As the need for higher volumetric productivity in biomanufacturing grows, biopharmaceutical companies are increasingly investing in a perfusion cell culture process, most commonly one that uses a hollow fiber filter as the cell retention device. A current challenge with using hollow fiber filters is fouling of the membrane, which reduces product sieving and can increase transmembrane pressure (TMP) past process limitations. In this work, the impact of hollow fiber filter geometries on product sieving and hydraulic membrane resistance profiles is evaluated in a tangential flow filtration (TFF) perfusion system. The hollow fibers tested had lengths ranging from 19.8 to 41.5 cm, inner diameters (IDs) ranging from 1.0 to 2.6 mm, and pore sizes of 0.2 or 0.65 μm. The results showed that the shortest hollow fibers experienced higher product sieving while larger IDs contributed to both higher product sieving and lower hydraulic membrane resistances, illustrating the impact of filter geometry on process performance. The results also showed 0.2 μm pore size filters maintain higher product sieving, but also higher membrane resistances compared to 0.65 μm pore size filters. This study highlights the need for optimized hollow fiber filter geometries to maximize use of the membrane area, which in turn can reduce production costs and increase scalability of the perfusion process.

中文翻译：

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灌注细胞培养过程中内径、过滤器长度和孔径对中空纤维过滤器结垢的影响

随着生物制造对更高体积生产率的需求不断增长，生物制药公司越来越多地投资于灌注细胞培养工艺，最常见的是使用中空纤维过滤器作为细胞保留装置。当前使用中空纤维过滤器面临的挑战是膜污染，这会减少产品筛分，并可能增加跨膜压力 (TMP) 超过工艺限制。在这项工作中，在切向流过滤 (TFF) 灌注系统中评估中空纤维过滤器几何形状对产品筛分和液压膜阻力分布的影响。测试的中空纤维长度范围为19.8至41.5厘米，内径（ID）范围为1.0至2.6毫米，孔径为0.2或0.65微米。结果表明，最短的中空纤维经历了更高的产品筛分，而较大的内径有助于更高的产品筛分和更低的水力膜阻力，这说明了过滤器几何形状对工艺性能的影响。结果还表明，与 0.65 μm 孔径过滤器相比，0.2 μm 孔径过滤器可保持更高的产品筛分率，但膜阻力也更高。这项研究强调需要优化中空纤维过滤器的几何形状，以最大限度地利用膜面积，从而降低生产成本并提高灌注过程的可扩展性。