EDQM修订了其“CEP证书变更/更新要求指南“，其中包括了”上市许可变更申报的稳定性试验“新修订指南的要求，增加了在一个CEP中使用另一个CEP作为起始物料的变更类型。修订后指南于2014年10月1日生效。文中蓝色字体为修订过/新增的内容。
The EDQM has revised the “Guideline on requirements for revision/renewal of certificates of suitability to the European Pharmacopoeia monographs”:
- to include the requirements of the revised EU guideline on “Stability testing for applications for variations to a marketing authorisation” (EMA/CHMP/CVMP/QWP/441071/2011 Rev 2).
- to describe the types of revision to be submitted when a CEP for a starting material is used in an application for another CEP (cf.PA/PH/CEP (14) 06).
The revised document has an implementation date of 1st October 2014.
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Certification of Substances Division
PPR/CB
PUBLIC DOCUMENT
((LEVEL 1))
English only/Anglais seulement
PA/PH/CEP (04) 2, 6R
Strasbourg, July 2014
Certification of suitability to Monographs of the European Pharmacopoeia
CEP证书
GUIDELINE ON REQUIREMENTS FOR REVISION/RENEWAL
OF CERTIFICATES OF SUITABILITY
TO THE EUROPEAN PHARMACOPOEIA MONOGRAPHS
CEP证书变更/更新要求指南
Address: 7, allée Kastner, CS 30026
F - 67081 Strasbourg (France)
Telephone: 33 (0) 3 88 41 30 30 - Fax: 33 (0) 3 88 41 27 71 - e-mail: cep@edqm.eu
GUIDELINE ON REQUIREMENTS FOR REVISION/RENEWAL
OF CERTIFICATES OF SUITABILITY
TO THE EUROPEAN PHARMACOPOEIA MONOGRAPHS
Table of content
目录
1 Introduction 概述
2 Classification of Changes 变更分级
3 Documentation to be Provided 需要提供的文件
4 List of Changes 变更清单
4.I Administrative Changes 行政类变更
4.II Quality Changes 质量类变更
4.II.1 Manufacture 生产
4.II.2 Control of the final substance 成品控制
4.II.3 Container closure system 容器密闭系统
4.II.4 Stability 稳定性
4.II.5 Design space and Post-Approval Change Management Protocols 设计空间和批准后变更管理方案
4.III TSE Changes TSE变更
4.IV Use of CEP in an application for another CEP 在一个CEP申报中引用另一个CEP
5 Renewal 更新
6 Transfer of holdership 持有人转移
Date of implementation: 1st October 2014
生效日期：2014年10月1 日
1. INTRODUCTION: 概述
The holder of a certificate of suitability (CEP) shall inform the EDQM of any change to information in the CEP application by sending an appropriate request for revision demonstrating that the conditions laid down in the present guideline are met.
CEP持有人应将所有CEP申报文件中的变更通知EDQM，应提交适当的变更申请，说明符合指南中列出的哪些情况。
In addition, this guideline describes the requirements for the renewal of CEPs and for a transfer of holdership.
另外，本指南描述了CEP更新的要求，以及持有人转移证书的情况。
2. CLASSIFICATION OF CHANGES: 变更分级
The changes are classified in different categories [annual notification (AN)/immediate notification (IN)/minor (MIN)/major (MAJ)] depending on the potential impact of the change on the quality of the final substance. These categories are based on those (IA-IAIN/IB/II) of the European Commission Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products.
变更根据对成品质量的潜在影响分为不同级别【通知（AN）、立即通知（IN）、轻微（MIN）、重大（MAJ）】。该级别划分是根据欧洲法令1234/2008关于已上市人用和兽用药品的变更检查分类（IA-IAIN/IB/II）进行定义的。
Any change not classified as a notification or a major change should be classified as a minor change,except in the following cases where a new CEP application should be submitted:
所有未列在通知或重大变更中的变更，均归类为轻微变更，但在以下情况时，应提交新的CEP申请
l Addition of a new route of synthesis and/or a new manufacturing site where the specification of the final substance is different from the one already approved. And ?
l 增加新的合成路线和/或新的生产场所，且成品质量与已批准的不同，以及
l Transfer to a new holder, where the transfer does not occur because of a merger or because the company is sold, and where the manufacturer does not take out the CEP in their own name.
l 持有人转移，转移理由不是并购或公司被出售，CEP的生产商名称不再是原有生产商名称
For the convenience of applicants, some frequent minor changes are listed in this guideline, however this list should not be considered exhaustive.
