Justification and Impact of Reduced Sampling Flow Rates for Total Particle Counting in Grade A Environments

The increasing evaluation and adoption of Biofluorescent Particle Counters (BFPCs) for Grade A environments have introduced instruments that operate at lower flow rates, such as 5 L/min, to simultaneously count both viable and total particles. This flow rate differs from the conventional 28.3 L/min referenced in the current EU GMP Annex 1 for total particle counting. The divergence is motivated by the higher effectiveness of viable particle detection achieved with a lower flow rate and by the suppression of a virtual impactor and its associated particle losses.The study provides supportive information for justifying a lower flow rate when sampling in Grade A environments with homogeneous, unidirectional airflow. The performance of two commercially available particle counters was compared to assess whether the lower flow rate is non-inferior in detecting deviations of environmental quality for both 0.5 μm and 5 μm total particles: one operating at the standard flow rate of 28.3 L/min (1 ft³/min) and the other at 2.83 L/min (0.1 ft³/min), representing a proportional flow rate relative to a 5 L/min Biofluorescent Particle Counter.Two distinct experimental setups representing Grade A environments were used: a laboratory-scale microbiological biosafety cabinet (BSC) featuring homogeneous unidirectional airflow at 0.45 m/s, and a custom-built room-sized Grade A chamber equipped with an integrated air purification system and controlled ventilation to simulate full-scale cleanroom conditions. Both setups exposed the particle counters to identical contamination events generated by external ventilators to evaluate performance across different spatial scales and airflow dynamics while maintaining Grade A compliance.The alert thresholds of the two standard particle counters deployed in this study showed a high level of concordance under unidirectional airflow. No consistent preference was observed for one counter over the other in terms of alert precedence. In the BSC setup, the lag time between the two instruments was limited to 1 minute in 96% of cases. Collectively, data from both experimental setups were strongly supportive to demonstrate that operating a particle counter at a lower flow rate is non-inferior to the standard flow rate, maintains equivalent environmental control, and underlines its suitability for application in Grade A zones.