Q1A中英文对照.docx

1、Q1A中英文对照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(R2)现第四版2003年 2月 6日制定Q1A(R2)文件历程原编码Q1Q1AQ1A(R)Q1A(R)历史在第二阶段被指导委员会批准并公开发布征求意见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 Q1A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。新编码日 期2005年 11月1992年9月 16日 Q11993 年10月 27日 Q1A1999年10月 7日 Q1A(R1)2000年

2、11月 8日 Q1A(R1)现第四版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（和气候带注Q1A(R2)Q1A(R2)2003年 2月 6日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。新原料药和制剂的稳定性试验 Q1A(R) 修订说明本修订的目的为了明确由于采用了 ICH Q1F“在气候带和注册申请的稳定性数据包”而使 Q1A(R) 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302 /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

3、-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3

4、0 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 302 /相对湿度 65%5% 下的实验资料。TABILITYTESTING OFNEWDRUG新原料药和制剂稳定性试验SSUBSTANCES AND PRODUCTS1. INTRODUCTION1.1. Objectives of the GuidelineThe following guideline is a revised version of the ICH Q1A

5、 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 area

6、s of the world.The guidelineseeks to exemplify thecorestabilitydatapackagefornewdrugsubstances andproducts,butleavessufficientflexibilitytoencompassthevariety of different practical situations thatmaybeencounteredduetospecificscientificconsiderationsandcharacteristicsofthematerialsbeingevaluated. Al

7、ternativeapproachescan beusedwhentherearescientificallyjustifiable reasons.1.2. Scope of the GuidelineThe 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 info

8、rmation tobe 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.1.导言1.1. 目的下述的指导原则是 ICH Q1A 的修订版本，并且它为新原料药和制剂在

9、欧洲、 日本、美国三个地区注册所需要的稳定性资料做出规定要求。它并不涵盖世界其它地区或出口到这些地区的注册要求。本指导原则试图去例证新原料药和制剂的核心稳定性数据，但是留有足够的弹性空间去适应由于特殊的科学考虑和被评估物质特殊性质而导致的各种不同的具体情况。在有科学依据和理由的情况下也可以采用替代的方案。1.2. 范围本指导文件所针对的是新分子实体及其相关制剂注册时需提交的信息。此指导文件并不寻求为简略或简化申请，变更申请和临床试验申请提供指导。在特定的密闭系统中的特殊剂型的抽样和检验的详细指导不包括在此指导文件的范Further guidance on new dosage forms an

10、d on biotechnological/biological products can be found in ICH guidelines Q1C and Q5C, respectively.1.3. General PrinciplesThepurposeofstabilitytestingistoprovideevidenceon how the qualityof adrugsubstanceordrugproductvarieswith time under the influence of a varietyofenvironmentalfactorssuchastempera

11、ture,humidity,and light,andtoestablish a re-test periodforthedrugsubstance or a shelf lifeforthedrugproductandrecommendedstorageconditions.The choice of test conditionsdefined in thisguidelineisbasedonananalysisoftheeffectsofclimaticconditions inthethreeregions of the EC, Japan and the UnitedStates.

12、 The mean kinetictemperature in anypart ofthe worldcanbederivedfromclimaticdata, and the worldcan be dividedinto four climatic zones, I-IV. This guidelineaddresses climaticzonesIandII.Theprinciplehas been established thatstabilityinformation generated in any one of the three regions of the EC, Japan

13、 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.围中。有关新剂型和生物技术 /生物制品进一步指导请分别参考 ICH Q1C 和 Q5C。1.3 通则稳定性试验的目的是为原料药或制剂的各种环境因素，如温度、湿度和光照等，影响下质量在如何随时间变

14、化提供证据，从而为原料药制定复检期或为制剂制定有效期，和推荐的贮存条件。本指导文件中的试验选择是基于对欧洲、日本、美国这三个地区的气候条件影响分析制定的。世界任何一个地带的平均动力学温度都可以从气象数据中获得，世界被分为四个气候带，本指导文件描述的是和气候带的情况。一个通用原则已经被确立，即欧洲、日本、美国这三个地区中的任一地区的稳定性资料都应被其他两个地区所互相接受，提供的资料应与本指导文件相一致，标签规格应与各自国家 /地区的要求相一致。2. GUIDELINES2.1. Drug Substance2.1.1. GeneralInformation on the stability of

