Bioprocess Research and Development Laboratories, Production Division, Kyowa Hakko Kirin Co., Ltd., Takasaki, Gunma 370-0013, Japan.
Bioprocess Research and Development Laboratories, Production Division, Kyowa Hakko Kirin Co., Ltd., Takasaki, Gunma 370-0013, Japan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Dec 1;1102-1103:1-7. doi: 10.1016/j.jchromb.2018.10.004. Epub 2018 Oct 5.
Activated carbon (AC) is a porous solid with a higher surface area and a lower cost than chromatography resins. AC is widely used in the pharmaceutical field in applications such as the manufacturing of low-molecular and hematological drugs and as a treatment for oral poisoning and hemocatharsis. In this work, AC was employed in the purification process of therapeutic monoclonal antibodies (mAb). After screening several kinds of ACs, we investigated the selected AC used in a flow-through mode (with impurities binding) and as a replacement for Protein A affinity chromatography (PrA). The recovery, purity, and clearance of the impurities were examined compared with those obtained from the Protein A platform purification process (PrA followed by anion exchange chromatography (AEX) and cation exchange chromatography (CEX)). Comparable clearance of impurities, high-molecular-weight species (HMW), low-molecular-weight species (LMW), host cell proteins (HCP), and DNA were observed in the purification processes, which were AC followed by AEX and CEX. In addition, we designed all flow-through processes using AC. Effective HMW, LMW, and HCP clearance were also obtained in this manner. From these results, it is expected that AC can be applied to industrial mAb purification as an alternative to PrA to improve process economy.
活性炭（AC）是一种多孔固体，其比表面积比层析树脂更高，成本更低。AC 在制药领域中的应用广泛，例如制造低分子和血液药物，以及用于治疗口服中毒和血液净化。在这项工作中，AC 被用于治疗性单克隆抗体（mAb）的纯化过程中。在筛选了几种 AC 之后，我们研究了用于流经模式（与杂质结合）和替代 Protein A 亲和层析（PrA）的选定 AC。与从 Protein A 平台纯化过程（PrA 后接阴离子交换层析（AEX）和阳离子交换层析（CEX））获得的结果相比，考察了杂质、高分子量物质（HMW）、低分子量物质（LMW）、宿主细胞蛋白（HCP）和 DNA 的回收率、纯度和清除率。在 AC 随后进行 AEX 和 CEX 的纯化过程中，观察到杂质、HMW、LMW 和 HCP 的清除率相当。此外，我们设计了所有使用 AC 的流经过程。以这种方式也获得了有效的 HMW、LMW 和 HCP 清除率。从这些结果可以预期，AC 可以作为替代 Protein A 应用于工业 mAb 纯化，以提高工艺经济性。
