Revision of the EU GMP Annex 15 for Qualification and Validation published

In our news EMA published a concept paper on the revision of the Annex 15 we reported about the planned revision of Annex 15. Now, the European Commission has published the draft of the Annex 15.
Compared to the original 11 pages of Annex 15 the draft has now 17 pages. The above-mentioned concept paper is mentioned as a reason for the revision, i.e. adjustments to changes partially to part 1 of the EU GMP Guide, changes in Annex 11, adjustments to the ICH Q8-11 documents, to the EMA Process Validation draft and changes in manufacturing technologies.
Below is a short summary of the major changes.
The revision is very extensive. Influences of the ICH Guidelines  Q8, 9, 10 (and 11) are clearly visible - even in the glossary. The subject Design Space (ICH Q8) is now also covered in the area Process Validation. Many risk considerations (ICH Q9) are now mandatory. The life cycle approach and process knowledge (ICH Q10) are now included as well. Deviation management gained in significance. Third party services are now authorized explicitly if the supplier has been qualified correspondingly. This is a positive adaptation to reality. The mention of preliminary approvals - e.g. in the case of deviations - is good for a next (validation / qualification) stage, if there is a documented assessment showing that there is no significant impact on the next stage. Unfortunately a clear differentiation between qualification (based on equipment and facilities) and validation (related to processes) is missing. This is a shortcoming that unfortunately exists in many European regulations.
Other important changes compared to the current version are:

  • There are new terms that are not explained in the glossary, such as "ongoing validation strategy" 
  • Retrospective validation and the notion of revalidation are gone completely - except  for one exemption
  • The qualification has become more extensive due to the integration of user requirements as a separate step and claim for a SAT. 
  • Information regarding the qualification of equipment in use have been omitted completely. 
  • The naming of transportation verification, packaging validation, validation of utilities and validation of analytical methods are completely new. 
  • In the Process Validation there are now 2 different approaches - a (modern) "continuous verification" approach and a traditional approach. The latter is still based on the classic 3 validation runs. But in any case, process robustness has to be proven. 
  • "Bracketing" approaches in the Process Validation are possible now - have to be justified though 
  • A hybrid approach between continuous verification and the traditional Process Validation approach remains somewhat "fuzzy" 
  • With regard to cleaning validation the 'visibly clean' criterion as the only acceptance criterion is no more acceptable. 
  • A grouping of equipment in the cleaning validation is explicitly possible now - but needs to be founded 
  • Acceptance criteria for a cleaning validation depend on toxicological data (permitted daily exposure, PDE) 
  • The statement that the number of cleaning validation runs has to be decided on the basis of a risk assessment is very interesting. The magic 3 is not mentioned explicitly here - unlike the Process Validation. 
  • The concept of cleaning verification for rarely manufactured products is also new 
  • The demand for "dirty and clean-hold times" is an adaptation to the state of the art

Conclusion: All in all there is an abundance of new requirements, which partly only represent the state of the current technology. And partly the "problems" remain in the details. A detailed analysis will follow.
The draft comment period is relatively short and ends (unfortunately) already end of May 2014.

Here you will find the Draft EU GMP Annex 15 for Download

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