Cleanrooms are controlled environments with low levels of pollutants used for manufacturing, scientific research, and other processes requiring contaminant-free spaces. The International Organization for Standardization (ISO) has established standards for cleanroom design, construction, and operation to achieve optimal levels of cleanliness. Adhering to ISO standards ensures cleanrooms meet quality benchmarks for particle counts, temperature, humidity, air changes, and more.
What is a cleanroom?
A cleanroom is a tightly enclosed space where environmental conditions including air quality, temperature, humidity, pressure, electrostatic charge, lighting, operations, and human contact are precisely controlled. The main goal of a cleanroom is to minimize the introduction, generation, retention, and circulation of particles, which could negatively impact manufacturing processes, research, or other activities.
Cleanrooms keep particle counts low through the use of high-efficiency particulate air (HEPA) filters, sticky floor mats, airflow management, cleaning procedures, specialized clothing, and more. Staff working in cleanrooms wear protective garments such as masks, gloves, goggles, boots, and coveralls to minimize contamination.
Why are cleanrooms used?
Cleanrooms provide contamination-controlled spaces for several industries and applications including:
- Microelectronics manufacturing – Semiconductors, computer chips, and other microelectronics components are sensitive to tiny particles.
- Pharmaceutical production – Drugs, injectables, and active pharmaceutical ingredients require sterile environments.
- Medical device manufacturing – Implantable devices and instruments for surgery must be assembled dust-free.
- Scientific research – Cleanrooms provide environments for nanotechnology, optics, and other fields.
- Aerospace – Spacecraft, satellites, and flight components are assembled in cleanrooms.
- Healthcare – Sterile cleanrooms are used for infection/outbreak control.
For these sensitive processes, cleanrooms maintain extremely low particle counts, strict temperature and humidity levels, airflow patterns to direct contaminants away from work areas, and other controls to eliminate risks.
ISO cleanroom standards
The ISO 14644 standard is the primary set of internationally recognized cleanroom classification and test methods. ISO 14644 provides standards for:
- Cleanroom design and construction
- Commissioning and certification
- Operations, including maintenance, cleaning, and monitoring
- Particle counting and testing methods
- Classification levels from ISO 1 (basic protection) to ISO 9 (ultra-high cleanliness)
The current version is ISO 14644-1:2015 which provides cleanroom classifications based on maximum concentration limits for airborne particles at specified sizes. It supersedes older versions such as ISO 14644-1:1999.
ISO 14644-1 particle concentration limits
ISO 14644-1 classifies cleanrooms into 9 exponentially increasing levels of air cleanliness based on the maximum number of ultrafine particles permitted per volume of air.
For each classification level, the standard sets limits for particles equal to and larger than specified diameters, usually measured in microns (μm). For example, for an ISO 5 cleanroom the particle concentration must not exceed:
- 3,520 particles ≥ 0.1 μm per cubic meter
- 293 particles ≥ 0.2 μm per cubic meter
- 29 particles ≥ 0.3 μm per cubic meter
- 3 particles ≥ 0.5 μm per cubic meter
- 1 particle ≥ 1.0 μm per cubic meter
Here is a table summarizing the ISO 14644-1 particle concentration limits for each classification level:
| ISO Class | Maximum particles/m3 ≥ 0.1 μm | Maximum particles/m3 ≥ 0.2 μm | Maximum particles/m3 ≥ 0.3 μm | Maximum particles/m3 ≥ 0.5 μm | Maximum particles/m3 ≥ 1 μm | Maximum particles/m3 ≥ 5 μm |
|---|---|---|---|---|---|---|
| ISO 1 | 10 | 2 | – | – | – | – |
| ISO 2 | 100 | 24 | 10 | 4 | – | – |
| ISO 3 | 1,000 | 237 | 102 | 35 | 8 | 29 |
| ISO 4 | 10,000 | 2,370 | 1,020 | 352 | 83 | 293 |
| ISO 5 | 100,000 | 23,700 | 10,200 | 3,520 | 832 | 2,930 |
| ISO 6 | 1,000,000 | 237,000 | 102,000 | 35,200 | 8,320 | 29,300 |
| ISO 7 | 352,000 | 83,200 | 293,000 | 100,000 | 2,370,000 | 10,200,000 |
| ISO 8 | 3,520,000 | 832,000 | 2,930,000 | 1,000,000 | 23,700,000 | 102,000,000 |
| ISO 9 | 35,200,000 | 8,320,000 | 29,300,000 | 10,000,000 | 237,000,000 | 1,020,000,000 |
Cleanroom applications by ISO class
Different cleanroom classes are suited for certain applications depending on required cleanliness levels. Typical uses include:
- ISO 1-3: Hospital pharmacies, autopsy rooms, medical device packaging
- ISO 4-5: Microelectronics, pharmaceutical tabletting
- ISO 6: Pharmaceutical powders, antibiotics production
- ISO 7-8: Medical device assembly, pharmaceutical sterile products
- ISO 9: Medical implants, spacecraft assembly, nanotechnology
ISO 14644-2 cleanroom design and construction
ISO 14644-2 provides guidelines for cleanroom layout, materials, filtration, airflow, pressure differentials, lighting, utilities, and other design and construction considerations. Key requirements include:
- Materials – Cleanroom surfaces should be smooth, non-shedding, impermeable, chemical resistant and fire retardant.
