A method for demonstrating appropriate environmental protection for capping aseptically filled and plugged vials

Conventional aseptic filling of drug product into vials ultimately includes a step that requires time and travel from the stoppering stage to the capping/crimping stage. Lyophilized product necessarily includes a partial stoppering step and, therefore, Grade A conditions. The level of environmental control that is required to protect the contents of fully stoppered, but uncapped, vials of sterile product from microbial contamination hasn't been formally defined. There is considerable range of opinion regarding this topic. This is the result of the lack of data that indicates the level of protection afforded by vials that are closed with a stopper, but that have not yet been capped. In order to provide some insight into the level of environmental control that is appropriate for vials at this stage of production, studies were conducted that consisted of exposing stoppered, uncapped vials containing sterile microbiological media to an aerosolized microbial challenge. The test samples were selected and assembled in such a way that a range of container/closure presentations was simulated. Furthermore, a microbial challenge was selected that was in excess of the environmental conditions to which product vials would be exposed. The results of this testing indicated a high level of confidence that stoppered, uncapped vials exposed to microbiologically challenging conditions would be expected to maintain the sterility of their contents.