Isaksson Madelène, Gomis-Fons Joaquín, Andersson Niklas, Nilsson Bernt
Department of Chemical Engineering, Lund University, SE-211 00 Lund, Sweden.
Department of Chemical Engineering, Lund University, SE-211 00 Lund, Sweden.
J Chromatogr A. 2023 Apr 26;1695:463942. doi: 10.1016/j.chroma.2023.463942. Epub 2023 Mar 24.
Buffer management for biopharmaceutical purification processes include buffer preparation, storage of buffers and restocking the buffers when needed. This is usually performed manually by the operators for small scale operations. However, buffer management can become a bottleneck when running integrated continuous purification processes for prolonged times, even at small scale. To address this issue, a buffer management system for the application in continuous lab-scale bioprocessing is presented in this paper. For this purpose, an ÄKTA™ explorer chromatography system was reconfigured to perform the buffer formulation. The system formulated all buffers from stock solutions and water according to pre-specified recipes. A digital twin of the physical system was introduced in the research software Orbit, written in python. Orbit was also used for full automation and control of the buffer system, which could run independently without operator input and handle buffer management for one or several connected buffer-consuming purification systems. The developed buffer management system performed automatic monitoring of buffer volumes, buffer order handling as well as buffer preparation and delivery. To demonstrate the capability of the developed system, it was integrated with a continuous downstream process and supplied all 9 required buffers to the process equipment during a 10-day operation. The buffer management system processed 55 orders and delivered 38 L of buffers, corresponding to 20% of its capacity. The pH and conductivity profiles observed during the purification steps were consistent across the cycles. The deviation in conductivity and pH from the measured average value was within ±0.89% in conductivity and ±0.045 in pH, well within the typical specification for buffer release, indicating that the prepared buffers had the correct composition. The operation of the developed buffer management system was robust and fully automated, and provides one solution to the buffer management bottleneck on lab scale for integrated continuous downstream bioprocessing.
生物制药纯化过程中的缓冲液管理包括缓冲液制备、缓冲液储存以及在需要时补充缓冲液。对于小规模操作，这通常由操作人员手动完成。然而，即使是小规模操作，在长时间运行集成连续纯化过程时，缓冲液管理也可能成为瓶颈。为了解决这个问题，本文介绍了一种用于连续实验室规模生物加工的缓冲液管理系统。为此，对ÄKTA™探索者色谱系统进行了重新配置以进行缓冲液配制。该系统根据预先指定的配方从储备溶液和水中配制所有缓冲液。在以Python编写的研究软件Orbit中引入了物理系统的数字孪生。Orbit还用于缓冲液系统的完全自动化和控制，该系统可以在无需操作员输入的情况下独立运行，并为一个或几个相连的消耗缓冲液的纯化系统处理缓冲液管理。所开发的缓冲液管理系统对缓冲液体积进行自动监测、处理缓冲液订单以及进行缓冲液制备和输送。为了证明所开发系统的能力，将其与连续下游工艺集成，并在10天的运行期间为工艺设备供应了所有9种所需的缓冲液。缓冲液管理系统处理了55个订单，输送了38升缓冲液，相当于其容量的20%。在纯化步骤中观察到的pH值和电导率曲线在各个循环中是一致的。电导率和pH值与测量平均值的偏差在电导率方面在±0.89%以内，在pH值方面在±0.045以内，完全在缓冲液放行的典型规格范围内，表明所制备的缓冲液成分正确。所开发的缓冲液管理系统运行稳健且完全自动化，为实验室规模的集成连续下游生物加工中的缓冲液管理瓶颈提供了一种解决方案。