为方便申请人，一些常见的轻微变更在本指南中列出，但该清单并未包括所有变更
Updates of CEP applications following Ph. Eur. monograph revisions or any other regulatory requirements are treated separately and generally initiated by the EDQM.
当EP各论更新或其它法规要求更新时引起CEP申请的更新，应单独进行，通常由EDQM发起。
3. DOCUMENTATION TO BE PROVIDED: 需要提供的文件
For any revision the documentation should consist of the CTD modules 1 & 3:
所有对文件的变更应由CTD模块1和3组成
For module 1, the following information is required:
对于模块1，需要提交以下信息
l A cover letter.
l 封面函
l A completed application form (specific for revisions) describing the kind of revision and listing all the changes applied for.
l 完整的申请表（说明是申请变更）描述变更类型，列出申请的所有变更
l A description of each change, together with a justification and supporting information as necessary.
l 对每个变更进行说明，同时说明理由，并在需要时提供支持性信息
l The differences between the approved and proposed text of module 3 must be presented as acomparative table (template of which is in annex of the application form).
l 模块3必须以比较表格形式展现已批准的文本和申请的文件之间的差异（模板参见申请表的附件）
l For notifications it must be shown how the conditions have been met.
l 对于通知性变更，必须说明是如何符合所要求的条件的
For module 3, the following information is required:
对于模块3，要求提交以下信息
l Each complete updated section which is affected by the change(s) being made.
l 受到变更影响的完整的更新部分
l Any changes to the text should be highlighted.
l 所有对正文的变更需要高亮显示
Each time batch data are needed: 所有需要批数据的情况下
— they should be in accordance with the specification of the current Ph. Eur. monograph and when relevant with the additional requirements of the CEP
— 批分析结果应符合现行EP各论的质量标准，以及如果与CEP附加要求相关时
— the manufacturing site, the manufacturing date and the size of the batches should be specified
— 需要载明生产场所、生产日期、生产批量
— quantitative results should be presented numerically (i.e. not in general terms such as “complies”) and with the appropriate number of decimal places.
— 定量性结果应采用数字表达（即，不可以概括性术语如“符合规定”表述），数字小数位应适当
Where necessary, the requirements of the “Guideline on stability testing for applications for variations to a marketing authorisation” (EMA/CHMP/CVMP/QWP/441071/2011) should be taken into account and relevant documentation should be provided. This applies namely to the items listed under sections 4.II.1 Manufacture and 4.II.3 Container closure system.
必要时，应考虑“上市许可变更申报中稳定性试验指南”(EMA/CHMP/CVMP/QWP/441071/2011)的要求，并提交相关的记录。该要求同样适用于“4.II.1生产”部分和“4.II.3容器密闭系统”中所列的项目。
Editorial changes should not be submitted as separate variations but may be reported at the same time as changes concerning the respective part of the dossier. In any case, a declaration should be provided that the content of the concerned part of the dossier has not been changed by the editorial changes (except for the change itself).
编辑性变更不应作为单独变更进行提交，但在相关部分文件相关变更发生时应进行报告。所有情况下，均应提供申明说明编辑性变更不对相关部分形成影响（除了变更本身）。
4. LIST OF CHANGES: 变更清单
The changes are presented in three sections, as described below: 变更归为以下三部分
— Administrative changes
— 行政类变更
— Quality changes
— 质量类变更
— TSE changes
— TSE变更
— Use of CEP in an application for another CEP
— 在一个CEP申报中使用另一个CEP
4.I. ADMINISTRATIVE CHANGES 行政类变更 |
This type of changes applies to chemical/ double /herbal and TSE certificates of suitability
本类变更适用于化学证/双证/草药和TSE证书
4.I.1 Changes in the name and/or address of the certificate holder
证书持有人名称和/或地址变更 | | Specific documentation 要求的文件 | |
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1. The certificate holder must remain the same legal entity (exception to this condition: where the company is sold or in case of a merger).
