Elemental Impurity Analysis

Elemental impurity analysis includes trace metal/heavy metal testing to evaluate pharmaceutical products for high concentrations of elements such as lead and arsenic, which are of major toxicological concern. In any product, impurities can delay development or cause a product recall on the market. Impurity analysis is particularly critical in pharmaceutical development because impurities threaten the safety and efficacy of final therapeutic products.

The elemental impurity guideline published by the International Council for Harmonization (ICH) defines the allowable daily exposures (PDEs) for essential impurities in pharmaceutical drug products. This includes specifications for oral, inhalation and parenteral drug products. Dermal drug product specifications are not provided, but recent publications offer recommendations. Based on this guideline, the US Pharmacopoeia (USP) has published sections entitled “Essential impurities - Limits” and “Essential impurities - Procedures”.

Based on extensive toxicological studies, the US Food and Drug Administration (FDA) has classified essential impurities into three groups:

• Class 1 (arsenic, cadmium, mercury and lead). Human toxicants with limited or no use in pharmaceutical manufacture.
• Class 2. This class of toxicity depends on the route of administration:
• Class 2A (cobalt, nickel and vanadium). Relatively high probability of being in the drug product
• Class 2B (silver, gold, iridium, osmium, palladium, platinum, rhodium, ruthenium, selenium, and thallium). Relatively low probability of being in the drug product
• Class 3 (barium, chromium, copper, lithium, molybdenum, antimony and tin). Relatively low toxicities (high PDEs) by oral administration, but need to be considered in risk assessment for inhalation and parenteral routes

Other elements do not have built-in PDEs but may need to be considered. For example, aluminum, boron, calcium, iron, potassium, magnesium, manganese, sodium, tungsten and zinc.

Sources of elemental impurity in pharmaceuticals are of four types:

• Residual catalysts or inorganic reagents intentionally added in synthesis
• Unintentionally added impurities by using impure active substance, excipients or reagents in the preparation of the drug product
• Contamination or leakage from production and processing equipment
• Leakage from container closing systems

Our organization also provides elemental impurity analysis services with its trained and expert staff and advanced technological equipment, among the numerous test, measurement, analysis and evaluation studies it provides for businesses in various sectors.