A revised ICH Q3D guideline (R2) on ‘Elemental Impurities’ (EMA/CHMP/ICH/353369/2013) will come into effect on 24 September 2022.

The guideline is revised:

• To amend permitted daily exposure (PDE)
• To amend monographs
• To add a section on limits for elemental impurities for cutaneous and transcutaneous formulations.

The revised guideline is available on the EMA website. You can find it by following this link

If Risk Assessment (RA) fails to demonstrate that an Elemental Impurities (EI) level is consistently less than the Control Threshold, then additional controls should be established to ensure that the EI levels does not exceed the PDE in the drug product.

Approaches that an applicant can pursue include but are not limited to:

• Modification of the manufacturing steps that result in reduction of EIs,
• Implementation of in-process controls,
• Establishment of specification limits for excipients or drug substance or drug product,
• Selection of appropriate container closure systems.

For marketed products, if the RA concludes that additional controls are to be established then the regulatory impact of these additional controls should be evaluated to see whether it triggers a variation(s) to the existing MA.

Ivowen is fully equipped to apply for any such variations on your behalf. Please contact us for more information and for support of your dossier compilation or updates.

Written by Nanda Naik