title: Airborne microbial challenges of Blow/Fill/Seal equipment: a case study.
abstract: Controlled microbial challenges, comprising air-dispersed spores of Bacillus subtilis var niger, have been generated within a containment room (around 54 m3 in volume) housing a Blow/Fill/Seal machine. 'Stirred-settling' conditions were created throughout the room and the airborne spore challenge was monitored to ensure homogeneity within the room for extended periods of time. The Blow/Fill/Seal machine was set to fill 2 cm3 ampoules with Tryptone Soya Broth at each of three airborne challenge levels of 10(4), 10(6) and 10(7) spores m-3 (about 10(2), 10(4) and 10(5) spores ft-3 respectively). A relationship has been established between the level of airborne micro-organisms in the machine operating environment and the extent of product contamination. This relationship allows prediction of operating conditions under which a level of sterility assurance, equal to that demanded of terminal sterilization, is attained. It is stressed that the findings apply only to the particular Blow/Fill/Seal machine and to the specific conditions of machine operation.
authors.affiliation: Fisons Pharmaceutical Division, Pharmaceutical Technical Development, Holmes Chapel, Cheshire, England.
authors.forename: A
authors.initials: A
authors.lastname: Bradley
authors.forename: S P
authors.initials: SP
authors.lastname: Probert
authors.forename: C S
authors.initials: CS
authors.lastname: Sinclair
authors.forename: A
authors.initials: A
authors.lastname: Tallentire
mesh_terms: D000391:Air Microbiology; D004340:Drug Contamination / Q000517:prevention & control*; D004349:Drug Packaging / Q000379:methods*; D004739:England; D004780:Environment, Controlled; D004867:Equipment Design; D013171:Spores, Bacterial / Q000737:chemistry