[转] 附录16-质量授权人认证与批次放行

残伤

EUROPEAN COMMISSION 欧盟委员会

HEALTH AND CONSUMERS DIRECTORATE-GENERAL 健康与消费者总司

Health Systems and Products 健康体系与产品

Medicinal Products - Quality, safety and efficacy 药品-质量、安全性与有效性

Brussels, <date> 布鲁塞尔，<日期>

EudraLex

The Rules Governing Medicinal Products in the European Union 欧盟药品管理法规

Volume 4 第四卷

EU Guidelines for 欧盟指南

Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use 人用与兽用药品生产质量管理规范

Annex 16 附录16

Certification by a Qualified Person and Batch Release 质量授权人认证与批次放行

Legal basis for publishing the detailed guidelines: 发布详细指南的法律依据：

Article 47 of Directive 2001/83/EC on the Community code relating to medicinal products for human use and Article 51 of Directive 2001/82/EC on the Community code relating to veterinary medicinal products. This document provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/EC for medicinal products for human use and Directive 91/412/EEC for veterinary use. 欧盟法规有关的人用药品的第2001/83/EC法令的第47款。本文件提供指南来解释在第2003/94/EC号法令下人用药品以及第91/412/EEC号法令下兽药药品生产管理规范(GMP)的原则与指导。

Status of the document: Revision 1. 文件状态：第一修订

Reasons for changes: 修订原因：

The Annex has been revised to reflect the globalisation of the pharmaceutical supply chains and the introduction of new quality control strategies. The revision has been carried out in the light of Directive 2011/62/EU amending Directive 2001/83/EC as regards the prevention of the entry into the legal supply chain of falsified medicinal products, and to implement ICH Q8, Q9 and Q10 documents, and interpretation documents, such as the MIA interpretation document, as applicable. Also, some areas, where the interpretation by member states has not been consistent, have been clarified. 对本附录进行修订以反映药品供应链全球化以及新质量控制策略引入。此次修订已经突显第2011/62/EU号法令对第2001/83/EC法令关于防止假药进入合法供应链的修订，以及实施ICH-Q8、Q9、Q10文件，如果使用，诸如生产与进口许可(MIA)解释文件这样的解释文件。此外，已经澄清在一些地区由于由成员国解释不一致。

Deadline for coming into operation: <6 months from publication> 实施日期：<发布后6个月>

Table of Contents 目录

1. Scope 第一章：范围 2. General principles 第二章：总原则 3. The process of certification 第三章：认证过程 4. Relying on GMP assessments by third parties e.g. audits 第四章：依托第三方药品生产质量管理规范评估，例如审计 5. Handling of unplanned deviations 第五章：非计划性偏差的处理 6. The release of a batch 第六章：一个批次放行 7. Glossary 第七章：术语

