MULTICENTRE STUDY ON INCUBATION PROGRAM FOR ENVIRONMENTAL MONITORING AND ASEPTIC PROCESS SIMULATION

Abstract

Environmental monitoring and aseptic process simulations represent an integral part of the microbiological quality control system of sterile pharmaceutical products manufacturing operations. However, guidance documents and manufacturers practices differ regarding recommendation for incubation time and incubation temperature and, consequently, the environmental monitoring and aseptic process simulation incubation strategy should be supported by validation data. To avoid any bias coming from in vitro studies or from single manufacturing in situ site studies, we performed a collaborative study at four manufacturing sites with four samples at the same location. The environmental monitoring study was performed with tryptic soy agar settle plates and contact plates, and the aseptic process simulation study with tryptic soy broth and thioglycolate broth. The highest recovery rate was obtained with settle plates (97.7%) followed by contact plates (65.4%) and less than 20% for liquid media ( tryptic soy broth 19% and thioglycolate broth 17%). Cocci Gram + and non-spore-forming Gram-positive rods were largely predominant with more than 95% of growth and recovered best at 32.5 °C. The highest recovery of moulds was obtained at 22.5 °C alone or as the first incubation temperature. Strict anaerobes were not recovered. At the end of the 5 days incubation no significant statistical difference was obtained between the four conditions. Based on these data a single incubation temperature at 32.5 °C could be recommended for these 4 manufacturing sites for both environmental monitoring and aseptic process simulation and a second plate could be used periodically incubated at 22.5 °C. Similar studies should be considered for all manufacturing facilities in order to determine the optimal incubation temperature regime for both viable environmental monitoring and aseptic process simulation.