EUROPEAN COMMISSION
ENTERPRISE DIRECTORATE-GENERAL
Single market, regulatory environment, industries under vertical legislation
Pharmaceuticals and cosmetics
Brussels, 30 March 2015
EudraLex
Volume 4
EU Guidelines for
Good Manufacturing Practice for
Medicinal Products for Human and Veterinary Use
Annex 15: Qualification and Validation
EU GMP附录15：确认和验证
Legal basis for publishing the detailed guidelines: 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.
公布详细指南的法律依据：指令2001/83/EC第47款关于人药共同体代码，和2001/82/EC第51款关于兽药共同体代码的要求。本文件为指令2003/94/EC中制订的人药GMP以及指令 91/412/EEC兽药GMP原则和指南提供诠释。
Status of the document: Revision
文件状态：修订
Reasons for changes: Since Annex 15 was published in 2001 the manufacturing and regulatory environment has changed significantly and an update is required to this Annex to reflect this changed environment. This revision to Annex 15 takes into account changes to other sections of the EudraLex, Volume 4, Part I, relationship to Part II, Annex 11, ICH Q8, Q9, Q10 and Q11, QWP guidance on process validation, and changes in manufacturing technology.
变更理由：自从附录15在2001年公布以来，生产和法规环境已发生了重大变化，有必要对此附录进行更新以反映环境的变化。本次对附录15的修订考虑了欧洲药事法卷4第一部分其它部分的变化，与第二部分、附录11、ICH Q8 Q9 Q10以及Q11、QWP的工艺验证指南的关系，以及生产技术的变化。
Deadline for coming into operation: 1 October 2015
最后实施时间：2015年10月1日
Principle 原则
This Annex describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products and may also be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, Part II. It is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. Any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, should be formally documented and the impact on the validated status or control strategy assessed. Computerised systems used for the manufacture of medicinal products should also be validated according to the requirements of Annex 11. The relevant concepts and guidance presented in ICH Q8, Q9, Q10 and Q11 should also be taken into account.
本附录描述了确认和验证的原则，该原则适用于药品生产用设施、设备、公用系统和工艺，也可用作活性物质的可选补充指南，但并不对欧盟药事法第4卷第二部分引入附加要求。GMP要求生产商通过在产品和工艺的整个生命周期中进行确认和验证，对其操作关键方面进行控制。所有可能影响产品质量的设施、设备、公用系统和工艺计划变更均应进行正式记录，并评估其对验证状态和控制策略的影响。用于药品生产的计算机化系统也应根据附录11的要求进行验证。同时还应考虑ICH Q8 Q9 Q10和Q11是的相关概念和指南要求。
General 通则
A quality risk management approach should be applied throughout the lifecycle of a medicinal product. As part of a quality risk management system, decisions on the scope and extent of qualification and validation should be based on a justified and documented risk assessment of the facilities, equipment, utilities and processes. Retrospective validation is no longer considered an acceptable approach. Data supporting qualification and/or validation studies which were obtained from sources outside of the manufacturers own programmes may be used provided that this approach has been justified and that there is adequate assurance that controls were in place throughout the acquisition of such data.
质量风险管理的方法应贯穿药品的整个生命周期。作为质量风险管理系统的一部分，决定确认和验证的范围和程度时应基于对设施、设备、公用系统和工艺的论证和书面风险评估。回顾性验证不再被认为是可以接受的方法。如果经过论证，并且获得数据的整个过程有足够控制保证，也可以使用从生产商自身程序以外获得的用于支持确认和/或验证研究的数据。
1. ORGANISING AND PLANNING FOR QUALIFICATION AND VALIDATION
1. 确认和验证的组织和计划
1.1. All qualification and validation activities should be planned and take the life cycle of facilities, equipment, utilities, process and product into consideration.
1.1. 所有确认和验证活动应进行计划，并考虑设施、设备、公用系统、工艺和产品的生命周期
1.2. Qualification and validation activities should only be performed by suitably trained personnel who follow approved procedures.
1.2. 确认和验证活动应由经过适当培训的人员实施，并遵守已批准的程序
1.3. Qualification/validation personnel should report as defined in the pharmaceutical quality system although this may not necessarily be to a quality management or a quality assurance function. However, there should be appropriate quality oversight over the whole validation life cycle.
1.3. 确认/验证实施人员应根据药品质量体系中指定的要求进行报告，尽管并不一定是报告给质量管理或质量保证部门。但是，对整个验证生命周期应有适当的质量监管。
1.4. The key elements of the site qualification and validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent document.
1.4. 应在验证主计划（VMP）或等同的文件中界定和记录工厂确认和验证程序的关键要素
1.5. The VMP or equivalent document should define the qualification/validation system and include or reference information on at least the following:
1.5. VMP或对等的文件中应定义确认/验证体系，并包括或引用至少以下信息：
i. Qualification and Validation policy;
i. 确认和验证方针
ii. The organisational structure including roles and responsibilities for qualification and validation activities;
ii. 组织结构，包括确认和验证活动中的工作和职责
iii. Summary of the facilities, equipment, systems, processes on site and the qualification and validation status;
iii. 现场设施、设备、系统、工艺总结和确认和验证状态
iv. Change control and deviation management for qualification and validation;
iv. 确认和验证变更控制和偏差管理
v. Guidance on developing acceptance criteria;
v. 可接受标准建立指南
vi. References to existing documents;
vi. 对已有文件的引用
vii. The qualification and validation strategy, including requalification, where applicable.
vii. 确认和验证策略，适当时应包括再确认
1.6. For large and complex projects, planning takes on added importance and separate validation plans may enhance clarity
1.7. 对于大型的复杂项目，增加计划重点和独立的验证计划将有助于明晰要做的工作
1.8. A quality risk management approach should be used for qualification and validation activities. In light of increased knowledge and understanding from any changes during the project phase or during commercial production, the risk assessments should be repeated, as required. The way in which risk assessments are used to support qualification and validation activities should be clearly documented.
1.9. 在确认和验证活动中应使用质量风险管理方法。鉴于项目期间或商业生产期间所有变更导致对工艺的理解和知识的增加，在需要时应重复风险评估。应清楚记录用于支持确认和验证活动的风险评估方法。
1.10. Appropriate checks should be incorporated into qualification and validation work to ensure the integrity of all data obtained.
