Jun 05, 2025

ISO Cleanroom Classifications

ISO Cleanroom Classifications: Understanding ISO 14644 Standards for Controlled Environments

Introduction: Why ISO Cleanroom Classifications Matter

In advanced manufacturing and life sciences environments, maintaining a controlled level of cleanliness is essential to ensuring product quality, regulatory compliance, and operational integrity. Whether producing sterile pharmaceuticals, assembling sensitive optical components, or manufacturing microelectronics, cleanroom environments serve as the protective barrier between precision processes and the microscopic threats that can compromise them. At the heart of designing, building, and validating these environments lies the ISO cleanroom classification system—a globally recognized standard that defines acceptable particulate levels in controlled spaces.

The International Organization for Standardization (ISO) has established a framework—ISO 14644—that classifies cleanrooms based on the concentration of airborne particles per cubic meter of air. These classifications range from ISO Class 1, the most stringent, to ISO Class 9, the least. The specific ISO class of a cleanroom determines everything from the number and type of filters required to the airflow patterns, pressure differentials, gowning protocols, and maintenance schedules.

For companies operating in highly regulated industries such as pharmaceuticals, biotechnology, aerospace, semiconductors, and medical devices, ISO classification is not a theoretical benchmark—it’s a core requirement for regulatory approval and product safety. It shapes how facilities are designed, how equipment is configured, how personnel behave, and how data is collected and reported. Moreover, it provides a universal language that regulators, manufacturers, and suppliers can use to align on environmental expectations across countries, markets, and product types.

In this article, we’ll explore what ISO cleanroom classifications are, how they’re determined, how they influence facility design and operations, and why they matter so deeply in the context of compliance, quality assurance, and business success. We’ll also examine how modular cleanroom systems—like those offered by G-CON—are engineered from the ground up to meet specific ISO classifications, providing a turnkey path to validation and operational readiness.

What Are ISO Cleanroom Classifications?

ISO cleanroom classifications define the allowable concentration of airborne particles within a controlled environment. Established under the ISO 14644-1 standard, this classification system provides a consistent, quantitative method for determining the cleanliness of air in cleanrooms and clean zones based on the number and size of particles present in a cubic meter of air. These standards are essential for designing and validating spaces where airborne contamination could affect product safety, performance, or regulatory compliance.

ISO 14644-1 replaced the older Federal Standard 209E, which categorized cleanrooms using designations like Class 100 or Class 1,000 based on particles per cubic foot. The ISO system, in contrast, uses a metric-based scale (particles per cubic meter) and includes a broader range of cleanliness classes, from ISO Class 1 to ISO Class 9. This allows for greater precision and international consistency in cleanroom design and regulation.

Each ISO class sets a limit for the number of particles of various sizes—typically 0.1 µm, 0.2 µm, 0.3 µm, 0.5 µm, 1.0 µm, and 5.0 µm—that can be present in a cubic meter of air. For example, an ISO Class 5 cleanroom allows no more than 3,520 particles of size 0.5 µm or larger per cubic meter, whereas an ISO Class 7 cleanroom permits up to 352,000 particles of the same size. As the ISO class number increases, so does the allowable particle count, indicating a less stringent environment.

Most regulated manufacturing environments use cleanrooms classified as ISO Class 5 through ISO Class 8. ISO Class 5 is commonly used in aseptic processing and fill-finish applications in pharmaceutical and cell therapy settings. ISO Class 7 often serves as the background environment for ISO 5 zones, and ISO Class 8 is frequently used in gowning areas, staging rooms, and less critical processing zones. Classes 1–4 are used in specialized applications such as semiconductor and nanotechnology manufacturing, where ultra-low particle levels are required.

Understanding ISO classifications allows manufacturers, designers, and regulatory bodies to define the cleanliness levels appropriate for specific processes and products. These classifications form the basis for cleanroom layout, air handling system requirements, validation testing protocols, and environmental monitoring strategies. For organizations pursuing GMP compliance or ISO 13485 certification, cleanroom classification is not optional—it is a prerequisite to operating in a regulated, quality-driven environment.

How ISO Cleanroom Classes Are Determined

ISO cleanroom classes are determined by measuring the concentration of airborne particles within a defined volume of air. The ISO 14644-1 standard specifies both the maximum allowable number of particles and the size thresholds used for classification. These measurements are typically taken using electronic particle counters during cleanroom certification and requalification procedures.

The core metric used in ISO classification is the number of particles per cubic meter of air at or above specific particle sizes—most commonly ≥0.1 µm, ≥0.5 µm, and ≥5.0 µm. The smaller the particle size and the fewer the particles allowed, the more stringent the classification. For example, an ISO Class 5 environment permits up to 3,520 particles per cubic meter at ≥0.5 µm, while ISO Class 7 permits 352,000 particles at the same size threshold.

