ICH-Q3D based elemental impurities study in an oral drug product: Risk assessment according to the component approach (option 2b) confirmed by the finished product analysis (option 3).

Abstract

Background: Elemental impurities (EIs) in pharmaceutical products pose potential health risks, requiring strict regulatory control. The ICH Q3D guideline outlines two approaches for assessing EIs: the component approach, which estimates impurity levels based on supplier data, and the finished product approach, which directly quantifies EIs in the final drug product. This study compares both methods to evaluate their reliability in ensuring compliance with safety limits.

Methods: A risk assessment of EIs in an oral effervescent drug product was performed using the component approach (ICH Q3D option 2b) by compiling impurity data from raw materials and packaging components. The estimated daily exposure levels were compared to permitted daily exposure (PDE) limits. To validate these findings, ICP-MS analysis (ICH Q3D option 3) was conducted on three batches of the finished product, quantifying 24 elemental impurities following USP <233> guidelines.

Results: The component approach have indicated that all estimated EI levels were well below 30% of PDE, suggesting no need for additional controls. ICP-MS analysis of the finished product confirmed these findings, with actual EI concentrations consistently lower than those predicted by the component approach.

Conclusion: Both the component and finished product approaches demonstrated compliance with ICH Q3D limits, confirming that no specific control strategy was required. While the finished product approach provides precise impurity quantification, the component approach offers a cost-efficient and predictive alternative, provided that data quality and supplier collaboration are ensured. This study underscores the importance of a risk-based assessment in elemental impurity control, balancing regulatory compliance with practical implementation in pharmaceutical manufacturing.