Real-time monitoring of non-viable airborne particles correlates with airborne colonies and represents an acceptable surrogate for daily assessment of cell-processing cleanroom performance

Background aimsAirborne particulate monitoring is mandated as a component of good manufacturing practice. We present a procedure developed to monitor and interpret airborne particulates in an International Organization for Standardization (ISO) class 7 cleanroom used for the cell processing of Section 351 and Section 361 products.MethodsWe collected paired viable and non-viable airborne particle data over a period of 1 year in locations chosen to provide a range of air quality. We used receiver operator characteristic (ROC) analysis to determine empirically the relationship between non-viable and viable airborne particle counts.ResultsViable and non-viable particles were well-correlated (r² = 0.78), with outlier observations at the low end of the scale (non-viable particles without detectable airborne colonies). ROC analysis predicted viable counts ≥ 0.5/feet³ (a limit set by the United States Pharmacopeia) at an action limit of ≥ 32 000 particles (≥ 0.5 µ)/feet³, with 95.6% sensitivity and 50% specificity. This limit was exceeded 2.6 times during 18 months of retrospective daily cleanroom data (an expected false alarm rate of 1.3 times/year). After implementing this action limit, we were alerted in real time to an air-handling failure undetected by our hospital facilities management.ConclusionsA rational action limit for non-viable particles was determined based on the correlation with airborne colonies. Reaching or exceeding the action limit of 32 000 non-viable particles/feet³ triggers suspension of cleanroom cell-processing activities, deep cleaning, investigation of air handling, and a deviation management process. Our full procedure for particle monitoring is available as an online supplement.