title: Microbial ingress through breaches in aseptic manufacturing systems: experimental investigation of pressure-driven leaks of liquids.
abstract: The ability of pressure-driven leaks to provide an effective barrier against microbial ingress was investigated experimentally. The leak was simulated by circulating growth promoting media through a section of flexible tubing that had a 3/4-inch breach. The flow rate of the media was adjusted until the leak was barely visible; the leak rate was minimized to enhance the possibility of microbial ingress through the breach. The site of the breach was repeatedly inoculated with an actively growing population of Pseudomonas aeruginosa--a highly motile bacterium--suspended in a nutrient-rich medium. The breach was exposed to approximately 140 million organisms over a period of 8 h. This level of contamination greatly exceeds the microbial exposure that a breach would be subjected to in an aseptic manufacturing environment. The data show that microbial ingress did not occur under the above conditions. This indicates that pressure-driven leaks in flexible tubing can provide an effective barrier against microbial ingress, and that the integrity of the sterile boundary can be maintained during such leaks. The results of this investigation could be used to perform risk assessment analyses of the potential for microbial ingress through breaches in aseptic manufacturing systems.
authors.affiliation: Merck & Co., Inc., Vaccines & Sterile Pharmaceuticals, West Point, PA, USA. rsharnez@amgen.com
authors.forename: Rizwan
authors.initials: R
authors.lastname: Sharnez
authors.forename: Robert
authors.initials: R
authors.lastname: Stianchi
authors.forename: Mark
authors.initials: M
authors.lastname: Stannard
authors.forename: P K
authors.initials: PK
authors.lastname: Yegneswaran
mesh_terms: D000465:Algorithms; D004340:Drug Contamination; D004345:Drug Industry / Q000295:instrumentation*; D011312:Pressure; D011550:Pseudomonas aeruginosa / Q000737:chemistry; D012828:Silicones; D013242:Sterilization
chemical_list: D012828:Silicones