ISO Cleanroom Classification System
International Standard ISO 14644 Series for Cleanroom Classification and Monitoring
The ISO 14644 series is a comprehensive set of international standards developed by the International Organization for Standardization (ISO) to provide consistent and globally recognized requirements for cleanrooms and associated controlled environments. These standards replaced various national standards, including the US Federal Standard 209E, creating a unified approach to cleanroom classification and operation.
The ISO 14644 series consists of multiple parts, each addressing specific aspects of cleanroom technology:
ISO 14644-1
Classification of air cleanliness by particle concentration. Defines ISO Classes 1-9 and provides the formula for calculating maximum particle concentrations.
ISO 14644-2
Specifications for testing and monitoring to prove continued compliance with ISO 14644-1. Provides requirements for periodic testing of cleanrooms.
ISO 14644-3
Test methods for cleanrooms and associated controlled environments. Describes various test procedures in detail.
ISO 14644-4
Design, construction, and start-up of cleanroom facilities. Provides guidance on cleanroom implementation.
ISO 14644-5
Operations of cleanrooms and associated controlled environments. Covers operational requirements and procedures.
ISO 14644-6
Vocabulary and terms used in cleanroom standards. Provides standardized definitions.
ISO 14644-7
Separative devices (clean air hoods, gloveboxes, isolators, and mini-environments).
ISO 14644-8
Classification of airborne molecular contamination (AMC). Addresses chemical contamination.
ISO 14644-9
Classification of surface cleanliness by particle concentration. Focuses on surface contamination.
ISO 14644-10
Classification of surface cleanliness by chemical concentration. For chemically clean surfaces.
ISO 14644-12
Classification of air cleanliness by nanoscale particle concentration. For particles smaller than 0.1μm.
ISO 14644-13
Cleaning of surfaces to achieve defined levels of cleanliness in terms of particle and chemical classifications.
The classification of cleanrooms is based on the maximum permitted concentration of airborne particles per cubic meter of air. The relationship between ISO class number, particle size, and maximum concentration is defined by the formula:
Cn = Maximum permitted concentration (particles/m³)
N = ISO classification number (1-9)
D = Particle size in micrometers (μm)
Note: The equation is valid for particle sizes ≥0.1μm to ≤5μm
Example: Calculate the maximum permitted concentration for 0.5μm particles in an ISO 7 cleanroom.
Given: N = 7, D = 0.5μm
Calculation: C7 = 107 × (0.1/0.5)2.08
First, calculate (0.1/0.5) = 0.2
Then, 0.22.08 = 0.22 × 0.20.08 ≈ 0.04 × 0.85 = 0.034
Now, 107 = 10,000,000
Finally, C7 = 10,000,000 × 0.034 = 340,000 particles/m³
Result: The maximum permitted concentration for 0.5μm particles in ISO 7 is approximately 340,000 particles/m³ (rounded to 352,000 in the standard table).
| ISO Class | Maximum concentration limits (particles/m³ of air) for particles equal to or larger than the considered sizes shown below | |||||
|---|---|---|---|---|---|---|
| ≥0.1 μm | ≥0.2 μm | ≥0.3 μm | ≥0.5 μm | ≥1 μm | ≥5 μm | |
| ISO 1 | 10 | Not defined | ||||
| ISO 2 | 100 | 24 | 10 | Not defined | ||
| ISO 3 | 1,000 | 237 | 102 | 35 | Not defined | |
| ISO 4 | 10,000 | 2,370 | 1,020 | 352 | 83 | Not defined |
| ISO 5 | 100,000 | 23,700 | 10,200 | 3,520 | 832 | 29 |
| ISO 6 | 1,000,000 | 237,000 | 102,000 | 35,200 | 8,320 | 293 |
| ISO 7 | Not defined | Not defined | Not defined | 352,000 | 83,200 | 2,930 |
| ISO 8 | Not defined | Not defined | Not defined | 3,520,000 | 832,000 | 29,300 |
| ISO 9 | Not defined | Not defined | Not defined | 35,200,000 | 8,320,000 | 293,000 |
Before ISO 14644, the US Federal Standard 209E was widely used for cleanroom classification. It defined cleanroom classes based on particles per cubic foot (rather than cubic meter) and used imperial measurements. The transition to ISO 14644 created the following approximate equivalencies:
| FS 209E Class | ISO 14644-1 Class | Particles per cubic meter (≥0.5μm) | Particles per cubic foot (≥0.5μm) |
|---|---|---|---|
| Class 1 | ISO 3 | 1,000 | 35 |
| Class 10 | ISO 4 | 10,000 | 350 |
| Class 100 | ISO 5 | 100,000 | 3,520 |
| Class 1,000 | ISO 6 | 1,000,000 | 35,200 |
| Class 10,000 | ISO 7 | Not defined* | 352,000 |
| Class 100,000 | ISO 8 | Not defined* | 3,520,000 |
*ISO 14644 defines limits for 0.5μm particles only for ISO 1-6. For ISO 7-8, it defines limits for ≥0.5μm particles.