证书持有人必须为同一法人实体（本条件例外情况：公司被出售或并购） |
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1. A formal document from a relevant official body (e.g. Chamber of Commerce) in which the new name and/or new address is mentioned.
官方正式文件（例如商务部门），文件中提到新的名称和/或新地址 |
2. All updated declarations (annexes to the application form)
更新所有申明（申请表的附件） |
4.I.2 Changes in the name and/or address of a manufacturing site or a quality control site for the final substance
成品生产地址或检测场所地址名称和/或地址变更 | | Specific documentation 要求的文件 | |
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1. The location of the manufacturing site must remain the same.
生产地点必须保持不变。 |
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1. A formal document from a relevant official body (e.g. Chamber of Commerce) in which the new name and/or new address is mentioned.
官方正式文件（例如商务部门），其中提到新名称和/或地址 |
2. Updated declarations of manufacture in accordance with the dossier and according to GMP rules and of willingness to be inspected.
更新申明：保证按照CEP文件生产、根据GMP要求生产、愿意接受检查 |
3. If needed, updated annexes to the CEP reflecting the change of name.
需要时，更新CEP附件以反映名称的变更 |
4.I.3 Changes in the name and/or address of a manufacturer of a starting material used in the manufacture of the final substance
成品生产所用的起始物料的生产商名称和/或地址变更 | | Specific documentation 要求的文件 | |
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1. The location of the manufacturing site must remain the same.
生产地点必须保持不变 |
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1. Updated list of approved and proposed manufacturers of starting material
更新后的已批准的和申请的起始物料的生产商 |
4.I.4 Changes in the name and/or address of a manufacturer of an intermediate used in the manufacture of the final substance
用于成品生产的中间体的生产商的名称和/或地址变更 | | Specific documentation 要求的文件 | |
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1. The location of the manufacturing site must remain the same.
生产地点必须保持不变 |
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1. Updated list of approved and proposed manufacturers of intermediate.
已批准的和申请的中间体生产商更新清单 |
2. Updated declarations of manufacture in accordance with the dossier and according to GMP rules and of willingness to be inspected.
更新申请：按照申报文件生产、根据GMP要求生产、愿意接受检查 |
4.I.5 Deletion of a manufacturer of intermediate or of a manufacturing site or quality control testing site for the final substance
删除中间体生产商，或删除成品生产场所或质量控制检测场所 | | Specific documentation 要求的文件 | |
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1. The deletion should not be due to critical deficiencies concerning manufacturing and at least one site should remain.
删除不是因为生产有关键缺陷，至少应保留一个场所 |
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1. The justification of the deletion.
删除的理由陈述 |
2. Updated list of approved and proposed sites.
已批准和申请的场所更新清单 |
4.I.6 Deletion of a manufacturer or a quality control site for a starting material used in the manufacture of the final substance
删除用于成品生产的起始物料的生产商或质量控制场所 | | Specific documentation 要求的文件 | |
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1. The deletion should not be due to critical deficiencies concerning manufacturing.
删除不是因为生产有关键缺陷 |
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1. The justification of the deletion.
删除的论述 |
2. Updated list of approved and proposed sites.
更新已批准的和申请的场所清单 |
4.I.7 Change in the code product/reference number and/or in the brand name of the final substance or any material used in its manufacture
对成品或用于生产的任何物料的产品代码、索引号和/或商标名称进行变更 | | Specific documentation 要求的文件 | |
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1. The change does not regard the quality of the final substance or the concerned material.
变更与成品和相关物料的质量无关 |
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1. Approved and proposed code product/ reference number / brand name.
