FORMAT AND CONTENT FOR THE CMC SECTION OF AN ANNUAL REPORT
年度报告CMC章节的格式和内容
I. PURPOSE
目的
To describe the information requested by the Center for Drug Evaluation and Research (CDER) in an Annual Report to a New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Abbreviated Antibiotic Application (AADA) submitted pursuant to 21 CFR 314.81(b)(2).
为了叙述CDER要求的根据21 CFR 314.81(b)(2) 递交的NDA，ANDA，或AADA的年度报告中需要的资料
The primary objective is to ensure consistency and completeness of information in the Annual Reports submitted by the pharmaceutical industry and to standardize the general format.
主要目的是为了确保药品企业递交的年度报告资料的一致性和完整性，将总的格式标准化
II. BACKGROUND
背景
The FDA regulations for the submission of Annual Reports are described in 21 CFR 314.70(d) and 21 CFR 314.81(b)(2). In the past, the reports submitted under these regulations have exhibited wide variability from firm to firm, and at times the information submitted has been inconclusive or insufficient
年度报告递交的FDA法规叙述在21 CFR 314.70(d)和21 CFR 314.81(b)(2)。在过去，在这些法规下递交的报告公司和公司间有宽泛的变化，有时递交的资料不得要领或不够充分
This guidance addresses information that should be included in an Annual Report. It may also be helpful to consult other Center guidances for information on the depth of technical information requested. For example, CDER's Guideline for Submitting Documentation for the Stability of Human Drugs and Biologics provides information on the design of stability protocols, the amount of stability data that should be provided to support specific changes to the application (e.g., packaging changes submitted under 314.70(d)(6)), and guidance on the extension of the expiration dating period. Complete information submitted in an easy to follow format will assist the reviewer in conducting an efficient review.
本指南叙述了年度报告中应包含的资料。关于需求技术资料的深度，可以参考其它中心的指南资料。如，用于递交人用药和生物药稳定性文件的CDER指南提供了稳定性方案的设计资料，提供的稳定性资料的量以支持申请的具体变更（如，根据314.70(d)(6)递交的包装材料的变更）以及有效期延长指南。符合格式的递交的简明的完整的资料可以帮助审核者进行有效的审核。
CDER encourages the applicant to contact the appropriate office or division if there is uncertainty whether the information should be submitted in an annual report or as a supplemental change to the approved application.
如果对资料是否需要递交于年度报告中或作为已批准申请的补充变更不确定时，CDER鼓励申请人联系适当的办公室或中心。
III. POLICY
方针
The NDA/ANDA/AADA holder should follow the procedure outlined in Form FDA 2252 when filing an Annual Report. Annual Reports should be filed for all approved NDA's, ANDA's and AADA's (including those for bulk antibiotic drugs), regardless of their activity status. For NDA's filed with the Offices of Drug Evaluation I or II, applicants should submit sufficient copies of the Annual Report for the jacket of each affected discipline so as to assure concurrent review.
当递交年度报告时，NDA/ANDA/AADA持有人应遵循FDA2252表中列出的程序。对于所有批准的NDA，ANDA和AADA（包括抗生素药），不管其活动状态。对于递交给评审办公室I或II的NDA，申请人应递交足够份数的年度报告，以考虑每一受影响的方面从而确保同步审核。
The applicant should follow the format described below and include all information when preparing an Annual Report. If no changes were made in a particular section during the reporting period, the applicant should state "No changes were made during the reporting period." Please note that even though the format described below may not be entirely complete, the firm remains responsible for complying with all requirements under current regulations.
在准备年度报告时，申请人应遵循下述的格式并包含所有的资料。在报告期间，特定的章节无变化，申请人应注明“在报告期间无变化”。请注意下述的格式可能也不是十分完整的，公司有责任符合当前法规下的所有要求。
IV. FORMAT
格式
SECTION I. SUMMARY OF NEW INFORMATION
章节I 新资料的概述
The firm should include a brief summary of all changes made to the application during the reporting period, including changes made in accordance with approved supplements under 21 CFR 314.70(b) and special supplements under 21 CFR 314.70(c). All changes should be highlighted or annotated within the Annual Report and should be included in the list of approved chemistry, manufacturing and control information described in Section IV of this document.
在报告期间，公司应包含对申请所做的所有变更的简明叙述，包括根据21 CFR 314.70(b)批准的补充和21 CFR 314.70(c)特定补充所做的变更。应突出所有的变更，或在年度报告中注释，并包含于本指南IV章节叙述的CMC批准的列表中。
SECTION II. DISTRIBUTION DATA [21 CFR 314.81(b)(2)(ii)]
章节 II 销售数据[21 CFR 314.81(b)(2)(ii)]
The firm should provide:
公司应提供：
A. The quantity distributed of each currently approved strength by package size (e.g. number of 30's, 100's for drug products or kg for bulk antibiotic drugs), or
每一当前批准剂量销售量（以包装大小计）
B. The statement "None distributed" along with the corresponding approved package size(s) if there is no distribution for that package size.
