ASSESSMENT AND CONTROL OF DNA REACTIVE(MUTAGENIC) IMPURITIES
IN PHARMACEUTICALS TOLIMIT POTENTIAL CARCINOGENIC RISK 为限制潜在致癌风险而对药物中DNA活性（诱变性）杂质进行的评估和控制 M7
Current Step 4 version dated 23 June 2014
This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA.
M7
Document History 文件历史 Code 文件代码 History 历史 M7 Date 日期 Approval by the Steering Committee under Step 2 6 February 2013 and release for public consultation. 第2阶段由筹委会批准，公开征求意见 M7 Approval by the Steering Committee under Step 4 5 June 2014 and recommendation for adoption to the three ICH regulatory bodies. 第4阶段由筹委会批准，推荐ICH三方药监局采用 Current Step 4 version 现行版本第4阶段 M7 Corrigendum to fix typographical errors and 23 June 2014 replace word “degradants” with “degradation products” throughout the document. 修正输入错误，将全文中“degradants”替换成“degradation products”. Legal Notice: This document is protected by copyright and may be used, reproduced, incorporated into other works, adapted, modified, translated or distributed under a public license provided that ICH's copyright in the document is acknowledged at all times. In case of any adaption, modification or translation of the document, reasonable steps must be taken to clearly label, demarcate or otherwise identify that changes were made to or based on the original document. Any impression that the adaption, modification or translation of the original document is endorsed or sponsored by the ICH must be avoided.
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ASSESSMENT AND CONTROL OF DNA REACTIVE (MUTAGENIC) IMPURITIES
IN PHARMACEUTICALS TO LIMIT POTENTIALCARCINOGENIC RISK 为限制潜在致癌风险而对药物中DNA活性（诱变性）杂质进行的评估和控制 ICH Harmonised Tripartite Guideline ICH三方协调指南
Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 5 June 2014, this Guideline is recommended for adoption to the three regulatory parties to ICH TABLE OF CONTENTS 1. INTRODUCTION 2. SCOPE OF GUIDELINE 3. GENERAL PRINCIPLES 目录 概述 指南范围 通用原则 4. CONSIDERATIONS FOR MARKETED PRODUCTS 上市产品应考虑的问题 4.1 Post-Approval Changes to the Drug 批准后原料药化学、生产和质量变更 Substance Chemistry, Manufacturing, and Controls 4.2 Post-Approval Changes to the Drug 批准后制剂的化学、生产和质量变更 Product Chemistry, Manufacturing, and Controls 4.3 Changes to the Clinical Use of Marketed 上市产品临床使用变更 Products 4.4 Other Considerations for Marketed 上市产品其它应考虑问题 Products 5. DRUG SUBSTANCE AND DRUG PRODUCT 原料药和制剂杂质评估 IMPURITY ASSESSMENT
5.1 Synthetic Impurities 5.2 Degradation Products 5.3 Considerations for 合成杂质 降解产物 Clinical 临床研发要考虑的问题 Development 6. HAZARD ASSESSMENT ELEMENTS 7. RISK CHARACTERIZATION 7.1 TTC-based Acceptable Intakes 7.2 Acceptable Intakes Based 危害性评估要素 风险特征 根据TTC制订可接受摄入量 on 根据化合物特定风险评估制订的可接受摄入量 Compound-Specific Risk Assessments 7.2.1 Mutagenic Impurities with Positive 致癌数据有利的诱变性杂质（表1中的第1Carcinogenicity Data (Class 1 in Table 1) 类） 7.2.2 Mutagenic Impurities with Evidence 具有实用阈值证据的诱变性杂质 for a Practical Threshold 7.3 Acceptable Intakes in Relation to LTL 与LTL暴露相关的可接受摄入量 Exposure 7.3.1 Clinical Development 7.3.2 Marketed Products 临床研发 已上市产品 7.4 Acceptable Intakes for Multiple 多个诱变性杂质的可接受摄入量 Mutagenic Impurities 7.5 Exceptions and Flexibility in 方法例外情况和弹性 Approaches 8. CONTROL 控制 8.1 Control of Process Related Impurities 工艺相关杂质的控制 8.2 Considerations for Control Approaches 控制方法要考虑的问题
ICH M7(step4)基因毒性杂质评估和控制中英模板
