Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.
Pharmaceutical Research and Development, Pfizer Inc., 1 Burtt Rd, Andover, Massachusetts, USA.
Biotechnol J. 2024 Feb;19(2):e2300450. doi: 10.1002/biot.202300450.
Glycoconjugate vaccines containing multiple serotypes of a bacterial capsular polysaccharide can provide strong immune protection against pathogenic infections. Sterile filtration is an important component of the fill and finish operations in the preparation of these vaccines, with the capacity of the sterile filter limited by membrane fouling. The objective of this study was to examine the performance of a range of commercial 0.2/0.22 µm nominal pore size sterilizing grade filters with both single-layer and dual-layer structures during filtration of a glycoconjugate vaccine drug product consisting of four polysaccharide serotypes. The highly asymmetric Millipore Express showed much higher capacity than the more homogeneous filters, with the support structure of the Express acting as a prefilter that was able to remove foulants thereby protecting the small pores in the size-selective skin layer. This behavior was confirmed by performing experiments with different batch prefilters and by examining the location of foulant deposition within the sterile filters using confocal microscopy. These results provide important insights into the factors controlling fouling by these multiserotype vaccines as well as a framework for increasing the capacity of the sterile filter.
含有多种细菌荚膜多糖血清型的糖缀合物疫苗可以为致病性感染提供强大的免疫保护。无菌过滤是这些疫苗制备中灌装和完成操作的重要组成部分，由于膜污染，无菌过滤器的容量受到限制。本研究的目的是研究一系列具有单层和双层结构的商业 0.2/0.22µm 公称孔径除菌级过滤器在过滤由四种多糖血清型组成的糖缀合物疫苗药物产品时的性能。高度不对称的 Millipore Express 比更均匀的过滤器具有更高的容量，Express 的支撑结构充当预滤器，能够去除污染物，从而保护尺寸选择性表皮层中的小孔。通过使用不同批次的预滤器进行实验，并使用共焦显微镜检查无菌过滤器中污染物沉积的位置，证实了这种行为。这些结果为控制多血清型疫苗污染的因素提供了重要的见解，以及提高无菌过滤器容量的框架。
