Determining the Delamination Propensity of Pharmaceutical Glass Vials Using a Direct Stress Method

Abstract

An accelerated lamellae formation (ALF) methodology has been developed to determine the delamination propensity and susceptibility of pharmaceutical glass vials. The ALF process consists of a vial wash and depyrogenation mimic procedure followed by stressing glass vials with 20 mM glycine pH 10.0 solution at 50 °C for 24 h and analyzing the resulting solutions by visual inspection for glass lamellae. ALF results demonstrate that while vial delamination propensity generally correlates with glass hydrolytic resistance, ALF is a more direct test of glass delamination propensity and is not affected by post-production vial washing that can affect results obtained using hydrolytic resistance tests. ALF can potentially be used by pharmaceutical companies to evaluate and screen incoming vial lots to minimize the risk of delamination during the shelf life of parenteral therapeutics, and by glass vial manufacturers to monitor and improve their vial manufacturing processes. Glass flakes can sometimes appear in liquid pharmaceutical drugs contained in glass vials. These glass flakes are a result of several factors related to the glass vial production process, glass vial sterilization procedures, and the formulation of the liquid pharmaceutical drug. Vial testing is routinely done in order to select glass vials that are less likely to form glass flakes. The factors leading to the formation of glass flakes were studied and applied to a method designed to directly screen vials for their propensity to form glass flakes. The washing of vials followed immediately by sterilization at high temperatures was determined to be a critical factor in the formation of glass flakes. As a result, a laboratory mimic of this procedure was incorporated into the newly developed method for screening vials. This mimic procedure as well as robust accelerated incubation conditions and a sensitive visual inspection procedure are key aspects of this vial screening method.