附件1
Annex 1
确认与验证
Qualification and Validation
（征求意见稿）
(Draft for Comments)
第一章范围
Chapter One Scope
第一条本附录适用于《药品生产质量管理规范》中涉及的所有确认与验证活动。Article 1 This appendix applies to all qualification and validation activities involved in Good Manufacturing Practice.
第二章原则
Chapter Two Principles
第二条企业应当确定需要进行的确认或验证工作，以证明有关操作的关键要素能够得到有效控制。确认和验证的范围和程度应根据风险评估的结果确认。确认与验证应当贯穿于产品生命周期的全过程。
Article 2 A manufacturer should determine the required qualification or validation activities to prove that the critical aspects of relevant operations can be effectively controlled. The scope and extent of qualification and validation should be determined bad on risk asssment results. Qualification and validation activities should be throughout the entire life cycle of a product.
第三章验证计划
Chapter Three Validation Plan
第三条所有的确认与验证活动都应当事先计划。确认与验证的关键要素都应在验证总计划或同类文件中详细说明。
Article 3 All Qualification and validation activities should be planned in advance. The critical aspects of qualification and validation should be specified in a validation master plan (VMP) or an equivalent document.
第四条验证总计划应当包含以下信息：
（一）确认与验证的方针；
（二）确认与验证活动的组织机构及职责；
（三）待确认或验证项目的概述；
（四）文件格式，包括确认或验证方案和报告的格式；
（五）计划和日程安排；
（六）在确认与验证中偏差处理和变更控制的管理；
（七）保持持续验证状态的策略，包括必要的再确认和再验证；
（八）所引用的文件、文献。
Article 4 The VMP should include the following information:
1) Qualification and validation policy;
2) The organization structure and responsibilities in qualification and
validation activities;
3) An overview of the qualification and validation items;
4) Document format, including the format of the qualification or validation
protocols and reports;
5) Planning and scheduling;
6) Deviation handling and change control management in the qualification
and validation activities;
7) Strategy to maintain the validated status, including requalification and
revalidation, where applicable;
8) The referenced files and documents.
第五条对于大型和复杂的项目，可制订单独的项目验证总计划。
Article 5 For a large and complex project, a parate project VMP could be established.
第四章文件
Chapter Four Documentation
第六条确认与验证方案应当经过审核和批准。确认与验证方案应当详述关键要素和可接受标准。
Article 6 A qualification or validation protocol should be subject to review and approval. The qualification or validation protocol should define in detail the critical factors and the acceptance criteria.
第七条供应商或第三方提供的确认与验证的方案、数据或报告，企业应当对文件的适用性和符合性进行审核、批准。
Article 7 Where qualification and validation protocols are supplied by a supplier or a third party, the manufacturer should review their suitability and compliance before approval.
第八条确认或验证活动结束后，应当及时汇总分析获得的数据和结果，撰写确认或验证报告。企业应当在报告中对确认与验证过程中出现的偏差进行评估，必要时进行彻底调查，并采取相应的纠正措施
和预防措施；对于已批准的确认与验证方案的变更，进行评估并采取相应的控制措施。确认或验证报告应当经过书面审核、批准。
Article 8 A qualification or validation report should be prepared in a timely manner, summarizing and analyzing the data and results obtained after qualification or validation activities are completed. The manufacturer should asss any deviations identified during the qualification and validation activities, and conduct a thorough investigation and take relevant corrective actions and preventive actions, if necessary. Any changes to an approved qualification or validation protocol should be assd and relevant control measures should be taken. The qualification and validation report should be reviewed and approved in written.
第九条当验证结果不符合预先设定的可接受标准时，应当进行记录并分析原因。企业如对原先设定的可接受标准进行调整，需进行科学评估，得出最终的验证结论。
Article 9 Any validation results that fail to meet the pre-defined acceptance criteria should be recorded and a cau analysis should be conducted. Any subquent changes to the pre-defined acceptance criteria should be scientifically justified and a final validation conclusion should be made.
第十条当确认或验证分阶段进行时，只有当上一阶段的确认或验证活动符合预定目标且经书面批准后，
方可进行下一阶段的确认或验证活动。上一阶段的确认或验证活动中某项预先设定标准不能满足或偏差处理未完成，经评估对下一阶段的确认或验证活动无重大影响，企业可对上一阶段的确认或验证活动进行有条件的批准。
Article 10 When the qualification or validation are conducted by phas, only when the qualification or validation activities of a proceeding pha meet the pre-defined objectives and are approved in written, can the qualification or validation activities of the subquent pha be started. A conditional approval to proceed to the next pha can be given by the manufacturer where certain pre-defined criteria can not be met or deviations have not been fully clod in the last qualification or validation pha and there is an asssment concluding that there is no significant impact on the next qualification or validation pha.
第五章确认
Chapter Five Qualification
第一节设计确认
Design Qualification
第十一条企业应当对新的厂房、设施、设备按照预定用途和本规范及相关法律法规要求制定用户需求，并经审核、批准。
Article 11 The ur requirement specification (URS) for a new facility, system or equipment should be defined according to the pre-defined usage, the requirements of this guideline and the relevant regulations and laws. The URS should be reviewed and approved.
第十二条设计确认应当证明设计符合用户需求，并有相应的文件。
The design qualification should prove and document that the design meets the URS requirements.
第二节安装确认
Installation Qualification (IQ)
第十三条新的或改造的厂房、设施、设备需进行安装确认。
IQ should be performed for new or modified facilities, systems and equipment.
