10.5. 应当对清洁工艺有哪些影响清洁效果和清洁性能的变量进行评估，例如操作员、程序中的细节像淋洗时间等，若变量经过证实，那么应考虑将最差条件作为清洁验证研究的基础。

10.6. Limits for the carryover of product residues should be based on a toxicological evaluation. The justification for the selected limits should be documented in a risk assessment which includes all the supporting references. Limits should be established for the removal of any cleaning agents used. Acceptance criteria should consider the potential cumulative effect of multiple items of equipment in the process equipment train.

10.6. 产品残留的携带限度应根据毒理学评价，限度选择的依据应在包含参考文件的风险评估中写明，还应当给出所使用清洁剂残留的限度，可接受标准制定时还应当考虑工艺设备清单中多个设备潜在的累积效应。

10.6.1.Therapeutic macromolecules and peptides are known to degrade and denature when exposed to pH extremes and/or heat, and may become pharmacologically inactive. A toxicological evaluation may therefore not be applicable in these circumstances.

10.6.1. 已知治疗性大分子和肽链在pH超过限制或加热的情况下会发生降解和变性，有可能失去药理学活性，基于毒理学的评价在这种情况下有可能不适用。 10.6.2.If it is not feasible to test for specific product residues, other

representative parameters may be selected, e.g. total organic carbon (TOC) and conductivity.

10.6.2. 如果没有办法可以检测特定的产品残留，可以使用其他代表性参数，比如总有机碳（TOC）和电导率。

10.7. The risk presented by microbial and endotoxin contamination should be considered during the development of cleaning validation protocols. 10.7.

在制定清洁验证方案时，应考虑可能出现的微生物和细菌内毒素风险。

10.8. The influence of the time between manufacture and cleaning and the time between cleaning and use should be taken into account to define dirty and clean hold times for the cleaning process.

10.8. 清洁工艺中，应考虑生产完成至清洁开始以及清洁后至再次使用的时间间隔，以明确脏设备和干净设备的存放时间。

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10.9. Where campaign manufacture is carried out, the impact on the ease of cleaning at the end of the campaign should be considered and the maximum length of a campaign (in time and/or number of batches) should be the basis for cleaning validation exercises.

10.9. 采用连续性生产时，应考虑在生产结束后进行清洁的难易程度，并将最长连续生产的时间（以时间和/或生产批次计）作为清洁验证的基础。 10.10. Where a worst case product approach is used as a cleaning validation model, a scientific rationale should be provided for the selection of the worst case product and the impact of new products to the site assessed. Criteria for determining the worst case may include solubility, cleanability, toxicity and potency.

10.10. 当采用最差条件产品的方法作为清洁验证模式时，应从溶解性、可清洁性、毒性和效价等方面科学合理的解释为什么选择该产品作为最差条件的产品，并在有新产品引入时应评估其影响。

10.11. Cleaning validation protocols should specify or reference the locations to be sampled, the rationale for the selection of these locations and define the acceptance criteria.

10.11. 清洁验证方案中应指明或引用取样位置，选择这些位置的理由，明确可接受标准。

10.12. Sampling should be carried out by swabbing and/or rinsing or by other means depending on the production equipment. The sampling materials and method should not influence the result. Recovery should be shown to be possible from all product contact materials sampled in the equipment with all the sampling methods used.

10.12. 可以根据生产设备选择擦拭、淋洗或其他方法进行取样，但取样材料和方法应不影响检测结果，应证明所使用的取样方法从与产品接触的不同材质的设备表面上取样的回收率都是适用的。

10.13. The cleaning procedure should be performed an appropriate number of times based on a risk assessment and meet the acceptance criteria in order to prove that the cleaning method is validated.

10.13. 应基于风险评估决定清洁程序应重复执行的次数，且清洁程序应符合可接受标准，以此证明清洁方法是经过验证的。

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10.14. Where a cleaning process is ineffective or is not appropriate for some equipment, dedicated equipment or other appropriate measures should be used for each product as indicated in chapters 3 and 5 of EudraLex, Volume 4, Part I.

10.14. 如第四卷第一部分第3章和第5章所述，若清洁工艺是无效的或不适合某类设备，那么对每个产品应使用专用设备或其他适宜的方法。

10.15. Where manual cleaning of equipment is performed, it is especially important that the effectiveness of the manual process should be confirmed at a justified frequency.

10.15. 当使用手工清洁设备时，须确定一个合适的频率以确认人工清洁的有效性是非常重要的。 11. CHANGE CONTROL 11. 变更控制

11.1. The control of change is an important part of knowledge management and should be handled within the pharmaceutical quality system.

11.1. 变更控制是知识管理中重要的一部分，应当在药品质量管理体系中得到应用。

11.2. Written procedures should be in place to describe the actions to be taken if a planned change is proposed to a starting material, product component, process, equipment, premises, product range, method of production or testing, batch size, design space or any other change during the lifecycle that may affect product quality or reproducibility.

11.2. 当出现起始物料、原辅料、工艺、设备、设施、产品范围、生产或检验方法、批量、设计空间或可能在产品生命周期中影响产品质量或重现性的其他变更等作为计划性变更被提出时，应有书面的程序来描述计划性变更出现时应采取的行动。

11.3. Where design space is used, the impact on changes to the design space should be considered against the registered design space within the marketing authorization and the need for any regulatory actions assessed.

11.3. 当涉及到设计空间时，应对照上市批准的注册设计空间，考虑变更对设计空间的影响以及是否需要采取一些法规行动。

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11.4. Quality risk management should be used to evaluate planned changes to determine the potential impact on product quality, pharmaceutical quality systems, documentation, validation, regulatory status, calibration,

maintenance and on any other system to avoid unintended consequences and to plan for any necessary process validation, verification or requalification efforts.

11.4. 应当使用质量风险管理来评估计划性变更对产品质量、药品质量系统、文件、验证、法规状态、校准、维护和其他系统带来的潜在性影响，以避免不可预料的后果和采取工艺验证、确认或再确认的必要性。

11.5. Changes should be authorised and approved by the responsible persons or relevant functional personnel in accordance with the pharmaceutical quality system.

11.5. 变更需要被授权，并经过负责人或质量管理体系中规定有相应职能的人员进行批准。

11.6. Supporting data, e.g. copies of documents, should be reviewed to confirm that the impact of the change has been demonstrated prior to final approval.

11.6. 支持性数据（如文件的复印）应进行审核，以确保变更的影响在变更最终审批前得到证实。

11.7. Following implementation, and, where appropriate, an evaluation of the effectiveness of change should be carried out to confirm that the change has been successful.

11.7. 后续执行及必要时候，应当对变更的有效性进行评估，以证明变更是成功的。

12. GLOSSARY 12. 词汇表

Definitions of terms relating to qualification and validation which are not given in other sections of the current EudraLex, Volume 4, are given below. 现行GMP第四卷其他部分关于确认和验证没有出现的术语定义如下： Bracketing approach.

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