批准的和申请的产品代码、索引编号、商标名称 |
4.II. QUALITY CHANGES 质量方面变更 |
This type of changes applies to chemical / double and herbal certificates of suitability
本类型变更适用于化学证/双证和草药证书
4.II.1 Manufacture 生产
4.II.1.1 Change in the manufacturer of a starting material/intermediate used in the manufacturing process of the final substance or change in the manufacturer (including where relevant quality control testing sties) of the final substance
变更用于成品生产的起始物料/中间体生产商，或变更成品生产商（包括相关的质量控制检测场所） | | Specific documentation 要求的文件 | |
a) The proposed manufacturer of the starting material/intermediate is part of the same group as the currently approved manufacturer
提议的起始物料/中间体生产商与已批准生产商属同一集团 | | | |
b) The proposed manufacturer of the starting material is not part of the same group as the currently approved manufacture.
提议的起始物料生产商与已批准生产商不属同一集团 | | | |
c) The proposed manufacturer of the intermediate is not part of the currently approved manufacturer.
提议的中间体生产与已批准生产商不属同一集团 | | | |
d) The proposed manufacturer of the starting material/intermediate uses a substantially different route of synthesis or manufacturing conditions, which are likely to change the qualitative and/or quantitative impurity profile of the final substance (eg. New reagents, solvents, materials are introduced in the synthesis)
提议的起始物料/中间体生产商采用显著不同的合成路线或生产条件，可能会对成品的杂质谱形成质和/或量的变化（例如合成中引入了新试剂、溶剂、物料） | | | |
e) The proposed manufacturer of the starting material is used in the manufacturing process of a biological substance
提议的起始物料生产商所生产的中间体用于生物制品生产 | | | |
f) The proposed manufacturer of the intermediate is used in the manufacturing process of a biological substance
提议的中间体生产商所生产的中间体用于生物制品生产 | | | |
g) The proposed manufacturer (manufacturing site/workshop) of the final substance is part of the same group as the currently approved manufacturer.
提议的成品生产商（生产场所/车间）是属于已批准生产商同一集团 | | | |
h) The proposed manufacturer (manufacturing site/workshop) of the final substance is not part of the same group as the currently approved manufacturer.
提议的成品生产商（生产场所/车间）不属于已批准生产商同一集团 | | | |
i) The proposed manufacturer is for a biological substance
提议的生产商为生物产品 | | | |
j) Changes to quality control testing for a starting material
变更起始物料的质量控制检测 | | | |
k) Changes to quality control testing for an intermediate or for the final substance
变更中间体或成品的质量控制检测 | | | |
l) Addition of an alternative sterilization site for the final substance using a PhEur method
增加成品替代性的采用EP方法灭菌的场所 | | | |
m) Introduction of an new site of micronisation
引入新的微粉生产场所 | | | |
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1. The specifications and the route of synthesis (including In-Process Controls, methods of analysis of all materials used) of the starting materials/intermediates are identical to those already approved.
起始物料/中间体的质量标准和合成路线（包括中控制、所用所有物料的检测方法）与已批准的一致 |
2. The final substance is not a biological substance or a sterile substance.
成品不是生物制品或无菌产品 |
3. The specifications (including in process controls, methods of analysis of all materials), method of preparation (including batch size) and detailed route of synthesis of the final substance are identical to those already approved.
成品的质量标准（包括中控制、所有物料检测方法）、制备方法（包括批量）和具体合成路线与已批准的完全相同 |
4. Method transfer from the old to the new site has been successfully completed.
从老场所转移至新场所的方法已成功完成 |
5. The proposed alternative sterilization site is part of the same group as the manufacturer of the final substance.
提议的替代性灭菌场所与成品生产商属同一集团 |
6. The particle size specification of the final substance and the corresponding analytical method remain the same and are already approved.
成品粒径质量标准和对应的分析方法与已批准的相同 |
7. A micronisation site is already approved.
微粉生产场所已批准 |
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1. A declaration from the holder of the Certificate of suitability that the specifications of the final substance are the same as those already approved.
