title: Determination of conditions for the production scale sterilization of prefilled syringes.
abstract: External and internal differences in pressure of prefilled syringes can cause plunger movement during sterilization, which might cause drug product contamination. Consequently the pressure inside the autoclave during sterilization should be controlled carefully to prevent contamination of the drug product by microorganism and particulates. A previously determined theoretical relationship of temperature to pressure in sealed bottles was modified for prefilled syringes to take plunger movement into account. This modification yielded a correction factor that includes a coefficient of linear thermal expansion for the syringe, thermal expansion of the plunger, and friction between the plunger and the syringe wall. To confirm the accuracy of this modified relationship, 100 mL polypropylene prefilled syringes with butyl rubber plungers, some of which carried pressure and temperature sensors, were used to test various sterilization conditions at the experimental scale. The results showed that the major problem in establishing the pressure conditions for production scale sterilization is temperature distribution throughout the load. However, an over pressure sterilization cycle at 121 degrees C and 0.34 MPa showed the best results. Microbial challenge and light-obscuration particle count tests were performed on the syringes from the worst-case location predicted from modified relationship; the results show that these conditions preserved the sterility of the drug product and protected it from particulate contamination.
authors.affiliation: Osaka Pharmaceutical Research Center, Daiichi Pharmaceutical Co. Ltd., Japan. nishi5og@daiichipharm.co.jp
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D004209:Disposable Equipment / Q000592:standards; D004340:Drug Contamination / Q000517:prevention & control*; D004349:Drug Packaging; D007267:Injections; D013242:Sterilization / Q000592:standards*; D013594:Syringes