Particulate generation mechanisms during bulk filling and mitigation via new glass vial

Abstract

Contamination with foreign particulate matter continues to be a leading cause of parenteral drug recalls, despite extensive control and inspection during manufacturing. Glass is a significant source of particulate matter contamination; however, the mechanism, source, and quantification have not been extensively analyzed. Quantification of particulate matter generation with lab simulations suggests that glass-to-glass contact on the filling line produces large quantities of glass particles of various sizes. A new strengthened glass vial with a low coefficient of friction surface is proposed to address this root cause of glass particle generation. Lab simulations and two line trials using this new vial demonstrated a substantial reduction of glass particulate generation, of resulting product contamination, as well as of the frequency of required filling line interventions. These results suggest that substantial reductions in particulate matter contamination of all types, glass and non-glass, can be achieved through the use of a new glass vial designed to effectively eliminate a root cause of glass particle generation.