ICH Q3D recommends that manufacturers conduct a product risk assessment by first identifying known and potential sources of elemental impurities. Manufacturers should consider all potential sources of elemental impurities, such as elements intentionally added, elements potentially present in the materials used to prepare the drug product, and elements potentially introduced from manufacturing equipment or container closure systems. Manufacturers should then evaluate each elemental impurity likely to be present in the drug product by determining the observed or predicted level of the impurity and comparing it with the established PDE. The present study is a practical approach to control elemental impurities where potential sources of elemental impurities identified based on the declarations from suppliers. In this study, five elements (cadmium, lead, cobalt, vanadium, and nickel) were determined by axial view inductively coupled plasma optical emission spectrometry in drug substance atazanavir and cobicistat. The RF power was used 1150 watts, nebulizer gas flow was used 0.50 mL/min, auxillary flow was kept at 12 L/min, and flush pump rate was kept at 100 rpm. Nitric acid in water is used as diluent. Specifically, three representative production scale batches of drug substance atazanavir and cobicistat were tested and the results were within the acceptance criteria as per ICH Q3D.
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