1. Scope第一章：范围
1.1	This Annex provides guidance on the certification by a Qualified Person (QP) and on batch release within the European Economic Area (EEA) of medicinal products for human or veterinary use holding a marketing authorisation or made for export. The principles of this guidance also apply to investigational medicinal products, subject to any difference in the legal provisions and more specific guidance in Annex 13 to the Guide. 本附录提供持有销售许可或为出口生产的人用或兽用药品的质量授权人(QP)认证以及批次在欧洲经济区(EEA)放行指南。基于法律条款的任何不同以及在GMP指南第13附录的更具体指南，本指南的基本原则也适用于研究药品。
1.2	The relevant legislative requirements are contained in Article 51 of Directive 2001/83/EC, in Article 55 of Directive 2001/82/EC and in Article 13.3 of Directive 2001/20/EC. Notice is taken of the arrangements referred to in Article 51(2) of Directive 2001/83/EC and Article 55(2) of Directive 2001/82/EC (e.g. Mutual Recognition Agreements MRA). 有关立法要求已经包含在第2001/83/EC号法令第51条、第2001/82/EC法令第55条以及第2001/20/EC号法令第 13.3条中。对第2001/83/EC号法令第51(2)条以及第2001/82/EC法令第55(2)条的约定已经进行通告(例如互认协议(MRA)。
1.3	This Annex does not address the “Official control authority batch release” which may be specified for certain blood and immunological products in accordance with Articles 109, 110, 113 and 114 of Directive 2001/83/EC, and Articles 81 and 82 of Directive 2001/82/EC. 按照第2001/83/EC号法令的第109、110、113与114条，以及第2001/82/EC法令的第81条与82条，该附录不解决“官方控制机构批次放行”可能指定某些血液和免疫产品。
1.4	The basic arrangements for batch release for a product are defined by its marketing authorisation. Nothing in this Annex should be taken as overriding those arrangements. 产品批次放行基础约定由上市许可所规定。本附件中不需要采取任何高于这些约定的措施。
2. General principles第二章：总原则
2.1	The ultimate responsibility for the performance of an authorised medicinal product over its lifetime; its safety, quality and efficacy lies with the marketing authorisation holder (MAH). 履行一个批准药品在其生命周期最终职责；其安全性、质量与有效性是上市许可持有人(MAH)的责任。
2.2	However, the responsibility for ensuring that a particular batch has been manufactured in accordance with its marketing authorisation, with EU Good Manufacturing Practice (GMP), or equivalent, and that it is in compliance with the laws in force in the Member State where certification takes place and of the destination country of the medicinal product, lies with the QP certifying that batch as being suitable for release. 然而，确保特定批次已经按照其上市许可进行生产、符合欧盟或等同药品生产质量管理规范(GMP)、符合认证发生地与药品目的国的欧盟成员国现行法律是质量授权人证明批次适合放行的责任。
2.3	The process of batch release comprises of: 批次放行过程包括：
2.3.1	The checking of the manufacture and testing of the batch in accordance with defined release procedures. 按照规定的放行规程核对该批次的生产与测试。
2.3.2	The certification of the finished product batch performed by a Qualified Person signifying that the batch is in compliance with EU GMP and the requirements of its marketing authorisation (MA). 由质量授权人签发该批次符合欧盟药品生产质量管理规范以及其上市许可(MA)要求进行成品批次认证。
2.3.3	Assigning of release status to the finished batch of product which takes into account the certification performed by the QP. This is the final step in the process which effectively releases the batch for sale or export. This could be done by the QP as an integral part of certification or it could be done afterwards by another person. In this case, this arrangement should be delegated by the QP in a SOP or contract. 为质量授权人考虑实施认证的成品批次指定放行状态。这是有效放行该批次进行销售或出口的过程最后步骤。这可以由质量授权人作为认证的一个组成部分，或随后由另一人进行。在这种情况下，质量授权人应在一个标准操作规程或合同中进行授权。
2.4	The purpose of controlling batch release is notably to ensure that: 批次放行控制目的是确保：
2.4.1	The batch has been manufactured and checked in accordance with the requirements of its marketing authorisation; 该批次已经按照上市许可要求进行生产并进行检查；
2.4.2	The batch has been manufactured and checked in accordance with the principles and guidelines of EU Good Manufacturing Practice, or equivalent; 该批次已经按照欧盟药品生产质量管理规范，或等同，基本原则与指南进行生产并进行检查；
2.4.3	Any other relevant legal requirements, e.g. of the destination country, are taken into account; 任何其它相关法律要求，例如目的国，都已经考虑在内；
2.4.4	In the event that a defect needs to be investigated or a batch recalled, to ensure that the QP, who certified the batch, and the relevant records are readily identifiable. 在缺陷需要进行调查或一个批次进行召回情况下，为了确保进行该批次认证质量授权人以及相关的记录，很容易被识别。
3. The process of certification第三章：认证过程
3.1	Each batch of finished product must be certified by a QP within the EEA before being released for sale or supply in the EEA or for export. 每个批次成品必须由在欧洲经济区(EEA)质量授权人在欧洲经济区(EEA)或出口放行销售或供应前 进行认证。
	Certification can only be performed by a QP of a Manufacturing and Importation Authorisation (MIA) holder named in the MA. 认证只能由在上市许可中指定的生产与进口许可(MIA)持有人的质量授权人进行。
