Kamga Mark-Henry, Cattaneo Maurizio, Yoon Seongkyu
a Bioprocess Development Division, Biovolutions Inc. , Woburn , MA , USA.
b Department of Chemical Engineering , University of Massachusetts Lowell , Lowell , MA , USA.
Prep Biochem Biotechnol. 2018 May 28;48(5):383-390. doi: 10.1080/10826068.2018.1446151. Epub 2018 Apr 23.
A new integrated continuous biomanufacturing platform for continuous production of antibodies at fixed cell volumes and cell concentrations for extended periods with immediate capture is presented. Upstream antibody production has reached technological maturity, however, the bottleneck for continuous biomanufacturing remains the efficient and cost-effective capture of therapeutic antibodies in an initial chromatography step. In this study, the first successful attempt at using one-column continuous chromatography (OCC) for the continuous capture of therapeutic antibodies produced through alternating tangential flow perfusion is presented. By performing upstream media optimizations, the upstream perfusion rate was reduced to one vessel volume per day (vv/d), increasing antibody titer and reducing the volume of perfusate. In addition, process improvements were performed to increase productivity by 80% over previously reported values. In addition, a real-time method for evaluating column performance to make column switching decisions was developed. This improved productivity coupled with the use of a single-column improved process monitoring and control in OCC compared to multi-column systems. This approach is the first report on using a single column for the implementation of an integrated continuous biomanufacturing platform and offers a cost-effective and flexible platform process for the manufacture of therapeutic proteins.
本文介绍了一种新的集成连续生物制造平台，该平台可在固定细胞体积和细胞浓度下长时间连续生产抗体，并能立即进行捕获。上游抗体生产已达到技术成熟阶段，然而，连续生物制造的瓶颈仍然是在初始色谱步骤中高效且经济高效地捕获治疗性抗体。在本研究中，展示了首次成功尝试使用单柱连续色谱法（OCC）连续捕获通过交替切向流灌注产生的治疗性抗体。通过进行上游培养基优化，上游灌注速率降低至每天一个容器体积（vv/d），提高了抗体滴度并减少了灌注液体积。此外，还进行了工艺改进，使生产率比先前报道的值提高了80%。此外，还开发了一种用于评估柱性能以做出柱切换决策的实时方法。与多柱系统相比，这种提高的生产率以及单柱的使用改进了OCC中的过程监测和控制。这种方法是关于使用单柱实施集成连续生物制造平台的首次报道，并为治疗性蛋白质的制造提供了一种经济高效且灵活的平台工艺。
