Elemental Impurities: The Next Steps for the Implementation of ICH Q3D into the European Pharmacopoeia

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12-14 December 2023

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In the course of the introduction of the ICH Q3D Guideline on elemental (metallic) impurities, a number of chapters and several monographs of the European Pharmacopoeia had to be revised. The timeframe available for this is the result of the deadline set by the Committee for Medicinal Products for Human Use (CHMP) from which the ICH Q3D requirements will have to be applied to already authorised medicinal products too. That deadline is the 1st December 2017. The European Pharmacopoeia Commission adapted the timetable for the implementation of ICH Q3D into the European Pharmacopoeia to this deadline.

The EDQM published the next steps for the implementation of ICH Q3D in a press release entitled "Update on the PH.EUR.Policy on Elemental Impurities" dated 11 January 2017. According to it, the plan for the revision of some general chapters and monographs will be as follows:

• General chapter 5.20 "Elemental Impurities": Parts of the scope and the introduction sections will be adopted literally from ICH Q3D and it will be referred to the guideline which can be found in full on the ICH website.
• General monograph "Pharmaceutical preparations" (2619): This monograph refers to Chapter 5.20. As a result, this chapter and by extension the ICH Q3D requirements will be legally binding.
• General monograph "Substances for pharmaceutical use" (2034): This monograph contains requirements for the control of elemental impurities intentionally added during production. Besides, the absence of a test for elemental impurities in certain monographs is explained.
• General method 2.4.20 "Determination of elemental impurities": Here, guidance is provided for aspects method development for determination of elemental impurities (e.g. sample preparation, method validation).

Those chapters and monographs were adopted at the 156th session of the European Pharmacopoeia Commission in November 2016. They are to be published in Supplement 9.3 (with an implementation date of 1st January 2018).

The European Pharmacopoeia Commission also decided to largely delete elemental impurities tests from monographs; except for monographs regarding substances from natural origin and monographs which describe metals for which no PDE limits have been set in the ICH Q3D guideline (e.g. aluminium and iron). Impurities tests originating from the production process will also be deleted. The control of those impurities is the responsibility of the API manufacturer.

The Commission is currently reviewing all monographs together with different groups of experts. A list of the monographs revised will be soon published.