Laterally-fed membrane chromatography (LFMC) device

生物制药行业在挽救生命的重组蛋白药物的上游生产能力方面取得了显著进展，无论是在反应器体积还是产品滴度方面。然而，下游加工，即这些产品的纯化和配方没有跟上。树脂基色谱柱被认为是下游加工的主要瓶颈。膜色谱是一种很有前途的替代方法，它使用一层吸附膜作为分离介质。它明显更快、更具可扩展性和成本效益。然而，目前可用的商用膜层析设备提供有限的产品分辨率（即纯度），因此它们的应用主要限于后期抛光步骤，其中杂质如宿主细胞蛋白（HCPs）， DNA和病毒以流动模式纯化。对这些设备的仔细评估清楚地表明，它们存在严重的设计缺陷。本项目提出的横向进料膜色谱（LFMC）装置就是为了解决这一挑战而设计和开发的。我们最近发表的研究表明，LFMC装置不仅明显优于其他类型的膜色谱装置，而且与树脂基柱的分离效果相当甚至更好。因此，这些设备代表了一种双赢的局面，即高生产率和高分辨率。我们认为LFMC设备将彻底改变生物制药行业的分离和纯化。总的来说，这项技术的开发将使拯救生命的治疗蛋白质更便宜，并将加快它们的开发时间表。

The biopharmaceutical industry has experienced remarkable progress in the upstream production capacity of life-saving recombinant protein drugs, both in terms of reactor volumes and product titers. However, downstream processing, which refers to the purification and formulation of these products have failed to keep up. Resin-based column chromatography is considered the main bottleneck in downstream processing. Membrane chromatography which uses a stack of adsorptive membranes as the separation media is one of the promising alternatives. It is significantly faster, more scalable, and cost-effective. However, currently available commercial membrane chromatography devices offer limited product resolution (i.e. purity) and therefore their application is largely limited to the late-stage polishing steps where impurities such as host cell proteins (HCPs), DNA, and viruses are purified in a flow-through mode. A careful evaluation of these devices clearly shows that they have serious design deficiencies. The laterally-fed membrane chromatography (LFMC) device proposed in this project was designed and developed to address this challenge. Our recently published studies have shown that not only are LFMC devices significantly better than other type of membrane chromatography devices, the separation obtained with these is comparable or even better than that obtained with resin-based columns. These devices therefore represent a win-win situation, i.e. high-productivity with high-resolution. We feel that the LFMC devices will revolutionize separation and purification in the biopharmaceutical industry. Overall, the exploitation of this technology would make the life-saving therapeutic proteins more affordable and will speed up their development timelines.