Elemental Impurities in Pharmaceutical Excipients

Area of Science:

• Pharmaceutical Analysis
• Analytical Chemistry
• Regulatory Science

Background:

• Elemental impurity control in pharmaceuticals is transitioning from component concentration limits to permitted daily exposures (PDEs).
• Manufacturers face uncertainty regarding the impact of these new regulations.
• A lack of public data on elemental impurity levels in pharmaceutical excipients contributes to this uncertainty.

Purpose of the Study:

• To survey elemental impurity levels in common pharmaceutical excipients and drug substances.
• To provide data supporting the transition to PDE-based control strategies.
• To assess the suitability of a new analytical method for elemental impurity determination.

Main Methods:

• Development of a microwave-assisted digestion and inductively coupled plasma mass spectrometry (ICP-MS) method.
• Analysis of 190 excipient samples and 15 drug substance samples.
• Method validation for elements relevant to USP <232> and ICH Q3D guidelines.

Main Results:

• The developed analytical procedure proved suitable for quantifying elemental impurities.
• Survey results indicate generally low levels of elemental impurities in the tested pharmaceutical materials.
• Data was collected from the International Pharmaceutical Excipient Council of the Americas.

Conclusions:

• The study provides valuable data on elemental impurity profiles of common pharmaceutical excipients and drug substances.
• The findings suggest that current pharmaceutical materials may comply with emerging PDE-based regulations.
• The developed analytical method offers a robust approach for routine elemental impurity testing.