Assessment of Elemental Impurity Exposure and Regulatory Compliance in Benzonatate Capsules

Abstract

The source of the elemental impurity in drug products might come from API, excipients, manufacturing equipment, water and container closure system. The element impurities in drug products must be controlled, in order to safeguard patient safety and comply with the regulatory guidance. The present report was designed to evaluate the elemental impurity risk assessment of Benzonatate Capsules USP 100 mg in accordance with the guideline Q3D of ICH.  The potential sources that contain elemental impurities were evaluated with the application of vendor declarations, certificates of analyses and also supplemented by analytical test data where available. It is determined the contribution from Class 1, Class 2A, and respective Class 2B elements within their corresponding permitted daily exposure (PDE) limits at oral administration. Contribution to elemental impurities from the manufacturing equipment, purified water, processing materials, container closure systems have also been evaluated. In summary, potential contribution to the element impurity has been found not to exceed its permitted safety limit and also below the 30% of PDE control limit, thus additional controls has not been deemed to be needed.