Minervini Mirko, Mohammadzadehmarandi Aylin, Behboudi Ali, Oppenheim Sheldon F, Zydney Andrew L
Department of Chemical Engineering, The Pennsylvania State University, Pennsylvania, USA.
Takeda Pharmaceuticals, Cambridge, Massachusetts, USA.
Biotechnol Bioeng. 2025 Sep;122(9):2410-2419. doi: 10.1002/bit.29038. Epub 2025 Jun 2.
There is increasing interest in the development of intensified processes that can provide significant reductions in manufacturing costs for monoclonal antibody (mAb) products. This study examines the performance of an integrated membrane process that combines single-pass tangential flow filtration (SPTFF) with high-performance countercurrent membrane purification (HPCMP) for the preconditioning of clarified culture fluid (CCF). The SPTFF step was operated with a single-pass concentration factor of 20x for 24 h filtration, with no evidence of membrane fouling; the transmembrane pressure remained < 30 kPa throughout the process. HPCMP was then performed on the pre-concentrated feed, resulting in a 60 ± 8% reduction in host cell proteins (HCPs) and more than a 30-fold removal of DNA while maintaining 94 ± 3% mAb step yield. The HPCMP process operated continuously for 36 h with a slight decline in HCP removal in the latter stages of operation due to membrane fouling. The buffer requirement for the integrated process was only 76 L/kg mAb. These results demonstrate the potential of using an integrated SPTFF-HPCMP process for preconditioning CCF as part of a highly intensified mAb manufacturing process with much lower cost of goods.
对于能够显著降低单克隆抗体（mAb）产品制造成本的强化工艺的开发，人们的兴趣与日俱增。本研究考察了一种集成膜工艺的性能，该工艺将单程切向流过滤（SPTFF）与高性能逆流膜纯化（HPCMP）相结合，用于澄清培养液（CCF）的预处理。SPTFF步骤在24小时过滤过程中以20倍的单程浓缩系数运行，没有膜污染的迹象；整个过程中跨膜压力保持在<30kPa。然后对预浓缩的进料进行HPCMP，宿主细胞蛋白（HCPs）减少60±8%，DNA去除超过30倍，同时单克隆抗体的步骤收率保持在94±3%。HPCMP工艺连续运行36小时，由于膜污染，在运行后期HCP去除率略有下降。集成工艺的缓冲液需求量仅为76L/kg单克隆抗体。这些结果表明，使用SPTFF-HPCMP集成工艺对CCF进行预处理，作为高度强化的单克隆抗体制备工艺的一部分，具有降低商品成本的潜力。
