经口吸入和鼻用药物制剂体外生物等效性统计学评价方法  

Statistical evaluation methods of in vitro studies for bioequivalence for orally inhaled and nasal drug products

作　　者：耿颖[1] 杨泉 张军[3] 王蕊 周颖[1] 郑静 宁保明[1] 魏宁漪[1] GENG Ying;YANG Quan;ZHANG Jun;WANG Rui;ZHOU Ying;ZHENG Jing;NING Bao-ming;WEI Ning-yi(National Institutes for Food and Drug Control,Beijing 102629,China;Merck Serono(Beijing)Pharmaceutical R&D Co.,Ltd.,Beijing 100000,China;Chinese Pharmacopoeia Commission,Beijing 100061,China)

机构地区：[1]中国食品药品检定研究院,北京102629 [2]默克雪兰诺(北京)医药研发有限公司,北京100000 [3]国家药典委员会,北京100061

出　　处：《药学学报》2021年第10期2630-2641,共12页Acta Pharmaceutica Sinica

基　　金：国家食品药品监督管理局化学药品研究与评价重点实验室资助项目。

摘　　要：本文系统阐述了经口吸入和鼻用药物制剂(orally inhaled and nasal drug products,OINDPs)生物等效性(bioequivalence,BE)研究评估背景,综述了中国及国际上对该类制剂生物等效性的要求及体外等效性评价指导原则,详细阐述了美国食品药品管理局(FDA)体外生物等效性(in vitro bioequivalence,IVBE)评估的统计学方法和计算公式。采用FDA颁布的布地奈德吸入混悬液指导原则拟定稿中的实例,通过R语言编程途径计算群体生物等效性(population bioequivalence,PBE)统计学参数,并将结果与指导原则中的结果进行对比,提供计算程序的伪代码。本文为OINDPs的研发、质量控制及仿制制剂的开发提供了有益的思路与参考。This article systematically reviews the background and regulatory requirements of bioequivalence of orally inhaled and nasal drug products(OINDPs),as well as the basic regulatory requirements for the assessment by the guidelines and guidance issued in China,the United States,and the European Union.Detailed statistical evaluation method considerations and calculations of the US FDA population bioequivalence(PBE)method were presented for the evaluation of in vitro bioequivalence(IVBE)for OINDPs.Using the example described in the FDA Draft Guidance for budesonide inhalation suspension,the PBE analysis statistical parameters were calculated via the R programming,and the results were compared with that in the guidelines.Moreover,pseudo-code for the PBE calculation program was provided.This paper aims to provide guidance and references for the research and development of new drug,as well as pharmaceutical quality control,and development of generic medicinal products for OINDPs.

关 键 词：经口吸入和鼻用药物 生物等效性 体外生物等效性 群体生物等效性 计算程序伪代码 布地奈德吸入混悬液 

分 类 号：R943[医药卫生—药剂学]