中美低剂量药物混合均匀度和中控剂量单位均匀度技术要求对比  

Comparison of Technical Requirements for Low-Dose Oral Solid Drug Blend Uniformity and In-Process Dosage Unit Uniformity Between China and the USA

作　　者：徐云 XU Yun(Nanjing Hicin Pharmaceutical Co.,Ltd.,Nanjing,Jiangsu,China 210046)

机构地区：[1]南京海辰药业股份有限公司,江苏南京210046

出　　处：《中国药业》2024年第5期29-34,共6页China Pharmaceuticals

摘　　要：目的为我国上市许可持有人进行药品国内注册申报、美国注册申报或中美双报时提供研究思路。方法调研中美制药行业关于低剂量口服固体药物全生命周期中混合均匀度和中控剂量单位均匀度研究背景及技术指南要求,对比分析中美技术指南的优势与不足,以阿哌沙班片为例,探讨中美技术指南中混合均匀度、中控剂量单位含量均匀度的研究和评估策略,并提出一地研发、中美双报时的研究建议。结果混合均匀度方面,中美技术指南取样方案基本一致,但评价标准中国技术指南要求更严格。中控剂量单位均匀度方面,取样方案中国技术要求采用分层取样,而美国技术要求采用系统取样,取样方案有差异但不显著,均可接受;评价标准方面,中国技术要求采用单纯的相对标准偏差值、单值及均值控制,而美国技术要求单值和统计学检验(90%置信区间/95%覆盖率),便于进行趋势检查分析(如位置内/位置间变异)。结论建议国内上市许可持有人在进行一地研发、中美双报时,需结合中美技术指南要求,在混合阶段和压片阶段应选择要求更高的技术指南进行均匀度评估。Objective To provide new ideas for marketing license holders'application for registration in China/the United States of American(USA)or both in China and the USA.Methods By investigating the research background and technical guidelines requirements of the pharmaceutical industry in China and the USA on the low-dose oral solid drug blend uniformity and in-process dosage unit uniformity in the entire life cycle.A comparative analysis of the advantages and disadvantages of the technical guidelines between China and the USA was conducted.Taking Apixaban Tablets as an example,the research and evaluation strategies of blend uniformity and in-process dosage unit uniformity in the technical guidelines in China and the USA were investigated,and the research suggestions for research and development in one region while application both in China and the USA were put forward.Results In terms of blend uniformity,the sampling plans in the technical guidelines in China and the USA were basically the same,but the evaluation criteria were more stringent according to the technical guidelines in China.In terms of the in-process dosage unit uniformity,the sampling plan in the technical guidelines in China required stratified sampling,while that in the USA required systematic sampling.There were differences in the sampling plan between the two countries,but they were not significant and could be accepted.In terms of evaluation criteria,the technology in China required the use of simple relative standard deviation(RSD)values,single values,and mean controls,while that in the USA required single values and statistical tests(90%confidence interval/95%coverage)to facilitate trend checking analysis(such as within/between position variations).Conclusion It is recommended that domestic marketing license holders should select higher technical guidelines to carry out the uniformity evaluation during the blending and tablet pressing stages based on the requirements of technical guidelines in China and the USA when conduct research and developmen

关 键 词：低剂量药物 混合均匀度 含量均匀度 中美双报 技术指南 

分 类 号：R95[医药卫生—药学]