who验证指南版.docx

1、who验证指南版who验证指南2016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 therefore an element of the pharmaceutical quality system. Validation, as a concept, incorporates qualification and s

2、hould be applied over the life cycle of, e.g. the applicable product, process, system, equipment or utility. 验证是包括GMP和GCP在内的良好规范的必要部分。因此是制药质量体系的组成部分。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 par

3、t, appendices 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则。除了主体部分外，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: 适用的原则如下: the execution of val

4、idation should be in compliance with regulatory expectations; 验证的执行应该符合监管预期 quality, safety and efcacy must be designed and built into the product; 质量、安全和效力应该被设计和构建到产品中 quality cannot be inspected or tested into the product; 质量不能通过检查或测试赋予产品 quality risk management principles should be applied in det

5、ermining the need, scope and extent of validation; 应该应用质量风险管理规则来决定验证的需求、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.应该进行持续的回顾来确保维持验证状态并识别持续改进的机会1.4 The implementation of validation work requires c

6、onsiderable resources such as: 验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 specialized personnel 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 collaboratio

7、n of experts from various disciplines (e.g. a multidisciplinary team, comprising quality 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 o

8、verall concept of validation and are not intended 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 prod

9、ucts (FPPs), as well as other areas. Validation 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检查官和生产商的基本指南， 本文件仅作为一个一般指南，其原则在其应用于起始物料

10、及制剂的生产和控制时会比较有用，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 different types of validation and it is, therefore, not intended to define and address all aspects related to one particular 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

11、的所有方面进行定义和说明。2.3 The general text in the main part of these guidelines may be applicable to validation and qualification of premises, equipment, utilities, systems, processes and procedures.这些指南的主体部分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

12、 in these guidelines. They may have different meanings 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 an

13、d pH), recording, and controlling, or the values 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

14、representatives of appropriate disciplines review proposed or actual 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 evaluated on the basis of past ex

15、perience 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 results. Qualification is often a part

16、(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.再验证：对先前已验证的系统（或它的一部分）的重复验证来确保持续符合

17、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; cleaning of premises and environmenta

18、l 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 consistently leads to the expected result

19、s.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 manufacturers overall philosophy and approach, to be used for establishing performance adequacy. It provides information on the manuf

20、acturers 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.验证主计划validation protocol. A document describing the activities to be performed during a validation, including

21、 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 proposals for the improvement of processes and/or systems

22、 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 encompassing the upper and lower processing limi

23、ts 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. RELATIONSHIP BETWEEN VALIDATION AND QUALIFICATION 验证与确认的关系4.1 Quali

24、fication and validation are essentially the same. The term qualication is normally used for equipment and utilities, and validation for systems and processes. In this sense, qualication 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，而验证则用于系统和工艺。在这层意义上，确认可以被看做是验证的一部分。4.2 Where the term “

25、validation” is used in the document, the same principles may be applicable for “qualification在文件中使用术语“验证”的规则同样适用于“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 quality, safety and efficacy throughout its life

26、 cycle. 生产商应该组织和计划验证以保证产品在其生命周期内的质量、安全和有效。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管理规则。5.3 Statistical calculations should be applied, where appropriate, and provide scientific evidence that the process, system or other

27、 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. 确认和验证应该按照预定的方案执行并且结果应被适当的记录，如在报告中。5.5 There should be an appropriate a

28、nd 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管理。5.6 Senior management should ensure that there are sufficient resources to perform validation in a timely manner. Management and persons responsible for quality assurance should be actively i

29、nvolved in the process and authorization of protocols and reports. 高级管理层应该确保充分的资源来及时地执行验证。管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。5.7 Personnel with appropriate qualification and experience should be 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 should be a specific programme or schedu

30、le to support planning and execution of validation activities. 应有专门的计划或时间表来支持计划和执行验证活动。5.9 Validation should be performed in a structured way according to the documented protocols and procedures. 验证应该按照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 should be performed: 确认和验证应该被执行： for new pr

31、emises, equipment, utilities and systems, and processes and 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 the outcome of periodic review. 基于定期回顾的结果表明需要的5.11 A written report on the out

32、come of the validation should be prepared. 应该对验证的结果准备一份书面报告。5.12 The scope and extent of validation should be based on knowledge and experience, and the outcome of quality risk management principles as described in the World Health Organization (WHO) guidelines on quality risk management. Where necessary worst-case situations or specific challenge tests should be considered for inclusion in the validation, for example, stress load and volume verification in computer syst