3.2	Any QP involved in the certification, or confirmation, of a batch must have detailed knowledge of the steps for which they are taking responsibility. The QPs should be able to demonstrate knowledge of the product type, production processes, technical advances and changes to GMP. 在一个批次认证，或确认，中涉及任何质量授权人必须有其承担责任步骤的详细知识。质量授权人应能够证明的产品类型、生产过程、技术进步与药品生产质量管理规范变更知识。
	There may be several sites involved in the various stages of manufacture, importation, testing and storage of a batch before it undergoes certification. Regardless of how many sites are involved, the QP performing certification of the finished product must ensure that all necessary steps have been completed through an agreed quality management system to assure compliance of the batch with GMP, the Marketing Authorisation, and any other legal obligations in the member state where certification is taking place or in the destination country. 有可能一个批次在经历认证前在不同的生产阶段、进口、测试与储存阶段涉及到一些现场. 无论涉及多少现场，成品进行认证的质量授权人必须通过一个商定的质量管理体系确保所有的步骤已经完成，来确保该批次与药品生产质量管理规范、上市许可，以及任何其它在认证发生的成员国或目的地国家法律义务符合性。
3.3	Manufacturing steps performed at sites in the EEA 生产步骤在欧洲经济区现场
	Each manufacturing site in the EEA must have at least one QP. 在欧洲经济区的每个生产现场必须至少有一名质量授权人。
	Where the site only undertakes partial manufacturing operations in relation to a batch then a QP at that site must at least confirm that the operations undertaken by the site have been performed in accordance with GMP and the terms of the written agreement detailing the operations for which the site is responsible. If the QP is responsible for confirming compliance of those operations with the relevant marketing authorisation then it is expected that the QP has access to the necessary details of the Marketing Authorisation to facilitate declaration of compliance. 当现场仅仅承担一个批次的部分生产运行时，在该现场的质量授权人必须至少确认在该现场的运营符合药品生产质量管理规范进行，并在 书面协议中详细规定负责现场的运营。如果质量授权人负责确认这些运营与相关上市许可符合性，期望质量授权人能读取上市许可必要的细节，以便进行符合性声明。
	The QP who performs certification of the finished product batch may assume full responsibility for all stages of manufacture of the batch or this responsibility may be shared with other QPs who have confirmed compliance of specified steps in the manufacture and control of a batch. These could be other QPs who are operating under the same manufacturing authorisation holder or QPs operating under different manufacturing authorisation holders. 实施成品批次认证的质量授权人可能会承担该批次生产所有阶段的全部责任，或者这个责任由其他确认在一个批次生产与控制特认定步骤质量授权人所分享。这可能是其他在相同生产许可持有人下运行或不同生产许可持有人下运行的质量授权人。
	Any division of responsibilities amongst QPs in relation to compliance of the finished batch with GMP, the marketing authorisation and any other legal requirement must be defined; 在质量授权人关于成品批次与药品生产质量管理规范符合性中任何责任分配，上市许可与任何其它法律规要求必须进行规定；
i)	in a written agreement between the sites where the QPs are located at different manufacturing authorisation holders. 在质量授权人位于不同的生产许可持有人现场时，在现场之间书面协议中规定。
ii)	in a procedure where the QPs are operating at a single manufacturing authorisation holder. 当质量授权人在单一的生产许可持有人下运营时，在一个规程中规定。
	The written agreement and procedure should include details on the responsibility for assessment of the impact of any deviations on compliance of the batch with GMP and the Marketing Authorisation. 书面协议与规程应包括评估任何偏差对批次与药品生产质量管理规范预计生产许可符合性影响责任详细规定。
	A template for the confirmation is presented as an Attachment. 确认书模板作为本附件进行展示。
3.4	Manufacturing site(s) outside the EEA 生产现场在欧洲经济区以外
	For medicinal products manufactured outside the EEA, physical importation, certification and batch release are the final stages of manufacturing. 对于在欧洲经济区外生产药品，物理进口、认证与批次放行是医品生产的最后阶段。
3.4.1	The process of certification as described in Section 3 of this Annex, applies to all medicinal products intended to be released for the EEA markets, or for export, irrespective of the complexity of the supply chain and the global locations of manufacturing sites involved. 本附录第三章中所描述的认证过程，适用于所有预期放行到欧洲经济区市场或用于出口的药品，不论供应链复杂性以及所涉及生产现场在全球的位置。
3.4.2	Importation activities including at least receiving, sampling, storage of the un-released and un-certified batch, quality control testing, certification and release should be conducted by authorised sites in the EEA according to the requirements of Directive 2001/83/EC, Directive 2001/82/EC and Directive 2001/20/EC. 进口活动，至少包括接收、取样、尚未放行与尚未认证批次的储存、质量控制测试、认证与放行，应该按照第2001/83/EC号法令、第2001/82/EC号法令以及第2001/20/EC法令要求在周周经济区已经授权的现场实施。
3.4.3	In accordance with the principles described in Section 3.3 of this Annex, the QP certifying the finished medicinal product batch may take account of the confirmation by, and share defined responsibilities with, other QPs in relation to any manufacturing or importation operations taking place at sites in the EEA where this other manufacturing authorisation holder is defined in the relevant marketing authorisation. 按照本附录第3.3节所述的原则，质量授权人认证成品药品批次可通过考虑得到确认：当在相关的上市许可规定了其他生产授权持有人情况下，与任何在欧洲经济区发生的生产或进口运营其他质量授权人分享规定的职责。