1.11. 应将适当的检查结合进确认和验证工作，以保证所获得的数据的完整性
2. DOCUMENTATION, INCLUDING VMP 文件记录，包括VMP
2.1. Good documentation practices are important to support knowledge management throughout the product lifecycle.
优良文件规范在支持整个产品周期中的知识管理方面是很重要的。
2.2. All documents generated during qualification and validation should be approved and authorised by appropriate personnel as defined in the pharmaceutical quality system.
所有在确认和验证期间产生的文件应由药品质量体系中指定的适当的人员批准和授权。
2.3. The inter-relationship between documents in complex validation projects should be clearly defined.
复杂验证项目中文件之间的内在关系应清楚界定。
2.4. Validation protocols should be prepared which defines the critical systems, attributes and parameters and the associated acceptance criteria.
应制订验证方案，在其中界定关键系统、属性和参数以及相关的可接受标准。
2.5. Qualification documents may be combined together, where appropriate, e.g. installation qualification (IQ) and operational qualification (OQ).
确认文件在适当时可以合并在一起，例如，安装确认（IQ）和运行确认（OQ）。
2.6. Where validation protocols and other documentation are supplied by a third party providing validation services, appropriate personnel at the manufacturing site should confirm suitability and compliance with internal procedures before approval. Vendor protocols may be supplemented by additional documentation/test protocols before use.
如果验证方案和其它文件记录由验证服务第三方提供，则应由生产场所的适当人员对文件记录的适用性进行确认，在批准前确认其符合内部程序。供应商方案在使用前可以进行文件记录/测试增补。
2.7. Any significant changes to the approved protocol during execution, e.g. acceptance criteria, operating parameters etc., should be documented as a deviation and be scientifically justified.
在实施期间，对已批准的方案进行任何重大变更，例如，可接受标准、操作参数等，均应记录为偏差并经过科学论证。
2.8. Results which fail to meet the pre-defined acceptance criteria should be recorded as a deviation and be fully investigated according to local procedures. Any implications for the validation should be discussed in the report
不符合既定可接受标准的结果应记录为偏差，并根据内部程序进行全面调查。验证产生的影响应在报告里讨论。
2.9. The review and conclusions of the validation should be reported and the results obtained summarised against the acceptance criteria. Any subsequent changes to acceptance criteria should be scientifically justified and a final recommendation made as to the outcome of the validation.
对验证进行的审核及所得出的结论应报告，所得到的结果应进行总结并与可接受标准对照。所有之后对可接受标准的变更应经过科学论证，对验证的结果应做出最后的建议。
2.10. A formal release for the next stage in the qualification and validation process should be authorised by the relevant responsible personnel either as part of the validation report approval or as a separate summary document. Conditional approval to proceed to the next qualification stage can be given where certain acceptance criteria or deviations have not been fully addressed and there is a documented assessment that there is no significant impact on the next activity.
在确认和验证过程中，应由相关责任人授权对一个阶段结果进行放行，指示可以进入一下阶段。该放行可以是验证报告批准的一部分，也可以是一份单独的总结文件。如果对某些可接受标准或偏差还没能进行全面说明，但进行了书面评估说明对下一阶段活动没有重大影响，则可以有条件的批准进入下一验证阶段。
3. QUALIFICATION STAGES FOR EQUIPMENT, FACILITIES, UTILITIES AND SYSTEMS. 设备、设施、公用系统和系统的确认阶段
3.1. Qualification activities should consider all stages from initial development of the user requirements specification through to the end of use of the equipment, facility, utility or system. The main stages and some suggested criteria (although this depends on individual project circumstances and may be different) which could be included in each stage are indicated below:
确认活动应将考虑从建立用户需求手册到设备、设施、公用系统或系统的最终使用所有阶段。主要阶段和一些可以包括在各阶段的建议标准（当然这会根据各项目环境不同而有差异）列出如下：
User requirements specification (URS) 用户需求手册
3.2. The specification for equipment, facilities, utilities or systems should be defined in a URS and/or a functional specification. The essential elements of quality need to be built in at this stage and any GMP risks mitigated to an acceptable level.
设备、设施、公用系统或系统的要求应在URS或功能性标准里界定。在这个阶段要建立起质量要素，应将所有GMP风险转移至可接受水平。
The URS should be a point of reference throughout the validation life cycle.
URS应该是整个验证生命周期中的参照点。
Design qualification (DQ)设计确认
3.3. The next element in the qualification of equipment, facilities, utilities, or systems is DQ where the compliance of the design with GMP should be demonstrated and documented. The requirements of the user requirements specification should be verified during the design qualification.
设备、设施、公用系统或系统的确认中下一个要素是DQ。在DQ中，要证明并记录设计的GMP符合性。用户需求手册中的要求在设计确认阶段应进行核对。
Factory acceptance testing (FAT) /Site acceptance testing (SAT) 工厂验收测试（FAT）和现场验收测试（SAT）
3.4. Equipment, especially if incorporating novel or complex technology, may be evaluated, if applicable, at the vendor prior to delivery.
设备，特别是结合了创新或复杂技术的设备，适用时，可以在供应商发货前进行评估。
3.5. Prior to installation, equipment should be confirmed to comply with the URS/functional specification at the vendor site, if applicable.
在安装之前，适用时，应在供应商的场所内确认设备符合URS功能性要求。
3.6. Where appropriate and justified, documentation review and some tests could be performed at the FAT or other stages without the need to repeat on site at IQ/OQ if it can be shown that the functionality is not affected by the transport and installation.
在适当并经过论证的情况下，在FAT阶段或其它阶段可以对文件记录进行审核，及进行一些测试，如果可以显示这些功能不会受到运输和安装的影响的话，那么这些测试可以不需要在安装确认和运行确认时重复。
3.7. FAT may be supplemented by the execution of a SAT following the receipt of equipment at the manufacturing site.
工厂验收测试可以在生产场所接收设备后由现场验收测试进行补充。
Installation qualification (IQ) 安装确认
3.8. IQ should be performed on equipment, facilities, utilities, or systems.
设备、设施、公用系统或系统应进行安装确认。
3.9. IQ should include, but is not limited to the following:
安装确认应包括，但不仅限于以下内容：
i. Verification of the correct installation of components, instrumentation, equipment, pipe work and services against the engineering drawings and specifications;
确认部件、仪表、设备、管道和服务均根据工程图纸和规格要求进行了正确安装。
ii. Verification of the correct installation against pre-defined criteria;
确认根据既定标准正确安装。
iii. Collection and collation of supplier operating and working instructions and maintenance requirements;
收集并核对供应商操作和工作手册和维护要求。
iv. Calibration of instrumentation;
仪表校正
v. Verification of the materials of construction.
