【生物药厂生产质控部门，生物药CMO企业】罕见病药厂使用ECL技术定量生物工艺的杂质

Implementation of electrochemiluminescence technology for quantification of bioprocess impurities
使用电化学发光技术ECL定量生物工艺中的杂质

发表时间：2008年
作者单位：乌普萨拉大学（瑞典语为Uppsala universitet），位居瑞典第一，欧洲第二十一及世界第七十一。
实验单位：Swedish Orphan Biovitrum公司（Sobi），现市值43亿美元。2015年，辉瑞意图收购这家瑞典研发治疗罕见病药物的制药公司。其主要研制罕见病药物，包括白血病、自身免疫性疾病、代谢性疾病、癌症支持疗法等。主要分布在欧洲、北美、澳大利亚、新西兰。公司在专科药领域进行开发，包括炎症/免疫疾病、溶酶体贮积症、血液病、肥胖症、蛋白替代疗法等。

2013 年 1 月 8 日，Swedish Orphan Biovitrum（Sobi）公司宣布，美国食品药品监督管理局（FDA）已批准 Kineret（anakinra，阿那白滞素）用于儿童与成人的早发性多系统炎症性疾病（NOMID）治疗。本品成为了第一也是唯一一种经 FDA 批准的 NOMID 治疗药物，NOMID 是 cryopyrin 蛋白相关的周期性综合征（CAPS）中最为严重的症状。这是本品第一次获批用于儿童患者中，之前也已获得了 FDA 的孤儿药认定。目前针对 NOMID 患者没有适宜的疗法，而基于该药物在疗效方面的巨大潜力，本品被授予了优先审查权。早在 2001 年，本品就获批用于成人类风湿性关节炎（RA）的治疗。

CAPS 是一种伴随终身并会引起人体严重衰弱的疾病，NOMID 则是该类别中最为严重的症状，与白介素 -1（IL-1）免疫系统蛋白的过度分泌有关。随着病情的进展，患者的听力和视力逐渐减退，认知功能产生障碍，并引起不同程度的关节变形。该药物长达 5 年的研究表明，本品除了能够控制日常症状，如发热、皮疹、头痛、关节痛等，对于稳定中枢神经系统（CNS）的功能（如听力和视力等）有着确切的疗效。

电化学发光技术：来自美国Meso Scale Discovery。

研究目的：使用MSD ECL替代ELISA，使得检测更快，更好。
In recombinant protein manufacturing for the purpose of producing protein-based drugs it is important to be able to demonstrate that impurities have been efficiently removed during the purification process and that the final product is pure. This project is involved in quantification of some of the impurities that may be found in a biopharmaceutical product; insulin, insulin like growth factor 1 (IGF-1) and host cell proteins (HCP). Analysis techniques that are to be used have to meet high demands in both sensitivity and in precision. Today the process related impurities are mainly analyzed with enzyme linked immunosorbent assays (ELISAs) that are available commercially as kits. However a new technique developed by Meso Scale Discovery (MSD) where the detection is based on electrochemiluminescence (ECL) technology is starting to replace ELISA. The reasons why the ECL assay may be superior to ELISA is that the measuring range is wider and the detection limit of the technique often is much lower, which means that the sensitivity is increased. Also the possibility to test multiple analytes in the same assay, a multiplex assay, reduces time and work load. This project evaluates this new technology by comparing results from the ECL assay with ELISA. Initially with one analyte at the time and if this comparison is successful the assays will be tested in a multiplex ECL assay format.

结论:
• The ECL assay is suitable for insulin and more sensitive than the ELISA currently used.
MSD电化学发光技术比ELISA更适用于胰岛素检测，其灵敏度比其使用的ELISA高
• The singleplex and duplex assay for HCP generate similar signals.
宿主细胞蛋白HCP的单因子检测和多因子检测信号一致(使用MSD多因子技术可以在一个孔内同时检测宿主细胞蛋白HCP和药物，节约时间和劳力）

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