Case study on the environmental monitoring for biological manufacturing using Time-lapse Shadow Image Analysis.

Bioburden control in the manufacturing facility is a serious concern regarding biologics due to the possibility of an significant economic impact due to batch failure from a bioburden incident. As a case study on effectively establishing a microbiological environmental monitoring program for cleanrooms, we focused on Time-lapse Shadow Image Analysis as a kind of Rapid Microbiological Method. In this study, the superior rapidity and accuracy were indicated for reference strains and environmental microbial on both 90 mm plate and RODAC plate at 25-30 °C. Especially superior performance in the counting was observed for B.subtilis, P.aeruginosa and A.brasiliensis. The first and the median of colony detection speed for environmental microbial were 12 h and 26 h, respectively. The colony detection rate was 90% at 40 h incubation. Additionally, the characterization of swarming behavior was recognized based on time-lapse image acquisition data at 30 min intervals. This case study indicated that the application for environmental monitoring can contribute to reducing the bioburden excursion risk due to both the rapid detection of colonies and real-time detection for swarming behavior. TSIA would be more acceptable and easier option for biologics due to providing simple interpretations for the results and reducing the time consumption.