核对部件材质
Operational qualification (OQ) 运行确认
3.10. OQ normally follows IQ but depending on the complexity of the equipment, it may be performed as a combined Installation/Operation Qualification (IOQ).
运行确认一般是在安装确认后面，但根据设备的复杂性，它也可以与安装确认合并成为安装运行确认（IOQ）。
3.11. OQ should include but is not limited to the following:
运行确认应包括但不仅限于以下内容
i. Tests that have been developed from the knowledge of processes, systems and equipment to ensure the system is operating as designed;
测试根据工艺、系统和设备知识建立的测试项目，以保证系统如设计的一样运行
ii. Tests to confirm upper and lower operating limits, and /or “worst case” conditions.
测试以确认最高和最低操作限度，和/或“最差情形”条件。
3.12. The completion of a successful OQ should allow the finalisation of standard operating and cleaning procedures, operator training and preventative maintenance requirements.
运行确认成功完成应使得标准操作规程和清洁程序、操作人员培训和维保要求可以定稿。
Performance qualification (PQ) 性能确认
3.13. PQ should normally follow the successful completion of IQ and OQ. However, it may in some cases be appropriate to perform it in conjunction with OQ or Process Validation.
性能确认一般是在安装确认和运行确认成功完成之后。但是，在有些情况下，也可以将其与运行确认或工艺验证合并进行。
3.14. PQ should include, but is not limited to the following:
性能确认应包括，但不仅限于以下内容
i. Tests, using production materials, qualified substitutes or simulated product proven to have equivalent behaviour under normal operating conditions with worst case batch sizes. The frequency of sampling used to confirm process control should be justified;
使用生产物料、确认过的替代品或已证明在一般操作条件下与最差的批量下具有等同的行为特性的模拟产品进行测试。用于确认工艺控制的取样频次应进行论证。
ii. Tests should cover the operating range of the intended process, unless documented evidence from the development phases confirming the operational ranges is available.
测试应覆盖既定工艺的操作范围，除非在研发阶段有记录的证据能确认操作范围。
4. RE-QUALIFICATION 再确认
4.1. Equipment, facilities, utilities and systems should be evaluated at an appropriate frequency to confirm that they remain in a state of control.
设备、设施、公用系统和系统应以适当的频次进行评估，以确认其仍处于受控状态。
4.2. Where re-qualification is necessary and performed at a specific time period, the period should be justified and the criteria for evaluation defined. Furthermore, the possibility of small changes over time should be assessed.
如果需要在一个特定时间周期内进行再验证，则应对该时间周期进行论证，并确定评估的标准。另外，应评估在此期间进行小型变更的可能性。
5. PROCESS VALIDATION 工艺验证
General 总则
5.1. The requirements and principles outlined in this section are applicable to the manufacture of all pharmaceutical dosage forms. They cover the initial validation of new processes, subsequent validation of modified processes, site transfers and ongoing process verification. It is implicit in this annex that a robust product development process is in place to enable successful process validation.
本部分列出的要求和原则适用于所有制剂的和平。它们包括了新工艺的初始验证，变更工艺后的验证、场所转移和进行中工艺确认。本附录中不言而喻的意思是应有一个坚实的药品研发过程来保证成功的工艺验证。
5.2. Section 5 should be used in conjunction with the current EMA guideline on Process Validation.
第5部分应该与现行EMA关于工艺验证的指南联合使用。
5.2.1. The guideline on Process Validation is intended to provide guidance on the information and data to be provided in the regulatory submission only. However GMP requirements for process validation continue throughout the lifecycle of the process
工艺验证指南仅意在提供关于法规申报所需提供的资料和信息的指南。而GMP对工艺验证的要求是贯穿工艺的整个生命周期中。
5.2.2. This approach should be applied to link product and process development. It will ensure validation of the commercial manufacturing process and maintenance of the process in a state of control during routine commercial production.
本方法应该应用于链接产品与工艺研发过程。它能保证商业生产工艺的验证，在日常商业生产中维护工艺处于受控状态。
5.3. Manufacturing processes may be developed using a traditional approach or a continuous verification approach. However, irrespective of the approach used, processes must be shown to be robust and ensure consistent product quality before any product is released to the market. Manufacturing processes using the traditional approach should undergo a prospective validation programme, wherever possible, prior to certification of the product. Retrospective validation is no longer an acceptable approach.
生产工艺研发可以采用传统的方法，或持续确认的方法。但是，不管使用什么方法，工艺必须显示出其耐用性，在产品放行上市前能保证产品质量的一致性。使用传统方法的生产工艺应进行前瞻性验证，可能时，应在批准产品前完成。回顾性验证不再是可以接受的方式。
5.4. Process validation of new products should cover all intended marketed strengths and sites of manufacture. Bracketing could be justified for new products based on extensive process knowledge from the development stage in conjunction with an appropriate ongoing verification programme.
新产品的工艺验证应覆盖所有要上市的剂量和所有的生产场所。基于研发期间对工艺的广泛知识，结合适当的进行中工艺确认计划，新产品可以经过论证采用括号法。
5.5. For process validation of products which are transferred from one site to another or within the same site, the number of validation batches could be reduced by the use of a bracketing approach. However, existing product knowledge, including the content of the previous validation, should be available. Different strengths, batch sizes and pack sizes/container types may also use a bracketing approach, if justified.
从一个场所转移至另一个场所，或在同一场所内转移的产品的工艺验证，可以采用括号方法减少验证的批次。但是，已有的产品知识，包括之前验证的内容应可以获得。如果经过论证，不同剂量、批量和包装规格/容器类型也可以使用括号法。
5.6. For the site transfer of legacy products, the manufacturing process and controls must comply with the marketing authorisation and meet current standards for marketing authorisation for that product type. If necessary, variations to the marketing authorisation should be submitted.
将遗留的产品进行场所转移时，生产工艺和控制必须符合上市许可内容，并符合该类型产品上市许可的现行标准。必要时，应提交上市许可变更申报。
5.7. Process validation should establish whether all quality attributes and process parameters, which are considered important for ensuring the validated state and acceptable product quality, can be consistently met by the process. The basis by which process parameters and quality attributes were identified as being critical or non-critical should be clearly documented, taking into account the results of any risk assessment activities.
