who验证指引2016年版

1、who验证指南2021年版1. INTRODUCTION简介1.1 Validation is an essential part of good practices including good manufacturing practices (GMP) (4) and good clinical practices (GCP). It is thereforean element of the pharmaceuticalquality system. Validation,as aconcept, incorporates qualification and should be appl

2、ied over the life cycle of, e.g. the applicable product, process,system, equipment or utility.验证是包括GMPFD GCPft内的良好标准的必要局部.因此是制药质量体系的组成局部. 验证这个概念包括确认并且应该在产品、工艺、系统、设备或设施的整个生命周期中被使用.1.2 These guidelines cover the general principles of validation and qualification. In addition to the main part, appendic

3、es on validation and qualification (e.g. cleaning, computer and computerized systems, equipment, utilities and systems, and analytical methods) are included.这个指南包括验证和确认的一般原那么.除了主体局部外,还包括确认和验证附件(如清洁、计算机和计算机化系统、设备、设施和系统以及分析方法).1.3 The following principles apply:适用的原那么如下：the execution of validation sho

4、uld be in compliance with regulatory expectations;验证的执行应该符合监管预期quality, safety and ef ?cacy must be designed and built into the product;质量、平安和效力应该被设计和构建到产品中quality cannot be inspected or tested into the product;quality risk management principles should be applied in determining the need, scope and e

5、xtent of validation;应该应用质量风险治理规那么来决定验证的需求、范围和程度ongoing review should take place to ensure that the validated state is maintained and opportunities for continuing improvement are identified.应该进行持续的回忆来保证维持验证状态并识别持续改良的时机1.4 The implementation of validation work requires considerable resources such as:验

6、证工作的完成需要大量资源,例如time: generally validation work is subject to rigorous time schedules;时间：一般验证工作需要有一个严密的时间表financial:validation often requires the time of specializedpersonnel and expensive technology.资金：验证经常需要专业人员和昂贵的技术human: validation requires the collaboration of experts from various disciplines (

7、e.g. a multidisciplinaryteam, comprisingquality assurance, engineering, information technology, manufacturing and other disciplines, as appropriate.).人员：验证需要不同学科专家的协作例如一个多学科小组,视情况可能包括 QA工程、信息技术、生产以及其他学科人员2. SCOPE范围2.1 These guidelines focus mainly on the overall concept of validation and are not int

8、ended to be prescriptive in specific validation requirements. This document serves as general guidance only and the principles may be considered useful in its application in the manufacture and control of starting materials and finished pharmaceutical products (FPPs), as well as other areas. Validat

9、ion of specific processes and systems, for example, in sterile product manufacture, requires much more consideration and a detailed approach that is beyond the scope of this document.这些指南主要关注验证的整体概念,无意规定具体的验证要求.用作GMP佥查官和生产 商的根本指南,本文件仅作为一个一般指南,其原那么在其应用于起始物料及制剂的生 产和限制时会比拟有用,也应用于其他领域.特定工艺和产品的验证,例如无菌产品生

10、 产,需要考虑更多内容,和更详细的方法,不在本文件范围之内.2.2 There are many factors affecting the differenttypes of validationand it2.3 therefore, not intended to define and address all aspects relatedto oneparticular type of validation here.有很多因素会对不同类型的验证产生影响,因此,这里不会对某个特定类型的验证相关的所有方面进行定义和说明.2.4 The general text in the main p

11、art of these guidelines may be applicable to validation and qualification of premises, equipment, utilities, systems, processes and procedures.这些指南的主体局部的一般内容可能适用于设施、设备、公用设施和系统、工艺和程序的验证和确认.3. GLOSSARY术语The definitions given below apply to the terms used in these guidelines. They may have different me

12、anings in other contexts.本指南使用的术语定义如下.它们在其它环境中可能有不同的含义calibration . The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (for example, weight, temperature and pH), recording, and controlling, or the value

13、s represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established.校准：change control (including change management). A formal system by which qualified representatives of appropriate disciplines revi

14、ew proposed or actual changes that might affect a validated status. The intent is to determine the need for action that would ensure that the system is maintained in a validated state (reference working document QAS/15.639/Rev.1 - unpublished).变更限制(包括变更治理)cleaning validation. Documented evidence to

