Jackobek Ryan, Herrick-Wagman Sarah, Zhu Lily, Francis Christopher, Solbrand Anita, Eriksson Christer, Berg Mikael, Go Daniel, D'Antona Aaron M
BioMedicine Design, Medicinal Sciences, Pfizer Worldwide R&D, Andover, MA 01810, United States.
BioMedicine Design, Medicinal Sciences, Pfizer Worldwide R&D, Andover, MA 01810, United States; CRISPR Therapeutics, Cambridge, MA 02139, United States.
J Chromatogr A. 2020 Sep 12;1630:461537. doi: 10.1016/j.chroma.2020.461537.
As discovery research organizations push more molecules and new modalities through their company pipelines, there comes a need to widen purification development and production bandwidth by increasing automation and throughput. Continuous processing technologies have the unique property of reducing manufacturing floor space and reducing costs. We can speed development and production by implementing automation and continuous process technologies early in discovery research. Here we describe an automated continuous instrument made up of an ÄKTA™ pcc for initial capture by protein A, an ÄKTA pure 150 retrofitted to automatically condition protein A eluate, and a second ÄKTA pure 150 built for flow-through anion exchange chromatography. The continuous instrument we have designed and built recirculates protein A eluate from the ÄKTA pcc in a closed loop while signals from the pH and conductivity meters direct addition of titrant for accurate and precise adjustments to the pH and salt concentration. The instrument is run without user intervention and can be used continuously for production or for development as a tool for screening running conditions on the anion exchange step.
随着发现研究机构在其公司流程中推进更多分子和新的药物形式，有必要通过提高自动化程度和通量来扩大纯化开发和生产的能力范围。连续处理技术具有减少生产占地面积和降低成本的独特特性。我们可以通过在发现研究的早期阶段实施自动化和连续工艺技术来加快开发和生产速度。在此，我们描述一种自动化连续仪器，它由用于通过蛋白A进行初始捕获的ÄKTA™ pcc、改装后用于自动调节蛋白A洗脱液的ÄKTA pure 150以及为流通式阴离子交换色谱而构建的第二台ÄKTA pure 150组成。我们设计和构建的连续仪器在闭环中循环来自ÄKTA pcc的蛋白A洗脱液，同时pH计和电导率仪的信号引导滴定剂的添加，以便对pH值和盐浓度进行精确调整。该仪器无需用户干预即可运行，可连续用于生产或作为筛选阴离子交换步骤运行条件的工具用于开发。
