Elemental impurities in drug products may arise from several sources, e.g., catalysts, manufacturing processes (including drug substances) or excipients used, container closure systems. Since elemental impurities do not provide any therapeutic benefits, their levels in drug product should be controlled within acceptable limits. The ICH guideline Q3D on elemental impurities was adopted by constantly increasing attention towards drug product safety.
The exposure level should be established for each element – Permitted Daily Exposure (PDE). The elements are placed into three classes, based on their toxicity (PDE) and occurrence likelihood in the drug product. Class 1: As, Cd, Hg, and Pb. Class 2A: Co, Ni and V.Class 2B: Ag, Au, Ir, Os, Pd, Pt, Rh, Ru, Se and Tl. Class 3: Ba, Cr, Cu, Li, Mo, Sb, and Sn. Other elements with PDE not established: Al, B, Ca, Fe, K, Mg, Mn, Na, W and Zn.
Selvita’s capabilities and expertise in metal contamination approach covers the following areas:
- Complex samples matrix preparation/ mineralization method establishment against impurity level determination (vessel microwave digestion system)
- Non-GMP screening determination of elemental impurities level in drug product for risk assessment and quality control purposes; comprehensive elemental impurities of 1, 2A, 2B and 3 classes and other elements can be examined, using ICP-MS system
- Analytical methods development with limits corresponding to PDEs level requirements, ICP-MS or ICP-OES or AAS
- Analytical method verification/validation in line with cGMP regulations, ICP-MS or ICP-OES or AAS
- Drug products cGMP release testing