3.4.4	Conditions of storage and transport should be taken into account by the QP during certification of a batch. 在 质量授权人认证一个批次使，应考虑储存与运输条件。
3.4.5	The QP certifying the finished product is responsible for ensuring that each finished medicinal production batch has been manufactured in accordance with GMP and the MA. Also, unless an MRA or similar agreement is in place between the EEA and the exporting country, that it has undergone in a Member State a full qualitative analysis, a quantitative analysis of at least all the active substances and all the other tests or checks necessary, or in accordance with an approved Real Time Release Testing programme to ensure the quality of medicinal products in accordance with the requirements of the marketing authorisation. 质量授权人对成品认证是对确保每个成品药品生产批次已按照药品生产质量管理规范以及上市许可生产负责。此外，除非在欧洲经济区一出口国家质检有互认协议(MRA)或类似协议，其在一个成员国经历了一个完整的定性分析、至少所有原料药定量分析以及其它所有必要的测试或检查，或按照一个已经批准的实时放行测试程序来按照上市许可要求保证药品质量。
3.4.6	Sampling of imported product should in full be representative of the batch and, therefore, be taken after arrival in the EEA 进口产品取样应在充分代表批次，因此，应在抵达的欧洲经济区(EEA)后进行。
3.4.7	Where there is a risk that any sample would not appropriately represent the batch (e.g. sample for sterility test of an aseptically filled batch), it may be necessary to take additional samples during processing in the third country. Such an approach should be technically justified. These samples should be shipped with and under the same conditions as the batch they represent. If sent separately it should be demonstrated that the samples are still representative of the imported batch. 当任何样品有不能恰当代表该批次风险(例如，无菌灌装批次无菌测试样品)，可能需要在第三国加工期间进行另行取样。应对这种办法进行技术合理性说明。这些样品应其所代表的批次在 相同条件下运输。如果单独发送，应证明该样品其仍然具进口批次代表性。
3.4.8	When different finished product batches originating from the same bulk product batch are imported, the QPs certifying the different finished product batches may base their decision on the quality control testing of another imported finished batch originating from the same bulk product batch provided that the ID and assay testing are conducted on each occasion within the EEA and there is secured documented evidence that: 当进口的不同成品源自相同半成品批次时，质量授权人认证不同的成品批次可以基于其它进口的仙童半成品批次成品质量控制测试，提供每次鉴别与含量分析测试在欧洲经济区进行，并且有安全的文件证据：
·	The finished product batch originates from the same bulk product batch; 成品批次源于相同的半成品批次；
·	The finished products have been stored and transported in similar conditions; 成品已经在类似的条件下储存与运输；
·	The bulk product has been stored in similar conditions before completed packaging; 半成品在完成包装前已经存储在类似的条件下；
·	The samples tested are representative of the whole batch. 测试的样品代表整个批次。
3.5	Operational responsibilities of the QP prior to certification of a batch for release to market or for export, the QP must personally ensure that: 质量授权人认证一个批次来放行到市场或出口前运行职责，质量授权人须亲自确保：
3.5.1	Certification is permitted under the terms of the manufacturing/importation authorisation (MIA). 在生产/进口许可(MIA)条款下许可认证。
3.5.2	Any additional duties and requirements of national legislation are complied with. 符合任何额外的国家法律职责与要求。
3.5.3	Certification is recorded in a register or equivalent document. 在登记或同等文件记录认证。
	In addition the QP has responsibility for ensuring the following points 3.5.4 - 3.5.22. These may be delegated to appropriately trained personnel or third parties. It is recognised that the QP will need to rely on a quality management system. The QP should have on-going assurance that this reliance is well founded. 此外，质量授权人有责任确保以下几点3.5.4-3.5.22。这些可委托给经过适当培训人员或第三方。已经认识到，质量授权人必需依靠质量管理体系。质量授权人应持续保证，这依赖的基础是良好的。
3.5.4	All activities associated with manufacture and testing of the medicinal product have been conducted in accordance with the principles and guidelines of EU GMP. 与药品生产与测试相关的所有活动已进行按照欧盟药品生产质量管理规范的基本原则与指南实施。
3.5.5	The entire supply chain of the medicinal product, starting from the manufacturing sites of the starting materials and components, and including all parties involved in any manufacturing and importation activities of the medicinal product, is documented and available for the QP. The document should preferably be in the format of a comprehensive diagram, where each party, including subcontractors of critical steps such as e.g. the sterilisation of components and equipment for aseptic processing, are included. 药品整个供应链，从起始物料与成分的生产现场基地开始，包括在药品任何生产与进口活动所有涉及到的各方，都进行记录并提供给质量授权人。该文件应最好是一个全面图的格式，包括关键步骤的分承包方面，例如，成分以及无菌加工设备的灭菌，也包括在内。