第十四条企业应当根据设计确认中的技术要求对厂房、设施、设备进行验收并记录。安装确认可包括但不限于以下方面：
The manufacturer should conduct and document an acceptance inspection on the facilities, systems and equipment according to the technical specifications of the DQ. IQ should include, but is not limited to the following:
（一）根据最新的工程图纸和技术要求，检查设备、管道、公用设施和仪器的安装是否符合设计标准；
(I) Check the installation of equipment, pipe work, utility rvices and instruments against the current engineering drawings and technical specifications to e whether the design specifications are met.
（二）收集及整理（归档）由供应商提供的操作指南、维护保养手册；
(II) Collect and collate (archive) the operating and maintenance manuals provided by the supplier.
（三）相应的仪器仪表应进行必要的校准。
(III) Relevant instruments should be calibrated as necessary.
第三节运行确认
Operational Qualification (OQ)
第十五条企业应当证明厂房、设施、设备的运行符合设计标准。运行确认可包括但不限于以下方面：
Article 15 The compliance of the operation of the facilities, systems and equipment with design specifications should be demonstrated by the manufacturer. OQ should include but is not limited to the following:
（一）根据设施、设备的设计标准制定运行测试项目。
(I) Tests developed bad on the design specifications of the facilities, systems and equipment.
（二）试验/测试应在一种或一组运行条件之下进行，包括设备运行的上下限，必要时采用“最差条件”进行确认。
(II) Tests should be conducted under one type or one t of operation conditions, including the upper and lower operating limits, and “worst ca” conditions should be ud if necessary.
第十六条运行确认完成后，应当建立必要的操作、清洁、校准和预防性维护保养的操作规程，并对相关人员培训。
Article 16 After the completion of the OQ, necessary operation, cleaning, calibration and preventive maintenance SOPs should be established, and operators shall be trained.
第四节性能确认
Performance Qualification (PQ)
第十七条安装和运行确认完成并符合要求后，方可进行性能确认。在某些情况下，性能确认可与运行确认或工艺验证结合进行。
Article 17 PQ can be initiated only after the successful completion of IQ and OQ. In some cas, PQ can be performed in conjunction with OQ or Process Validation.
第十八条应当根据已有的生产工艺、设施和设备的相关知识制定性能确认方案，使用生产物料、适当的替代品或者模拟产品来进行试验/测试；应当评估测试过程中所需的取样频率。
Article 18 PQ protocol should be developed bad on the knowledge of the process and the facilities, systems or equipment. And production materials, appropriate placebos or simulated products can be ud for the tests. The frequency of sampling during testing should be assd.
第六章工艺验证
Process Validation
第一节一般要求
General Requirement
第十九条工艺验证应当证明一个生产工艺按照规定的工艺参数能够持续生产出符合预定用途和注册要求的产品。工艺验证应当包括首次验证、影响产品质量的重大变更后的验证、必要的再验证以及在产品生命周期中的持续工艺确认，以确保工艺始终处于验证状态。
Article 19 The process validation should prove that the process, operated within the established parameters, can reproducibly produce a medicinal product meeting its predetermined usage and registration requirements. Process validation should cover the initial validation, the subquent validation of critical changes which can impact
the product quality and necessary re-validation, and continuous process verification during the life-cycle of the product, ensuring the validated status of the process.
第二十条企业应当有书面文件确定产品的关键质量属性、关键工艺参数、常规生产和工艺控制中的关键工艺参数范围，并根据对产品和工艺知识的理解进行更新。
Article 20 The manufacturer should have a written document defining the critical quality attributes,
critical process parameters, and critical process parameter ranges for routine production and process control, which should be updated bad on the understanding of product and process knowledge.
第二十一条首次工艺验证应当涵盖该产品的所有规格及使用的生产线。企业可根据风险评估的结果采用简略的方式进行后续的工艺验证，如选取有代表性的产品规格或包装规格、最差工艺条件进行验证，或适当减少验证批次。
Article 21 The initial process validation should cover all the strengths and the production lines ud. The abbreviated approach can be applied for subquent process validation by the manufacturer bad on the risk asssment results. For example, the reprentative strength or packing size, the worst process conditions can be lected for the validation. Or the number of validation bathes can be reduced appropriately.
第二十二条工艺验证批的批量一般应当与预定的商业批的批量一致，当批量不一致时，应当进行评估。
Article 22 Normally batches manufactured for process validation should be of the same size as the intended commercial scale batches and the u of any other batch sizes should be justified.
第二十三条工艺验证前至少应当完成以下工作：
Article 23 At least the following works should be completed prior to process validation:
（一）厂房、设施、设备经过确认并符合要求，分析方法经过验证或确认。
(I) Facilities, systems, utilities and equipment ud for process validation should be qualified and the analytical methods should be validated or qualified.
（二）日常生产操作人员应当参与工艺验证批次生产，并经过适当的培训。
(II) Routine production operators should be involved in the production of process validation batches and they shall be appropriated trained.
（三）用于工艺验证批次生产的关键物料应当由批准的供应商提供，否则需评估可能存在的风险。
The critical starting and packaging materials ud for the manufacture of validation batches should be provided by qualified suppliers. Otherwi the possible quality risks should be assd.
第二十四条企业应当根据质量风险管理原则确定工艺验证批次数和取样计划，以获得充分的数据来评价工艺和产品质量。
Article 24 The number of batches to be manufactured and the number of samples to be taken should be determined bad on quality risk management principles by the manufacturer, to obtain sufficient data for the evaluation of process and product quality.
第二十五条如未按照第二十四条要求进行预先的风险评估，企业应当至少进行连续三批成功的工艺验证。对产品生命周期中后续商业生产批次获得的信息和数据，进行持续的工艺确认。
