发布时间 : 星期二 文章欧盟GMP附录15：确认与验证（修订版英文+中文）更新完毕开始阅读
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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5.13. It is especially important that the underlying process knowledge for the design space justification (if used) and for development of any mathematical models (if used) to confirm a process control strategy should be available. 5.13. 需要特别强调的是，基于设计空间（如有使用）和工艺开发数学模型（如有使用）的基础知识确定的工艺控制策略是可接受的。
5.14. Where validation batches are released to the market, this should be pre-defined. The conditions under which they are produced should fully comply with GMP, with the validation acceptance criteria, with any continuous process verification criteria (if used) and with the marketing authorisation or clinical trial authorisation.
5.14. 验证批上市之前，应确定产品的生产环境应完全符合GMP、验证可接受标准、持续工艺确认标准（如有使用），并获得上市许可或临床许可。 5.15. For the process validation of investigational medicinal products (IMP), please refer to Annex 13. 5.15.
临床试验用药品（IMP）的工艺验证，参见附录13。
Concurrent validation 同步验证
5.16. In exceptional circumstances, where there is a strong benefit-risk ratio for the patient, it may be acceptable not to complete a validation programme before routine production starts and concurrent validation could be used. However, the decision to carry out concurrent validation must be justified, documented in the VMP for visibility and approved by authorised personnel. 5.16. 在特殊情况下，如果对患者利益明显大于风险，允许在常规商业化生产前没有完成验证程序而使用同步验证。然而，进行同步验证的决定必须进行论证，并在验证主计划中明确，且经被授权的人批准。
5.17. Where a concurrent validation approach has been adopted, there should be sufficient data to support a conclusion that any given batch of product is uniform and meets the defined acceptance criteria. The results and conclusion should be formally documented and available to the Qualified Person prior to certification of the batch.
5.17. 当采用同步验证的时候，应有足够数据支持做出“批次间产品是均一的且符合预定可接受标准”的结论。结果和结论应进行正式记录，并在批放行前通过
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