相应的批准包装的“未销售”声明，如过此包装无销售
C. Quantities distributed for domestic use and quantities distributed for foreign use.
出售供国内使用的量和出售供国外使用的量
D. For bulk antibiotic drug AADA's, a current list of all persons authorized to reference the application and any person whose authorization has been withdrawn.
对于抗生素原料药，所有授权参考申请的和授权被取消的人员的最新列表
Distribution information should be distributor-specific.
销售信息应是直销的
SECTION III. LABELING [21 CFR 314.70(d), 21 CFR 314.81(b)(2)]
章节III 标签[21 CFR 314.70(d), 21 CFR 314.81(b)(2)]
Generally, any labeling change submitted in an Annual Report should include supportive documentation (e.g. submission of a statement of the currently approved composition to support upgrading insert labeling to include previously unlisted inactive ingredients).
一般说来，年度报告中递交的所有标签变更应包含支持性的文件（如，当前批准组分声明的递交以支持升级的标签说明书以支持当前的未列出的非活性组分）。
Information submitted under 21 CFR 314.81(b)(2)(iii), should include the following:
根据21 CFR 314.81(b)(2)(iii)递交的资料，应包含如下：
A. All currently used labeling, including a representative sample of package labels. This should include all package inserts and examples of the immediate container labels. It may be useful to include labels of distributors. Samples of all labeling which has undergone a change during the reporting period, including immediate container labels, carton labeling, and insert labeling, should be provided in the Annual Report.
所有最新使用的标签，包含包装标签的样本。这应包含所有产品说明书和直接容器的样本。包含销售标签也是很有作用的。在报告期间有变化的所有标签的样本，包括直接接触容器标签，纸板桶，和标签说明书，应提供在年度报告中。
B. A summary of any changes made in the labels/labeling since the last Annual Report, listed chronologically by implementation date.
自上次年度报告，对标签所做的所有变化的概述，按执行的时间先后顺序列出
SECTION IV. CHEMISTRY MANUFACTURING AND CONTROLS CHANGES
章节 IV 化学制造和控制的变更
CDER requests that a current list of approved chemistry, manufacturing and control information be provided yearly in the Annual Report to better document the changes occurring in applications. This index is not for review purposes, but will serve as a reviewer aid. The list should include all information shown in Attachment 1 and the use of the format in the attachment is encouraged.
CDER要求对批准的化学，制造和控制资料的最新列表在年度报告中每年提供，以更好地将申请中发生的变更文件化。其并不是用于审核的目的，而是用于帮助审核者。清单应包含附件1中所有的资料和鼓励使用附件中使用的格式。
The information should include the type and date of each change to each component, the type of submission used to report the change (Original, Supplemental or Annual Report), and the date the change was reported and approved, if it was.
资料应包含对每一组分，每一变更的类别和日期，用于报告变更递交的类别（初始递交，增补或年报），变更报告和批准的日期。
Regulatory specifications and analytical methods for the drug substance and drug product should be listed individually as illustrated below:
原料药和制剂的法规的质量标准和分析方法应单个列出：
III. SPECIFICATIONS AND METHODS FOR THE DRUG SUBSTANCE
原料药的质量标准和方法
Test Specification Method (#, Reference)
检测 质量标准 方法（#参考）
Description Clear, Colorless Liquid Visual (CZT2001, Original[2-3-86])
外观 澄清，无色液体 视觉
Assay 98 - 102% HPLC (CZT2019, S-003[4-11-81])
外观 98-102% HPLC(CZT2019, S-003[4-11-81])
Examples of chemistry, manufacturing and controls changes that should be reported include but should not be limited to the following information:
应报告的化学，制造和控制变更的例子，包含但无限定于如下资料
A. Compendial Changes [21 CFR 314.70(d)(1)]
药典变更[21 CFR 314.70(d)(1)]
Changes made to comply with changes in an official compendium should include:
所做的符合法定文件的变更应包括：
(1) Full description of changes in test methods and limits.
检验方法和限度变更的完整叙述
(2) Data demonstrating the suitability of the compendial change for the drug product.
证明制剂法定变更的适应性的资料
B. Formulation [21 CFR 314.70(d)(4)]
制剂[21 CFR 314.70(d)(4)]
Deletion of an ingredient intended only to affect the color of the drug product should be reported and include:
仅仅旨在影响制剂颜色的组分的删除，应报告并包含：
(1) A comparative component and composition statement, with all changes highlighted or annotated.
组分和组成的比较声明，强调或注释所有的变更
(2) A statement of the current component and composition in subsequent Annual Reports, including reference to the change (i.e. date, Annual Report Number, or Supplement Number).
