iv. Calibration of instrumentation; iv.
仪表校准。
v. Verification of the materials of construction. v.
核对部件的材质。
Operational qualification (OQ) 运行确认（OQ）
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).
3.10. OQ一般紧跟着IQ，但是根据设备的复杂情况，OQ也可以合并在安装/运行方案中执行(IOQ)。
3.11. OQ should include but is not limited to the following: 3.11.
运行确认包括但不限于以下内容：
i. Tests that have been developed from the knowledge of processes, systems and equipment to ensure the system is operating as designed;
i. 根据工艺、系统和设备的相关知识开展测试，以确保其可以像设计的那样运行。
ii. Tests to confirm upper and lower operating limits, and /or “worst case” conditions. ii.
对其上下操作线或最差工况进行测试。
3.12. The completion of a successful OQ should allow the finalisation of standard operating and cleaning procedures, operator training and preventative maintenance requirements.
3.12. 成功的完成OQ后，就可以进行标准操作规程、清洁规程、员工培训、预防性维护的最终定稿。 Performance qualification (PQ) 性能确认（PQ）
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.
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3.13. 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: 3.14.
性能确认包括但不限于以下内容：
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;
i. 设备使用生产物料、合格替代物或模拟产品在最差批量工况的正常操作条件下进行测试，被证明具有等同表现。工艺控制的取样频次应当经过充分证明。
ii. Tests should cover the operating range of the intended process, unless documented evidence from the development phases confirming the operational ranges is available.
ii. 测试应覆盖预期工艺的操作范围，除非有文件证明在研发阶段确认过操作范围。
4. RE-QUALIFICATION 4. 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. 4.1. 应当对设备、设施、公用工程和系统保持合适的评估频率，以确保其依然在受控状态。
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. 4.2. 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。此外，应评估随着时间推移产生小变更的可能性。 5. PROCESS VALIDATION 5. 工艺验证 General 通则
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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.
5.1. 本节提出的要求和原则适用于所有药品剂型，包括新工艺的初次验证、工艺变更后的验证、现场转移及持续的工艺验证。本附录认为一个成熟稳定的研发工艺有助于确保工艺验证的成功。
5.2. Section 5 should be used in conjunction with the current EMA guideline on Process Validation.
5.2. 第五节应该和现行的欧洲药品局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
5.2.1. 本工艺验证指南仅仅为提交给药政当局的相关信息和数据提供指导。然而，GMP对工艺验证的要求依然是贯穿于工艺的整个生命周期。 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.
5.2.2. 本方法适用于关联产品和工艺开发，它可以确保商业化的生产工艺和工艺维护在商业化生产期间处于受控状态。
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.
5.3. 可以使用传统方法或持续改进的方法对生产工艺进行开发。但是，不管使用
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何种方法，工艺都必须是成熟稳定的，并确保在产品上市之前其质量的一致性。使用传统方法开发的生产工艺在产品放行前都应当经过前验证。回顾性验证不再是可接受的方式。
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.
5.4. 新产品的工艺验证应当包括所有计划上市的规格和生产场所。基于开发阶段大量的工艺知识，结合适当的正在进行中的验证程序，新产品可以经过论证采用界定法。
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.
5.5. 对于同一地点内或者两个不同地点之间的场地转移的工艺验证，可以使用界定法减少验证批次。但是，必须保证现有的产品知识（包括上一次的验证内容）可用。不同之处在于，可以使用界定法决定批量、包装规格、包装容器类型。 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.
5.6. 对于老产品的生产地址转移,生产工艺和控制应符合上市监督管理要求，产品类型应符合相应的现行上市标准。必要的时候还应当提交上市许可的变更。 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.
5.7. 工艺验证应当证明是否所有的质量属性和工艺参数（被认为可以确保验证状态和产品质量的重要项目）能够与工艺持续相符。应当根据风险评估的结果，在
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文件中明确哪些工艺参数和质量属性是关键的或者不关键的。
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. 5.8. 工艺验证批次与计划商业化生产的上市批次的批量应保持一致，使用其他批量应按照第四卷其他部分相关的要求进行评估和说明。
5.9. Equipment, facilities, utilities and systems used for process validation should be qualified. Test methods should be validated for their intended use. 5.9. 设备、设施、公用工程和系统在工艺验证前应经过确认，预定用途的检验方法应经过验证。
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.
5.10. 与所使用的方法无关，除非经过其他评估，所有产品在研发阶段或者其它来源的工艺知识应当被生产工厂做接收，并作为验证活动开展的基础。 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.
5.11. 对于工艺验证批而言，生产、研发或者其他现场转移的人员均需要参加。验证批次必须由按照GMP文件规定培训合格的人员进行生产，这样有助于生产人员通过工艺验证批次生产加深对工艺的理解。
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.
5.12. 在工艺验证开始之前，应审核起始物料、包装材料的供应商，以确定其资质。否则，应当根据风险管理的原则来证明不这样做的理由。
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欧盟GMP附录15：确认与验证(修订版英文+中文)
