Compendial and regulatory requirements for elemental impurities have moved forward with the Steering Committee of the International Conference on Harmonization (ICH) announcing that it plans to move its guideline for elemental impurities (ICH Q3D) to Stage 4 of the ICH process in September 2014. Stage 4 is reached when the Steering Committee agrees that there is sufficient consensus on the draft guideline and adopts an ICH Harmonized Tripartite Guideline. Following that step, Step 5 is implementation by the regulatory authorities of the ICH Triparite, which consists of the United States, European Union, and Japan. In response, the European Pharmacopoeia Commission has validated a strategy for the revision of the related texts in the European Pharmacopoeia (Ph. Eur.) to ensure that a consistent approach between the licensing authorities and the Ph. Eur. continues to be applied. ICH had met in early June 2014 and made the decision for adoption following that meeting.
Currently, the European Medicines Agency 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." It decided as a first step to revise Chapter 5.20 by replacing its content with the ICH Q3D guideline as soon as it has moved to Stage 5 in the ICH process in the European Union. 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 jurisdiction of the Committee for Medicinal Products for Human Use (CHMP).
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 ninth edition with an implementation date of January 1, 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 decided at its last meeting in June 2014 to start the discussions on the harmonization of its respective chapters on elemental impurities.
Source: European Pharmacopoeia Commission