- Measurement Units: FS 209E used particles per cubic foot; ISO uses particles per cubic meter
- Classification Logic: FS 209E classes were based on round numbers; ISO uses logarithmic scale based on 10N
- Particle Size Ranges: ISO covers broader range of particle sizes with consistent methodology
- International Recognition: ISO is globally recognized; FS 209E was primarily US standard
- Occupancy States: ISO clearly defines three occupancy states; FS 209E was less specific
ISO 14644-2 specifies the testing requirements needed to demonstrate compliance with ISO 14644-1 and to monitor cleanroom performance over time. The standard distinguishes between three types of tests:
Type Tests
- Performed initially to verify the cleanroom meets specified classification
- Comprehensive testing of all parameters
- Includes particle count test, airflow test, pressure difference test, etc.
- Must be performed in all three occupancy states if required
Performance Tests
- Routine tests to ensure continued compliance
- May be less comprehensive than type tests
- Frequency determined by risk assessment
- Typically includes particle counting and pressure monitoring
Monitoring Tests
- Continuous or frequent testing of critical parameters
- Real-time monitoring of particles, pressure, temperature, humidity
- Provides immediate feedback on cleanroom performance
- Essential for aseptic processing areas
| Test Parameter | ISO 5 and cleaner | ISO 6 | ISO 7 | ISO 8 | ISO 9 |
|---|---|---|---|---|---|
| Particle count test | Mandatory | Mandatory | Mandatory | Mandatory | Optional |
| Airflow test | Mandatory | Mandatory | Mandatory | Mandatory | Optional |
| Air pressure difference | Mandatory | Mandatory | Mandatory | Mandatory | Optional |
| Installed filter leakage | Mandatory | Mandatory | Mandatory | Optional | Optional |
| Airflow direction | Mandatory | Mandatory | Mandatory | Optional | Optional |
| Temperature | As required | As required | As required | As required | As required |
| Humidity | As required | As required | As required | As required | As required |
| Recovery test | As required | As required | As required | As required | As required |
| Containment leakage | As required | As required | As required | As required | As required |
Using discrete particle counters with size discrimination capabilities. Must sample sufficient air volume to achieve statistical significance.
Measured with anemometers at multiple locations, especially for unidirectional flow areas.
Continuous monitoring with pressure sensors, alarms for out-of-spec conditions.
DOP/PAO testing for HEPA/ULPA filters, photometer or particle counter method.
Smoke tests or fog generators to visualize airflow patterns and detect turbulence.
Measures time to recover from a contamination event to specified cleanliness level.
ISO 14644-3 provides detailed methodologies for conducting tests specified in ISO 14644-2. Proper test execution is critical for obtaining reliable and reproducible results. Key test methods include:
Annex A: Particle Count Test
- Determines airborne particle concentration
- Specifies sampling locations, number of samples, and sampling volume
- Minimum number of sampling points = √A (where A is area in m²)
- Minimum sampling volume based on particle concentration
- Must sample for at least 1 minute at each location
Annex B: Airflow Test
- Measures airflow velocity and volume
- For unidirectional flow: measure at approximately 15cm from filter face
- For non-unidirectional flow: measure at air supply outlets
- Grid pattern with measurements at regular intervals
- Acceptance criteria: average velocity within ±20% of specified value
Annex C: Air Pressure Difference
- Measures pressure differential between areas
- Using calibrated manometer or pressure gauge
- Measurements with doors closed and under static conditions
- Typical requirement: minimum 10-15 Pa between adjacent areas of different classification
Annex D: Filter Leak Test
- Verifies HEPA/ULPA filter integrity
- Using aerosol photometer or particle counter method
- Upstream challenge of PAO or similar aerosol
- Scanning downstream of filter at 2-5cm from surface
- Acceptance: leakage ≤0.01% of upstream concentration
Annex E: Airflow Direction Test
- Visualizes airflow patterns
- Using smoke, fog, or tracer gas
- Documents flow direction and identifies dead zones or turbulence
- Particularly important for unidirectional flow applications
Annex F: Recovery Test
- Measures cleanroom's ability to recover from contamination
- Introduce aerosol challenge, then measure time to return to specified cleanliness
- Important for assessing cleanroom robustness
- Typical requirement: recovery to ISO class within 15-20 minutes
| Pharmaceutical Process Area | ISO Classification | Equivalent PIC/S Grade | Key Requirements |
|---|---|---|---|
| Aseptic filling zone | ISO 5 | Grade A | Unidirectional airflow, 0.45 m/s ±20%,
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