随后的年度报告中当前组分和组成的声明，包括变更的参考（如，日期，年度报告号码，或补充号码）
(3) Revised labeling as required by 21 CFR 314.70(d)(2) reflecting the change in formulation.
21 CFR314.70(d)(2) 要求的修改后的标签，反映组成的变化
C. Expiration Period [21 CFR 314.70(d)(5)]
失效日期[21 CFR 314.70(d)(5)]
Extension of the expiration dating period should be accompanied by full shelf-life stability data for the proposed expiry dating on a minimum of three production lots and a justification for the change in the expiration date. The data should be obtained using the stability protocol approved in your application.
失效期的延长应附有拟定的失效日期的至少三批大生产的货价寿命的完整的数据，以及失效日期的变更的合理性说明。使用申请中批准的稳定性方案获得的数据的。
D. Container/Closure [21 CFR 314.70(d)(6)]
包装/密闭系统[21 CFR 314.70(d)(6)]
Changes within the approved container and closure system for a solid oral dosage form may be included in the annual report (e.g., one HDPE to another HDPE). The description of this change should be accompanied by the following information:
固体口服制剂的批准的容器和密闭系统的变更可能会包含在年度报告中（如，一个HDPE变成另一个HDPE）。此变更的叙述应附有如下的资料：
(1) Components and manufacturer. Letters of authorization allowing reference to other documents (e.g., DMFs) should be included if appropriate.
成分和制造商。允许参考其它文件（如，DMF）的授权信应包含在内
(2) Testing results that demonstrate the equivalency of the changed container and closure system to the original system in accordance with compendial requirements or a protocol approved in the application.
证明变更后的容器和密闭系统和之前的系统等效的，法规要求或申请中批准方案一致的检验结果
(3) A Statement of Commitment to place the drug product using the changed container and closure system in stability studies using the approved stability protocol.
采用批准的稳定性方案将使用了变更后的容器和密闭系统的制剂进行稳定性研究的承诺声明
E. Test Methods [21 CFR 314.70(d)(7)]
检验方法[21 CFR 314.70(d)(7)]
The applicant should submit the following information for the addition or deletion of an alternate method:
申请人应递交如下的资料用于增加或删除替代的方法：
F. Container/Closure [21 CFR 314.70(d)(8)]
容器/密闭系统[21 CFR 314.70(d)(8)]
A change in the size of a container for a solid oral dosage form, without a change from one container and closure system to another, should be consistent with the Center for Drug Evaluation and Research Guideline for Submitting Documentation for the Stability of Human Drugs and Biologics.
固体口服剂型的尺寸的变化，容器和密闭系统之间无变化，应和用于递交人用和生物药的CEDR指南相一致。
G. Status Report [21 CFR 314.81(b)(2)(vii)]
状态报告[21 CFR 314.81(b)(2)(vii)]
CDER strongly recommends that the stability report format for the Annual Report include the following information along with the data accumulated from your ongoing stability studies:
CDER强烈地建议年报中稳定性报告的格式包括如下资料，以及正在进行稳定性研究的数据
NAME/STRENGTH: BATCH #/STUDY #: BATCH/SIZE:
名称/剂量 批号/研究号 批/尺寸
DATE MANUFACTURED: MANUFACTURING SITE: CONTAINER SIZE/SUPPLIER:
生产日期 生产地址 容器大小/供应商
DATE PACKAGED: PACKAGER/SITE: CONTAINER RESIN:
包装日期 包装人/地址 容器树脂
DATE STUDY STARTED: PURPOSE OF STUDY: CLOSURE/SUPPLIER:
研究启动日期 研究目的 密闭/供应商
DATE OF EXPIRY: STORAGE CONDITIONS SEAL/SUPPLIER:
(INCLUDE ORIENTATION):
失效日期 储存条件（包括朝向） 封口/供应商
FILLER:
填装人
DRUG SUBSTANCE MANUFACTURER/SITE/LOT#:
原料药制造商/地址/批号
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ATTRIBUTES 特征 |
METHODS SOP# 方法 SOP号 |
SPECIFICATION (LOW / HIGH) 质量标准 （低/高） |
Time (months) 时间（月份） | ||||||
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0 |
3 |
6 |
9 |
12 |
18 |
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APPEARANCE 外观 |
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ASSAY 含量 |
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PURITY 纯度 DEG PROD A 降解产物 A DEG PROD B 降解产物 A DEG PROD C 降解产物 A |
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pH |
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ETC... |
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ANUUAL TEST 年度检测 |
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The actual date that the sample(s) were tested should be included in the bottom row of the table.
样品检测的检测的实际日期应包含在表格的底部。
If there was no product distribution during the reporting period, the firm should state the status of the ongoing stability program as stated in the approved protocol.
如果在报告期间无产品销售，公司应说明正在进行的批准方案说明的稳定性的方案
Approved by CMC CC:
Charles Kumkumian, Ph.D. Roger L. Williams, M.D.
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