Background

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.

Potential Sources of Elemental Impurities

The ICH Q3D guidelines

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.

The United States Pharmacopoeia (USP) and the European Pharmacopoeia (EP) Change

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:

  • Chapter USP <232>: Elemental impurities in Pharmaceutical Products – Limits
  • Chapter USP <233>: Elemental impurities in Pharmaceutical Products – Procedures
  • Chapter USP <2232>: Elemental contaminants in Dietary Supplements
  • European Pharmacopoeia, 9th Edition, supplement 9.3., General Chapter 5.20 and 2.4.20

How to accurately test for elemental impurities

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:

  • Produced and analyzed under ISO 17025 and ISO 17034; values traceable to at least two independent references (NIST®, BAM or SI unit kg)
  • Unique level of accuracy and lot-specific value
  • Sophisticated packaging and comprehensive documentation, including proper uncertainty calculation, expiry date and storage information.
  • Packaged in special fluoropolymeric, opaque bottles and gas-tight aluminum foil bags for extended stability. Certificates are included in the packaging.
  • Convenient 100 mL package size

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

Elemental impurity mixes according to ICH Q3D guidelines for USP<232> , USP <2232> and Ph.Eur. General Chapter 5.20

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