3.5.6	All sites of manufacture, analysis and certification are compliant with the terms of the marketing authorisation (MA) for the intended territory. 所有生产、分析与认证现场符合预期进入领土的上市许可(MA)条款。
3.5.7	All manufacturing activities and testing activities are consistent with those registered in the marketing authorization. 所有生产活动与测试活动符合在已经注册的上市许可。
3.5.8	The source and specifications of starting materials and packaging materials used in the batch are compliant with the MA. A supplier quality management system is in place which ensures that only materials of the required quality have been supplied. 在该批次中所使用的起始物料与包装材料的来源与规格标准符合上市许可。供应商有一个质量管理体系，确保仅仅供应所需要的质量的物料。
3.5.9	The active substances used in the manufacturing of the finished products have been manufactured in accordance with GMP and, where required, imported and distributed in accordance with Good Distribution Practices (GDP). When imported, and as relevant, the requirements of Article 46b of Directive 2001/83/EC are met. 在制剂产品中所使用的原料药已经按照药品生产质量管理规范进行生产，并在有需要时，按照药品分销质量管理规范(GDP)进行进口与分销。当进口时，如果相关，符合第2001/83/EC号法令的第46B条。
3.5.10	The excipients used in the manufacturing of the finished product have been manufactured, as relevant, in accordance with the ascertained manufacturing practice referred to in Article 46 (f) of Directive 2001/83/EC, where required. 在制剂生产中所使用辅料已经制造，如果相关，符合第2001/83/EC号法令第46(f)条所涉及查明生产实践中。
3.5.11	When relevant, the TSE (Transmissible Spongiform Encephalopathy) status of all materials used in batch manufacture is compliant with the terms of the authorisation. 如果有关，所有在批次生产中所使用的物料符合官方传染性海绵状脑病(TSE)状态条款。
3.5.12	All records are complete and endorsed by appropriate personnel. All required in-process controls and checks have been made. 所有记录完整并由恰当人员签字。已经实施所有中间过程控制以及检查。
3.5.13	All manufacturing and testing processes remain in the validated state. Personnel are trained and qualified where required. 所有生产与测试过程仍然处于经过验证状态。如果需要，已经对人员进行培训并具有资质。
3.5.14	Finished product quality control (QC) test data complies with the registered Finished Product Specification, or where authorised, the Real Time Release Testing programme. 制剂产品质量控制(QC)的测试数据符合已经注册的制剂规格标准，或授权，实时放行测试程序。
3.5.15	Any post marketing commitments relating to manufacture or testing of the product in the authorisation have been addressed. On-going stability data continues to support certification. 任何在许可中有关产品生产或测试上市后承诺已得到解决。持续稳定性的数据继续支持认证。
3.5.16	The impact of any change to product manufacturing or testing has been evaluated and any additional checks and tests are complete. 已经评价任何变更对产品生产或测试的影响，并已经完成任何额外的检查与测试。
3.5.17	All investigations pertaining to the batch being certified (including out of specification and adverse trend investigations) have been completed to a sufficient level to support certification. 所有有关该批次认证的调查(包括超出规格标准与不良趋势调查)已经完成，并达到足够支持认证的水平。
3.5.18	Any on-going complaints, investigations or recalls do not negate the conditions for certification of the batch in question. 任何进行中的投诉、调查或召回都不否定该问题批次认证的条件。
3.5.19	Required technical agreements are in place. 需要有技术协议。
3.5.20	The self-inspection programme is active and current. 自检程序是有效并且现行的。
3.5.21	The appropriate arrangements for distribution and shipment are in place. 有对于分销与运输适当约定。
3.5.22	In the case of human medicinal products intended to be placed on the market in the Union, the presence of the safety features referred to in Article 54 of Directive 2001/83/EC have been verified, where appropriate. 在人用药品预期投放到欧盟市场上情况下，如果恰当，已经确证参照第2001/83/EC法令第54条所涉及的安全功能。
3.6	For certain products, special guidance may apply, such as Annex 3 of the Guide for radiopharmaceuticals. 对于某些产品，可应用特殊指南，例如附录3的放射性药物指南。
3.7	Parallel importation and parallel distribution 平行进口以及并行分销
3.7.1	Prior to certification of a batch the QP should confirm compliance with national rules for parallel importation and EU rules for parallel distribution. 在一个批次认证之前，质量授权人应确认符合国家平行进口的规则以及欧盟平行分销法规。
3.7.2	The QP of the MIA holder, who is named responsible for the certification of the batch in the MA of the repackaged finished product, certifies that the repackaging has been performed in accordance with the relevant Authorisation pertaining to the repackaged product and GMP. 生产与进口许可持有人的质量授权人，其是指定负责对重现包装制剂产品上市许可进行批次认证，证明重新包装已经按照相关重新包装许可以及药品生产质量管理规范实施。
3.7.3	The re-packager should ensure that product intended for repackaging has been obtained from the authorised supply chain and that each sourced batch has undergone certification by a QP prior to its release into the supply chain. 重新包装企业应确保预期用于重新包装产品已获得供应链授权，并且每个采购批次在放行到供应链之前已经经过质量授权人认证。
3.7.4	The re-packager must ensure authenticity by verifying safety features, where applicable. 如果适用，重新包装企业必须通过确证来确保真实性。
