to monitoring, to determine compliance with the GMP principles.
为检查GMP条例的落实力度，而使用的除监控之外的方法、程序、试验和其它评估分析措施。
worst case 最差状况
A condition or set of conditions 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 con-ditions. Such conditions do not necessarily include product or process failure.
系指导致产品或工艺失败的概率高于正常运行工艺的某个条件或一组条件（包括SOP中规定的运行参数和状态的上限和下限），这些状况不一定包括产品或工艺的失败。
4. Relationship between validation and quali? cation 验证和确认之间的联系
Validation and quali?cation are essentially components of the same concept. The term quali?cation is normally used for equipment, utilities and systems, and validation for processes. In this sense, quali?cation is part of validation.
验证和确认系同一概念的基本组成部分，即是说它们是同义词。―确认‖这个词往往用在设备、公用工程和系统以及工艺验证中；在这层意义上，确认是验证的一部分。 5. Validation 验证
5.1 Approaches to validation
验证方法
5.1.1 There are two basic approaches to validation — one based on evi-dence obtained through testing (prospective and concurrent validation), and one based on the analysis of accumulated (historical) data (retrospective validation). Whenever possible, prospective validation is preferred. Retro-spective validation is no longer encouraged and is, in any case, not appli-cable to the manufacturing of sterile products.
验证有两种基本方法——其一是以试验（前验证和同步验证）获取的证据为基础，另一种则以积累的（历史）数据（回顾性验证）为基础。验证时，应当尽可能的使用前验证，而不鼓励执行回顾性验证；要特别指出的是，无论何时，回顾性验证都不适用于无菌产品的生产。
5.1.2 Both prospective and concurrent validation, may include: 前验证和同步验证可能包括的内容如下：
13 extensive product testing, which may involve extensive sample testing (with the estimation of con?dence limits for individual results) and the demonstration of intra- and inter-batch homogeneity;
大量产品测试，包括大量的样品测试（以及单个结果的置信限的评估）和批间及
批内均一性的证明；
14 simulation process trials; 模拟生产试验；
15 challenge/worst case tests, which determine the robustness of the process; and 挑战性/最差状况试验，以证明工艺的耐用性；以及
16 control of process parameters being monitored during normal production runs to obtain additional information on the reliability of the process. 监控正常运行的生产过程的工艺参数的控制措施，以获取可证明该工艺的可靠性的资料。
5.2 Scope of validation 验证范围
5.2.1 There should be an appropriate and suf?cient system including organizational structure and documentation infrastructure, suf?cient personnel and ?nancial resources to perform validation tasks in a timely manner. Management and persons responsible for quality assurance should be involved. 为了及时执行验证工作，应当建立一个适当且能满足需要的系统，包括组织机构和文件管理的下层组织结构、充足的人力和财政资源，同时还应指定质量保证的管理和责任人。
5.2.2 Personnel with appropriate quali?cations and experience should be responsible for performing validation. They should represent different departments depending on the validation work to be performed.
执行验证工作的人员应当具备相应的资格和经验，并对验证负责。根据待执行的验证工作的需要，决定由哪些部门的人员参与验证工作的执行。
5.2.3 There should be proper preparation and planning before validation is performed. There should be a speci?c programme for validation activities.
执行验证之前，应有充分的准备和计划。应针对具体的验证活动，制订专门的计划。
5.2.4 Validation should be performed in a structured way according to the documented procedures and protocols.
应根据成文的程序和方案，以设计好的方式执行验证工作。 5.2.5 Validation should be performed: 验证应：
— for new premises, equipment, utilities and systems, and processes and procedures; 在新的厂房建筑、设备、公用工程和系统、工艺和方法上执行； — at periodic intervals; and 定期执行；
— when major changes have been made. 在发生了重大变更后执行。
(Periodic revalidation or periodic requali?cation may be substituted, where appropriate, with periodic evaluation of data and information to establish whether
requali?cation or revalidation is required.) （在适当的情况下，可用数据和资料的定期评估代替定期再验证或定期再确认，以确定是否需要进行再验证或再确认。）
5.2.6 Validation should be performed in accordance with written protocols. A written report on the outcome of the validation should be produced.
应根据书面方案执行验证。验证的结果应当以书面报告的形式给出。 5.2.7 Validation should be done over a period of time, e.g. at least three consecutive batches (full production scale) should be validated, to demon-strate consistency. Worst case situations should be considered. 验证项目的执行时间的设定应能证明验证对象的持续性。如验证应当至少在三个连续批上开展（生产规模）。验证时，要考虑最差状况。
5.2.8 There should be a clear distinction between in-process controls and validation. In-process tests are performed during the manufacture of each batch according to speci?cations and methods devised during the develop-ment phase. Their objective is to monitor the process continuously.
过程控制和验证之间应有明显的区别。为监测工艺的连续性，应根据针对研发阶段设计的技术标准和方法，开展每批产品生产的过程测试。
5.2.9 When a new manufacturing formula or method is adopted, steps should be taken to demonstrate its suitability for routine processing. The de?ned process, using the materials and equipment speci? ed, should be shown to result in the consistent yield of a product of the required quality.