15、establish that cleaning procedures are removing residues to predetermined levels of acceptability, taking into consideration factors such as batch size, dosing, toxicology and equipment size.清洁验证commissioning. The setting up, adjustment and testing of equipment or a system to ensure that it meets al

16、l the requirements, as specified in the user requirement specification, and capacities as specified by the designer or developer. Commissioning is carried out before qualification and validation. 试车 computer validation (including computerized system validation). Confirmation by examination and provi

17、sion of objective documented evidence that computerized system specifications conform to user needs and intended uses, and that all requirements can be consistently fulfilled.计算机验证(包括计算机化系统验证)concurrent validation. Validation carried out during routine production of products intended for sale. 同步验证d

18、esign qualification. Documented verification that the proposed design of facilities, systems and equipment is suitable for the intended purpose.设计确认good engineering practices. Established engineering methods and standards that are applied throughout the project life -cycle to deliver appropriate, co

19、st-effective solutions. 良好工程标准installation qualification. Documented verification that the installations (such as machines, computer system components, measuring devices, utilities and manufacturing areas) used in a processor system are appropriately selected and correctly installed in accordance wi

20、th established specifications.安装确认operational qualification. Documented verification that the system or subsystem operates as intended over all anticipated operating ranges.运行确认performance qualification. Documented verification that the equipment or system performs consistently and reproducibly with

21、in defined specifications and parameters in its normal operating environment (i.e. in the production environment). (In the context of systems, the term “ procesalidationmay also be used.)性能确认process validation. The collection and evaluation of data, throughout the product life cycle, which provides

22、documented scientific evidence that a process is capable of consistently delivering quality products.工艺验证prospective validation. Validation carried out during the development stage on the basis of a risk analysis of the production process, which is broken down into individual steps; these are then e

23、valuated on the basis of past experience to determine whether they may lead to critical situations. 前验证qualification. Documented evidence that premises, systems or equipment are able to achieve the predetermined specifications properly installed, and/or work correctly and lead to the expected result

24、s. Qualification is often a part (the initial stage) of validation, but the individual qualification steps alone do not constitute process validation.确认revalidation. Repeated validation of a previously validated system (or a part thereof) to ensure continued compliance with established requirements.

25、再验证：对先前已验证的系统(或它的一局部)的重复验证来保证持续符合既定标准.standard operating procedure. An authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material but of a more general nature (e.g. equipment operation, maintenance and cleaning; validation; clea

26、ning of premises and environmental control; sampling and inspection). Certain standard operating procedures may be used to supplement product -specific master batch production documentation.标准操作规程validation. Action of proving and documenting that any process, procedure or method actually and consist

27、ently leads to the expected results.验证validation master plan. The validation master plan is a high-level document that establishes an umbrella validation plan for the entire project and summarizes the manufacturer 's overall philosophy and approach, to be used for establishing performance adequa

28、cy. It provides information on the manufacturer 's validation work programme and defines details of and timescales for the validation work to be performed, including a statement of the responsibilities of those implementing the plan. 验证主方案validation protocol. A document describing the activities

29、 to be performed during a validation, including the acceptance criteria for the approval of a process or system -or a part thereof -for intended use.验证方案validation report. A document in which the records, results and evaluation of validation are assembled and summarized. It may also contain proposal

30、s for the improvement of processesand/or systems and/or equipment.验证报告verification. The application of methods, procedures, tests and other evaluations, in addition to monitoring, to determine compliance with established requirements and specifications.核实worst case. A condition or set of conditions

31、encompassing the upper and lower processing limits for operating parameters and circumstances, within SOPs, which pose the greatest chance of product or process failure when compared to ideal conditions. Such conditions do not necessarily include product or process failure.最差条件4. RELATIONSHIPBETWEEV

32、ALIDATION ANDQUALIFICATION验证与确认的关系4.1 Qualification and validation are essentially the same. The term quali ?cation is normally used for equipment and utilities, and validation for systems and processes. In this sense, quali ?cation can be seen as part of validation.确认和验证本质上是一样的.确认通常用于设备和设施,而验证那么用于系