工艺验证应证明工艺能持续满足所有质量属性和工艺参数，即那些保证验证状态和可接受的产品质量的重要因素。工艺参数和质量属性被识别为关键或非关键的基础应清楚记录，并考虑所有风险评估活动的结果。
5.8. Normally batches manufactured for process validation should be the same size as the intended commercial scale batches and the use of any other batch sizes should be justified or specified in other sections of EudraLex, Volume 4.
通常，工艺验证生产的批次应与既定的商业规模批具有相同的批量，如果使用了其它的批量，则应进行论证，或在欧盟药事法第4卷的其它部分中进行说明。
5.9. Equipment, facilities, utilities and systems used for process validation should be qualified. Test methods should be validated for their intended use.
用于工艺验证的设备、设施、公用系统和系统应进行确认。应验证检验方法符合其既定用途。
5.10. For all products irrespective of the approach used, process knowledge from development studies or other sources should be accessible to the manufacturing site, unless otherwise justified, and be the basis for validation activities.
所有产品，不管使用什么方法，从研发阶段或其它来源获得的工艺知识应在生产场所可以获得，除另有论证外，并成为验证活动的基础。
5.11. For process validation batches, production, development, or other site transfer personnel may be involved. Batches should only be manufactured by trained personnel in accordance with GMP using approved documentation. It is expected that production personnel are involved in the manufacture of validation batches to facilitate product understanding.
生产、研发或其它场所转移人员应参与工艺验证批次。验证批次应由受过培训的人员生产，并符合GMP要求，使用经过批准的文件。期望生产人员能参与验证批次的生产以增强对产品的理解。
5.12. The suppliers of critical starting and packaging materials should be qualified prior to the manufacture of validation batches; otherwise a justification based on the application of quality risk management principles should be documented.
关键起始物料和包装材料的供应商应在验证批次生产前进行确认，否则，应根据质量风险管理原则要求进行论证并记录。
5.13. It is especially important that the underlying process knowledge for the design space justification (if used) and for development of any mathematical models (if used) to confirm a process control strategy should be available.
尤其重要的是用于确认工艺控制策略的关于设计空间论证（如采用），和任何数学模型建立（如采用）的潜在工艺知识应可以获得。
5.14. Where validation batches are released to the market, this should be pre-defined. The conditions under which they are produced should fully comply with GMP, with the validation acceptance criteria, with any continuous process verification criteria (if used) and with the marketing authorisation or clinical trial authorisation.
如果将验证批次放行上市销售，则应预先进行界定。其生产条件应完全符合GMP要求，符合验证可接受标准，符合所有持续工艺确认标准（如使用），符合上市许可或临床试验批准的要求。
5.15. For the process validation of investigational medicinal products (IMP), please refer to Annex 13.
临床前药品（IMP）的工艺验证，请参见附录13。
Concurrent validation 同步验证
5.16. In exceptional circumstances, where there is a strong benefit-risk ratio for the patient, it may be acceptable not to complete a validation programme before routine production starts and concurrent validation could be used. However, the decision to carry out concurrent validation must be justified, documented in the VMP for visibility and approved by authorised personnel.
在例外情形下，如果对患者利益明显大于风险，也可以接受不需要在常规生产前完成整个验证流程，这时，可以使用同步验证。但是，进行同步验证的决定必须进行论证，并记录在VMP里，并由授权人进行批准。
5.17. Where a concurrent validation approach has been adopted, there should be sufficient data to support a conclusion that any given batch of product is uniform and meets the defined acceptance criteria. The results and conclusion should be formally documented and available to the Qualified Person prior to certification of the batch.
如果已采用同步验证方法，则应有足够的数据来支持指定的产品批是均一的结论，并符合既定的可接受标准。结果和结论应进行正式记录，并在放行该批前提交给QP。
Traditional process validation 传统工艺验证
5.18. In the traditional approach, a number of batches of the finished product are manufactured under routine conditions to confirm reproducibility.
在传统方法中，在常规生产条件生产数批成品确认其可重复性。
5.19. The number of batches manufactured and the number of samples taken should be based on quality risk management principles, allow the normal range of variation and trends to be established and provide sufficient data for evaluation. Each manufacturer must determine and justify the number of batches necessary to demonstrate a high level of assurance that the process is capable of consistently delivering quality product.
生产的批数和取样的数量基于质量风险管理原则，可以建立常规变化范围和趋势，提供足够的数据进行评估。每个生产商必须决定并论证所需的批数，即为了证明在一个较高的水平保证工艺能够持续产生符合质量要求的产品所需的批数。
5.20. Without prejudice to 5.19, it is generally considered acceptable that a minimum of three consecutive batches manufactured under routine conditions could constitute a validation of the process. An alternative number of batches may be justified taking into account whether standard methods of manufacture are used and whether similar products or processes are already used at the site. An initial validation exercise with three batches may need to be supplemented with further data obtained from subsequent batches as part of an on-going process verification exercise.
在对5.19并没有偏见的情况下，一般接受在常规条件下最少3个连续批次可以构成一个工艺的验证。考虑是否使用了标准的生产方法，是否类似产品或类似工艺已在工厂使用的情况，可以论证其它的批数来替代3批。采用3批进行初始验证的情况下，可能需要使用后续生产批次中获得的更多数据，作为持续工艺确认的一部分对初始验证进行补充。
5.21. A process validation protocol should be prepared which defines the critical process parameters (CPP), critical quality attributes (CQA) and the associated acceptance criteria which should be based on development data or documented process knowledge.
应制订一份工艺验证方案，在其中说明关键工艺参数（CPP），关键质量属性（CQA）和相关的可接受标准，这些应基于研发数据或记录的工艺知识。
5.22. Process validation protocols should include, but are not limited to the following:
工艺验证方案应包括，但不仅限于以下内容
i. A short description of the process and a reference to the respective Master Batch Record;
对工艺的简短描述，对相应主批记录引用
ii. Functions and responsibilities;
工作和职责分配
iii. Summary of the CQAs to be investigated;
需要调查的CQA汇总
iv. Summary of CPPs and their associated limits;
CPP和其相关限度的汇总
v. Summary of other (non-critical) attributes and parameters which will be investigated or monitored during the validation activity, and the reasons for their inclusion;
其它（非关键）在验证活动期间要进行调查或监控的属性和参数的汇总，以及包括这些内容的理由
vi. List of the equipment/facilities to be used (including measuring/monitoring/recording equipment) together with the calibration status;
将使用的设备、设施的清单（包括测量、监控、记录装置）及其校正状态
vii. List of analytical methods and method validation, as appropriate.
