Review of Elemental Impurities in Pharmaceuticals Arena

Abstract

Elemental impurities in drug products may arise from several sources; they may be residual catalysts that were added intentionally in the synthesis or may be present as impurities (e.g., through interactions with processing equipment or container/closure systems or by being present in components of the drug product). Because elemental impurities do not provide any therapeutic benefit to the patient, their levels in the drug product should be controlled within acceptable limits. The main objective of the International Conference on Harmonization (ICH) (Q3D) guideline applies to new finished drug products and new drug products containing existing drug substances. The drug products containing purified proteins and polypeptides. This guideline does not apply to herbal products, radiopharmaceuticals, vaccines, cell metabolites, DNA products, allergenic extracts, cells, whole blood, cellular blood components, or blood derivatives, including plasma and plasma derivatives. The evaluation of the toxicity data for potential elemental impurities; the establishment of a permitted daily exposure (PDE) for each element of toxicological concern; application of a risk-based approach to control elemental impurities in drug products. Different analytical techniques for elemental impurities detection: flame atomic absorption spectrometry (FAAS), graphite furnace atomic absorption spectrometry (GFAAS), atomic fluorescence spectrometry, X-ray fluorescence spectrometry (XRF), instrumental neutron activation analysis (INAA), inductively coupled plasma-atomic emission spectroscopy (optical emission spectroscopy, ICP-OES), inductively coupled plasma mass spectrometry (ICP-MS), and microwave plasma atomic emission spectrometry (MP-AES).