Health Canada Notice on ICH Q3D (R1) the Guideline for Elemental Impurities

By: Pinky Mazumder

On May 31st, 2019, Health Canada issued a Notice titled the Release of the Finalised Guideline for ICH Q3D (R1): Guideline for Elemental Impurities and announced the implementation of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q3D (R1) Guideline.  The Guideline was developed by the ICH Expert Working Group and the final version was recommended for implementation by the members of ICH, including Health Canada.  Health Canada endorses the principles and practices described in the Guideline.
The ICH Elemental Impurities guidance establishes Permitted Daily Exposures (PDEs) for 24 elemental impurities for oral, parenteral, and inhaled drug products.  The factors considered in establishing the PDEs include:

 -the oxidation state of the element in the drug product;
 -human exposure and safety data;
 -relevant animal study;
 -route of administration; and,
 -relevant endpoints

The Guideline lists the PDEs for elements in Appendix 1 of the Guideline.  In addition to the PDEs, the Guideline also mentions that when levels of elemental impurities are higher than the mentioned PDE, it can be justified in the following situations:

 -intermittent dosing;
 -short term dosing (i.e. less than 30 days); and,
 -specific indications

Based on the likelihood of toxicity, the Guideline also classifies the elements into Class 1, Class 2, and Class 3 categories in order of decreasing toxicities.  In March 2019, the Guideline was revised due to a revision in the PDE level for Cadmium.  The potential sources of elemental impurities include residual impurities from the formulation or preparation of the drug product or its ingredients, elemental impurities that were introduced from the manufacturing equipment, and elemental impurities leached from the container closure systems.

The ICH Q3D (R1) Guideline applies to drug products including drug products containing purified proteins and polypeptides, however it does not apply to herbal products, vaccines, radiopharmaceuticals, among other drug products.  Moreover, the Guideline on Elemental Impurities does not apply to drug products under clinical research.  For detailed information on the Elemental Impurities Guideline, please refer to the Guideline cited in the Reference section below.

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Reference:
ICH Q3D(R1): Guideline for Elemental Impurities
https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3D/Q3D-R1EWG_Document_Step4_Guideline_2019_0322.pdf