Laterally-fed membrane chromatography (LFMC) device

生物制药行业在救命重组蛋白药物的上游生产能力方面取得了显著进展，无论是在反应器容量还是产品效价方面都是如此。然而，下游加工，指的是这些产品的提纯和配方未能跟上。树脂柱层析被认为是下游加工的主要瓶颈。以多层吸附薄膜为分离介质的膜层析是一种很有前途的替代方法。它速度更快、可伸缩性更强、成本效益更高。然而，目前商用的膜层析设备提供的产品分辨率(即纯度)有限，因此它们的应用在很大程度上局限于后期抛光步骤，在该步骤中，宿主细胞蛋白(HcP)、DNA和病毒等杂质以流动模式进行纯化。对这些设备的仔细评估清楚地表明，它们在设计上存在严重缺陷。本项目中提出的横向进给膜色谱(LFMC)装置就是为了应对这一挑战而设计和开发的。我们最近发表的研究表明，LFMC装置不仅显著优于其他类型的膜色谱装置，而且其分离效果与树脂基柱相当，甚至更好。因此，这些设备代表着一种双赢的局面，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提纯。总体而言，这项技术的开发将使救命的治疗性蛋白质更容易负担得起，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.