Regulatory News

EMA Gives Details on New Elemental Impurity Guideline

The European Medicines Agency (EMA) has released its recommendations for implementing a newly adopted international standard for limiting elemental impurities in drug products.

Background

Elemental impurities are traces of metals that can end up in finished drug products. These impurities can come from multiple points in the manufacturing process, such as residual catalysts from a product’s synthesis or from contact with manufacturing equipment, containers and other materials.

Elemental impurities do not contribute to a product’s therapeutic effect, and depending on the impurity, can pose risks to patients. To address this issue, the International Conference on Harmonisation (ICH) developed its Guideline for Elemental Impurities (Q3D), intended to establish standards for limiting elemental impurities through:

• “The evaluation of the toxicity data for potential elemental impurities;
• The establishment of a Permitted Daily Expose (PDE) for each element of toxicological concern;
• Application of a risk-based approach to control elemental impurities in drug products.”

The guideline also considers the effect of different impurities based on whether the drug is administered through oral, parenteral or inhalation routes. Q3D also establishes classifications for different elements based on their level of toxicity and the probability of occurring in drug products.

EU Implementation

EMA adopted Q3D in December 2014, following a public consultation the previous year. EMA has released an implementation guide as a reminder to companies that will be required to comply with the guideline. Companies that are applying for new marketing authorizations for new and established active substances will be required to comply with Q3D by June 2016. Products currently being marketed will have until December 2017 to comply.

The agency is instructing national regulators to inform marketing authorization holders (MAHs) of their responsibilities related to the new guideline. Companies are told to conduct risk assessments to determine possible sources of elemental impurities. The agency says these risk assessments will “form the basis for a control strategy to ensure compliance.”

If the risk assessment finds that a variation is necessary to reduce the risk of an elemental impurity, EMA says companies should submit a summary of their findings along with their request for variation.

EMA Implementation Guide