ISO Class 5 classification refers to cleanroom standards that specify maximum allowable concentrations of airborne particles. Cleanrooms with ISO Class 5 rating have very stringent requirements for air quality and contamination control. This class is commonly used for industries like pharmaceuticals, medical devices, and semiconductor manufacturing that require exceptionally clean environments.
What does ISO Class 5 mean?
ISO Class 5 is one of the cleanliness classifications defined in ISO 14644-1 standards. It signifies the cleanroom environment with very low levels of airborne particles. Here are the key specifications of ISO Class 5 cleanrooms:
- Allows no more than 3,520 particles of 0.5 μm size per cubic meter of air.
- Permits no more than 20 particles of 5.0 μm size per cubic meter.
In simpler terms, an ISO 5 cleanroom has just 352 particles of 0.5 microns and larger per cubic feet of air volume. This is around 10 times cleaner than the air in a typical office building.
Why is ISO Class 5 important?
Such a high level of cleanliness is critical for manufacturing sensitive products like pharmaceuticals, biologics, medical devices, electronics, etc. Here are some reasons why ISO Class 5 is important for these industries:
- Prevents contamination of products: Any foreign particles can compromise the purity and quality of drugs, biopharmaceuticals, medical equipment, or electronic components.
- Avoids defects: Particles cause defects in microelectronics like semiconductors, computer chips, MEMS, etc. ISO Class 5 cleanliness prevents this.
- Maintains product integrity: Particle contamination can affect the sterility, safety, and efficacy of healthcare products.
- Complies with regulatory standards: ISO Class 5 or stricter is mandated for sterile pharmaceuticals manufacturing as per cGMP and EU GMP.
Classification criteria for ISO Class 5
ISO 14644-1 defines the classification method for cleanrooms and clean zones. There are two criteria used to classify ISO Class 5 environments:
- Concentration limits for airborne particulates: This includes assigning limits for different particle sizes. ISO Class 5 permits 352 particles of 0.5 μm per cubic foot of air volume and just 20 particles of 5.0 μm size.
- Airflow patterns and velocities: Unidirectional laminar airflow of 0.45 m/s ± 20% is required for achieving ISO Class 5. The airflow must have ultra-low turbulence and be uniform across the entire clean zone.
Both these criteria must be satisfied simultaneously for meeting the requirements of ISO 5 cleanroom classification.
Maximum concentration limits
Here is a table summarizing the maximum particulate concentration limits for ISO Class 5 cleanrooms as per ISO 14644-1 standards:
| Particle Size (μm) | Maximum Concentration (particles/m3 of air) |
|---|---|
| ≥ 0.1 | 10,000 |
| ≥ 0.2 | 2,370 |
| ≥ 0.3 | 1,020 |
| ≥ 0.5 | 352 |
| >= 1 | 83 |
| >= 5 | 20 |
Particle counts must be tested at the operator position in the cleanroom to verify compliance with these concentration limits.
Differences from other ISO classes
ISO 14644-1 defines cleanroom classes from ISO Class 1 to Class 9 with descending levels of cleanliness. Here is how ISO Class 5 differs from the other important classifications:
- ISO Class 4: Allows 1,020 particles of 0.5 μm size vs 352 particles for ISO Class 5. So ISO 4 is slightly less stringent than ISO 5.
- ISO Class 6: Permits 3,520 particles of 1 μm size rather than 0.5 μm for ISO 5. Also allows significantly more particles than ISO Class 5 for all sizes.
- ISO Class 7: Cleanliness limit is 352,000 particles of 0.5 μm per cubic meter. This is 1,000 times higher than the ISO Class 5 limit.
- ISO Class 8: Maximum particles allowed is 3,520,000 particles of 0.5 μm size. Ten times higher contamination level than ISO Class 7.
So we see that each sequential ISO class allows progressively higher concentrations of airborne particles. Jumping from one class to another signifies a 10X change in the permissible particle levels.
How is ISO Class 5 achieved?
Maintaining ISO Class 5 cleanliness requires stringent contamination controls and airflow management. Here are the key requirements:
- HEPA filtration of incoming air to remove particles.
- Pressurization of cleanroom to avoid ingress of unfiltered air.
- Unidirectional laminar airflow to sweep particles away from the product.
- Use of low-shedding materials that minimize particle generation.
- Airlocks and pressure cascades between adjoining spaces.
- Stringent gowning procedures for personnel and equipment.
- Environmental monitoring to ensure continuous compliance.
Automation and isolator technology are commonly employed in ISO Class 5 cleanrooms to minimize human interventions and maintain cleanliness.