3.8	Recording of the certification 认证记录
3.8.1	The certification of a medicinal product is recorded by the qualified person in a register or equivalent document provided for that purpose. The record should show that each production batch satisfies the provisions of Article 51 of Directive 2001/83/EC or Article 55 of Directive 2001/82/EC. The record must be kept up to date as operations are carried out and must remain at the disposal of the agents of the competent authority for the period specified in the provisions of the Member State concerned and in any event for at least five years. 药品认证由质量授权人在记录或提供此目的的等同文件中进行记录。该记录应当现实每个批次产品符合第2001/83/EC法令的第51条或第2001/82/EC法令的第55条规定。记录必须在操作实施时进行更新，并必须保持在主管机关处置下，保存期间由成员国有关规定所规定，在任何情况下，至少保存五年。
3.8.2	The control report referred to in Article 51 of Directive 2001/83/EC or Article 55 of Directive 2001/82/EC or another proof of certification for release to the market in question based on an equivalent system should be made available for the batch in order for the batch to be exempted from the controls when entering another Member State. 每个批次应提供第2001/83/EC号法令第51条或第2001/82/EC号法令第55条有关的控制报告或其它基于一个等同的体系放行到市场认证证明，以便批次进入其他成员国时免除控制。
4. Relying on GMP assessments by third parties e.g. audits第四章：依托第三方药品生产质量管理规范评估，例如审计
In some cases the QP will rely on the correct functioning of the quality management system of sites involved in the manufacture of the product and this may be derived from audits conducted by third parties. 在某些情况下，质量授权人将依靠产品在生产中所涉及现场的质量管理体系正确功能，其可能是来自第三方进行审计。
4.1	Relying on assessment by third parties (eg. audits) should be in accordance with Chapter 7 of the EU GMP Guide in order to appropriately define, agree and control any outsourced activity. 依赖第三方评估(如审计)应该按照欧盟药品生产质量管理规范的第7章，以便恰当规定、批准与控制任何外包活动。
4.2	Special focus should be set on the approval of audit reports: 应特别关注审计报告的批准：
4.2.1	The audit report should address general GMP requirements, as for example the quality management system, all relevant production and quality control procedures related to the supplied product, e.g. API manufacturing, quality control testing, primary packaging, etc. All audited areas should be accurately described resulting in a detailed report of the audit. 审计报告应解决药品生产质量管理规范总要求，例如质量管理体系，与供应产品相关的所有生产和质量控制规程，例如：原料药生产、质量控制测试，内包装等。应在一个详细的审计报告中准确描述所有审计领域结果。
4.2.2	It should be determined whether the manufacture and quality control of API and medicinal products follows GMP at least equivalent Article 46 of Directive 2001/83/EC and Article 50 of Directive 2001/82/EC. 需要确定是否原料药与制剂的生产与质量控制遵循的药品生产质量管理规范至少等同于第2001/83/EC号法令第46条与第2001/82/EC法令第50条。
4.2.3	In case of outsourced activities compliance with the Marketing Authorisation should be verified. 在外包活动情况下，应确证与上市许可符合性。
4.2.4	The QP should ensure that a written final assessment and approval of third party audit reports has been made by the company according to the company′s requirements. 质量授权人应确保公司按照公司要求已经作出书面最终评估并批准第三方审计报告。
4.2.5	Outsourced activities with critical impact on the product quality should be defined in accordance with the principles of Quality Risk Management such as described in Part III of the EU GMP Guide. According to this, the QP should be aware of the outcome of an audit with critical impact on the product quality before certifying the relevant batches. 关键影响产品质量的外包活动应按照欧盟药品生产质量管理规范指南第三部分所描述的质量风险管理的基本原则进行规定。根据这一点，质量授权人应在认证该批次前意识到关键影响产品质量审计结果。
4.2.6	Repeated audits should be performed in accordance with the principles of Quality Risk Management. 按照质量风险管理基本原则，应反复进行审计。
5. Handling of unplanned deviations第五章：非计划性偏差的处理
5.1	As long as registered specifications for active substances, excipients and finished products are met, a QP may, taking the following guidance into account, consider confirming compliance / certifying a batch where an unplanned and unexpected deviation from details contained within the Marketing Authorisation and/or GMP has occurred. 当发生一个与上市许可细节，和/或，药品生产质量管理规范的非计划与非期望的偏差时，只要原料药、辅料、制剂产品符合注册规格标准，一个质量授权人可以，考虑采取以下指南，考虑确认符合性/认证一个批次。
5.2	Where a deviation has occurred during manufacture or testing of a batch of finished product it may be considered to meet the requirements of the marketing authorisation and GMP when the details described below have been taken into account: 当偏差已经在一个批次成品的生产或测试发生，当考虑以下详细描述时，可以考虑符合上市许可与药品生产质量管理规范要求：
5.2.1	The deviation is unexpected, unplanned and relates to the manufacturing process and/or the analytical control methods as described in the Marketing Authorisation. 偏差是非期望、计划外并有关在上市许可中描述的生产过程，和/或，分析控制方法。
