Determination of ICH-Q3D Elemental Impurity Leachables in Glass Vials by Inductively Coupled Plasma Mass Spectrometry.

Abstract

Container closure systems that are used for packaging pharmaceutical products are required to satisfy numerous safety requirements. Maximum permitted limits on the concentrations of numerous toxic elemental impurities that potentially leach from the packaging are one such requirement. The implementation of ICH-Q3D Guideline for Elemental Impurities, in conjunction with the 2018 publication of USP <232> Elemental Impurities-Limits and USP <233> Elemental Impurities-Procedures, requires a critical risk assessment of all container closure systems to evaluate their contribution of certain elemental impurities to the enclosed drug product. ICH-Q3D has established limits for each specific elemental impurity that considers relevant toxicological data and administration route (oral, parenteral, or inhalation) and presents them as permitted daily exposures based on the maximum daily dosage of the final drug product. A study was undertaken to assess the degree of elemental impurity leaching from one type of pharmaceutical glass vial under specific, fixed environmental controls. Multiple buffer systems representing a broad spectrum of possible parenteral drug product formulations were used in the study. Resulting buffer solutions that had been in contact with a single type of glass vial under specific conditions were subsequently analyzed using an inductively coupled plasma mass spectrometry (ICP-MS) method developed and validated specifically for the purpose of quantifying elemental impurity leachables in a variety of parenteral formulations. Results indicated that the degree of elemental impurity leachables imparted by the specific type of glass vial evaluated during this study posed no risk to patient safety, regardless of the drug product buffer formulation. Following this evaluation, the ICP-MS method developed for the determination of elemental impurities leachables has been successfully applied to the assessment of elemental impurities in a number of different biological parenteral drug product formulations currently under development. These data can be leveraged for inclusion in elemental impurities component ICH-Q3D risk assessments to satisfy the container closure system contribution.