| Location | ≥0.5 µm | ≥5 µm |
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| Location | ≥0.5 µm | Status | ≥5 µm | Status |
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ISO 14644-1 classification requires measuring airborne particle concentrations at sampling locations distributed across the cleanroom. The number of sampling locations equals the square root of the room area in m², rounded up (minimum 1). At each location, collect a sample volume large enough to detect at least 20 particles at the class limit. For rooms with 2-9 locations, calculate the 95% upper confidence limit (UCL) of the mean. The room passes if the UCL is at or below the concentration limit for the target ISO class.
The 95% upper confidence limit is UCL = mean + t × SD / √N, where N is the number of sampling locations and t is from the Student's t-distribution at 95% confidence with N-1 degrees of freedom. For 1 location, the measured value is used directly. For 2-9 locations, the UCL formula applies. For 10+ locations, the arithmetic mean is sufficient per ISO 14644-1:2015.
Grade A = ISO 5 (at rest and in operation, ≤20 particles ≥5 µm). Grade B = ISO 5 at rest / ISO 7 in operation. Grade C = ISO 7 at rest / ISO 8 in operation. Grade D = ISO 8 at rest (in-operation not defined). The EU GMP limits for Grade A at ≥5 µm (20/m³) are stricter than the ISO 5 formula limit (29/m³).
The concentration limit formula is Cn = 10N × (0.1/D)2.08. For ≥0.5 µm: ISO 5 = 3,520, ISO 6 = 35,200, ISO 7 = 352,000, ISO 8 = 3,520,000 particles/m³. For ≥5 µm: ISO 5 = 29, ISO 6 = 293, ISO 7 = 2,930, ISO 8 = 29,300 particles/m³. These are also equivalent to FS 209E Class 100, 1,000, 10,000, and 100,000 respectively.
At-rest monitoring measures particle counts when the HVAC is running and equipment is installed but no personnel are present. In-operation monitoring measures counts during normal production. At-rest demonstrates the room's baseline capability; in-operation reflects real manufacturing conditions. EU GMP requires classification in both states, with in-operation limits typically one or two ISO classes higher than at-rest.
ISO 14644-1 requires a minimum of ⌈√A⌉ sampling locations, where A is the room area in m². For example: 10 m² needs 4 locations, 25 m² needs 5, 50 m² needs 8, 100 m² needs 10. Locations should be evenly distributed with additional points near HEPA outlets, doorways, and critical workstations.
For ISO Class 7 the maximum permitted airborne concentration is 352,000 particles/m³ at the ≥0.5 µm threshold and 2,930 particles/m³ at the ≥5 µm threshold. This falls straight out of Cn = 10N × (0.1/D)2.08 with N = 7. ISO 7 is equivalent to the older FS 209E Class 10,000 designation and maps to EU GMP Grade B in operation and Grade C at rest. A cleanroom passes ISO 7 when the measured value (or 95% UCL for 2 to 9 sampling locations) is at or below both limits.
Air changes per hour = total supply air volume (m³/h) ÷ room volume (m³). For example a 50 m³ ISO 7 cleanroom supplied with 3,000 m³/h of HEPA-filtered air runs at 60 ACH. Typical ISO 14644-4 design targets are 5 to 20 ACH for ISO 8, 30 to 60 ACH for ISO 7, 60 to 90 ACH for ISO 6, and 240 to 480 ACH (unidirectional flow) for ISO 5. Actual ACH is driven by heat load, particle generation from personnel and equipment, and required recovery time rather than ISO class alone.
ISO 14644-1 recognises three occupancy states. As-built is the empty room with HVAC running but no equipment installed or personnel present, used at commissioning. At rest is the room with equipment installed and running but no personnel or operations, used to qualify baseline environmental performance. In operation is measured during normal production with personnel and processes active. EU GMP Annex 1 requires both at-rest and in-operation classification, and in-operation limits are typically one or two ISO classes higher than at-rest limits for the same room.