A toolbox for early detection of glass delamination in vials.

Glass delamination is a gradual process that may not become apparent until late in storage. Over the past three decades, it has been a leading cause of drug product recalls due to glass particulate contamination. The appearance of glass particles in the solution marks the final stage of glass delamination. Therefore, it is crucial to develop rapid methods for detecting glass delamination at its earliest stages. We utilized three model buffer solution systems and examined three glass vials from two vendors (Vial 1, Vial 2A, and Vial 2B) to assess their resistance to glass delamination. We leveraged the high refractive index of glass particles in air and employed the Background Membrane Imaging (BMI) method as a high-throughput and sensitive technique to detect subvisible glass particles (SVGP). We compared the effectiveness of BMI and Flow Imaging Microscopy (FIM) in detecting SVGP. Our findings indicate that the BMI results are more consistent with other glass delamination detection techniques. Vial 1 exhibited a 5-28 fold increase in the number of SVGP compared to Vial 2A and Vial 2B after one month of storage, depending on the buffer type. Additionally, Vial 1 showed higher methylene blue staining, 1.15-2.5 fold higher silicon leachable, and the most significant surface attack based on our Scanning Electron Microscopy (SEM) results. Overall, the BMI method can be considered the quickest and most sensitive quantitative technique for detecting glass delamination at its early stages, providing valuable insights for selecting glass containers that minimally interact with drug product formulations.