Application of rapid microbiological methods for the risk assessment of controlled biopharmaceutical environments.

摘要

Aims: To assess the different operational states within a biopharmaceutical grade clean room, using a rapid microbiological method. The method was a novel system, based on spectrometry, designed for sampling, discriminating, and enumerating airborne particles. Central to the study was the aim to determine the microbiological levels as a clean room went from standard use through maintenance and shutdown, disinfection, and then back to standard use. The objective was to evaluate whether a rapid method could replace conventional environmental monitoring using growth-based media. Methods and Results: The instrument evacuated was a BioVigilant IMD-AReg. System, which is a real-time and continuous monitoring technology based on optical spectroscopy that can differentiate between biological particles and inert ones (biological particles expressed as bio-counts based on the detection of microbial metabolites). The results indicated that certain activities lead to a high generation of biological particles and in showing an increase over the baseline, would be regarded as presenting a microbiological risk to the cleanroom. These activities include removing HEPA filter grilles, turning off an air handing unit, and tasks which requires an active personnel presence, such as cleaning and disinfection. Conclusions: The optical instrument can be used to process sufficient information, so that clean rooms can be returned to use following a period of unexpected downtime or following maintenance without the need to wait for the results from growth-based methods. As such, this type of rapid microbiological method is worth exploring further for clean room air monitoring. Significance and Impact of the Study: Few studies have been undertaken which examine air-monitoring devices that can both enumerate and discriminate particulates, in a volume of air as 'inert' or 'biological'. This study extends this limited field. Furthermore, the data collected in relation to cleanrooms is of interest in helping microbiologists understand that risks posed by different activities in relation to clean air-handling systems and personnel particle shedding.