The ICH (International Conference on Harmonisation) guideline, known as Q3D, was released in early August for consultation. The guideline lays out its policy for limiting metal impurities in drugs, APIs (active pharmaceutical ingredients) and excipients to evaluate the toxicity data for potential elemental impurities; establish of a Permitted Daily Exposure (PDE) for each element of toxicological concern; and to develop controls designed to limit the inclusion of elemental impurities.
In light of CHMP’s decision and to ensure consistency between the licensing authorities and the European Pharmacopeia, the commission has deferred publication of the revised version of the general monograph, which cross-references Chapter 5.20.
As a consequence, the chapter on metal catalyst or metal reagent residues will not become legally binding as of April 1, 2014, the EDQM says.
The EMA (European Medicines Agency) guideline is already applicable to new products since Sept. 2008 and should have become applicable to existing marketed products as of 1 September 2013, according to the EDQM (European Directorate for the Quality of Medicines and HealthCare).
In its April 2012 session, the European Pharmacopeia Commission decided to reproduce the EMA guideline in one of its chapters and to introduce a cross-reference to this chapter in the general monograph -- Substances for pharmaceutical use (2034) -- at a later stage.
But the reproduction of a guideline in a chapter “does not make it legally binding as long as the chapter is not referenced in a Ph. Eur. Monograph,” according to the EDQM.
This decision by the EU follows similar moves made by USP (US Pharmacopeia) in June to delay the implementation of these limits.