Evaluation of Bacillus oleronius as a Biological Indicator for Terminal Sterilization of Large-Volume Parenterals.

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.