Airborne contamination during blow-fill-seal pharmaceutical production.

The routes of airborne contamination, during Blow-Fill-Seal (BFS) production, were studied using tracer gas, particles and bacteria. The prevention of airborne contamination, by the air shower at the point of fill, was effective (> 99.2% efficient). However, microbe-carrying particles could gain access, by deposition or air exchange, when the containers were cut open and before they shuttled under the protection of the air shower. The use of SF6 tracer gas demonstrated that when the air shower was not on, 50% of the air within the containers came from the area round the machine. When the air shower was switched on, only about 5% of the air came from the surroundings. Airborne microbial contamination of containers is in proportion to: the number of airborne microbes around the machine, the time the container is open, the neck area and the amount of air left within the container. The likely microbial contamination rate can be calculated from a model incorporating these variables. Microbial contamination of containers during BFS manufacturing is normally very low, but by increasing the naturally occurring bacteria in the air of the production rooms by about 100-fold, it was possible to verify the accuracy of this model. The contamination model agrees well with the observation that microbial contamination levels of between 1 in 10(5) and in 10(7) will be found when small containers (< 10 ml) are filled in conventionally ventilated rooms. To achieve similar contamination rates when filling of larger bottles, it is likely that unidirectional flow, or barrier technology will be required.