In the following press statement, the European Pharmacopoeia Commission validated its strategy regarding elemental impurities and the implementation plan of the upcoming ICH Q3D guideline.
Following its last meeting in early June 2014, the ICH Steering Committee announced the plan to move their Guideline for elemental impurities (ICH Q3D), to Stage 4 in September 2014. As the sign off of this new tripartite guideline approaches, a strategy for the revision of the Ph. Eur. texts concerned has been drawn up by the European Pharmacopoeia Commission to ensure that a consistent approach between the licensing authorities and the Ph. Eur. continues to be applied.
Currently, the EMA Guideline on the specification limits for residues of metal catalysts or metal reagents (EMEA/CHMP/SWP/4446/2000), which is reproduced verbatim in chapter 5.20 “Metal catalyst or metal reagent residues” of the Ph. Eur., is applicable to new drug products to be marketed in Europe.
In its June session, the European Pharmacopoeia Commission endorsed the proposed revision strategy of the current “Heavy metals chapters” and decided as a first step to revise chapter 5.20, to replace its content by the ICH Q3D guideline as soon as it has moved to Stage 5 in the European Union. Indeed, the decision to replace the EMA guideline on the specification limits for residues of metal catalysts or metal reagents by the ICH Q3D guideline is under the remit of the Committee for Medicinal Products for Human Use (CHMP).
The reproduction of a Guideline in a Ph. Eur. Chapter does not make it legally binding as long as the Chapter is not referenced in a Ph. Eur. monograph. In line with a previous decision taken in April 2012, the Ph. Eur. intends to introduce a cross-reference to this revised chapter in the general monographs Substances for pharmaceutical use (2034) and Pharmaceutical preparations (2619) at a later stage, making the requirements of the ICH Q3D Guideline legally binding. The exact timing of this step will depend on the implementation decisions of other European regulation bodies, mainly the CHMP.
In addition, it is planned to delete cross-references to the wet chemical tests for “heavy metals” described in chapter 2.4.8 from all individual monographs, except for monographs on products for veterinary use only. The list of all impacted monographs will be published in Pharmeuropa, in January 2015 (issue 27.1). It is currently foreseen to publish the revised individual monographs in the 9th edition with an implementation date of 1 January 2017.
From then on, the choice of an appropriate analytical strategy will be left to the user, in line with the ICH Q3D guideline. Chapter 2.4.20, currently entitled “Determination of metal catalyst and metal reagent residues”, which focuses on sample preparation and method suitability, will provide additional guidance. Together with other general chapters related to elemental impurities analysis, it will be thoroughly reviewed to align them, if necessary, with the latest requirements and possibilities given by the ICH Q3D guideline.
Additionally, the Pharmacopoeial Discussion Group (PDG) decided at its last meeting in June 2014 to start the discussions on the harmonisation of their respective chapters on elemental impurities.
Source: European Pharmacopeia Commission