[关键词]
[摘要]
运用量化模型估计药品有效期是长期稳定实验的核心及新药申报中的重要节点。通过对比最新《中国药典(2015版)》中的对应规定(第IV部,9001章)与国际法规ICH Q1E中的估计方法,阐明ICH Q1E是符合国内法规的。其次,通过理论分析解释了国内与国际法规中量化模型所隐含的假设及局限性。最后,通过蒙特卡洛模拟得出有效期估计值的经验分布,表明取均值为最终有效期估计值的方法,可能比ICH Q1E中的方法更倾向于低估真实有效期,从而置制造方于不必要的劣势。
[Key word]
[Abstract]
Shelf-life estimation is the core of stability tests and critical to the final label claim on the package of new drug. Firstly, this paper depicts the methods of ICH Q1E for shelf-life estimation, compares it to the counterpart in the newest version of Chinese Pharmacopeia (Ch. P 2015, IV-9001), and proves its compliance. Secondly, this paper also unfolds the latent assumptions and hinged limitations of the quantitative methods in the guidelines. Finally, the empirical distributions of the shelf-life estimators are obtained via Monte-Carlo simulation to facilitate better understanding of properties of the estimators. It is shown that the approach that takes the average as final shelf-life estimate is likely to further underestimate the true shelf-life comparing to the ICH Q1E approach, and hence puts the manufacturers in unnecessary disadvantage.
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[基金项目]