33、统和工艺.在这层意义上,确认可以被看做是验证的一局部.4.2 Where the term avalidation “ is used in the document, the sameprinciples may be applicable for aqualification在文件中使用术语“验证的规那么同样适用于“确认5. VALIDATION验证Approaches to validation验证的方法5.1 Manufacturers should organize and plan validation in a manner that will ensure product qu

34、ality, safety and efficacy throughout its life cycle. 生产商应该组织和方案验证以保证产品在其生命周期内的质量、平安和有效.5.2 The scope and extent of qualification and validation should be based on risk management principles.确认和验证的范围和程度应该基于风险治理规那么.5.3 Statistical calculations should be applied, where appropriate, and provide scienti

35、fic evidence that the process, system or other related aspect is appropriately validated.适当时,应该使用统计学计算并提供工艺、系统或其它相关方面有效的科学证据5.4 Qualification and validation should be done in accordance with predetermined protocols, and the results appropriately documented, e.g. in reports.确认和验证应该根据预定的方案执行并且结果应被适当的记

36、录,如在报告中.5.5 There should be an appropriate and effective quality system ensuring the organization and management of validation.应有适当的和有效的质量体系来保证验证的组织和治理.5.6 Senior management should ensure that there are sufficient resources to perform validation in a timely manner. Management and persons responsible

37、 for quality assurance should be actively involved in the process and authorization of protocols and reports.高级治理层应该保证充分的资源来及时地执行验证.治理层和质量保证负责人应该积极参与方案和报告的批准活动中.and experience should be5.7 Personnel with appropriate qualification responsible for performing validation.有适当资质和经验的人员应该对验证的执行负责.5.8 There

38、should be a specific programme or schedule to support planning and execution of validation activities.应有专门的方案或时间表来支持方案和执行验证活动.5.9 Validation should be performed in a structured way according to the documented protocols and procedures.验证应该根据文件化的方案和规程以一种有组织的方式执行.5.10 Qualification and validation shoul

39、d be performed:确认和验证应该被执行：and systems, and processes and? for new premises, equipment, utilities procedures;新设施、设备、公用设施和系统,以及新的工艺和程序；? when changes are made, depending on the outcome of risk assessment;当发生变更时,根据风险评估的结果；? where necessary or indicated based on基于定期回忆的结果说明需要的5.11 A written report on the

40、 outcome of应该对验证的结果准备一份书面报告.5.12 The scope and extent of validationthe outcome of periodic review.the validation shouldshould be based onexperience, and the outcome of quality risk managementprinciplesbe prepared.knowledge andas describedin the World Health Organization (WHO)guidelines on quality ri

41、sk managemenWhere necessary worst - case situations or specific challenge tests should befor example, stress load and volumeconsidered for inclusion in the validation, verification in computer system validation.验证的范围和程度应该基于知识和经验,以及描述于WH颂量风险治理指南中的质量风 险治理治理规那么的结果来决定.6. DOCUMENTATION文件6.1 - Qualificati

42、on and validation should be done according to written procedures.确认和验证应该根据书面程序执行6.2 Documents associated with qualification and validation include:与确认和验证相关的文件包括：? validation master plan (VMP);验证主方案(VMP? standard operating procedures (SOPs);标准操作规程(SOP? specifications;标准? protocols and reports;方案和报告?

43、risk assessmentoutcomes;风险治理结果? process flow charts;工艺流程图? operator manuals;操作手册? training records;培训记录? calibration procedures and records;校准规程和记录? sampling plans;取样方案? testing plans and methods;测试方案和方法? statistical methods and results;统计学方法和结果? history of qualification or validation;确认或验证历史? plan

44、for ensuring review of validation status;保证回忆验证状态的方案? plan for ensuring maintaining a validated state.保证维持验证状态的方案7. VALIDATION MASTERPLAN验证主方案7.1 A manufacturer should have a VMP which reflects the key elements of validation. It should be concise and clear and contain at least the following:生产商应有一份V

45、M阪映验证的关键要素.它应该简洁清楚并至少包括：? title page and authorization (approval signatures and dates);书名页和批准(批准签名和日期)? table of contents;目录? abbreviations and glossary;缩写和术语? validation policy;验证方针? philosophy, intention and approach to validation;验证的原理、目的和方法? roles and responsibilities of relevant personnel;相关人员的

