Grünberg Mario, Kuchemüller Kim B, Töppner Katrin, Busse Ricarda A
Sartorius Stedim Biotech GmbH, August-Spindler-Strasse 11, 37339 Goettingen, Germany.
Membranes (Basel). 2022 Jun 30;12(7):677. doi: 10.3390/membranes12070677.
The recombinant monoclonal antibody capture step represents the current bottleneck in downstream processing. Protein A resins are diffusion-limited chromatography materials which require low flow rates to achieve a binding capacity above 30 g L with the result of low productivity. Here, we present a novel chromatography membrane combining superior binding capacities with high flow rates for high productivity while achieving comparable product quality as state-of-the-art protein A resins. Further, we demonstrate full scalability of this convecdiff technology with experimental data demonstrating suitability for bioprocessing at different scales. This technology results in more than 10-fold higher productivity compared to Protein A resins, which is maintained during scale up. We demonstrate the influence of residence times, feed titers and the cleaning regime on productivity and indicate optimal utilization of the convecdiff membrane based on feed titer availability. The underlying high productivity and short cycle times of this material enable the purification of monoclonal antibodies with 10-times less chromatography material used per batch and utilization of the membrane within one batch. Provided in disposable consumables, this novel technology will remove column handling in bioprocesses and resin re-use over multiple batches.
重组单克隆抗体捕获步骤是下游加工过程中的当前瓶颈。蛋白A树脂是受扩散限制的色谱材料，需要低流速才能实现30 g/L以上的结合容量，导致生产率较低。在此，我们展示了一种新型色谱膜，它结合了卓越的结合能力和高流速，以实现高生产率，同时获得与现有蛋白A树脂相当的产品质量。此外，我们通过实验数据证明了这种对流扩散技术的完全可扩展性，表明其适用于不同规模的生物加工。与蛋白A树脂相比，该技术的生产率提高了10倍以上，并且在放大过程中得以保持。我们展示了停留时间、进料浓度和清洗方式对生产率的影响，并根据进料浓度的可用性指出对流扩散膜的最佳使用方法。这种材料潜在的高生产率和短循环时间使得每批使用的色谱材料减少10倍即可纯化单克隆抗体，并且可在一批内使用该膜。该新技术以一次性耗材形式提供，将消除生物加工过程中的柱操作和多批次树脂再利用。
