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

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.

Assessment of Tablet Surface Hardness by Laser Ablation and Its Correlation With the Erosion Tendency of Core Tablets.

Surface erosion of uncoated tablets results in processing problems such as dusting and defects during coating and is governed by the strength of particle bonding on tablet surface. In this study, the correlation between dusting tendency of tablets in a coating pan with friability and laser ablation surface hardness was assessed using tablets containing different concentrations of magnesium stearate and tartaric acid. Surface erosion propensity of different batches was evaluated by assessing their dusting tendency in the coating pan. In addition, all tablets were analyzed for crushing strength, friability, modified friability test using baffles in the friability apparatus, and weight loss after laser ablation. Tablets with similar crushing strength showed differences in their surface erosion and dusting tendency when rotated in a coating pan. These differences did not correlate well with tablet crushing strength or friability but did show reasonably good correlation with mass loss after laser ablation. These results suggest that tablet surface mass loss by laser ablation can be used as a minipiloting (small-scale) tool to assess tablet surface properties during early stages of drug product development to assess the risk of potential large-scale manufacturing issues.