46、角色和责任? resources to ensure validation is done;保证验证执行的资源? outsourced services (selection, qualification, management through lifecycle;外包效劳选择、确认和生命周期治理? deviation management in validation;验证偏差治理? change control in validation;验证变更限制? risk management principles in validation;验证风险治理规那么? training;培训? scop

47、e of validation;验证的范围? documentation required in qualification and validation such as procedures,certificates,protocols and reports;确认和验证所需的文件,如规程、证书、方案和报告? premises qualification;设施确认? utilities qualification;公用设施确认? equipment qualification;设备确认? process validation;工艺验证? cleaning validation;清洁验证? p

48、ersonnel qualification such as analyst qualification;人员确认例如分析人员确认? analytical method validation;分析方法验证? computerized system validation;计算机化系统验证? establishing acceptance criteria;建立接受标准? life -cycle management including retirement policy;生命周期治理包括退役的方针? requalification and revalidation;再确认和再验证? relati

49、onship with other quality management elements;与其他质量治理要素的关系? validation matrix;验证矩阵? references.参考文献7.2 The VMPShould be reviewed at regular intervals and kept up to date according to current GMP.VM应该每隔一段时间回忆并保持持续符合现行GMP8. QUALIFICATIONANDVALIDATION PROTOCOLS确认和验证方案8.1 There should be qualification a

50、nd validation protocols describing the qualification and validation to be performed.应有确认和验证方案描述所要执行确实认和验证.8.2 As a minimum the protocols should include the following significant background information: 方案应该至少包括以下重要的背景信息：? the objectives;目的? the site;场所? the responsible personnel负责的人员? description of

51、 the standard operating procedures (SOPs) to be followed;所遵循的标准操作规程描述? equipment or instruments to be used;所使用的设备或仪器? standards and criteria as appropriate;适当的标准? the stage of validation or qualification;验证或确认的阶段? the processes and/or parameters;工艺和/或参数? sampling, testing and monitoring requirements

52、;取样,测试和监测需求? stress testing where appropriate;压力测试(如适用)? calibration requirements;校准需求? predetermined acceptance criteria for drawing conclusions;预定的用于下定结论的接受标准? review and interpretation of results;结果的审核和分析? change control, deviations;变更限制、偏差? archiving and retention.归档和保存8.3 There should be a desc

53、riptionof the way in which the results will be analysed,including statistical analysiswhere appropriate.应有一个结果分析方法,包括统计学分析如使用的描述8.4 The protocol should be approved prior to use. Any changes to a protocol should be approved prior to implementationof the change.方案应该在使用前被批准.方案的任何变更应在实施前被批准.9. QUALIFICA

54、TIONANDVALIDATION REPORTS should approve the completed report.确认和验证报告9.1 There should be written performed.应有所执行确实认和验证的书面报告9.2 Reports should reflect the at least the title and objectivereports on the qualificationand validationprotocols and procedures followed and includeof the study; make referenc

55、e to the protocol;reference to the appropriate risk assessment; details programmes and cycles used; procedures and test traceability.报告应该反映所遵循的方案和规程并至少包括题目和目的；of materials, methods with方案的参考;equipment, appropriate适当的风险评估的参考；所使用的材料、设备、方案和周期的描述；适当的规程和测试方法追溯 9.3 Results should be recorded and be in com

56、pliance with good data management practices.应该记录结果并符合良好数据和记录治理标准.9.4 Results should be reviewed, analysed and compared against the predetermined acceptance criteria, interpreted and statisticallyand recordjustifiedanalysedwhere appropriate.结果应该被回忆、分析并与预定的接受标准比拟,解释和统计学分析如适用9.5 Results specificationsh

57、ould meet the acceptance criteria.Deviations, out - of -and out - of - limit results should be documented and investigatedaccording to appropriate procedures. If these deviations are accepted, this should be justified. Where necessary, further studies should be performed.结果应该符合接受标准.偏差、OOSF超限结果应该根据适当的程序记录和调查.如接受这些偏差,应有正当理由.必要时,应进行更进一步的研究.9.6 The conclusion of the report should state whether or not the outcome of the qualificationand/or validation was considered successful, and should makrecommendations for future monitoring and setting ofalert and action limitswh