5.2.2	An assessment has been performed by the manufacturer using an appropriate approach such as described in Quality Risk Management in Part III of the EU GMP Guide, and which supports a conclusion that the occurrence does not have an adverse effect on quality, safety or efficacy of the product. 已经由生产企业使用在欧盟药品生产质量管理规范指南第三部分中描述的质量管理中描述的恰当方法实施一个评估，并支持发生这样偏差没有对产品质量、安全性或有效性产生不良影响的结论。
5.2.3	The risk management has evaluated the need for inclusion of the affected batch/ batches in the on-going stability programme. 风险管理已经评价需要在持续稳定性程序中纳入受影响的批次。
5.2.4	For biological medicinal products in particular, the risk management has taken into consideration that even minor changes to the process can have an unexpected impact on safety or efficacy. 特别是对于生物药品，风险管理已经考虑即使是过程微小变更可以有非期望的安全性或有效性影响。
5.3	The QP performing certification should be aware and take into consideration any deviations which have potential impact for compliance with GMP or the Marketing Authorisation. 质量授权人实施认证应意识到并考虑到有潜在影响与药品生产质量管理规范或上市许可符合性的任何偏差。
6. The release of a batch第六章：一个批次放行
6.1	Batches of licensed medicinal products should only be released for sale or supply to the market after certification by a QP as described above. Until a batch is released it should remain at the site of manufacture or be shipped under quarantine to another authorised site. 许可的药品批次仅仅应在由上述描述的质量授权人认证后才放行用于销售或供应。直到一个批次放行，其应保持在生产现场或在待检下运输到另一个授权现场。
6.2	Safeguards to ensure that uncertified batches are not released should be in place and may be physical (via the use of segregation and labelling) or electronic (via the use of validated computerised systems). When uncertified batches are moved from one authorised site to another the safeguards to prevent premature release should remain. 应有防护措施来确保未经过认证批次不会放行并可能是物理(通过使用隔离与标签)或电子(通过验证的计算机系统)。当从一个未经过认证的批次从一个授权的现场移动到另一个时，应保持防护措施防止过早放行。
6.3	Notification by a QP to the releasing site that certification has taken place should be formal and unambiguous and should be subject to the requirements of Chapter 4 of the EU GMP Guide. 由质量授权人给放行现场已经进行认证通知应该是正式和明确，并应遵守欧盟药品生产质量管理规范指南第四章的要求。
7. Glossary第七章：术语
Certain words and phrases in this annex are used with the particular meanings defined below. Reference should also be made to the Glossary in the main part of the Guide. 本附录中的某些单词与短语是用来定义见下文特定的涵义。还应该参考药品生产质量管理规范指南的主部分中的术语。
Bulk production batch: a batch of product, of a size described in the application for a Marketing authorisation, either ready for assembly into final containers or in individual containers ready for assembly to final packs. (A bulk production batch may, for example, consist of a bulk quantity of liquid product, of solid dosage forms such as tablets or capsules, or of filled ampoules, or the first blending of an API and an excipient). 半成品生产批次：在上市许可申请中描述批量的一个批次的产品，无论是准备组装到最终容器，或在单个容器中准备装配到最终包装容器。 (一个半成品批次可能，例如，由一些数量液体、诸如片剂或胶囊固体剂型、已经灌装到安瓿中、首次将一个原料药与一个赋形剂混合构成)。
Certification of the finished product batch: the certification in a register or equivalent document by a Q.P., as defined in Article 51 of Directive 2001/83/EC and Article 55 of Directive 2001/82/EC, before a batch is released for sale or distribution. 成品批次认证：在第2001/83/EC号法令第51条与第2001/82/EC号法令第55条中规定质量授权人在产品放行到销售或分销前，在注册登记中或等同文件中认证。
Confirmation (Confirm and confirmed have equivalent meanings): a signed statement by a QP that a process or test has been conducted in accordance with GMP and the relevant marketing authorisation, product specification file and/or technical agreement, as applicable, as agreed in writing with the QP responsible for certifying the finished product batch before release. The QP providing a confirmation takes responsibility for those activities being confirmed. 确认(确认与确认的具有同等意义)：一个由质量授权人签发的声明，过程与测试已经按照药品生产质量管理规范以及相关上市许可、产品规格标准文件，和/或，技术协议(如果适用)实施，在放行前由负责质量授权人书面同意认证成品批次。质量授权人提供一个确认这些活动被确认。
Finished product batch: with reference to the control of the finished product, a finished product batch is defined in Part 1 Module 3 point 3.2.2.5 of Directive 2001/83/EC2, and mentioned in Part 2 section F1 of Directive 2001/82/EC. In the context of this annex the term in particular denotes the batch of product in its final pack for release to the market. 成品批次：参考成品的控制，成品批次在第2001/83/EC号法令第一部分模块三的3.2.2.5定义，以及第2001/82/EC号法令第二部分第F1节中提到。在本附录环境中表示在放行到市场最终包装中的产品批次。
Importer: the holder of the authorisation required by Article 40.3 of Directive 2001/83/EC and Article 44.3 of Directive 2001/82/EC for importing medicinal products from third countries. 进口商：第2001/83/EC号法令第40.3条与第2001/82/EC号法令第44.3条所要求的从第三国进口药品许可持有人。
Qualified Person (QP): the person defined in Article 48 of Directive 2001/83/EC and Article 52 of Directive 2001/82/EC. 质量授权人(QP)：地2001/83/EC号法令第48条与第2001/82/EC号法令第52条中定义的人。

