title: Monitoring minimization of grade B environments based on risk assessment using three-dimensional airflow measurements and computer simulation.
abstract: A practical, risk-based monitoring approach using the combined data collected from actual experiments and computer simulations was developed for the qualification of an EU GMP Annex 1 Grade B, ISO Class 7 area. This approach can locate and minimize the representative number of sampling points used for microbial contamination risk assessment. We conducted a case study on an aseptic clean room, newly constructed and specifically designed for the use of a restricted access barrier system (RABS). Hotspots were located using three-dimensional airflow analysis based on a previously published empirical measurement method, the three-dimensional airflow analysis. Local mean age of air (LMAA) values were calculated based on computer simulations. Comparable results were found using actual measurements and simulations, demonstrating the potential usefulness of such tools in estimating contamination risks based on the airflow characteristics of a clean room. Intensive microbial monitoring and particle monitoring at the Grade B environmental qualification stage, as well as three-dimensional airflow analysis, were also conducted to reveal contamination hotspots. We found representative hotspots were located at perforated panels covering the air exhausts where the major piston airflows collect in the Grade B room, as well as at any locations within the room that were identified as having stagnant air. However, we also found that the floor surface air around the exit airway of the RABS EU GMP Annex 1 Grade A, ISO Class 5 area was always remarkably clean, possibly due to the immediate sweep of the piston airflow, which prevents dispersed human microbes from falling in a Stokes-type manner on settling plates placed on the floor around the Grade A exit airway. In addition, this airflow is expected to be clean with a significantly low LMAA. Based on these observed results, we propose a simplified daily monitoring program to monitor microbial contamination in Grade B environments. To locate hotspots we propose using a combination of computer simulation, actual airflow measurements, and intensive environmental monitoring at the qualification stage. Thereafter, instead of particle or microbial air monitoring, we recommend the use of microbial surface monitoring at the main air exhaust. These measures would be sufficient to assure the efficiency of the monitoring program, as well as to minimize the number of surface sampling points used in environments surrounding a RABS.
authors.affiliation: Pharmaceutical Research & Technology Laboratories, Astellas Pharmaceutical Inc., Shizuoka, Japan. hirohito.katayama@jp.astellas.com
authors.forename: Hirohito
authors.initials: H
authors.lastname: Katayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Higo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tokunaga
authors.forename: Shigeo
authors.initials: S
authors.lastname: Katoh
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hiyama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Morikawa
mesh_terms: D000391:Air Microbiology / Q000592:standards; D000392:Air Movements; D000393:Air Pollutants / Q000032:analysis / Q000737:chemistry; D003198:Computer Simulation; D004784:Environmental Monitoring / Q000379:methods* / Q000706:statistics & numerical data; D008962:Models, Theoretical; D010316:Particle Size; D012212:Rheology / Q000379:methods; D018570:Risk Assessment / Q000379:methods / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards; D013997:Time Factors; D014691:Ventilation / Q000379:methods* / Q000592:standards
chemical_list: D000393:Air Pollutants