Excite Pharma Services routinely performs contract services according to the USP 232 (Elemental Impurities Limits), USP 233 (Elemental Impurities Procedures) and USP2232 (Elemental Contaminants in Dietary Supplements) and ICH Q3D metals testing guidelines; analyzing elemental impurities in drug substances (APIs), drug products and excipients. The USP and ICH have harmonized their guidance.
Elemental impurities are defined as catalysts and environmental contaminants which may occur naturally, added intentionally or introduced inadvertently. Because such impurities do not provide any therapeutic benefit to the patient, their levels in drug product should be controlled within acceptable limits. The guidelines mentioned above are meant to present a process to assess and control elemental impurities in drug products, substances and excipients.
The USP/ICH have designated three classes of elements, based on their toxicity and likelihood of occurrence in the drug product. The toxicity of an elemental impurity is related to its extent of exposure (bioavailability).
Class 1 elements are known human toxicants that have limited or no use in the manufacture of pharmaceuticals. Their presence in drugs products typically comes from commonly used materials (ex. mined excipients). Because of their inherent risks, these four elements MUST be tested under all circumstances. Impurities listed in Class 1 are As, Cd, Hg and Pb.
Class 2A elements have relatively high probability of occurrence in the drug product and thus require risk assessment across all potential sources of elemental impurities and routes of administration. Impurities listed in Class 2A are Co, Ni and V.
Class 2B elements have a reduced probability of occurrence in the drug product related to their low abundance and low potential to be co-isolated with other materials. As a result, they may be excluded from the risk assessment unless they are intentionally added during the manufacture of drug substances, excipients or other components of the drug product. Impurities listed in Class 2B are Ag, Au, Ir, Os, Pd, Pt, Rh, Ru, Se and TI.
Class 3 elements have relatively low toxicities by the oral route of administration, but may require consideration in the risk assessment for inhalation and parenteral routes. Unless these elements are intentionally added, they do not need to be considered during the risk assessment for oral routes of administration. For parenteral and inhalation products, the potential for inclusion of these elemental impurities should be evaluated during the risk assessment, unless the route specific PDE is > 500µg/day. Impurities listed in Class 3 are Ba, Cr, Cu, Li, Mo, Sb and Sn.
If you have any questions or are interested in more details of our elemental impurities / metals analysis capabilities, please contact us.