Particle count in each class is measured based on particles of a certain size per cubic meter. As the class number decreases and requirements become stricter, the allowed number of particles is reduced, as well as the size of those particles. You can see, for example, the difference between particle count and size allowed in Class 7 cleanrooms (352,000 particles ≥0.5µm per cubic meter) versus a Class 5 cleanroom (only 3,520 ≥0.5µm per cubic meter). 

Particle size is measured in microns (µm) per cubic meter. In stricter classes, even the tiniest particles can interfere with and contaminate products and operations within a controlled cleanroom environment. As the classification becomes more stringent, specialized filters must capture smaller particles before they can compromise operations. A carefully designed airflow pattern helps filters trap and remove contaminants efficiently, continuously replacing room air with fresh, contaminant-free air. The rate at which this process completely changes and replaces the room’s air is called the air change rate (ACH).

In ISO Classes 6-9, air change rates are expressed as the rate per hour the air in the cleanroom is completely refreshed (ACH = air changes per hour). As cleanroom classifications become more stringent, the air change rate must increase to remove particles and keep the air cleaner. In Class 5 and lower, Classes 1-4, the strictest cleanroom classifications, the air change rate is so rapid it is expressed instead as airflow velocity, either in meters per second or feet per minute. These cleanroom environments require air that is extremely clean, so the constant changing of contaminant-free air is vital to maintain classification standards.

Upgrading to a stricter classification requires increasing both filtration capacity and air change rate. For example, ISO Class 7 requires between 60-90 ACH and allows for 352,000 particles at 0.5 microns per cubic meter. To move to an ISO Class 6, the facility would need to increase to 150-240 ACH to filter all but 35,200 particles at 0.5 microns per cubic meter. The more stringent the classification, the more extreme the standards of cleanliness. Extremely clean cleanrooms require extensive filtration and powerful HVAC systems to maintain classification standards.

US Pharmacopeia (USP) is a scientific organization that develops standards and science‑based solutions to help ensure the quality of medicines, dietary supplements, and food ingredients. These standards support product safety, purity, and consistency across healthcare.

In cleanroom environments, the USP standards most commonly referenced are those governing pharmaceutical compounding, outlining environmental and procedural requirements and cleanroom conditions needed to safely prepare compounded medications.

• USP 795: non-sterile pharmaceutical compounding
• USP 797: sterile non-hazardous compounding
• USP 800: hazardous compounding (sterile and non-sterile)

USP Standards exist to ensure product strength, quality, and purity so that all compounds are certified to be high quality, safe to use, and effective for patient use.

What is the difference between HEPA and ULPA filters?

Depending on your cleanroom classification, you must filter out a certain number of particles of a specific size. HEPA and ULPA filters remove contaminants from the air to provide a consistent, contaminant-free environment, with the appropriate filter type determined by target particle size:

• HEPA filters, or High-Efficiency Particulate Air filters, remove 99.99% of particles 0.3µm or larger in diameter. 
• ULPA filters, or Ultra Low Particulate Air filters, function similarly to HEPA filters, but are rated to remove 99.999% of all contaminants larger than 0.12µm.

Most cleanrooms utilize multi-stage filtration to extend the life of HEPA filters and trap contaminants more effectively and efficiently. To accomplish this, pre-filters draw out larger particles before air reaches the HEPA or ULPA filters. Prefilters are generally replaced every other month, while HEPA and ULPA filters can last up to 7 years.

Airflow patterns are critical to maintaining a consistent flow of clean air and assist filters in doing their job effectively. Higher-classification cleanrooms (those with a lower ISO number) typically use laminar, or unidirectional, airflow, which pushes clean air in a single direction through the space to prevent particles and contaminants from settling or accumulating. By contrast, lower-classification cleanrooms may use turbulent, or non-unidirectional, airflow instead, which is less precise but sufficient for less stringent environments.

Layout plays an equally important role. Your cleanroom should allow the air to flow according to its pattern without creating spaces where contaminants could build up or block filters. During the design phase, computational fluid dynamics software can be used to model airflow patterns to determine the optimal placement of FFUs, cleanroom walls, and even equipment and cleanroom furniture.

Pressure within the cleanroom is determined by the amount and direction of air flowing in and out of the cleanroom environment, and getting it right is an important part of cleanroom design. Most cleanrooms use positive pressure, meaning more air is filtered into the space than removed. As a result, unfiltered outside air cannot leak in through doors, seams, or any crevices to cause contamination. 

Some cleanrooms, particularly those working with hazardous or infectious substances, use negative pressure instead. In these environments, more air is exhausted out than is brought in, keeping any dangerous contaminants from escaping into surrounding areas. Negative pressure cleanrooms are still fully filtered and controlled environments; the pressure differential simply contains what’s inside rather than protecting against what’s outside.

Per ASTM E2352, aerospace cleanrooms must meet ISO 14644-1 standards, starting from a minimum ISO Class 7 (Federal Standard 209 Class 10,000) requirement. More stringent standards apply for highly sensitive applications, where airborne particle concentrations must be strictly controlled, such as in the development of spacecraft hardware, fine electronics, or optical devices.

Medical cleanrooms encompass a range of applications, from research laboratories to device manufacturing, and typically fall within ISO Class 5–8. The required classification depends on the risk level of contamination to operations and the safety of the end product.

Device production, assembly, and packaging each carry different cleanliness requirements and often fall under separate classifications. Most medical device manufacturing cleanrooms must comply with ISO 5–8 standards per ISO 14644-1, while medical device packaging typically requires ISO 7–8.  In addition, all medical device cleanrooms must also comply with ISO 13485:2016, which designates a quality management system to ensure product quality and assess risk throughout the device’s lifetime.

Medical research laboratories have their own set of cleanroom requirements, generally falling within ISO Class 5–7. As with device manufacturing, the rigorousness of the standard is dictated by the sensitivity of the research and the risk level of contaminants to cleanroom operations and safety.

Life sciences cleanrooms support a broad range of research and production activities, including pharmaceutical manufacturing, biotechnology, genomics, and cell and gene therapy. These environments typically fall within ISO Class 5–7, though the specific classification depends on the sensitivity of the work being performed.

For pharmaceutical cleanrooms, the minimum standard is generally ISO 5 (Federal Standard 209 Class 100), which requires high air change rates and significant ceiling coverage to maintain a tightly controlled particle environment. Beyond ISO standards, pharmaceutical cleanrooms must also follow regulations from the US Pharmacopeia (USP Standards) and, for biologics and drug manufacturing, the FDA.

Because life sciences applications frequently involve biological materials, contamination control goes beyond particle counts alone. Microbial contamination is an equally important concern, and for that reason, cleanrooms in this sector are often designed to meet both ISO 14644-1 particulate standards and the biosafety level (BSL) requirements set by the CDC and NIH. Furthermore, clean-in-place (CIP) and sterilize-in-place (SIP) systems are also common features in life sciences cleanrooms to support aseptic processing and reduce contamination risk between production runs.