European Medicines Agency  Veterinary Medicines and Inspections
7 Westferry Circus, Canary Wharf, London, E14 4HB, UK
Tel. (44-20) 74 18 84 00    Fax (44-20) 74 18 84 47
E-mail: mail@emea.europa.eu    a.europa.eu London, 19 February 2007
Doc.
Ref.EMEA/CVMP/VICH/899/99-Rev.1
VICH Topic GL3
Step 7 (after revision at step 9)
GUIDELINE ON STABILITY: STABILITY TESTING OF NEW VETERINARY DRUG
SUBSTANCES AND MEDICINAL PRODUCTS
ADOPTION BY CVMP FOR RELEASE FOR CONSULTATION    5 October 2005
TRANSMISSION TO INTERESTED PARTIES October 2005
END OF CONSULTATION    5 January 2006
ADOPTION BY CVMP  14 February 2007
DATE FOR COMING INTO EFFECT January 2008
VICH GL3(R) (Q UALITY)
January 2007
Revision at Step 9
For Implementation at Step 7
稳定性：兽药新品种和药品的稳定性试验（修订版）
S TABILITY: S TABILITY T ESTING OF
N EW V ETERINARY D RUG S UBSTANCES AND M EDICINAL
P RODUCTS (R EVISION)
Recommended for Adoption
at Step 7 of the VICH Process
in January 2007 by the VICH SC
for implementation in January 2008
This Guideline has been developed by the appropriate VICH Expert Working Group and is subject to consultation by the parties, in accordance with the VICH Process.  At Step 7 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA.
Secretariat : C/O IFAH, rue Defacqz, 1 - B - 1000 Bruxelles (Belgium) - Tel. +32-2-543.75.72, Fax +32-2-543.75.85
TABLE OF CONTENTS
1. INTRODUCTION (4)
1.1. Objectives of the Guideline (4)
1.2. Scope of the Guideline (4)
1.3. General Principles (4)
2. GUIDELINES (5)
2.1. Drug Substance (5)
2.1.1 General (5)
2.1.2. Stress Testing (5)
2.1.3. Selection of Batches (5)
2.1.4. Container Closure System (6)
2.1.5. Specification (6)
2.1.6. Testing Frequency (6)
2.1.7. Storage Conditions (6)
2.1.8. Stability Commitment (8)
2.1.9. Evaluation (9)
2.1.10. Statements/Labeling (7)
2.2. Medicinal product (10)
2.2.1. General (10)
2.2.2. Photostability Testing (10)
2.2.3. Selection of Batches (10)
2.2.4. Container Closure System (10)
2.2.5. Specification (11)
2.2.6. Testing Frequency (11)
2.2.7. Storage Conditions (12)GL甜文推荐
2.2.8. Stability Commitment (16)
2.2.9. Evaluation (17)
2.2.10. Statements/Labeling (18)
3. GLOSSARY (18)
4. REFERENCES (22)
1. INTRODUCTION
1.1. Objectives of the Guideline  The following guideline is a revised version of the VICH GL3 guideline and defines the stability data package for a new drug substance or medicinal product that is sufficient for a registration application within the three regions of the EC, Japan, and the United States.  It does
not seek to address 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 Guidance
The guideline addresses the information to be submitted in registration applications for new
molecular entities and associated medicinal products.  This guideline does not currently seek
to cover the information to be submitted for abbreviated or abridged applications, variations,
or 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, medicated premixes, and on
biotechnological/biological products can be found in VICH guidelines GL4, GL8, and GL17,
respectively. Stability testing following first use of the product (e.g., first broaching of a vial)
is not covered within this guideline.
1.3. General Principles
The purpose of stability testing is to provide evidence on how the quality of a drug substance
or medicinal 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 medicinal 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 guidance and the labeling
is in accord with national/regional requirements.
简介
指导原则的目标
以下指南是VICH GL3指南的修订版，定义了一种新的药物或药品的稳定性数据包，该数据包足以在EC 、日本和美国三个地区内进行注册申请。它不寻求解决在世界其他地区注册或出口到其他地区的测试问题。该指南旨在举例说明新药物和新产品的核心稳定性数据包，但仍留有足够的灵活性，以涵盖由于具
体的科学考虑和所评估材料的特性而可能遇到的各种不同实际情况。当有科学合理的理由时，可以使用替代方法。该指南涉及新分子实体和相关医药产品注册申请中应提交的信息。本指南目前并不试图涵盖为简化或简化申请、变更或临床试验申请等提交的信息。1.2 指导范围本指南不包括特定剂型在其拟用容器封盖中的取样和测试的具体细节。关于新剂型、药物预混料和生物技术/生物制品的进一步指南，可分别在VICH 指南GL4、GL8和GL17中到。本指南不包括产品首次使用后的稳定性测试（例如，小瓶的首次拉削）。
稳定性试验的目的是提供药物或药品在温度、湿度和光照等多种环境因素影响下的质量随时间变化的证据，并为原料药或药品建立一个复验期或药品的保质期，并提出建议储存条件。  1.3 一般原则本指南中定义的试验条件的选择基于对欧共体、日本和美国三个地区气候条件影响的分析。世界任何地区的平均动力温度可从气候数据中得出，世界可分为四个气候区，即I-IV 。本指南涉及气候带I 和II 。已确立的原则是，在欧共体、日本和美国三个区域中的任何
一个区域生成的稳定性信息都可以被其他两个区域相互接受，前提是信息与本指南一致，且标签符合国家/地区要求。
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 Testing  Stress 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 medicinal 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 (in 10°C increments (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 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 VICH GL5.  Examining degradation products under stress conditions is useful in establishing degradation pathways and developing and validating suitable analyt
ical procedures.  However, it may not be necessary to examine 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 integral part of the information provided to regulatory
authorities.
2.1.
3. Selection of Batches
Data from formal stability studies should be provided on 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
process to be used for, production batches.  The overall quality of the batches 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.
影响因素试验 美 /fo ʊˈt ːl əs ɪs/ 有关原料药稳定性的信息是稳定性评估系统方法的组成部分。
2指导方针
2.1 药物2.1.1总则
药物的影响因素测试有助于识别可能的降解产物，进而有助于建立降解途径和分子的内在稳定性，并验证所用分析程序的稳定性指示能力。影响因素测试的性质将取决于单个药物和所涉及的药品类型。影响因素试验很可能只对一批原料药进行。它应包括温度（以10°C 的增量（例如，50°C 、60°C 等）高于加速试验的温度）、合适的湿度（如75%RH 或更高）、氧化和光解对原料药的影响。测试还应评估原料药在溶液或悬浮液中时在各种pH 值范围内水解的敏感性。光稳定性测试应该是压力测试的
一个组成部分。光稳定性测试的标准条件在VICH GL5中描述。在影响条件下检测降解产物有助于建立降解途径，开发和验证合适的分析程序。但是，如果已经证明某些降解产物不是在加速或长期储存条件下形成的，则可能没有必要专门检查这些降解产物。这些研究的结果将构成提供给监管机构的信息的一个组成部分。
应提供至少三批原料药的正式稳定性研究数据。这些批次应采用与生产批次相同的合成路线，并采用模拟生产批次的最终工艺的制造方法和程序，以达到最小的中试规模。进行正式稳定性研究的各批原料药的总体质量应代表按生产规模生产的材料的质量。2.1.3 批次选择可提供其他支持资料