15、 the drugsubstance is an integral part of thesystematic 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

16、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 ona single batch of the drug substance. It should include the

17、effect of temperatures (in 10 Cincrements (e.g., 50 C, 60 C,etc.) above that for accelerated testing), humidity (e.g., 75% RH or greater) where appropriate, oxidation, and photolysis on the drug substance. The testing should also evaluate the susceptibility of the drug substance to hydrolysis across

18、 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 establishing degradation pat

19、hways and developing and validating suitable analytical procedures. However, it may not be necessary toexamine specifically for certain degradation products if it has been demonstrated that they are not formed under accelerated or long term storage conditions.Results from these studies will form an

20、integral part of the information provided to regulatory authorities.2.指导文件2.1 原料药2.1.1 概述原料药的稳定性资料是系统评估稳定性的一个主要组成部分。2.1.2 影响因素试验原料药的影响因素试验能帮助确定可能的降解物，这些降解物能依次帮忙确立降解路径，确立分子的内在稳定性和确定验证方法的稳定性指示能力，影响因素试验的本质取决于具体的原料药及所涉及的制剂类别。影响因素试验可以在一个批次的原料药中展开研究，它包括温度的影响（以 10为增量单位，如 50， 60等，高于加速试验的温度），湿度的影响（例如 75%相对湿度

21、或更高），适当情况下氧化和光照的影响。当在溶液中或悬浮液中时，试验也可以通过一定范围的 pH 值评估原料药水解作用的敏感性。光稳定性试验是影响因素试验的一个主要组成部分。光稳定性试验的标准条件在ICH Q1B 中描述。在影响因素试验条件下检查降解产物能有帮助确立降解路径和开发验证合适的分析方法。但是，对于已知的并且经证明在加速和长期试验条件下没有形成的降解产物没有必要再做特别的检查。这些试验的结果是向监管部门提交资料的组成部分。2.1.3. Selection of BatchesData from formal stability studies should be provided on

22、at least three primary batches of the drug substance. The batches should be manufactured to a minimum of pilot scale by the same synthetic route as, and using a method of manufacture and procedure that simulates the final processto be used for, production batches. The overall quality of the batches

23、of drug substance placed on formal stability studies should be representative of the quality of the material to be made on a production scale.Other supporting data can be provided.2.1.4. Container Closure SystemThe stability studies should be conducted on the drug substance packaged in a container c

24、losure system that is the same as or simulates the packaging proposed for storage and distribution.2.1.3 批的选择在正式稳定性研究试验中需要至少提供3 个申报批次原料药的研究资料。 这些批次应该至少在中式规模下生产，并且与生产批次采用一样的合成路线，一样的生产方法和与最终过程相似的步骤。正式稳定性研究中原料药批次的整体质量应该能够代表生产批次的整体质量。其他支持性材料也可以提供。2.1.5. SpecificationSpecification,whichisa listoftests,2.

25、1.4 容器密闭系统referencetoanalyticalprocedures,and原料药在稳定性试验中的包装容器应该proposed acceptance criteria, is addressed与拟上市储存和运输的包装相同或相似in ICH Q6A and Q6B. Inaddition,specification for degradation products in adrug substance is discussed in Q3A.Stabilitystudies shouldincludetesting ofthose attributes of the drug s

26、ubstance that aresusceptible to change during storage and are2.1.5 质量标准likely toinfluencequality, safety, and/orefficacy.Thetestingshouldcover, as质量标准是由一系列的测试项目，参考appropriate,thephysical,chemical,的分析方法和拟研究标准组成，在ICHQ6Abiological, and microbiologicalattributes.和 Q6B 中有详细描述。另外，原料药降解产Validatedstability-

27、indicatinganalyticalprocedures should be applied. Whether and to物的质量标准在 Q3A 中做讨论。what extent replication should be performed稳定性研究应该包含对原料药一些储存will depend on the results from validation studies.2.1.6. Testing FrequencyFor long term studies, frequency of testing should be sufficient to establish the st

28、ability profile of the drug substance. For drug substances with a proposed re-test period of at least 12 months, the frequency of testing at the long term storage condition should normally be every 3 months over the first year, every 6 months over the second year, and annually thereafter through the proposed re-test period.At the accelerated storage condition, a minimum of three time points, including the initial and final time points (e.g., 0, 3, and 6 months), from a 6-month study is recommended. Where an expectation (based on development experience) exists that results from accelerated st