分析方法和方法验证的清单，适用时
viii. Proposed in-process controls with acceptance criteria and the reason(s) why each in-process control is selected;
所拟中控及可接受标准，以及为什么选择这些中控的理由
ix. Additional testing to be carried out with acceptance criteria;
要实施的附加测试及可接受标准
x. Sampling plan and the rationale behind it;
取样计划及其合理性
xi. Methods for recording and evaluating results;
结果的记录和评估方法
xii. Process for release and certification of batches (if applicable).
放行产品的过程（适用时）
Continuous process verification 持续工艺确认
5.23. For products developed by a quality by design approach, where it has been scientifically established during development that the established control strategy provides a high degree of assurance of product quality, then continuous process verification can be used as an alternative to traditional process validation.
对于采用质量源于设计方法研发的药品，由于其工艺在研发期间已被科学地建立，所建立的控制策略提供了高水平的产品质量保证，这时可以使用持续工艺确认来替代传统工艺验证。
5.24. The method by which the process will be verified should be defined. There should be a science based control strategy for the required attributes for incoming materials, critical quality attributes and critical process parameters to confirm product realisation. This should also include regular evaluation of the control strategy. Process Analytical Technology and multivariate statistical process control may be used as tools. Each manufacturer must determine and justify the number of batches necessary to demonstrate a high level of assurance that the process is capable of consistently delivering quality product.
要对所采用的工艺确认方法进行界定。对于所要求的进厂物料的属性、关键质量属性和关键工艺参数，应该有一个基于科学的控制策略来确认产品的可实现性。这也应包括对控制策略的常规评估。过程分析技术和多变量统计过程控制也可以用作工具。每个生产商都必须决定并论证所需的批数，即为了证明在一个较高的水平保证工艺能够持续产生符合质量要求的产品所需的批数。
5.25. The general principles laid down in 5.1 – 5.14 above still apply.
上述5.1-5.14中设定的通则仍适用于持续工艺验证。
Hybrid approach 混合方法
5.26. A hybrid of the traditional approach and continuous process verification could be used where there is a substantial amount of product and process knowledge and understanding which has been gained from manufacturing experience and historical batch data.
如果已从生产经验和历史批次数据中获得了大量的产品和工艺知识和了解，则可以将传统方法和持续工艺确认方法混合作为混合方法来使用。
5.27. This approach may also be used for any validation activities after changes or during ongoing process verification even though the product was initially validated using a traditional approach.
即使一个产品的初始验证是采用传统方法，也可以将本方法用于所有变更后，及进行中工艺确认期间的验证活动。
Ongoing Process Verification during Lifecycle 生命周期中的进行中工艺确认
5.28. Paragraphs 5.28-5.32 are applicable to all three approaches to process validation mentioned above, i.e. traditional, continuous and hybrid.
5.28-5.32段内容适用于上述所有三种工艺验证方法，即传统方法、持续方法和混合方法。
5.29. Manufacturers should monitor product quality to ensure that a state of control is maintained throughout the product lifecycle with the relevant process trends evaluated.
生产商应监控产品质量，并进行相关的工艺趋势评估，以保证在产品的生产周期维护其受控状态。
5.30. The extent and frequency of ongoing process verification should be reviewed periodically. At any point throughout the product lifecycle, it may be appropriate to modify the requirements taking into account the current level of process understanding and process performance.
进行中工艺确认的程度和频次应定期进行审核。在产品生命周期的任何时间，在考虑现行工艺理解和工艺性能的水平后，都可以对要求进行修订。
5.31. Ongoing process verification should be conducted under an approved protocol or equivalent documents and a corresponding report should be prepared to document the results obtained. Statistical tools should be used, where appropriate, to support any conclusions with regard to the variability and capability of a given process and ensure a state of control.
进行中工艺确认应根据批准的方案或等同的文件实施，应制订相应的报告记录所获得的结果。适用时，应使用统计学工具来支持所有关于给定工艺变动性和能力的结论，以保证其受控状态。
5.32. Ongoing process verification should be used throughout the product lifecycle to support the validated status of the product as documented in the Product Quality Review. Incremental changes over time should also be considered and the need for any additional actions, e.g. enhanced sampling, should be assessed.
在产品的整个生命周期中应使用进行中工艺确认来支持产品质量回顾（PQR）中载明的产品的验证状态。还要考虑随时间而增加的变更，以及评估是否需要采取额外的行动，例如，增加取样。
6. VERIFICATION OF TRANSPORTATION 运输确认
6.1. Finished medicinal products, investigational medicinal products, bulk product and samples should be transported from manufacturing sites in accordance with the conditions defined in the marketing authorisation, the approved label, product specification file or as justified by the manufacturer.
制剂成品、临床前药品、散装药品和样品在从生产场所运出时，应符合上市许可、批准的标签、产品规格文件或由生产商论证的指定条件。
6.2. It is recognised that verification of transportation may be challenging due to the variable factors involved however, transportation routes should be clearly defined. Seasonal and other variations should also be considered during verification of transport
我们知道对运输条件进行确认可能很难，因为其中牵涉的变动因素太多，但是运输路线应清楚说明。在运输确认中还要考虑季节和其它变量。
6.3. A risk assessment should be performed to consider the impact of variables in the transportation process other than those conditions which are continuously controlled or monitored, e.g. delays during transportation, failure of monitoring devices, topping up liquid nitrogen, product susceptibility and any other relevant factors.
要进行风险评估，以考虑在运输过程中除受到持续控制或监控条件以外的变化的影响，例如，运输延误、监控装置失效、补充液氮、产品易感性和其它相关因素。
6.4. Due to the variable conditions expected during transportation, continuous monitoring and recording of any critical environmental conditions to which the product may be subjected should be performed, unless otherwise justified.
由于运输期间可预见的条件变化，在运输期间应对产品可能经受的所有关键环境条件进行监控和记录，另有论证者除外。
7. VALIDATION OF PACKAGING 包装验证
7.1. Variation in equipment processing parameters especially during primary packaging may have a significant impact on the integrity and correct functioning of the pack, e.g. blister strips, sachets and sterile components, therefore primary and secondary packaging equipment for finished and bulk products should be qualified.
