European Pharmacopoeia plans revisions of elemental impurities guideline
Following its last meeting in early June 2014, the ICH Steering Committee announced the plan to move their guideline for elemental impurities, known as 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 texts concerned has been drawn up by the European Pharmacopoeia Commission to ensure that a consistent approach between the licensing authorities and the commission continues to be applied.
The ICH unveiled the guideline for comment in August, noting that limiting metal impurities is contingent on evaluating toxicity data, establishing a Permitted Daily Exposure (PDE) rate for the elements of concern, and ensuring that rate isn’t met by any of a treatment’s ingredients.
The European Pharmacopoeia Commission endorsed the proposed revision by the ICH of the current “Heavy metals chapters” and decided as a first step to revise a chapter on metal catalyst or reagent residues to replace its content by the ICH Q3D guideline as soon as it has moved to Stage 5 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 remit of the Committee for Medicinal Products for Human Use (CHMP).
Currently, the EMA Guideline on the specification limits for residues of metal catalysts or metal reagents is located in chapter 5.20: “Metal catalyst or metal reagent residue,” which is applicable to new drugs to be marketed in Europe.
In line with a decision from April 2012, the European Pharmacopoeia intends to introduce a cross-reference to this revised chapter in two general monographs: Substances for pharmaceutical use (2034) and Pharmaceutical preparations (2619) at a later stage. The cross-references would make 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.
Monograph Changes
In addition, it is planned to delete cross-references to the wet chemical tests for “heavy metals” 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. The European Pharmacopoeia says it foresees publishing revised individual monographs in the 9th edition with an implementation date of 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, the new guideline will be thoroughly reviewed to align them, if necessary, with the latest requirements from 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.
The changes come as IPEC (International Pharmaceutical Excipient Council) Americas in April asked its member companies to compile information on elemental impurities.
Meanwhile, the ICH M7 Guideline on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk is now entering the implementation period.
