基于NMR指纹谱相关分析的生物类似药高级结构评价

建立了基于1H NMR指纹技术的生物类似药高级结构相似性分析方法,利用相关系数r和决定系数R2定量评估生物类似药与其原研药的结构相似度。将该方法应用在一种分子量为1620的抗菌性脂肽达托霉素上,比较了其类似药的活性原料成分(API)、类似药制剂与原研药克必信的高级结构相似性。实验结果显示,3个达托霉素样品的谱图存在显著差异,表明达托霉素类似药与其原研药在水溶液中存在结构差异。将该方法应用在分子量为145423的单克隆抗体药物曲妥珠单抗的高级结构比对上。对1个批次的赫赛汀原研药、4个批次的类似药的1H NMR谱进行相似性分析,相关系数r和决定系数 R2的结果显示,曲妥珠单抗的类似药与赫赛汀原研药相似度很高;进一步采用局部相关系数进行谱图分析,得到了曲妥珠单抗类似药与赫赛汀原研药之间的微小差异。研究表明,有效结合NMR指纹分析技术和统计分析方法,将在生物类似药质量控制中发挥重大的作用。     

Charge profiling and stability testing of biosimilar by capillary isoelectric focusing

CIEF was developed for the rapid analysis of charge heterogeneity of trastuzumab biosimilar using commercially available fluorocarbon‐coated capillary. The CIEF master mix was composed of 0.30% w/v methyl cellulose, 2.3 M urea, 56.8 mM l ‐arginine, 1.52 mM iminodiacetic acid, 4.5% v/v carrier ampholytes (broad‐range pI 3–10 and narrow‐range pI 8–10.5 with ratio of 3:1), and 0.45% v/v 10.0, 9.5, 7.0, 5.5, 4.1 pI markers. To get a robust method to analyze charge heterogeneity, some separation parameters, including focusing time and separation temperature, were investigated and optimized. The optimized method gave good precision in estimated pI values of charge variants with RSDs of not more than 0.16% intraday analysis (n = 6) and < 0.18% interday analysis (n = 9). In addition, the applications of this method including purity, stability, lot consistency, peptide N‐glycosidase F digest, and C‐terminal lysine variants characterization were also investigated.     

Cutting‐edge mass spectrometry characterization of originator,biosimilar and biobetter antibodies

The approval process for antibody biosimilars relies primarily on comprehensive analytical data to establish comparability and high similarity with the originator. Mass spectrometry (MS) in combination with liquid chromatography (LC) and electrophoretic methods are the corner stone for comparability and biosimilarity evaluation. In this special feature we report head‐to‐head comparison of trastuzumab and cetuximab with corresponding biosimilar and biobetter candidates based on cutting‐edge mass spectrometry techniques such as native MS and ion‐mobility MS at different levels (top, middle and bottom). In addition, we discuss the advantages and the limitations of sample preparation and enzymatic digestion, middle‐up and ‐down strategies and the use of hydrogen/deuterium exchange followed by MS (HDX‐MS). Last but not least, emerging separation methods combined to MS such as capillary zone electrophoresis‐tandem MS (CESI‐MS/MS), electron transfer dissociation (ETD), top down‐sequencing (TDS) and high‐resolution MS (HR‐MS) that complete the panel of state‐of‐the‐art MS‐based options for comparability and biosimilarity evaluation are presented. Copyright © 2015 John Wiley & Sons, Ltd.     

生物类似药显露头角医药研发成本不断攀升——2016年重磅新药研发热点回眸

 2016年,全球医药市场规模超过1万亿美元,医药研发成本不断攀升,小分子新药获批数量日益降低,抗肿瘤药物、孤儿药研发势头依旧不减。随着生物药专利悬崖逐渐显现,生物类似药崭露头角。遴选了2016年上市的部分重磅新药,盘点了抗感染、抗肿瘤、中枢神经系统等领域的新药研发进展,回顾了2016年国内药学领域的相关热点事件。