Typical applications
Here are some examples of processes and industries that require ISO Class 5 cleanroom environments:
- Pharmaceutical manufacturing: Sterile filling and packing of injectable drugs, production of oral solid dosage forms.
- Biotechnology: Manufacturing of vaccines, biologics, APIs produced by cell culture or fermentation.
- Medical devices: Assembly of surgical instruments, implants, catheters, stents.
- Microelectronics: Photolithography, etching, doping processes for semiconductors.
- Nanotechnology: Production and handling of nanoparticles.
- Optics: Manufacturing and assembly of precision optical systems.
The high cost of building and operating ISO Class 5 cleanrooms limits their use to critical processes where high value products are manufactured.
Regulations
ISO Class 5 environments are mandated by several regulatory standards worldwide. Some key ones include:
- US FDA cGMP regulations for drug and biologics manufacturing.
- EU GMP Annex 1 for sterile medicinal products.
- WHO GMP recommendations for pharmaceutical preparations.
- ISO 13408 and ISO 14698 standards for aseptic processing.
- GB/T 24001-2004 standards for Chinese sterile medical device manufacturers.
Adhering to ISO 14644-1 is critical for cleanrooms used in regulated industries to comply with these quality standards.
Testing and monitoring
Cleanrooms require constant monitoring and testing to verify continued compliance with ISO 14644-1. Important quality control activities include:
- Airborne particle counting: Using optical particle counters to measure concentrations of different particle sizes.
- Viable sampling: Microbiological assay using settle plates, air samplers, and surface swabs.
- Airflow velocity measurements: Using thermal anemometers to map laminar airflow velocities across the entire cleanroom.
- Room pressurization testing: Differential pressure gauges to check room-to-room pressure cascades.
- HEPA filter integrity testing: Using thermal dust disseminators and photometers to detect leakages.
The cleanroom should be recertified at least annually to verify continued compliance with ISO Class 5 specifications.
Design and construction
Cleanroom design aspects like layout, materials, and utilities have to be carefully engineered for meeting ISO Class 5 standards. Here are some important design considerations:
- Avoiding external walls to minimize risks of leaks, gaps, and loss of pressurization.
- SS 304/316 grade steel construction for smooth, impervious surfaces.
- Coved floor to wall joints for easy cleaning.
- Use of low-shedding construction materials.
- Separate air handling units supplying filtered air to the cleanroom.
- Raised floors for ducting air, piping, cables neatly underneath.
Highly specialized engineering input is essential right from the design stage for building cleanrooms that can meet ISO Class 5 specifications.
Cost implications
Achieving ISO Class 5 cleanliness demands substantial investments. Here are some factors that increase costs:
- Expensive HEPA filters and ULPA filters if needed.
- Stainless steel furnishings and construction materials.
- High airflow rates requiring large capacity air handling units.
- Automated systems preferred over manual cleaning.
- Energy-intensive pressurization and ventilation.
- Trained personnel for gowning, cleaning, monitoring.
- Ongoing costs for certification and maintenance.
The high capital and operating costs restrict use of ISO Class 5 cleanrooms to specialized industries like pharmaceuticals and semiconductor manufacturing.
Advantages
Some benefits of using ISO Class 5 cleanrooms include:
- Prevents contamination of pharmaceuticals, medical devices, electronics.
- Maintains sterility and integrity of healthcare products.
- Avoids defects in precision devices like semiconductors or MEMS.
- Increased yields and profitability for manufacturers.
- Safer products with lower risks for end-users.
- Compliance with regulatory standards for quality.
Disadvantages
Some potential downsides of ISO Class 5 cleanrooms are:
- Very high capital expenditure and operating costs.
- Increased energy consumption for HVAC systems.
- Complex gowning and personnel training requirements.
- Higher reject rates if improperly operated or monitored.
- Difficulty achieving Class 5 in existing facilities.
- Significant downtime needed for recertification.
Conclusion
ISO Class 5 represents extremely high levels of cleanliness with just 352 particles of 0.5 μm size per cubic foot of air volume. This degree of contamination control is essential for manufacturing sensitive pharmaceuticals, biologics, medical devices, and microelectronics. However, the costs and complexities of achieving ISO Class 5 cleanliness also make it prohibitive for many applications. Regulated industries like pharmaceutical manufacturing have made the investments to build and operate ISO 5 cleanrooms due to stringent quality standards mandated by regulatory agencies. For other applications, alternative technologies like isolators and restricted access barrier systems may provide more practical solutions at lower cost.