Sterile Filtration of Highly Concentrated Protein Formulations: Impact of Protein Concentration, Formulation Composition, and Filter Material
Sterile Filtration of Highly Concentrated Protein Formulations: Impact of Protein Concentration, Formulation Composition, and Filter Material
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DOI：
10.1002/jps.24561
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发表时间：
2015-10-01
影响因子：
3.8
通讯作者：
Fischer, Stefan
中科院分区：
文献类型：
--
作者：
Allmendinger, Andrea;Mueller, Robert;Fischer, Stefan
在生物制剂的无菌药品生产过程中，观察到浓缩蛋白制剂过滤行为的差异，具体取决于制剂成分。本研究使用聚偏二氟乙烯 (PVDF) 或聚醚砜 (PES) 过滤器研究小规模装置中单克隆抗体制剂的过滤力。评估了不同的因素，如与粘度差异相关的配方组成和蛋白质浓度，以及不同的过滤速率。本研究表明，过滤行为受到配方中是否存在表面活性剂的影响，表面活性剂定义了滤膜和表面活性配方成分之间的相互作用。这可能导致过滤器阻力（PES 过滤器）发生变化，与所使用的缓冲系统无关。过滤行为还由流变非牛顿流动行为定义。数据显示，小孔径和高达 1.0 bar 的过滤压力产生的高剪切速率会导致高浓度蛋白质配方的剪切稀化行为。非牛顿行为的差异归因于与排斥和吸引相互作用的差异相关的离子强度。本研究表明，配方组成、过滤材料和过滤速率的相互作用可以解释在高浓度蛋白质配方中观察到的过滤行为/过滤通量的差异，从而指导过滤器的选择。 (c) 2015 年 Wiley 期刊公司。
Differences in filtration behavior of concentrated protein formulations were observed during aseptic drug product manufacturing of biologics dependent on formulation composition. The present study investigates filtration forces of monoclonal antibody formulations in a small-scale set-up using polyvinylidene difluoride (PVDF) or polyethersulfone (PES) filters. Different factors like formulation composition and protein concentration related to differences in viscosity, as well as different filtration rates were evaluated. The present study showed that filtration behavior was influenced by the presence or absence of a surfactant in the formulation, which defines the interaction between filter membrane and surface active formulation components. This can lead to a change in filter resistance (PES filter) independent on the buffer system used. Filtration behavior was additionally defined by rheological non-Newtonian flow behavior. The data showed that high shear rates resulting from small pore sizes and filtration pressure up to 1.0 bar led to shear-thinning behavior for highly concentrated protein formulations. Differences in non-Newtonian behavior were attributed to ionic strength related to differences in repulsive and attractive interactions. The present study showed that the interplay of formulation composition, filter material, and filtration rate can explain differences in filtration behavior/filtration flux observed for highly concentrated protein formulations thus guiding filter selection. (c) 2015 Wiley Periodicals, Inc.