FDA工业指南：ANDA：药物和产品的稳定性测试

Guidance for Industry

ANDAs: Stability Testing of Drug Substances and Products



指导行业
药品及制品的稳定性试验


















U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER)

June 2013

Generics

美国卫生与公众服务部食品和药物管理局药物评价和研究中心(CDER)

2013年6月
仿制药


Guidance for Industry

ANDAs: Stability Testing of Drug Substances and Products




Additional copies are available from:

Office of Communications
Division of Drug Information, WO51, Room 2201
Center for Drug Evaluation and Research
Food and Drug Administration
10903 New Hampshire Ave., Silver Spring, MD 20993
Phone: 301-796-3400; Fax: 301-847-8714
druginfo@fda.hhs.gov
http://www.fda.gov/Drugs/Guidanc ... idances/default.htm



其他副本可从:
办公室沟通
药物信息司，WO51室，2201室
药物评价和研究中心
食品和药物管理局
马里兰州银泉市新汉普郡大街10903号，邮编20993
电话:301-796-3400;
传真:301-847-8714
druginfo@fda.hhs.gov
http://www.fda.gov/Drugs/Guidanc ... idances/default.htm









U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER)

June 2013

Generics


TABLE OF CONTENTS




I.        INTRODUCTION        1

II.        BACKGROUND        1

III.        DISCUSSION        2







目录
I.        引言………………………………………………………………………………………..1
II.      背景…………………………………………………….…………………………………..1
III.    讨论………………………………………………………………………………………...2
Guidance for Industry1
ANDAs: Stability Testing of Drug Substances and Products
指导行业1
药品及制品的稳定性试验




This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.

















I.        INTRODUCTION
I.             引言

This guidance recommends that abbreviated new drug applications (ANDAs) submitted under section 505(j) of the Federal Food, Drug and Cosmetic Act, and the drug master files (DMFs) that support ANDAs, follow the stability recommendations provided in the International Conference on Harmonisation (ICH) stability guidances.
本指南建议，根据联邦食品、药物和化妆品法第505(j)条提交的简短新药申请(ANDAs)，以及支持ANDAs的药物主文件(DMFs)，应遵循国际协调会议(ICH)稳定性指南中提供的稳定性建议。在本指南的扉页上列出的序号。

FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.
FDA的指导文件，包括本指南，没有建立法律上可执行的责任。相反，指南描述了该机构当前对某个主题的想法，应该只将其视为建议，除非引用了具体的监管或法律要求。在机构指南中使用should这个词意味着某事被建议或推荐，但不是必需的。

II.        BACKGROUND
Ⅱ.   背景

Over the past few years, the Office of Generic Drugs (OGD) has received numerous inquiries about what stability data FDA expects in ANDA submissions. Currently, the only published direction from OGD is contained in a 1995 letter to industry which states that OGD will accept ICH recommended long-term room temperature conditions for stability studies (i.e., 25±2°C, 60±5% RH). Although adequate in the context of other guidance existing at that time, this recommendation is no longer sufficient to serve as a basis for stability testing for ANDAs.
在过去的几年里，仿制药办公室(OGD)收到了许多关于FDA期望ANDA提交的稳定性数据的询问。
目前，OGD唯一发表的指导意见载于1995年致工业界的一封信中，信中说，OGD将接受ICH推荐的长期室温稳定性研究条件。（ 25±2℃，60±5% RH)。
虽然在当时存在的其他指导范围内这一建议是充分的，但这一建议已不再足以作为ANDAs稳定性测试的基础。

The following existing ICH guidances address stability for new drug substances and products:
现有的ICH指南针对新药物物质和产品的稳定性:

1.        Q1A (R2) Stability Testing of New Drug Substances and Products.
Q1A (R2)新型药物物质和产品的稳定性检测。

2.        Q1B Photostability Testing of New Drug Substances and Products.
Q1B新型药物物质和产品的光稳定性测试。

3.        Q1C Stability Testing for New Dosage Forms.
新剂型Q1C稳定性检测。





1        This guidance has been prepared by the Office of Generic Drugs, Office of Pharmaceutical Science in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration.

1本指南由美国食品和药物管理局(fda)药物评价与研究中心(CDER)的仿制药办公室和药物科学办公室编写。
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4.        Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products.
Q1D新型药物物质和产品稳定性测试的支架和基质设计。

5.        Q1E Evaluation of Stability Data.2
Q1E稳定性数据评估2

In the discussion that follows, these guidances are referred to as ICH stability guidances.
在接下来的讨论中，这些指南被称为ICH稳定性指南。

III.        DISCUSSION
Ⅲ.   讨论

Although the ICH stability guidances were developed by ICH to provide guidance on the information that should be provided in new drug applications to ensure the stability of new drug substances and drug products, we believe the recommendations also should be applied to ANDAs.
虽然ICH制定的稳定性指南是为了指导新药的应用，以确保新药物质和药物产品的稳定性，但我们认为这些建议也应该适用于ANDAs。

When following the ICH stability recommendations, you, the applicant, should:
在符合ICH稳定性建议时，申请人应:

1.        Submit data from three pilot scale batches or two pilot scale batches and one small scale batch. If the size of the pilot scale batch does not follow ICH recommendations, the applicant should provide a justification.
提交三个试点批次或两个试点批次和一个小规模批次的数据。
如果试点批次的规模不符合ICH的建议，申请人应提供一个理由。

2.        At the time of submission, provide 6 months of data that include accelerated and long-term conditions. FDA recommends following ICH guidelines with respect to utilization of intermediate conditions to support shelf-life.
在提交时，提供6个月的数据，包括加速和长期条件。
FDA建议遵循ICH指导方针，利用中间条件来支持货架期。

3.        Use multiple lots of drug substance as appropriate.
适当使用多种药物。

4.        Manufacture and package the drug product using principles that are representative of the commercial process.
使用代表商业过程的原则生产和包装药品。

5.        Provide a fully packaged primary batch.
提供完整包装的主批处理。

6.        Use drug product from all three primary batches when using bracketing and matrixing designs under ICH Q1D.
当使用ICH Q1D下的包装和基质设计时，使用所有三个原产批次的药品。

7.        Provide statistical analysis of the data as appropriate, in accordance with ICH Q1E, Appendix A.
根据ICH Q1E，附录A提供数据的统计分析。

If you choose not to follow the above recommendations, you should provide FDA with a justification for the approach you intend to follow in your ANDA submissions to ensure stability.

如果您选择不遵循上述建议，您应该向FDA提供您打算在ANDA提交中遵循的方法的正当理由，以确保稳定性。






2        We update guidances periodically. To make sure you have the most recent version of these guidances, check the FDA Drugs guidance Web page at http://www.fda.gov/Drugs/Guidanc ... dances/default.htm.
2我们定期更新指南。
要确保您有这些指南的最新版本，请查看http://www.fda.gov/Drugs/Guidanc ... idances/default.htm的FDA药物指南网页。

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