CEP持有人的申明：成品的质量标准与已批准的相同 |
2. A declaration from the holder of the Certificate of suitability that the synthetic route/manufacturing process (or in case of herbal material, where appropriate, the method of preparation, geographical source and production), the specifications and the quality control procedures of the starting material or intermediate are the same as those already approved.
CEP持有人申明：合成路线/生产工艺（或如果是草药物料，适当时，制备方式、地理来源和生产），起始物料或中间体的质量控制程序和质量标准与已批准的相同 |
3. A list of approved and proposed manufacturers/sites.
已批准的和提议的生产商/场所的清单 |
4. Batch analysis data (in a comparative tabular format) for at least two batches (minimum pilot scale) of the final substance from the approved and proposed manufacturers/sites.
已批准的和提议的生产商/场所的至少两批（最小为中试批量）成品的分析数据（采用比较表格） |
5. Declarations of manufacture in accordance with the dossier and according to GMP rules and of willingness to be inspected for the proposed site/manufacture. Information on sources and route of synthesis of starting materials used by the new manufacturer.
针对提议的场所/生产商的申明：按照申报资料进行生产、根据GMP要求进行生产、愿意接受检查。新生产商所用的起始物料的来源信息和合成路线信息。 |
6. Batch analysis data (in a comparative tabular format) for at least three batches (minimum pilot scale) of the final substance from the approved and the proposed manufacturers/sites.
至少3批（最小批量为中试批量）已批准的和提议的生产商/场所的成品的批分析数据（采用比较表格） |
7. A declaration from the holder of the Certificate of suitability that the synthetic route /manufacturing process (or in case of herbal material, where appropriate the method of preparation, geographical source and production), quality control procedures and specifications of the final substance are the same as those already approved.
CEP持有人申明：合成路线/生产工艺（或如果是草药物料，适当时，制备方法，地址来源和生产），成品质量控制程序和质量标准与已批准的相同 |
8. Declarations that sterilization is performed in accordance with the dossier and according to EU GMP, Part I and of willingness to be inspected for the proposed site/manufacturer.
提议的生产场所/生产商的申明：灭菌与申报文件一致、根据欧盟GMP第I部分生产、愿意接受检查。 |
9. A declaration from the holder of the Certificate of suitability that the proposed alternative sterilization site is part of the same group as the manufacturer of the final substance.
CEP持有人申明：提议的替代性灭菌场所与成品生产商属同一集团 |
* If applicable supportive stability data as listed in current version of the “Guideline on stability testing for applications for variations to a marketing authorisation” (EMA/CHMP/CVMP/QWP/441071/2011).
如果在“上市许可变更申报中稳定性试验指南”(EMA/CHMP/CVMP/QWP/441071/2011)现行版本中已列出了适用的支持性稳定性数据。 |
4.II.1.2 Change in the manufacturing process of a starting materials, intermediate or final substance
起始物料、中间体或成品生产工艺变更 | | Specific documentation 要求的文件 | |
a) Minor change in the manufacturing process of the final substance
成品生产工艺和轻微变更 | | | |
b) Substantial change to the manufacturing process/addition of an alternative manufacturing process for a starting material, intermediate or final substance likely to change the qualitative and/or quantitative impurity profile of the final substance (eg. New reagents, solvents, materials are introduced in the synthesis)
起始物料、中间体或成品生产工艺显著变更、增加一个替代性生产工艺，可能会对成品杂质谱产生质的和/或量的影响（例如合成中引入新试剂、溶剂、物料） | | | |
c) Change in the manufacturing process of the final substance that regards the sterilization step(s), including change in batch size of sterile substance
成品灭菌步骤生产工艺变更，包括无菌产品批量变更 | | | |
d) Changes in the manufacturing process of a herbal substance related to geographical source or production
与地理来源或生产有关的草药产品生产工艺变更 | | | |
e) Minor change in the manufacturing process of a biological substance
生物制品生产工艺轻微变更 | | | |
f) For a “double” Certificate of suitability (for chemical purity and microbiological quality and for TSE risk), change in source of a material used in the preparation of the final substance from a TSE risk material to a vegetable, synthetic, or non-TSE risk material
双证（化学纯度和微生物质量和TSE风险）中用于用于成品生产的物料的来源变更，该成品生产是采用TSE风险原料生产植物、合成或非TSE风险物料 | | | |
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1. The specifications of the final substance or intermediates are unchanged and there is no adverse change in qualitative and quantitative impurity profile.
