重组人生长激素体外生物学活性测定Nb2-11细胞增殖法的联合验证  

A collaborative study to evaluate the NB2-11 cell proliferation bioassay for human recombinant growth hormone

作　　者：张孝明 李鹤洋 邓哲 齐乃松 吴熙 李懿 王绿音 吕萍[1,2] 梁成罡 李晶[1,2] ZHANG Xiao-ming;LI He-yang;DENG Zhe;QI Nai-song;WU Xi;LI Yi;WANG Li-yin;LU Ping;LIANG Cheng-gang;LI Jing(NHC Key Laboratory of Research on Quality and Standardization of Biotech Products,NMPA Key Laboratory for Quality Research and Evaluation of Biological Products,National Institutes for Food and Drug Control,Beijing 102629,China;State Key Laboratory of Drug Regulatory Science,Beijing 102629,China;College of Life Science,Jilin University,Changchun 130012,China;Henan Institute for Drug and Medical Device Inspection,Henan Vaccine Issuance Center,Zhengzhou 450008,China;Shenzhen Institute for Drug Control,Shenzhen 518057,China)

机构地区：[1]中国食品药品检定研究院,国家卫生健康委生物技术产品检定方法及其标准化重点实验室,国家药品监督管理局生物制品质量研究与评价重点实验室,北京102629 [2]药品监管科学全国重点实验室,北京102629 [3]吉林大学生命科学学院,吉林长春130012 [4]河南省药品医疗器械检验院,河南省疫苗批签中心,河南郑州450008 [5]深圳市药品检验研究院,广东深圳518057

出　　处：《药学学报》2025年第3期784-790,共7页Acta Pharmaceutica Sinica

基　　金：2023年《中华人民共和国药典》药品标准提高课题(2023S08);药品监管科学全国重点实验室第一批课题(2023SKLDRS0108)。

摘　　要：为探索基于Nb2-11细胞增殖的重组人生长激素(rhGH)体外生物学活性测定方法的标准化,本研究首先检测了2批rhGH原液,3批注射用rhGH和24批rhGH注射液的生物学活性,初步制订了实验有效标准。进一步按照《中华人民共和国药典》2020年版通则9401进行方法学验证。随后联合7家实验室采用本方法测定来自4家不同生产企业的6批制剂及2批原液的体外生物学活性,分别对实验室间一致性,实验室内和实验室间精密度进行了研究。用本方法和体内动物法分别检测28批rhGH原液,进行体内外结果一致性研究。最后检测多批不同效期rhGH样品,进行标准限度研究。联合验证结果表明,本方法具有良好的实验室内及实验室间重现性,拟订实验有效标准通过率为100%。本方法与体内动物法检测结果具有良好的一致性。动物实验获得中国食品药品检定研究院实验动物福利伦理委员会批准[批准号:中检动(福)第2024(B)004号]。本方法适用于国内外不同生产厂家的rhGH原液与制剂,可作为测定rhGH类产品生物学活性的标准化方法替代体内动物法应用于rhGH的质量控制和放行检验。To explore the standardization of the in vitro Nb2-11 cell proliferation bioassay for recombinant human growth hormone(rhGH),we first tested the biological activity of 2 batches of rhGH drug substances,3batches of rhGH for injection,and 24 batches of rhGH injections,based on which we proposed the experimental effective criteria.Furthermore,we conducted methodological validation in accordance with General Rule 9401 of the 2020 edition of the Pharmacopoeia of the People's Republic of China.Subsequently,the inter-laboratory consistency,intra-laboratory and inter-laboratory precision of seven labs were studied by determining the in vitro bioactivity of six batches of rhGH products and two batches of rhGH drug substances from four different manufacturers using this method.The consistency of the in vitro and in vivo bioassays was assessed by evaluating 28 batches of rhGH drug substances with both methods.Finally,multiple batches of rhGH samples with different expiration dates were tested to determine the standard limits of the bioassay.The results of this collaborative study indicate that the Nb2-11 cell bioassay exhibits good intra-and inter-laboratory reproducibility,with a 100%pass rate for the experimental effective criteria.The Nb2-11 cell bioassay had high consistency with in vivo animal bioassay.Animal experiments were approved by the Experimental Animal Welfare Ethics Committee of China National Institute of Food and Drug Control(approval number:NIFDC(Fu)No.2024(B)004).This method is applicable to rhGH drug substances and products from different manufacturers.Collectively,the Nb2-11 cell bioassay can be used as a standardized method for determining the biological activity of rhGH products,replacing in vivo animal methods for quality control and release testing.

关 键 词：重组人生长激素 生物学活性 细胞增殖法 方法学验证 联合验证 

分 类 号：R917[医药卫生—药物分析学]