Module 3 Presentations

07/05/2024

Qualification of Impurities • Based on levels dosed in pre-clinical (Tox) studies • 0,1,3,6 mg/kg/day for 3 months • No treatment related clinical signs • Plasma concentrations proportional to dose • No toxicological effect at any dose studied 

6 mg/kg/day represents 1000 multiples of human exposure based on:  Acceptance Criterion of 0.8%  Maximum daily dose of 40 mg  Average patient weight of 50 kg • Impurity has no structural alerts; therefore only general toxicology needs to be considered to qualify the impurity Genotoxic impurities would need to be considered according to the principles of ICH M7.

Developing Specifications for the Active Ingredient

The Organisation for Professionals in Regulatory Affairs

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Testing Requirement: ICH Q3D Elemental Impurities

• ICH Q3D advocates the use of a risk-based approach to assessing the potential presence of elemental impurities in drug products.

https://www.ema.europa.eu/en/ich-q3d-elemental-impurities-scientific-guideline

Developing Specifications for the Active Ingredient

The Organisation for Professionals in Regulatory Affairs

18