What aresuitable Cycles for Re-Qualification?

如何确定合适的再确认周期？

With the revision of Annex 15 in October 2015, the topic ofrequalification has become more important. In the former Annex 15 dated 2001,the topic of requalification was 'hidden' under the general demandfor revalidation (point 45). With the revision of Annex 15, there-qualification has now its own chapter with - among other things - therequirements for :

随着2015年10月附录15（注：欧盟GMP 附录15）的修订，再确认的话题变得更加重要。在2001年的前附录15中，在验证的一般要求(第45点)下“隐藏”了再验证的主题。随着附录15的修订，再确认现在有单独的章节，除其它事项外，规定:

·where requalification is required, the time intervals should bejustified and the criteria for evaluation should be established.

·在需要再确认的情况下，应合理确定时间间隔，并建立评估标准。

In practice, it is sometimes difficult to establish such timelinesand criteria for evaluation. In the sterile area, there are sometimes specificreferences from the regulations to individual devices and processes. Forexample, according to the FDA Aseptic Guide, HEPA filters in cleanroom class 5should be tested twice a year. Annex 1 of the EU GMP Guidelines also provides guidelines on this subject (e.g. for sterilisation).

在实践中，有时很难确定这样的时间表和评价标准。在无菌区，有时会有特定的法规规定个别设备和工艺来进行具体参考。例如，根据FDA的无菌指南，洁净室5级的HEPA过滤器应该每年进行两次测试。欧盟GMP附录1也对这方面提供指南(例如：灭菌)。

What about equipment inother areas?

在其他区域的设备呢？

Periodic Review accordingto ISPE Baseline Commissioning & Qualification, 2019

2019年 ISPE 调试和确认中提到定期审核

In this case, chapter 9 of the revisedISPE Baseline No 5 Commissioning & Qualification from June 2019on the periodic review can be helpful. The 'review' approach,i.e. the evaluation, is presented in two phases.

在这种情况下，从2019年6月修订的ISPE基准指南 5调试和确认的第9章可能会对定期审核有所帮助。对“审核”方法，即评价，提出分两个阶段。

In phase 1, the existing'direct impact systems' are categorised. Depending on the complexityof the system (complex vs. standard) and the influence on the product quality,the systems are exemplarily divided into the categories 0-3. Each category,except category 0, is then assigned to a 'review ' period. Category 0refers to existing systems and the existence of monitoring data. In thisrespect, no review of these category 0 systems (e.g. water systems) isnecessary. There are already data available to be evaluated. For systems incategory 1, e.g. autoclaves, the specifications above from the sterileregulations apply. For category 2 systems, e.g. buffer storage tanks, thebaseline suggests a two-year interval. For category 3 systems, e.g. tablet presses,the Baseline recommends a three-year review interval.

在第1阶段，对现有的“直接影响系统”进行分类。根据系统的复杂性(复杂vs.标准)和对产品质量的影响，可以将系统分为0-3类。除第0类外，每个类别都被有一个“审核”周期。0类是指现有系统存在监测数据。这种情况，没有必要审核这些0类系统(例如制药用水系统)。已经有数据可供评估。对于第1类系统，例如高压灭菌柜，适用于无菌法规的要求。对于第2类系统，例如缓冲罐，指南建议间隔两年。对于第3类系统，如压片机，指南建议间隔3年进行检查。

In phase two, the'review' is executed. The review itself takes place as a three-stepprocess:

在第2阶段，执行审核。审核本身分3个步骤进行：

·   Step 1: an initial assessment regarding GMP compliance, history ofchanges, maintenance/calibration and deviations.

第一步:对GMP符合性、变更历史、维护/校准和偏差进行初步评估。

·  Step 2: based on the result of step 1, the systems examined instep 1, the results of which are questionable, are examined in greater depth bySubject Matter Experts (SMEs). The SMEs should come from the same departmentsthat were also involved in the evaluation in step 1. 

· 第2步:基于第1步的结果，第1步中检查的系统，如果其结果是有问题的，将由主题专家(SME)进行更深入的检查。SME应来自同样参与第一步评估的部门。 

If the evaluation in step 2comes to the conclusion that a system could no longer be in qualified status,the next step, step 3, takes place. Otherwise the process ends here.

如果第2步的评估得出系统不再处于合格状态的结论，则进行下一步，即第3步。否则，这个过程就到此结束。

· Step 3: based on the result of step 2, the systems examined in step 2,the results of which are questionable, are examined in greater depth by SMEs.The SMEs should come from the same departments that were also involved in theevaluation in steps 1 and 2. If necessary, measures should be taken to bringthe system back to a qualified state. A deviation document should be created tocontrol the actions taken.

·第三步:基于第二步的结果，SME对第二步中检查的系统进行了更深入的检查，检查结果存在疑问。SME应来自同样参与第1步和第2步评估的部门。如有必要，应采取措施使该系统恢复到有条件的状态。应该创建一个偏差文件来控制所采取的操作。

According to the baseline,the entire process should be managed by someone with a wealth of experience.The review itself should at least be approved by the system owner and thequality unit. A review form is part of the baseline as Appendix 11 and an exampleis given in Appendix 12.

根据该基准指南，整个过程应该由经验丰富的人来管理。评审本身至少应得到系统所有者和质量部门的批准。评审表是指南的一部分，如附录11所示，附录12给出了一个案例。

英文来自ECA新闻，翻译仅供参考~