22/23 February 2024
In August 2016, the EDQM released a policy document entitled "Implementation of ICH Q3D in the Certification Procedure" (PA/PH/CEP(16)23). According to the literal adoption of the ICH Q3D Guideline in the General Chapter 5.20 of the European Pharmacopoeia, regulating the handling with elemental impurities within the CEP procedure is the next step for a consistent implementation of this guideline.
The document describes in two main chapters which data on elemental impurities are required for a new CEP application and for the revision/renewal of an existing CEP. An important part of the document is the Annex 1 providing the example of a risk management summary (RMS) which lists the 24 elements of the ICH Q3D guideline in a table. Applicants have to enter in the table limits and information about each element which is involved in the risk management or which has been added intentionally. Moreover, the intended routes of administration of the API, as well as its intended use have to be indicated.
Please find hereafter a short summary of the data on elemental impurities expected by the EDQM from an applicant or a CEP holder.
New application for a CEP with submission of a RMS
The EDQM points out that the submission of a RMS is in any case advantageous.
New application for a CEP without submission of a RMS
Requirements for existing CEPs and CEP revisions
With the publication of edition 9.0 of the European Pharmacopoeia (January 2017), General Chapter 2.4.8 (Test for Heavy Metals) will be removed from the monographs for substances which fall under the scope of ICH Q3D. CEP holders won't be contacted individually by the EDQM unless their CEP contains a limit for elemental impurities which has been calculated according to option 2a of the General Chapter 5.20 set in edition 8 of the European Pharmacopoeia. In that case, a revision of the CEPs will be automatically initiated by January 2017.
In the following cases, CEPs revisions are possible, respectively necessary:
The same requirements apply to CEPs whose renewal is pending. The EDQM recommends to submit a RMS in the course of the renewal of a CEP.
The regulations described in this policy document will apply as of September 1st 2016 for all new, renewed or revised CEPs. Notwithstanding the above, the document can be commented on via the EDQM helpdesk.
Note: At the 19th APIC/Cefic European Conference on Active Pharmaceutical Ingredients on 23 - 25 November 2016 in Barcelona, Spain, Hélène Bruguera - head of EDQM's certification division - will present the latest developments in the CEP procedure. You can find more information at: www.api-conference.org.