Elemental Impurities - Binding Risk Assessment for Authorised Medicinal Products

The provisions laid down in the ICH Guideline Q3D "Elemental Impurities" for new authorisations of medicinal products have been applying since June 2016. Already authorised and marketed products have to comply with those requirements as of December 2017.

Beside the document "Implementation strategy of ICH Q3D guideline" (see also "EMA's new Guideline on the Implementation of the ICH Q3D Guideline in the EU"), the EMA's website also offers another document which was already published in February 2015 and is intended to provide support for medicinal product manufacturers when applying ICH Q3D to existing marketed products: "Elemental impurities in marketed products. Recommendations for implementation" - EMA/CHMP/QWP/109127/2015. One of the central statements of the document is that medicinal product manufacturers shall perform in any case a risk assessment for existing products already during the transition period and - if necessary - hold it ready in case of an authority inspection.

Moreover, clarification is provided regarding questions about the necessity to submit a variation application to the regulatory authority. According to the outcome of the risk assessment, no variation procedure is required when:

• There is no need for a control on elemental impurities to materials for the API (starting material), the API and its intermediates and the excipients.
• No change is required in the production equipment or in the source of supply of the starting materials, APIs and excipients,
• No change is needed in the manufacturing process.

When one or more of these conditions doesn't apply, a variation application has to be submitted. The variation should also contain a short summary of the risk assessment and its conclusions.

In the event that a control strategy is required for one or several elemental impurities, an elemental specific analytical method has to be used. A non-specific compendial procedure for heavy metals won't be accepted.