title: Evaluation of Bacillus oleronius as a Biological Indicator for Terminal Sterilization of Large-Volume Parenterals.
abstract: In the production of large-volume parenterals in Japan, equipment and devices such as tanks, pipework, and filters used in production processes are exhaustively cleaned and sterilized, and the cleanliness of water for injection, drug materials, packaging materials, and manufacturing areas is well controlled. In this environment, the bioburden is relatively low, and less heat resistant compared with microorganisms frequently used as biological indicators such as Geobacillus stearothermophilus (ATCC 7953) and Bacillus subtilis 5230 (ATCC 35021). Consequently, the majority of large-volume parenteral solutions in Japan are manufactured under low-heat sterilization conditions of F0 <2 min, so that loss of clarity of solutions and formation of degradation products of constituents are minimized. Bacillus oleronius (ATCC 700005) is listed as a biological indicator in "Guidance on the Manufacture of Sterile Pharmaceutical Products Produced by Terminal Sterilization" (guidance in Japan, issued in 2012). In this study, we investigated whether B. oleronius is an appropriate biological indicator of the efficacy of low-heat, moist-heat sterilization of large-volume parenterals. Specifically, we investigated the spore-forming ability of this microorganism in various cultivation media and measured the D-values and z-values as parameters of heat resistance. The D-values and z-values changed depending on the constituents of large-volume parenteral products. Also, the spores from B. oleronius showed a moist-heat resistance that was similar to or greater than many of the spore-forming organisms isolated from Japanese parenteral manufacturing processes. Taken together, these results indicate that B. oleronius is suitable as a biological indicator for sterility assurance of large-volume parenteral solutions subjected to low-heat, moist-heat terminal sterilization.
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan Izumi.Masamitsu@otsuka.jp.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Izumi
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujifuru
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Okada
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Takai
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Udagawa
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Naruyama
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Nishioka
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Yoden
authors.affiliation: Sterilization Study Group, Intravenous Solutions Society, Tokyo, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Aoki
mesh_terms: D001407:Bacillus / Q000302:isolation & purification* / Q000502:physiology; D003470:Culture Media / Q000032:analysis / Q000592:standards; D004345:Drug Industry / Q000379:methods / Q000592:standards*; D006801:Humans; D007202:Indicators and Reagents / Q000032:analysis / Q000592:standards; D057947:Parenteral Nutrition Solutions / Q000032:analysis / Q000592:standards*; D019999:Pharmaceutical Solutions / Q000032:analysis / Q000592:standards; D013242:Sterilization / Q000379:methods / Q000592:standards*
chemical_list: D003470:Culture Media; D007202:Indicators and Reagents; D057947:Parenteral Nutrition Solutions; D019999:Pharmaceutical Solutions
keywords: Bacillus oleronius; Bioburden; Biological indicator; Large-volume parenteral solution; Moist-heat sterilization; Terminal sterilization