Content of the confirmation of the partial manufacturing of a medicinal product / investigational medicinal product 药品/研究药品平行生产确认内容
[LETTER HEAD OF MANUFACTURER WHO CARRIED OUT THE MANUFACTURING ACTIVITY] [实施生产活动的生产企业信头]
1.	Name of the product and description of the manufacturing stage (e.g. paracetamol 500 mg tablets, primary packaging into blister packs) 产品名称与生产阶段描述(例如，对乙酰氨基酚500毫克片剂，泡罩包装内包装)
2.	Batch number 批号
3.	Name and address of the site carrying out the partial manufacturing 实施部分生产现场的名称与地址
4.	Reference to the Technical Quality Agreement (in accordance with Chapter 7 of the Guide) 参考技术质量协议(按照药品生产质量管理规范指南第七章)
5.	Confirmation statement 确认声明
	I hereby confirm that the manufacturing stages referred to the Technical Quality Agreement have been carried out in full compliance with the GMP requirements of the EU and the terms described in the Agreement for ensuring compliance with the requirements of the Marketing Authorisation(s) of the destination country/countries as provided by [Contract Giver/manufacturer certifying and releasing the batch]. 我在此确认，由[合同供方/生产企业认证与放行批次]提供在技术质量协议中的生产阶段已经按照符合欧盟药品生产质量管理规范以及在协议中描述的符合目的国上市许可要求条款要求进行。
6.	Name of the Qualified Person confirming the partial manufacturing. 确认部分生产的质量授权人姓名。
7.	Signature of Qualified Person confirming the partial manufacturing. 确认部分生产质量授权人签字。
8.	Date of signature 签字日期

hongwei2000

谢谢分享，不过中文有点看不懂，是用软件翻译的吗

残伤

hongwei2000 发表于 2013-7-16 15:56
谢谢分享，不过中文有点看不懂，是用软件翻译的吗

估计是吧 我也是从别处看到 转发过来的

piao0923

谢谢分享。

天蝎谢肥肥

谢谢分享~~

avr163

中国可行吗

cgc717

谢谢分享

残伤

cgc717 发表于 2013-7-19 16:06
谢谢分享

不客气

唐延进

中文有点看不懂，是用软件翻译的吗

hoogle

谢谢分享！！！！

gdqyhjs

谢谢分享。

yang_jur

太好了，非常感谢这些提供英中对照的达人们！

明朝花开

终于找到COC的来源了，
其实就是国内质量受权人签署的批放行文件的平替

ndj2001

谢谢分享！！！