Formulation of biotherapeutics using single pass tangential-flow filtration (SPTFF) is a critical step in continuous manufacturing processes for many drugs including monoclonal antibodies (mAbs). The concentration of the mAb in the final formulation is a critical quality attribute which affects safety and efficacy and is determined by the concentration factor achieved by the process material stream in a single pass through an SPTFF module. Modern SPTFF modules consist of multiple smaller membranes connected in different series and parallel configurations to increase the overall membrane area and residence time of the process material in order to achieve high concentration factors in a single pass. The present work leverages the gel polarization model of protein ultrafiltration to develop a model for the permeate flux vs. time profile of a single membrane inside an SPTFF module based on three key resistances, namely the boundary layer resistance, resistance of the deposited protein layer over time, and intrinsic membrane resistance. Correlations are developed to predict the key mechanistic parameters across the typical operating range of flow rate, bulk concentration and transmembrane pressure in downstream mAb processing steps. The single membrane model is then used as a building block to model complex SPTFF configurations with diverse tree structures, and to facilitate in-silico design of customized SPTFF configurations based on operating targets.

使用单程切向流过滤 (SPTFF) 配制生物治疗剂是包括单克隆抗体 (mAb) 在内的许多药物的连续生产过程中的关键步骤。最终制剂中 mAb 的浓度是一个关键的质量属性，它会影响安全性和有效性，并由工艺材料流单次通过 SPTFF 模块所达到的浓度系数决定。现代 SPTFF 模块由多个以不同串联和并联配置连接的较小膜组成，以增加总膜面积和工艺材料的停留时间，从而在单次通过中实现高浓缩系数。目前的工作利用蛋白质超滤的凝胶极化模型来开发渗透通量与渗透通量的模型。基于三个关键电阻的 SPTFF 模块内单个膜的时间曲线，即边界层电阻、沉积蛋白质层随时间的电阻和固有膜电阻。开发相关性以预测下游 mAb 加工步骤中流速、体积浓度和跨膜压力的典型操作范围内的关键机械参数。然后将单膜模型用作构建块，对具有不同树结构的复杂 SPTFF 配置进行建模，并促进基于操作目标的定制 SPTFF 配置的计算机内设计。开发相关性以预测下游 mAb 加工步骤中流速、体积浓度和跨膜压力的典型操作范围内的关键机械参数。然后将单膜模型用作构建块，对具有不同树结构的复杂 SPTFF 配置进行建模，并促进基于操作目标的定制 SPTFF 配置的计算机内设计。开发相关性以预测下游 mAb 加工步骤中流速、体积浓度和跨膜压力的典型操作范围内的关键机械参数。然后将单膜模型用作构建块，对具有不同树结构的复杂 SPTFF 配置进行建模，并促进基于操作目标的定制 SPTFF 配置的计算机内设计。