Following experience gained since the introduction of the revised EDQM Guideline on requirements for revision/renewal of certificates of suitability to the European Pharmacopoeia Monographs (PA/PH/CEP (04) 2, 7R corr) in January 2019, this announcement is intended to clarify a couple of items.
The EDQM Guideline on requirements for revision/renewal of certificates of suitability to the European Pharmacopoeia Monographs states that a separate CEP application should be made when a new substantially different route of synthesis is introduced (even when the impurity profile of the final substance is equivalent). For lifecycle management and transparency for all concerned parties, the EDQM expects that a separate application is made also when the route of synthesis is replaced by a new one, and the EDQM reserves the right to reject any such requests for revision for which a separate application would need to be made.
In addition, where different grades of material with different specifications are applied, the EDQM would also expect separate applications to be made (i.e. different polymorphic forms, different hydrates or sterile/non-sterile grades, whilst different particle sizes may still be included in the same CEP application when the impurity profile is shown equivalent).
There are also frequent situations where requests have been misclassified by CEP holders as a minor revision instead of a major revision, or as a notification instead of a minor revision. The EDQM Revisions guideline gives examples of changes which are to be considered as a major revision and the possibility is offered to consult via the EDQM Helpdesk or via email on the classification of a change prior to submission. Due to the increasing frequency of misclassifications, and taking into account the negative effects this has on workflows and deadlines, CEP holders are now informed that misclassifications of revisions or notifications will lead to the rejection of all submitted changes at any stage of the process, and the need to resubmit the changes correctly classified together with the settlement of the appropriate fees (i.e. there will be a need to pay twice). CEP holders are also reminded that major revisions should not be submitted simultaneously with a request for renewal but should be submitted either before or after.