设备工艺参数的变化，尤其是在内包期间，可能对包装的完整性和正确工作产生重要影响，例如泡罩条、小袋和无菌成分，因此应对成品和散装药品的内包和外包设备进行确认。
7.2. Qualification of the equipment used for primary packing should be carried out at the minimum and maximum operating ranges defined for the critical process parameters such as temperature, machine speed and sealing pressure or for any other factors.
应对内包设备中被定义为关键工艺参数，例如温度，机器速度和密封压力，或其它任何因素，的最大和最小操作范围进行确认。
8. QUALIFICATION OF UTILITIES 公用系统确认
8.1. The quality of steam, water, air, other gases etc. should be confirmed following installation using the qualification steps described in section 3 above.
蒸汽、水、空气、其它气体等的质量应在安装后使用以上第3部分所述的确认步骤进行确认。
8.2. The period and extent of qualification should reflect any seasonal variations, if applicable, and the intended use of the utility.
确认周期和程度应反映季节性变化，如果适用的话，符合公用系统的既定用途。
8.3. A risk assessment should be carried out where there may be direct contact with the product, e.g. heating, ventilation and air-conditioning (HVAC) systems, or indirect contact such as through heat exchangers to mitigate any risks of failure.
应对直接与产品接触的系统，例如，空调净化系统（HVAC），或间接接触系统，如通过换热器与产品接触的系统，进行风险评估，以转移失败的风险。
9. VALIDATION OF TEST METHODS 检验方法验证
9.1. All analytical test methods used in qualification, validation or cleaning exercises should be validated with an appropriate detection and quantification limit, where necessary, as defined in Chapter 6 of the EudraLex, Volume 4, Part I.
所有用于确认、验证或清洁过程中的检验方法均应根据欧盟药事法第4卷第一部分第6章的要求进行验证，必要时应证明其具备适当的检测限和定量限。
9.2. Where microbial testing of product is carried out, the method should be validated to confirm that the product does not influence the recovery of microorganisms.
如果产品检测了微生物项目，则检验方法应进行验证以确认产品不会对微生物的回收率产生影响。
9.3. Where microbial testing of surfaces in clean rooms is carried out, validation should be performed on the test method to confirm that sanitising agents do not influence the recovery of microorganisms.
如果洁净区进行了微生物测试，则应对测试方法进行验证，以确认消毒剂不会对微生物的回收率产生影响。
10. CLEANING VALIDATION 清洁验证
10.1. Cleaning validation should be performed in order to confirm the effectiveness of any cleaning procedure for all product contact equipment. Simulating agents may be used with appropriate scientific justification. Where similar types of equipment are grouped together, a justification of the specific equipment selected for cleaning validation is expected.
应进行清洁验证，以确认所有与产品接触的设备的所有清洁程序的有效性。有适当的科学论证时，可以使用模拟试剂。如果对同类设备进行分组后验证，则要论证为什么选择那个特定的设备来来进行清洁验证。
10.2. A visual check for cleanliness is an important part of the acceptance criteria for cleaning validation. It is not generally acceptable for this criterion alone to be used. Repeated cleaning and retesting until acceptable residue results are obtained is not considered an acceptable approach.
目视检查清洁度是清洁验证中可接受标准的一个重要部分。一般仅使用该标准是不被接受的。重复清洁和检测直至获得可接受残留结果的方法是不被接受的。
10.3. It is recognised that a cleaning validation programme may take some time to complete and validation with verification after each batch may be required for some products, e.g. investigational medicinal products. There should be sufficient data from the verification to support a conclusion that the equipment is clean and available for further use.
我们知识清洁验证程序可能需要一些时间来完成，有些产品可能需要在每批生产之后均进行确认，例如，临床前药品。在确认中应有足够的数据来支持设备是清洁的并适用于其未来使用的结论。
10.4. Validation should consider the level of automation in the cleaning process. Where an automatic process is used, the specified normal operating range of the utilities and equipment should be validated.
验证中应考虑清洁过程中自动化的水平。如果使用了一个自动化工艺，则应验证该公用系统或设备所指定的正常操作范围。
10.5. For all cleaning processes an assessment should be performed to determine the variable factors which influence cleaning effectiveness and performance, e.g. operators, the level of detail in procedures such as rinsing times etc. If variable factors have been identified, the worst case situations should be used as the basis for cleaning validation studies.
对所有清洁工艺均应进行评估，以决定影响清洁效果和表现的变化因素，例如，操作员、程序详细程度例如淋洗时间等。如果已经识别了变化的因素，则应使用最坏情形作为清洁验证研究的基础。
10.6. Limits for the carryover of product residues should be based on a toxicological evaluation[1]. The justification for the selected limits should be documented in a risk assessment which includes all the supporting references. Limits should be established for the removal of any cleaning agents used. Acceptance criteria should consider the potential cumulative effect of multiple items of equipment in the process equipment train. 产品残留带入下一产品的限度应基于毒性评估来确定。应在风险评估中记录对所选择的限度的论证，其中应包括所有支持性文献。应建立所有使用的清洁剂的清除限度。应考虑工艺设备链中设备的多次使用部件的潜在累积效应的可接受标准。
10.6.1.Therapeutic macromolecules and peptides are known to degrade and denature when exposed to pH extremes and/or heat, and may become pharmacologically inactive. A toxicological evaluation may therefore not be applicable in these circumstances.
已知治疗用大分子和多肽在暴露于pH极值和/或记温时会降解及变性，可能变得无药物活性。这种情况下可能不适用毒性评估。
10.6.2.If it is not feasible to test for specific product residues, other representative parameters may be selected, e.g. total organic carbon (TOC) and conductivity.
如果测量特定的产品残留不现实，则可以选择其它的代表性参数，例如，总有机碳（TOC）和电导率。
10.7. The risk presented by microbial and endotoxin contamination should be considered during the development of cleaning validation protocols.
在制订清洁验证方案时应考虑微生物内毒素污染所呈现的风险。
10.8. The influence of the time between manufacture and cleaning and the time between cleaning and use should be taken into account to define dirty and clean hold times for the cleaning process.
应考虑生产完成后和清洁之间间隔时间，以及清洁后和再次使用之间的间隔时间，对清洁工艺中脏设备放置时间和清洁后放置时间进行界定。
10.9. Where campaign manufacture is carried out, the impact on the ease of cleaning at the end of the campaign should be considered and the maximum length of a campaign (in time and/or number of batches) should be the basis for cleaning validation exercises.
