人用药品注册技术要求国际协调会ICH三方指导文件新原料药和制剂的稳定性试验 Q1A现第四版2003年2月6日制定Q1A文件历程原编码历史日 期新编码2005年11月Q1在第二阶段被指导委员会批准并公开发布征求意见1992年9月16日Q1Q1A在第四阶段被指导委员会批准并推荐给ICH三方当局征求意见.Q1A从命名为Q1A1993年10月27日Q1AQ1A第一次修订文本得到指导委员会批准并公开发布征求指导意见1999年10月7日Q1AQ1A在第四阶段第一版被指导委员会批准并推荐给ICH三方当局征求意见.2000年11月8日Q1A现第四版Q1A第四阶段第二版直接被指导委员会批准,没有公开发布征求意见.此文本包含了因采纳Q1F〔Ⅲ和Ⅳ气候带注册申请的稳定性数据包〕所引起的改变,并推荐给ICH三方当局采纳.2003年2月6日Q1A新原料药和制剂的稳定性试验Q1A修订说明本修订的目的为了明确由于采用了ICH Q1F"在气候带Ⅲ和Ⅳ注册申请的稳定性数据包"而使Q1A而产生的变更.这些变更如下：1. 在下面章节中将中间储存条件从温度30℃±2℃/相对湿度60%±5%修改为温度30℃±2℃/相对湿度65%±5%：2.1.7.1 原料药-储存条件-一般情况2.2.7.1 制剂-储存条件-一般情况2.2.7.3 在半渗透性容器中包装的制剂3 术语-"中间试验"2. 在下面章节中可以使用温度30℃±2℃/相对湿度65%±5%替代温度25℃±2℃/相对湿度60%±5%作为长期稳定性试验的条件：2.1.7.1 原料药-储存条件-一般情况2.2.7.1 制剂-储存条件-一般情况3.在温度25℃±2℃/相对湿度40%±5%的基础上增加了温度30℃±2℃/相对湿度35%±5%作为长期稳定性试验条件,并且在后面的章节中包括了失水比率相关举例的相关情况：2.2.7.3 在半透性容器中包装的制剂在试验阶段中间将中间将储存条件从温度30℃±2℃/相对湿度60%±5%调整为温度30℃±2℃/相对湿度65%±5%是可以的,但相应的储存条件和调整的日期要在注册申报资料中清楚地说明和列出.如果适用的话建议ICH三方在公布和执行此修订指南三年后,注册申请资料中完整的试验能够包含在中间储存条件,即温度30℃±2℃/相对湿度65%±5%下的实验资料.STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTS1. INTRODUCTION 1.1. Objectives of the Guideline The following guideline is a revised version of the ICH Q1A guideline and defines the stability data package for a new drug substance or drug product that is sufficient for a registration application within the three regions of the EC, Japan, and the United States. It does not seek necessarily to cover the testing for registration in or export to other areas of the world. The guideline seeks to exemplify the core stability data package for new drug substances and products, but leaves sufficient flexibility to encompass the variety of different practical situations that may be encountered due to specific scientific considerations and characteristics of the materials being evaluated. Alternative approaches can be used when there are scientifically justifiable reasons. 1.2. Scope of the Guideline The guideline addresses the information to be submitted in registration applications for new molecular entities and associated drug products. This guideline does not currently seek to cover the information to be submitted for abbreviated or abridged applications, variations, clinical trial applications, etc. Specific details of the sampling and testing for particular dosage forms in their proposed container closures are not covered in this guideline. Further guidance on new dosage forms and on biotechnological/biological products can be found in ICH guidelines Q1C and Q5C, respectively.1.3. General Principles The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light, and to establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions. The choice of test conditions defined in this guideline is based on an analysis of the effects of climatic conditions in the three regions of the EC, Japan and the United States. The mean kinetic temperature in any part of the world can be derived from climatic data, and the world can be divided into four climatic zones, I-IV. This guideline addresses climatic zones I and II. The principle has been established that stability information generated in any one of the three regions of the EC, Japan and the United States would be mutually acceptable to the other two regions, provided the information is consistent with this guideline and the labeling is in accord with national/regional requirements.2. GUIDELINES 2.1. Drug Substance 2.1.1. General Information on the stability of the drug substance is an integral part of the systematic approach to stability evaluation. 2.1.2. Stress TestingStress testing of the drug substance can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic stability of the molecule and validate the stability indicating power of the analytical procedures used. The nature of the stress testing will depend on the individual drug substance and the type of drug product involved. Stress testing is likely to be carried out on a single batch of the drug substance. It should include the effect of temperatures above that for accelerated testing>, humidity where appropriate, oxidation, and photolysis on the drug substance. The testing should also evaluate the susceptibility of the drug substance to hydrolysis across a wide range of pH values when in solution or suspension. Photostability testing should be an integral part of stress testing. The standard conditions for photostability testing are described in ICH Q1B. Examining degradation products under stress conditions is useful in establis。
