| 姜小林,董素萍,舒靖能.ICH Q3D新药制剂元素杂质评估及控制的要点解读[J].中国药事,2017,(8):854-860 |
| ICH Q3D新药制剂元素杂质评估及控制的要点解读 |
| Interpretation of Key Points of Assessment and Control of Elemental Impurities in New Drug Preparations for ICH Q3D Guideline |
| 投稿时间：2017-04-29 |
| DOI：10.16153/j.1002-7777.2017.08.005 |
| 中文关键词: 新药制剂 元素杂质 风险评估 日允许暴露量 元素浓度限度 药品质量 |
| 英文关键词: new drug preparation elemental impurities risk assessment permitted daily exposure elemental impurity limit drug quality |
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| 中文摘要: |
| 目的：药品中可能有多个来源的元素杂质，由于元素杂质不能给病人提供任何治疗益处，因而药品生产中元素杂质含量应被控制在可接受的限度内。国际人用药物注册技术协调会议（ICH）Q3D元素杂质指南是新药制剂元素杂质控制的质量指南，旨在为新药制剂和其赋形剂中元素杂质的定性和定量控制提供全球性方针。本文介绍Q3D元素杂质指南，对相关要点进行解读。方法：详细描述元素杂质指南的主要内容，侧重于对元素风险评估及设定制剂中各组分元素杂质的限度进行具体分析。根据《美国药典》39和《欧洲药典》9.0中相关金属元素杂质的通则，汇总这些指导性文件与ICH Q3D的不同之处。结果与结论：Q3D主要包括潜在元素杂质的安全性评价、类别、元素杂质的风险评估和控制、日允许暴露量（Permitted Daily Exposure，简称PDE）与浓度限度之间的转换。元素杂质的风险评估应考虑潜在元素杂质的来源和药物服用方式，将特定元素杂质水平与PDE进行比较，评价该元素在药品中存在的可能性。经风险评估需要进行控制的元素杂质，可以根据药物服用剂量和PDE用3种方法设定元素浓度限度，这有利于帮助药品生产企业通过风险评估来决定对哪些元素进行额外控制，从而有效保障药品质量。 |
| 英文摘要: |
| Objective: Elemental impurities in drug products may arise from several sources. Since the elemental impurities do not provide any therapeutic benefits for the patients, the content of them in the drug products should be controlled within acceptable limits. ICH Q3D elemental impurities guidance is a quality guideline for the control of elemental impurities in new drug preparations and aims to provide a global policy for limiting elemental impurities qualitatively and quantitatively. This article is to introduce the ICH Q3D elemental impurities guidance and interpret the relevant key points. Methods: The main content of the ICH Q3D elemental impurity guidance were described in detail, focusing on risk assessment of elemental impurities and how to set the limit of elemental impurities for drug preparations. The differences among the ICH Q3D guideline, general rule of the United States Pharmacopoeia 39 and European Pharmacopoeia 9.0 were summarized. Results and Conclusion: The ICH Q3D guideline mainly includes safety assessment of potential elemental impurities, classification of element, risk assessment and control of elemental impurities, conversion between permitted daily exposure (PDE) and concentration limits. The risk assessment should consider the sources of elemental impurities and administration routes of drug. The presence of a particular elemental impurity in the drug product was evaluated by determining the observed level of the impurity and comparing with the established PDE. The elemental impurity limits that should be controlled after risk assessment might be established using three methods and based on daily intakes and PDE. It is useful for manufacturers to determine which elemental impurity should be controlled additionally after risk assessment and effectively ensure drug quality. |
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