如果采用的周期生产的方法，则要考虑在周期结束后清洁的难易程度的影响，清洁验证实施应以最长生产周期为基础（按时间和/或批数计）。
10.10. Where a worst case product approach is used as a cleaning validation model, a scientific rationale should be provided for the selection of the worst case product and the impact of new products to the site assessed. Criteria for determining the worst case may include solubility, cleanability, toxicity and potency.
如果使用了最差情形产品作为清洁验证模式，则应科学合理地论证所选择的最差情形产品，以及新产品对已评估的场所的影响。最差情形的决定标准可以包括溶解度、清洁难易度、毒性和效价。
10.11. Cleaning validation protocols should specify or reference the locations to be sampled, the rationale for the selection of these locations and define the acceptance criteria.
清洁验证方案中应说明，或引用取样位置，说明选择这些位置的合理性，并制订可接受标准。
10.12. Sampling should be carried out by swabbing and/or rinsing or by other means depending on the production equipment. The sampling materials and method should not influence the result. Recovery should be shown to be possible from all product contact materials sampled in the equipment with all the sampling methods used.
取样应根据生产设备的情况采用擦拭法和/或淋洗法，或其它方法。取样材料和方法不应对结果产生影响。所有采用的取样方法，被取样设备的所有与产品接触材质可能的回收率均应说明。
10.13. The cleaning procedure should be performed an appropriate number of times based on a risk assessment and meet the acceptance criteria in order to prove that the cleaning method is validated.
应根据风险评估的结果执行清洁程序若干适当次数，结果应符合可接受标准，以证明该清洁方法是被验证的。
10.14. Where a cleaning process is ineffective or is not appropriate for some equipment, dedicated equipment or other appropriate measures should be used for each product as indicated in chapters 3 and 5 of EudraLex, Volume 4, Part I.
如果清洁程序没有效果，或不适用于一些设备，则应如欧盟药事法第4卷第一部分第3章和第5章所要求的，对每个产品使用专用设备或采取其它适当的措施。
10.15. Where manual cleaning of equipment is performed, it is especially important that the effectiveness of the manual process should be confirmed at a justified frequency.
如果对设备进行手动清洁，则采用论证的频次对手动工艺的有效性进行确认就尤其重要，
11. CHANGE CONTROL 变更控制
11.1. The control of change is an important part of knowledge management and should be handled within the pharmaceutical quality system.
变更控制是知识管理的一个重要部分，应药品质量管理体系里处理。
11.2. Written procedures should be in place to describe the actions to be taken if a planned change is proposed to a starting material, product component, process, equipment, premises, product range, method of production or testing, batch size, design space or any other change during the lifecycle that may affect product quality or reproducibility.
应有书面程序描述，当提议对起始物料、产品组分、工艺、设备、设施、产品范围、生产方法或检测方法、批量、设计空间或任何生命周期中其它可能对产品质量或可重复性产生影响的变更时，将要采取的措施。
11.3. Where design space is used, the impact on changes to the design space should be considered against the registered design space within the marketing authorization and the need for any regulatory actions assessed.
如果使用了设计空间，则应考虑对设计空间的变更的影响，与上市许可中注册的设计空间进行对比，并评估所有法规行动。
11.4. Quality risk management should be used to evaluate planned changes to determine the potential impact on product quality, pharmaceutical quality systems, documentation, validation, regulatory status, calibration, maintenance and on any other system to avoid unintended consequences and to plan for any necessary process validation, verification or requalification efforts.
应使用质量风险管理来评估计划的变更，以决定对产品质量、药品质量体系、文件记录、验证、法规状态、校正、维护和其它系统的潜在影响，避免产生不希望的后果，并计划所有必要的工艺验证、确认或再确认。
11.5. Changes should be authorised and approved by the responsible persons or relevant functional personnel in accordance with the pharmaceutical quality system.
变更应由负责人或相关的责任人根据药品质量体系进行授权和批准。
11.6. Supporting data, e.g. copies of documents, should be reviewed to confirm that the impact of the change has been demonstrated prior to final approval.
应对支持性数据，例如文件复印件，进行审核，以在最终批准前已对变更的影响进行证明。
11.7. Following implementation, and, where appropriate, an evaluation of the effectiveness of change should be carried out to confirm that the change has been successful.
在变更实施后，适用时，应对变更的有效性进行评估，以确认变更是成功的。
12. GLOSSARY 术语
Definitions of terms relating to qualification and validation which are not given in other sections of the current EudraLex, Volume 4, are given below.
在本附件中用到，但在欧盟药事法卷4其它部分中未收载的与确认和验证相关的术语定义如下
Bracketing approach. 括号法（分组法）
A science and risk based validation approach such that only batches on the extremes of certain predetermined and justified design factors, e.g. strength, batch size and/or pack size, are tested during process validation. The design assumes that validation of any intermediate levels is represented by validation of the extremes. Where a range of strengths is to be validated, bracketing could be applicable if the strengths are identical or very closely related in composition, e.g. for a tablet range made with different compression weights of a similar basic granulation or a capsule range made by filling different plug fill weights of the same basic composition into different size capsule shells. Bracketing can be applied to different container sizes or different fills in the same container closure system.
一种基于风险的科学验证方法，采用该方法进行工艺验证的过程中，只对预定或经过论证的设计因素，例如，剂量、批量和/或包装规格，的极端条件进行测试。该设计假定所有中间水平的验证可以由极端情况的验证来代表。如果要验证的是一个范围的剂量，这些剂量的组成是相同的或相近的，例如，有类似的基本制粒过程，但片重不同的一系列片剂，或具有相同的基本组成，都是采取填充形式装入不同大小的胶囊壳中的胶囊制剂，就可以应用分组法，括号法可以用于不同包装规格或同一容器密闭系统里不同灌装规格。
Change Control 变更控制
A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect the validated status of facilities, systems, equipment or processes. The intent is to determine the need for action that would ensure and document that the system is maintained in a validated state.
一个正式的体系，在该体系中，具有资质的代表根据适当的原则对提议或实际已发生的、可能影响设施、系统、设备或工艺的验证状态的变更进行评价，以决定是否需要采取行动来保证和记载系统维持在经过验证过的状态。
Cleaning Validation. 清洁验证
Cleaning validation is documented evidence that an approved cleaning procedure will reproducibly remove the previous product or cleaning agents used in the equipment below the scientifically set maximum allowable carryover level.