- Filtration – HEPA or ULPA filters are typically used for the supply air.
- Airflow – Unidirectional vertical laminar flow is recommended for higher cleanliness levels.
- Pressure – Cleanrooms should maintain positive pressure relative to surrounding areas.
- Entryways – Air showers, airlocks and gowning rooms help minimize contamination at entries.
- Monitoring – Particle counters, pressure gauges, and other sensors enable continuous verification.
The standard recommends layout considerations to reduce particle generation and optimize airborne particle removal. Cleanrooms are designed with clean-to-dirty workflows, separate entrances/exits, smooth transitions between rooms, Ergonomic layouts, and zones specified for each cleanliness level.
ISO 14644-3 cleanroom commissioning and certification
ISO 14644-3 provides requirements for commissioning newly installed cleanrooms as well as periodic recertification during operation. Commissioning demonstrates a cleanroom meets ISO 14644-1 particle concentration limits prior to use. Key activities include:
- HEPA filter installation leak testing
- Airflow velocity and volume testing
- Air pressure differential testing
- Airflow pattern and visualization tests (e.g. using smoke tracers)
- Particle counting tests for each cleanliness classification
- Microbiological tests for bio-safety levels
Recertification is conducted at least annually to verify the cleanroom continues meeting particle and microbial limits. Unscheduled recertification may also be required following events such as filter changes, construction, or contamination incidents.
ISO 14644-4 cleanroom operations
ISO 14644-4 provides guidance on cleanroom operational procedures required to maintain desired cleanliness levels. This includes:
- Access control – Procedures for personnel entry, gowning requirements, authorized activities, etc.
- Cleaning methods – Details on techniques, chemicals, equipment and schedules.
- Monitoring – Particle counting, pressure checks, microbiological monitoring.
- Maintenance – Filter change intervals, fan maintenance, repair protocols.
The standard recommends documentation, standard operating procedures (SOPs), training, audits, and other practices to ensure cleanroom operations comply with ISO 14644-1 requirements on an ongoing basis.
ISO 14644 testing and monitoring methods
ISO 14644 parts 1, 2 and 3 cite various test methods for cleanroom qualification and monitoring. Key techniques include:
Viable Particle Counting
Viable airborne particle sampling using impactors, slit samplers or centrifugal air samplers. Culturing and counting of microbial colonies determines concentration of viable particles.
Airborne Particle Counting
Optical particle counters draw air through a sensor which counts and sizes particles based on light scattering. Provides real-time data on air cleanliness.
airflow Visualization
Using smoke tracers to visualize airflow patterns and reveal potential contamination issues. Helps optimize airflow design.
Pressure Differential Monitoring
Pressure gauges continuously monitor differential between cleanroom and external areas. Alerts indicate breaches.
Filter Leak Testing
Scan for leaks in HEPA filters using discrete particle counters or photometers to detect upstream particles.
Surface Particle Counts
Wipe sampling of critical surfaces analyzes particles via microscopy. Indicates cleanliness of surfaces.
Conclusion
ISO 14644 cleanroom standards provide rigorous benchmarks and methods to achieve optimal cleanliness for contamination-sensitive processes. Classifying cleanrooms according to standardized particle concentration limits enables selection of appropriate cleanliness levels for each application. Adhering to ISO 14644 guidelines for cleanroom design, construction, commissioning, operation and monitoring ensures cleanrooms meet ongoing quality requirements with continual verification through particle counting and other testing procedures.
