ECA关于清洁验证的7个最新问答！

1. Question: Regarding visualinspection of surfaces in Annex 15: Is during operator qualification a trainingon the relevant SOP sufficient or should a training, comparable to those forvisual inspection operators, be established (incl. periodic eye sight test)?
问题：关于GMP附录15《确认与验证》中清洁表面的目视检查：在操作人员资格认证时，对相关SOP进行培训是否足够？还是应该建立与灯检人员类似的培训（包括定期视力检查）？

Answer: A solely theoretical SOP-training is not sufficient. Practical trainingwith surface samples spiked with different concentration of the respective productneeds to be performed. This needs to be performed by collecting data todemonstrate down to which level of residues visual cleanliness can be detected.
答：仅仅进行理论性的SOP 培训是不够的。应使用载有不同浓度的代表性产品的表面样品进行实际训练。这需要通过收集数据来证明什么水平的残留可以被目视洁净度检测出来。

2. Question: Are directsampling methods necessary for transfer lines or other inaccessible equipmentparts? Those parts can neither be tested visually nor via swab testing. Wouldfinal rinse testing be sufficient?
问：对于输送管道或其他无法够及的设备部件，是否需要采用直接取样方法？这些部件既无法进行目视测试，也无法通过擦拭取样。最终淋洗测试是否足够？

Answer: This clearly depends on factors like pipe length, flowconditions, percentage of surface area that cant be inspected and shouldbe addressed in a risk assessment. Additional measurements like endoscopicinspection as part of maintenance could also be beneficial. Taking thesolubility of residues into consideration final rinse sampling could besufficient.
答：这显然取决于管道长度、流量条件、无法检查的表面积百分比等因素，应进行风险评估。作为维护的一部分，内窥镜检查等其他检查方法也可能有用。如已考虑残留物的溶解性，最终淋洗取样是足够的。

3. Question: Are PDE values applicablein products that are only applied once or twice (e.g. vaccines)?
问：PDE是否适用于仅使用一次或两次的产品(例如疫苗)?

Answer: Yes, PDE values derived from HBEL are also applicable. They need to beestablished for every medicinal product. Only if inactivation during thecleaning process could be shown a risk based strategy could be developed whereapplying the PDE is not needed:
答:是的，由HBEL导出的PDE值也适用。每一种药品都需要建立相应的标准。只有当在清洁工艺中出现灭活时，才可以在不需要应用PDE的情况下制定基于风险的策略:

"In view of this, the determination of health-based exposure limits usingPDE limits of the active and intact product may not be required."
有鉴于此，是有可能不需要使用活性成分和完整产品的PDE 值制定基于健康的暴露限值的。

4. Question: If you introducea new product in a multi-purpose facility and identify this product as worstcase; do you have to revalidate the cleaning process for existing equipment?
问题：如果在共线设施中引入新产品，并确认该产品为最差情况；是否必须重新验证现有设备的清洁过程？

Answer: Yes, a revalidation is necessary. The extent needs to be defined in arisk assessment.
答：是的，需要重新验证。范围需要在风险评估中定义。

5. Question: Is there a reasonwhy a CHT and Sterile Hold Time (SHT) could not be shown within one singlevalidation protocol? In the way that sampling will just be done at the end ofSHT?
5. 问题：CHT （洁净保持时间）和无菌保持时间（SHT）不能在1个验证方案中执行的原因是什么？是否可以在无菌保持时间结束时取样？

Answer: Yes, testing for CHT is first performed before sterilization havingdata within the accepted limit for bioburden (rinsing, swabbing or contactplate sampling) prior sterilization. This also is the minimum bioburden toinactivate via sterilization (excl. buffer ? SAL) - basis for sterilizationvalidation.
答：是的，CHT洁净保持时间在灭菌之前进行测试，以获取灭菌前生物负荷（冲洗、擦拭或接触皿取样）的接受限度之内的数据。这也是通过灭菌程序灭活的最低生物负荷——即，灭菌验证的基础。

SHT has nothing to do with cleaning validation. It is linked to sterilizationvalidation, aseptic processing and aseptic process simulation (media fill).Validity can either be shown via sampling or can be covered, based on aprofound risk assessment, in an aseptic process simulation.
SHT无菌保持时间与清洁验证没有任何关系。它与灭菌验证、无菌加工和无菌工艺模拟（模拟分装）相关。其有效性可以通过样品来显示，也可以根据深入的风险评估，在无菌过程模拟中加以涵盖。

If you sample only after SHT you have no data for bioburden prior sterilizationand therefore no data for CHT.
如果在 SHT无菌保持时间后进行取样，没有灭菌之前生物负荷的数据，因此没有 CHT 洁净保持时间的数据。

The only scenario I could imagine to skip CHT is a CIP/SIP process wheresterilization is automatically directly started after the cleaning process.Therefore there is no CHT, so only SHT needs to be validated. But at least youneed data for endotoxins after cleaning.
我唯一可以想象跳过CHT的方案是一个CIP/SIP工艺，在清洁完成后自动直接开始灭菌。因此，没有 CHT，因此只需要验证 SHT。但至少需要清洁后内毒素的数据。

6. Question: What aboutsampling of wire-mesh filters of fabrics filters?
问：织物过滤器的丝网过滤器的如何取样？

Answer: According to my experience sampling wire mesh filters of fabricsfilters is only possible via rinse sampling.
答：根据我的经验，织物过滤器的丝网过滤器只能通过冲洗取样。
 
7. Question: Can theworst-case substance regarding to cleaning also be determined by onlyperforming theoretical calculations and w/o performing any practical smallscale studies in the lab?
问题：清洁的最差条件物质是否只通过理论计算来确定，而不在实验室中进行任何实际小规模试验？

Answer: Based on my experience with several research projectspredicting cleanability of a product or component solely based on theoreticaldata like physico-chemical parameters and model assumptions are insufficientand lead to a "trial &error"-like cleaning validation.
答：根据我在多个研究项目中的经验，仅根据物理化学参数和模型假设等理论数据预测产品或组分的可清洁性是不够的，并导致"试验与错误"式的清洁验证。

       文章来源： GMP办公室

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