指记录的证据，说明一个经过批准的清洁程序能可再现地清除之前的产品或设备中所用的清洁剂达到科学设备的最大可接受残留水平。
Cleaning verification. 清洁确认
The gathering of evidence through chemical analysis after each batch/campaign to show that the residues of the previous product or cleaning agents have been reduced below the scientifically set maximum allowable carryover level.
通过每个生产周期批次完成后进行化学分析来收集证据，以证明前一产品或清洁剂的残留已被降低至科学设定的最大允许残留水平。
Concurrent Validation. 同步验证
Validation carried out in exceptional circumstances, justified on the basis of significant patient benefit, where the validation protocol is executed concurrently with commercialisation of the validation batches.
在例外情形下实施的验证，基于重大的患者利益进行论证，将验证方案的与验证批次的商业化同步实施。
Continuous process verification. 持续工艺验证
An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated. (ICH Q8)
对生产工艺性能进行持续监控和评估的替代性工艺验证方法。
Control Strategy. 控制策略
A planned set of controls derived from current product and process understanding that ensures process performance and product quality. The controls can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications and the associated methods and frequency of monitoring and control. (ICH Q10)
从现行产品和工艺理解中获得的，用以保证工艺性能和产品质量的一系列有计划的控制。控制可以包括与药用物质和药品物料和组成、设施和设备操作条件、中控、成品质量标准和相关的方法，以及监控频次相关的参数和属性(ICH Q10)
Critical process parameter (CPP). 关键工艺参数（CPP）
A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (ICH Q8)
变化时会对关键质量属性产生影响，因此应该受到监控以保证工艺生产出所需的质量的一个工艺参数。（ICH Q8）
Critical quality attribute (CQA). 关键质量属性（CQA）
A physical, chemical, biological or microbiological property or characteristic that should be within an approved limit, range or distribution to ensure the desired product quality. (ICH Q8)
一个应符合批准的限度、范围或分布，以保证所需的产品质量的物理、化学、生物或微生物性质或特征。（ICH Q8）
Design qualification (DQ) 设计确认（DQ）
The documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose.
书面确认一个提议的设施、系统和设备设计适用于既定的目的。
Design Space. 设计空间
The multidimensional combination and interaction of input variables, e.g. material attributes, and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval. (ICH Q8)
被证明能保证质量的输入变量，如物料属性，和工艺参数的多维组合和相互作用。在设计空间之内工作不是变更。超出设计空间的移动被认为是一种变更，一般会启动上市后变更的法规过程。设计空间由申报人提议，经过法规评审和批准。（ICH Q8）
Installation Qualification (IQ)安装确认（IQ）
The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manufacturer’s recommendations.
书面确认设施、系统和设备的安装或改造符合批准的设计和生产商的建议。
Knowledge management. 知识管理
A systematic approach to acquire, analyse, store and disseminate information. (ICH Q10)
获得、分析、存贮和传播知识的系统性方法（ICH Q10）
Lifecycle. 生命周期
All phases in the life of a product, equipment or facility from initial development or use through to discontinuation of use.
一个产品、设备或设施从开始研发或使用直到使用终止的所有阶段。
Ongoing Process Verification (also known as continued process verification).进行中工艺确认（也称为持续工艺确认）
Documented evidence that the process remains in a state of control during commercial manufacture.
证明工艺在商业生产期间保持在受控状态的文件化证据。
Operational Qualification (OQ)运行确认（OQ）
The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges.
书面确认设备、系统和设备在经过安装或改造后，满足期望的操作范围。
Performance Qualification (PQ). 性能确认（PQ）
The documented verification that systems and equipment can perform effectively and reproducibly based on the approved process method and product specification.
书面确认系统和设备可以根据批准的工艺方法和产品质量标准可以重复地有效运行。
Process Validation 工艺验证
The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes.
书面确认根据已建立的参数，某工艺可以有效地重复生产一种药品，并符合预定的质量标准和质量属性。
Product realisation. 产品实现
Achievement of a product with the quality attributes to meet the needs of patients, health care professionals and regulatory authorities and internal customer requirements. (ICH Q10)
获得具有满足患者需要、保健专业要求和法规部门及内部客户要求的产品。（ICH Q10）
Prospective Validation 前验证
Validation carried out before routine production of products intended for sale.
在用于销售产品的常规生产前进行的验证。
Quality by design. 质量源于设计
A systematic approach that begins with predefined objectives and emphasises product and process understanding and process control, based on sound science and quality risk management.
从定义目标开始，强调产品与工艺理解和工艺控制，基于合理科学和质量风险管理的一个系统性的方法。
Quality risk management. 质量风险管理
A systematic process for the assessment, control, communication and review of risks to quality across the lifecycle. (ICH Q9)
在生命周期中对质量风险进行评估、控制、交流和审核的一个系统性的过程。（ICH Q9）
Simulated agents. 模拟剂
A material that closely approximates the physical and, where practical, the chemical characteristics, e.g. viscosity, particle size, pH etc., of the product under validation.
一种物理特性和化学特性，如粘度、颗粒度、pH值等，与需要验证的产品非常接近的物料。
State of control. 受控状态
A condition in which the set of controls consistently provides assurance of acceptable process performance and product quality.
用以持续保证工艺性能可接受及产品质量的一系列的控制的情形。
Traditional approach. 传统方法
A product development approach where set points and operating ranges for process parameters are defined to ensure reproducibility.
一种产品研发方法，在其中定义了工艺参数设置点和操作范围，以保证其可重复性。
Worst Case 最坏情况
A condition or set of conditions encompassing upper and lower processing limits and circumstances, within standard operating procedures, which pose the greatest chance of product or process failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure.
一个或一系列条件，包括了在标准操作程序中较高和较低工艺限度和环境，与理想条件相比最可能导致产品或工艺失败的条件。这些条件并不一定会导致产品或工艺失败。
User requirements Specification (URS). 用户需求手册
The set of owner, user and engineering requirements necessary and sufficient to create a feasible design meeting the intended purpose of the system.
一套收集了所有者、用户和工程所需要求，足以创建符合既定目的的系统的可行设计的手册。
[1] See EMA Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities 参见EMA“共用设施中生产不同药品的风险识别所用基于健康暴露限度设定指南”
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