15/16 February 2024
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 newer documents 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?