Analytical Centrifugal Ultrafiltration as a Tool for High Throughput Process Development in Virus Removal Filtration

分析型离心超滤作为病毒去除过滤中高通量工艺开发的工具

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Abstract

Virus removal filtration constitutes an essential component in biopharmaceutical manufacturing processes for both recombinant and plasma-derived protein products. The increasing demand for protein-based therapies necessitates expedited analytical screening methodologies for virus filtration materials and process parameters utilizing high-throughput development (HTPD) platforms. This study examines a novel HTPD methodology, specifically the implementation of analytical centrifugal ultrafiltration, as a scaled-down virus removal filtration tool. A nanocellulose-derived filter membrane of controlled porosity (33 µm thickness, 23 nm) was integrated into a centrifugal ultrafiltration apparatus. The system underwent comprehensive evaluation to determine centrifugal ultrafiltration flux characteristics, product yield across varying buffer viscosities, virus removal capacity utilizing model MS2 (27 nm) and ΦX174 (28 nm) bacteriophages, and IgG throughput capacity. Application of centrifugal force facilitated the generation of multiple filtration pressure gradients suitable for small-volume sample processing. The resultant flux decay profiles exhibited high reproducibility, demonstrating superior IgG throughput and virus removal efficiency. Overall, the approach adds value to the arsenal of analytical tools useful for HTPD in biopharmaceutics.

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