采用新的生产配方或方法时，应证明它们对常规工艺的适应性。验证时，应使用规定的物料和设备，运行既定的工艺，持续得到的产品质量应符合要求。 5.2.10 Manufacturers should identify what validation work is needed to prove that critical aspects of their operations are appropriately controlled. Signi?cant changes to the facilities or the equipment, and processes that may affect the quality of the product should be validated. A risk assessment approach should be used to determine the scope and extent of validation required.
生产商需明白为了证明他们的操作的关键问题得到了合理的控制，应采取哪些验证工作。比如，对产品质量可能产生影响的厂房设施、设备和工艺的重大变更是需要验证的。为确定需要开展的验证的范围和验证的程度，可使用风险评估的方法。
6. Quali?cation 确认
6.1 Quali?cation should be completed before process validation is per-formed. The process of quali?cation should be a logical, systematic process and should start from the design phase of the premises, equipment, utilities and equipment.
确认应当先于工艺验证完成。确认工作应当是一个有条理的、系统的过程，并应从厂房建筑、设备、公用工程和公用设备的设计阶段着手开始。
6.2 Depending on the function and operation of the equipment, utility or system, only installation quali?cation (IQ) and operational quali?cation (OQ) may be
required, as the correct operation of the equipment, utility or system could be considered to be a suf?cient indicator of its performance (refer to Section 11 for IQ, OQ and performance quali? cation (PQ)). (The equipment, utility and system should then be maintained, monitored and calibrated according to a regular schedule.)
考虑到设备、公用设施或系统的具体功能和运作情况，可能只需要进行安装确认（IQ）和运行确认（OQ），因为这些设备、公用设备或系统的正确运转已经可以证明它们的性能（更多信息请查阅第11部分-IQ、OQ和性能确认（PQ））。（这些设备、公用设施和系统的维护、监控和校准应当根据计划定期执行。）
6.3 Major equipment and critical utilities and systems, however, require IQ, OQ and PQ.
对主要的设备、关键的公用设施和系统，还需要开展IQ、OQ和PQ。 7. Calibration and veri?cation 校准和核查
7.1 Calibration and veri?cation of equipment, instruments and other devices, as applicable, used in production and quality control, should be performed at regular intervals.
用于生产和质量控制的设备、仪器和其它器械应定期进行校准和核查。
7.2 Personnel who carry out calibration and preventive maintenance should have appropriate quali?cations and training.
执行校准和预防维护的人员应当具备相应的资格且得到过适当的培训。
7.3 A calibration programme should be available and should provide infor-mation such as calibration standards and limits, responsible persons, calibra-tion intervals, records and actions to be taken when problems are identi? ed.
应制订好校准计划，准备好资料，如校准标准和限度、负责人、校准间隔、记录和发生问题后所采取的措施。
7.4 There should be traceability to standards (e.g. national, regional or international standards) used in the calibration.
应当有可追溯的校准标准（如国家标准、地区标准或国际标准等）。
7.5 Calibrated equipment, instruments and other devices should be la-belled, coded or otherwise identi?ed to indicate the status of calibration and the date on which recalibration is due.
对于校准过的设备、仪器和其他器械，应贴好标签，编好代码或使用其它可指示校准状态和下次校准日期的方式来对之进行标识。
7.6 When the equipment, instruments and other devices have not been used for a certain period of time, their function and calibration status should be veri?ed and shown to be satisfactory before use.
如设备、仪器或其它器械已长时间未使用，在使用它们之前，应核实它们的功能和校准状态，确实它们可供使用。 17 Validation master plan 验证主计划
The validation master plan (VMP) should re?ect the key elements of the validation programme. It should be concise and clear and contain at least the
following: 验证主计划（VMP）应能反映验证项目的关键元素，它的内容应当简洁明了，且涵盖下列内容：
18 — a validation policy 验证方法
19 — organizational structure of validation activities 验证活动的组织机构
20 — summary of facilities, systems, equipment and processes validated and to be validated
已验证和待验证的设施、系统、设备和工艺的总览 21 — documentation format (e.g. protocol and report format) 文件格式（如方案和报告的格式） 22 — planning and scheduling 计划和进度设计 23 — change control 变更控制
24 — references to existing documents. 现有文件的参考资料。
9. Quali?cation and validation protocols 确认和验证方案
9.1 There should be quali?cation and validation protocols describing the quali?cation and validation study to be performed. 应有说明待执行的确认和验证的确认和验证方案。
9.2 As a minimum the protocols should include the following signi? cant background information:
方案中，应含有的重要背景资料至少应涵盖下列内容：
25 — the objectives of the study 研究对象
26 — the site of the study 研究地点
27 — the responsible personnel 负责人
28 — description of SOPs to be followed 需要遵从的SOP的说明
29 — equipment to be used; standards and criteria for the relevant products and processes
将用到的设备；相关产品和工艺的技术标准和合格指标 30 — the type of validation 验证的类型
31 — the processes and/or parameters 工艺和/或参数
32 — sampling, testing and monitoring requirements