Metallic contamination in drug products, referred to as elemental impurities, may arise from several sources. They may be added intentionally in synthesis, or may be present as contaminants, (e.g., through interactions with processing equipment or by being present in components of the drug product) and are consequently detectable in the drug product. Because elemental impurities pose a risk to patient health, due to toxicological effects, their levels should be controlled within acceptable limits in the drug product.
In 2009, the International Conference on Harmonization (ICH) proposed the development of a new harmonized guideline to provide a global policy for limiting metal impurities in drug products and ingredients. This approach provides clear regulatory guidance on specification limits for elemental impurities worldwide and logically should have an impact on the work of the national regulatory bodies in having transparent and comparable results.
The ICH categorized the various elemental impurities in four different classifications to facilitate decisions during the risk assessment process.
Starting January 1, 2018, the USP and the EP are adopting the ICH Q3D guidelines for elemental impurities limits in drug products, which results in a change of the analytical methods – from colorimetric determination of a metal sulfide precipitation (for USP) to analysis by ICP-OES or ICP-MS methods.
The revised chapters are:
We offer different element mixes as certified reference material standard mixes with element ratios corresponding to the oral, parenteral and inhalation elemental concentrations limits of the ICH Q3D guideline. Their features are:
For each classified and non-classified element, we offer single-element certified reference material solutions under the trademarks Certipur® and TraceCERT®, NIST® SRM single-element solutions as well as various multi-element mixes for ICP-OES and ICP-MS application in multiple concentrations (10g/L, 1g/L, 10mg/L, 1mg/L). Please refer to the list of products at the end of this page.
Elemental impurity mixes according to ICH Q3D guidelines for USP<232> , USP <2232> and Ph.Eur. General Chapter 5.20