-free mAb solution as a representative example. Both filtration methods were compared regarding their practicability as well as their scalability of the final filter throughput and the filtration time. The pressure-dependent filter fouling that occurred with the mAb solution and the model solution showed that using different pressures for small- and process-scale filtration runs could potentially influence the predicted filter capacity. Overall, good scalability of the final filter throughput was determined for filters ranging from small-scale flat disc filters (4.5 cm) to large pleated filter assemblies (5.4 m) in filtration runs at constant flow as well as for filter capsules (0.6 m) of up to 10" for filtration runs at constant pressure. Moreover, at constant flow, the filtration time could be accurately predicted because it was determined by the adjusted flow rate. However, at constant pressure, potential resistances in process-scale devices can result in lower fluid fluxes and, hence, a longer unpredictable filtration time compared with small-scale filter elements. This paper introduces a novel scaling method performed at constant pressure that compensates for the pressure losses resulting from process-scale device resistances. Improved scalability regarding final filter throughput and filtration time are shown here with this scaling method compared with scaling at constant pressure. Therefore, this study provides information essential in decision-making to achieve optimal scaling within biopharmaceutical process development.
在正常流过滤运行中，过滤通量的可扩展性是生物制药下游工艺开发的一个重要考虑因素。根据使用的过滤模式，过滤装置的几何形状会显著影响可扩展性。在这项研究中，使用颗粒模型溶液和无细胞 mAb 溶液作为代表性示例，在恒流和恒压两种过滤模式下，对不同的聚醚砜灭菌级过滤器进行了缩放。比较了这两种过滤方法在其实用性以及最终过滤通量和过滤时间的可扩展性方面的差异。mAb 溶液和模型溶液发生的压力依赖型过滤堵塞表明，对于小规模和工艺规模的过滤运行，使用不同的压力可能会影响预测的过滤容量。总体而言，在恒流过滤运行中，从小规模平板过滤器（4.5cm）到大型褶皱式过滤器组件（5.4m），以及在恒压过滤运行中，从过滤胶囊（0.6m）到高达 10"的过滤胶囊，最终过滤通量都具有良好的可扩展性。此外，在恒流条件下，过滤时间可以通过调整流速来准确预测。然而，在恒压条件下，由于工艺规模设备中的潜在阻力，导致流体通量降低，因此与小规模过滤器元件相比，过滤时间不可预测且更长。本文提出了一种在恒压下进行的新型缩放方法，可以补偿工艺规模设备阻力引起的压力损失。与恒压缩放相比，这种缩放方法在最终过滤通量和过滤时间方面显示出更好的可扩展性。因此，本研究提供了在生物制药工艺开发中实现最佳缩放的决策制定所必需的信息。
