ICH Opens Elemental Impurities Guideline for Consultation
The guideline named Q3D lays out a global policy for limiting metal impurities in drug products and ingredients, including APIs (active pharmaceutical ingredients) and excipients, with three components:
- The evaluation of the toxicity data for potential elemental impurities;
- The establishment of a Permitted Daily Exposure (PDE) for each element of toxicological concern; and
- The development of controls designed to limit the inclusion of elemental impurities in drug products to levels at or below the PDE.
The PDEs in the guideline are reported in micrograms per day and give “the maximum permitted quantity of each element that may be contained in the maximum daily intake of a drug product,” according to the ICH.
Dr. Todd Cecil, VP of monograph modernization and medicines compendium for USP, previously told In-Pharmatechnologist.com that USP delayed is due to industry comments on the feasibility of the deadline and concerns related to the ICH guidance.
He also said that despite some differences, the ICH and USP requirements are the same in terms of the options for calculating impurities, the PDE limits and the routes of administration. However, the ICH does include some additional metals not included in the USP general chapters, Dr. Cecil said.
Differences in limits between ICH and USP guidelines for elemental impurities may cause some issues with companies with currently marketed products or developing drugs, experts told us previously.
The deadline for comments from the US, EU and Japanese regulators has yet to be set but comments can be emailed to the ICH Secretariat at fgrc2pbzzragf@vpu.bet.
