Elemental Impurities Testing

Impurities: Guideline for Elemental Impurities

The ICH Guideline Q3D "Impurities: Guideline for Elemental Impurities" provides an international standard for testing for metals in the member regions, Europe, USA, and Japan.

These guidelines for the determination of heavy metals have been integrated into the American Pharmacopeia (USP/NF) in chapters <232> and <233>. For the European Pharmacopeia (Ph.Eur.), these guidelines appear in chapters 5.20 "Elemental impurities" and 2.4.20 "Determination of elemental impurities."

The previously used visual test from the corresponding pharmacopeias (e.g. USP <231>, Ph.Eur. 2.4.8) has thus been replaced by modern methods using instruments such as the ICP-MS and/or ICP-OES.

In Ph.Eur. 9.3 (published on July 1st 2017) ICH Q3D is now adopted within the chapters "Pharmaceutical preparations" and "Substances for pharmaceutical use".

There is a new paragraph "Elemental impurities" in the chapter "Pharmaceutical preparations":

"For pharmaceutical preparations outside the scope of the general chapter 5.20, manufacturers of these products remain responsible for controlling the levels of elemental impurities using the principles of risk management."

This means that for products outside the scope of ICH Q3D like herbal products etc. the marketing authorization holder (MAH) remains responsible for any possible input of elemental impurities due to production processes, containers or excipients!

The Ph.Eur. monograph "Substances for pharmaceutical use" still excludes herbal drugs, herbal drug preparations and homeopathic mother tinctures from this scope.

This leads to the phenomenon that the MAHs on the contradictory have to establish risk assessments for their products in the end too to fulfill their responsibility!

The GBA Group will gladly help you adapt to fulfill the new requirements by consulting, compilation of risk assessments, as well as analytical tests.