【讨论】Is the end of the periodic revalidation coming with the revision of A...

zhulikou431

The planned revision of Annex 15 doesn't provide for a periodic revalidation any more. Can it therefore be dropped in the future? The following is an overview of the actual requirements concerning the periodic revalidation or its possible cancellation.
Most GMP regulations (still) provide for a periodic revalidation. The actually (still) valid Annex 15 of the EU Guidelines to Good Manufacturing Practice solves this issue with a very welcome pragmatic approach in point 45 by also providing for the possibility of a document review as revalidation. On the other hand the Product Quality Review also provides at least for an annual review of the processes. Isn't this also a sort of (periodic) revalidation?
The development towards the cancellation of a periodic revalidation is not completely new. The periodic revalidation has - consistently - already been cancelled in the FDA Guidance Process Validation published in 2011. The process validation lifecycle described in this Guidance assumes in stage 3 "continued process verification" that the state of control of the process will be demonstrated there continuously. In the case of variations the corresponding actions can be taken or eventually a revalidation be carried out with regard to the cause. Hence, the periodic revalidation is dropped since the process should always be in a validated state.
Now, this process validation lifecycle approach with a comparable stage 3 (ongoing process verification) also is promoted in the draft of the revision of Annex 15. Insofar, neither this document provides for a periodic revalidation any more.
This means that in principle there are discrepancies between documents still requiring a periodic revalidation (such as Chapter 5 EU GMP Guide) and the ne*******uments of the FDA and the draft of the revision of Annex 15. Although the revision of Annex 15 isn't final yet it clearly tends in the direction of a validation lifecycle without periodic revalidation.
In the area of the sterile manufacture, especially as concerns the aseptic manufacture, however, there will still be periodic revalidations. Annex 1 of the EU Guidelines to Good Manufacturing Practice for example provides for media fills as process validation of the aseptic manufacturing process twice a year.
Conclusion: May the periodic revalidation be cancelled in the future? In the area of sterile manufacture periodic revalidations have been state of the art for years now and are likely to remain so. Insofar the answer to this question is: No. Newer regulations on validation that promote a process validation lifecycle (FDA, draft of the revision of Annex 15) do not contain the periodic revalidation any longer. This means, the answer to the question on the cancellation of the periodic revalidation would be "yes". But some older regulations still contain the periodic revalidation. Does this mean the answer is no-yes to express indecision?

笨丫头

不错,顶的人不多啊，快点继续

beiwei5du

确实在EU chapter 5 production和 annex 1 sterile medicinal products中还保留有revalidation/periodic revalidation的概念，但在FDA gudance process validation和EU VOLUME annex15 qualification and validation中并没有revalidation/periodic revalidation的概念了。我的理解针对于periodic revalidation应该会趋于取消吧，而针对于variation的revalidation是应该存在的，这两个revalidation应该是不同。可能需要看以后法规怎么发展。

beiwei5du

但是在最近WHO草案 WHO publishes Draft of an Umbrella Guideline on Process Validation
http://www.gmp-compliance.org/en ... ess-Validation.html
中仍然提及到revalidation/periodic revalidation概念，感觉各个地方现在关于这个（周期性）再验证还存在一些冲突啊。@julia朱玉姣  ？？？？

glm1024

beiwei5du 发表于 2016-7-12 19:41
但是在最近WHO草案 WHO publishes Draft of an Umbrella Guideline on Process Validation
http://www.gmp ...

我之前看EU 附录15的时候就发现了这个问题，所以，我个人的理解是工艺再验证已经没有存在的必要了，因为以后都是持续工艺确认了，持续工艺确认表明工艺受控就说明工艺很稳定了，再验证已经么有必要了，但对于设备/公用系统还是会再确认。

beiwei5du

别人半官方组织才说“Does this mean the answer is no-yes to express indecision?”现阶段都不确定，你就下结论了？？哈哈。设备，公用设施也不一定要再验证啊？？文章提到无菌模拟灌装的例子，现在法有些法规仍要求做再验证