成品或中间体的质量标准保持不变，对杂质谱没有质和量的负面影响。 |
2. The synthetic route remains the same, i.e. intermediates remain the same and there are no new reagents, catalysts or solvents used in the process. In the case of herbal medicinal products, the geographical source, production of the herbal substance and the manufacturing route remain the same.
合成路线保持不变，即中间体保持不变，没有新的试剂、催化剂或溶剂用于生产工艺。如果是草药产品，地理来源、草药产品的生产和生产路线保持不变。 |
3. The final substance is not a biological substance.
成品不是生物制品 |
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1. Batch analysis data (in comparative tabular format) of at least two batches (minimum pilot scale) of the final substance manufactured according to the approved and proposed process.
根据已批准的和提议的工艺生产的至少2批（最小批量为中试批量）成品的批分析数据（采用比较表格） |
2. Batch analysis data (in comparative tabular format) of at least three batches (minimum pilot scale) of the final substance manufactured according to the approved and proposed process.
根据已批准的和提议的工艺生产的至少3批（最小批量为中试批量）成品的批分析数据（采用比较表格） |
3. A direct comparison of the approved and the proposed process.
已批准和提议的工艺的直接对比 |
4. A declaration from the holder of the certificate of suitability that the specifications of the final substance are the same as those already approved.
CEP持有人申明：成品质量标准与已批准的相同 |
5. Specification of the proposed source of the material.
提议的来源的物料的质量标准 |
6. A declaration from the manufacturer of the material that it is purely of vegetable, synthetic or non-TSE risk origin (specifying the origin).
物料生产商的申明：物料为纯植物性、合成或无TSE风险来源（说明来源） |
7. A declaration from the holder of the certificate of suitability that there is no change in the manufacturing process and that the specifications of the final substance remain the same.
CEP持有人申明：生产工艺无变更、成品质量标准保持相同 |
* If applicable supportive stability data as listed in current version of the “Guideline on stability testing for applications for variations to a marketing authorisation” (EMA/CHMP/CVMP/QWP/441071/2011).
如果在“上市许可变更申报中稳定性试验指南”(EMA/CHMP/CVMP/QWP/441071/2011)现行版本中已列出了适用的支持性稳定性数据。 |
4.II.1.3 Change in the batch size of final substance or intermediate 成品或中间体批量变化 | | Specific documentation 要求的文件 | |
a) Up to 10-fold increase compared to the original approved batch size
批量增加至原批准批量的10倍 | | | |
b) Downscaling down to 10-fold
批量降低至1/10 | | | |
c) More than 10-fold increase compared to the originally approved batch size
批量增加超过原批准批量的10倍 | | | |
d) Change in batch size of a biological substance
微生物产品的批量变化 | | | |
|
1. Any change to the manufacturing methods are only those necessitated by scale-up or downscaling, e.g. use of different-sized equipment.
所有与生产相关的变更仅是因为批量放大或缩小，例如采用不同尺寸的设备 |
2. Test results of at least two batches of the final substance complying with the approved specifications should be available for the proposed batch size.
申请的批量下生产的至少两批成品的检验结果符合已批准的质量标准 |
3. The substance is not a biological substance or a sterile substance.
成品不是微生物产品或无菌产品 |
4. The change does not affect the reproducibility of the manufacturing process.
变更不影响生产工艺的再现性 |
5. The change should not be the result of unexpected events arising during manufacture or because of stability concerns.
变更原因不是生产中出现意外情况，或发生稳定性问题 |
6. The specifications of the final substance/intermediates remain the same.
成品/中间体的质量标准保持不变 |
7. The currently approved batch size was not approved via a notification.
目前批准的批量不是通过通知方式获得批准 |
|
1. The batch numbers of the tested batches having the proposed batch size.
检测的批数为提议的批量 |
2. Approved and proposed batch size.
批准的和申请的批量 |
3. Updated description of the full process specifying the proposed batch size.
按申请批量进行更新的全部工艺描述 |
4. A declaration from the certificate holder that the changes to the manufacturing methods are only those necessitated by scale up/downscaling, that the change does not adversely affect the reproducibility of the process, that it is not the result of unexpected events arising during manufacture or because of stability concerns and that the specifications of the final substance/intermediates remain the same.
CEP持有人申明：生产方法变更仅因为批量增加/降低而产生，变更对工艺重复性无负面影响，变更原因不是生产过程中意外事件，或稳定性原因，成品/中间体质量标准保持相同 |
5. Batch analysis data (in comparative tabular format) on a minimum of one production batch of the final substance manufactured according to both the approved and the proposed sizes.
批分析数据（以表格比较的格式） |
6. Batch analysis data (in comparative tabular format) of at least three batches (minimum pilot scale) of the final substance manufactured according to the approved and proposed process.
根据已批准的和提议的工艺生产的至少3批（最小批量为中试批量）成品的批分析数据（采用比较表格） |
7. A declaration from the holder of the certificate of suitability that the specifications of the final substance are the same as those already approved.
CEP持有人申明：成品质量标准与已批准的相同 |
4.II.1.4 Change to in-process tests or limits applied during the manufacture of the final substance
成品生产中的中控检测或其限度变更 | | Specific documentation 要求的文件 | |
a) Tightening of the limits of in-process testing
加严中控制检测限度 | | | |
b) Addition of a new in-process test and limit
增加新的中控检测和限度 | | | |
c) Deletion of a non-significant in-process test
删除不重要的中控检测 | | | |
d) Widening of approved in-process test limits, which may have a significant effect on the overall quality of the final substance
放宽已批准的中控检测限度，可能会对成品的整体质量造成显著影响 | | | |
e) Deletion of approved in-process test limits, which may have a significant effect on the overall quality of the final substance
删除已批准的中控检测限度，可能会对成品整体质量造成显著影响 | | | |
|
1. The change does not result from unexpected events arising during manufacture.
变更不是因为生产中意外事件引起 |
2. The test procedure remains the same, or changes in the test procedure are minor.
检测方法保持相同，或对检测方法仅有轻微变更 |
3. Any new test method does not concern a novel non-standard technique or a standard technique used in a novel way.
所有新的检测方法未采用新奇的非标准技术，或新奇的标准技术 |
4. The new test method is not a biological method or a method using a biological reagent for a biological substance (does not include standard pharmacopoeia microbiological methods).
新的检测方法不是生物方法，或采用生物制剂对生物制品进行检测的方法（不包括标准的药典微生物方法） |
5. The specification parameter does not concern a critical parameter for example any of the following: assay, impurities (unless a particular solvent is definitely not used in the manufacture of the active substance), any critical physical characteristics e.g. particle size, bulk or tapped density, identity test, water, any request for changing the frequency of testing.
质量标准项目与关键项目不相关，例如以下项目：含量、杂质（除非使用了特殊的溶剂用于活性成份生产），所有关键物理特性，例如粒径分布、松密度或击拍密度、鉴别检测、水分，其它检测频次变更要求 |
|
1. Comparative table of approved and proposed in-process tests.
已批准的和提议的中控检测的对比表格 |
2. Details of any new non-pharmacopoeial analytical method and validation data, where relevant.
相关时，新的非药典分析方法的详细描述和验证数据 |
3. Justification/risk assessment from the holder of the certificate of suitability that the in-process tests are non-significant.
CEP持有人对中控检测没有重大影响的原因论述/风险评估 |
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发表于 2014-8-9 18:26:40
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