Testing is performed at “at rest” and “in operation” states to evaluate both baseline cleanliness and the impact of personnel and process activity. Particle counters sample multiple locations within the cleanroom to ensure that cleanliness levels are consistent across all critical zones. The data is compared to ISO 14644-1 thresholds to determine compliance and inform certification.

The number of air changes per hour (ACH) required to maintain a specific ISO class also varies by classification. ISO Class 5 environments may require 240–480 ACH, while ISO Class 7 cleanrooms typically operate with 30–60 ACH. These high air change rates are achieved through the use of HEPA or ULPA filters integrated into the HVAC system, which remove airborne particulates from the recirculated air.

Airflow patterns, particularly unidirectional or laminar airflow in critical zones, are essential for controlling particle movement and maintaining classification. Pressure differentials between adjacent rooms are used to create containment barriers, ensuring that air flows from cleaner to less clean areas and not the reverse. For instance, an ISO Class 5 room should be positively pressurized relative to an ISO Class 7 background.

Ultimately, cleanroom classification is determined through a combination of design factors—air handling, filtration, pressure control—and empirical data gathered from environmental testing. Maintaining compliance requires not only building the space to specification, but also implementing robust monitoring, maintenance, and validation protocols.

Cleanroom Design by ISO Classification

The ISO classification of a cleanroom directly informs its design, construction, and operational strategy. Every aspect of the environment—from HVAC sizing to room zoning to material selection—is influenced by the cleanliness class the facility must maintain. Higher ISO classifications (e.g., ISO Class 5) require more stringent environmental controls, greater air filtration capacity, and tighter layout tolerances than lower classes (e.g., ISO Class 8).

In ISO Class 5 environments, which are often used for aseptic processing or sterile fill-finish operations, design elements must include unidirectional laminar airflow across critical work surfaces, high air change rates (up to 480 ACH), and tightly controlled pressure differentials. These spaces require extensive HEPA or ULPA filtration, smooth and non-shedding interior finishes, and minimal penetrations to reduce contamination risks. Equipment and personnel flows are strictly controlled, and gowning protocols are rigorous.

ISO Class 6 and Class 7 cleanrooms are frequently used as background environments that support Class 5 zones. These areas may house less critical operations such as component preparation or staging. Airflow patterns may be mixed or turbulent, and while air change rates are lower, they must still be sufficient to maintain the required particulate thresholds. Class 7 spaces are also used for activities like formulation, inspection, and sterile product support in pharmaceutical manufacturing.

ISO Class 8 cleanrooms are typically used for gowning, entry airlocks, and non-sterile compounding or packaging operations. While the cleanliness requirements are less demanding, these rooms still require HEPA-filtered air, positive pressure relative to adjacent uncontrolled areas, and cleanable surfaces that meet GMP expectations. ISO Class 8 zones serve as the first line of defense in a cleanroom suite, buffering internal environments from external contamination sources.

The classification also affects room layout and zoning. Higher-classified areas should be located in the core of the facility, surrounded by buffer zones with progressively lower classifications. This layout supports a pressure cascade and helps prevent backflow of contaminants. Doors and pass-throughs must be interlocked to maintain pressure differentials, and personnel must follow strict entry and gowning protocols aligned with the ISO class of each zone.

Designing cleanrooms to meet a specific ISO class is not just about achieving initial certification—it’s about enabling consistent, repeatable control of airborne contamination over time. Every design decision—from HVAC system capacity to furniture type to lighting placement—must contribute to maintaining the desired ISO classification during routine operations, cleaning, and maintenance.

Cleanroom Classification vs. Cleanroom Grade (EU Annex 1)

While ISO 14644 defines cleanroom classifications based on airborne particulate concentration, the EU GMP Annex 1 framework introduces a separate grading system—Grades A through D—designed specifically for sterile medicinal product manufacturing. Although both systems measure environmental cleanliness, they serve different regulatory purposes and are often used in tandem within GMP-regulated facilities. Understanding the relationship between ISO classes and EU Grades is essential for global companies operating in both U.S. and European markets.

ISO classifications provide a universal framework for measuring particle counts per cubic meter at various size thresholds. These metrics are quantitative and apply across a wide range of industries including semiconductors, aerospace, and pharmaceuticals. In contrast, the EU Annex 1 grading system focuses more narrowly on aseptic processing environments and incorporates both particulate and microbiological cleanliness requirements, as well as expectations for personnel practices, process design, and environmental monitoring.

A general alignment exists between ISO classes and EU Grades, although the mapping is not one-to-one. For example, Grade A environments—used for high-risk activities such as aseptic filling—typically require ISO Class 5 conditions at rest and in operation. Grade B, which serves as the background for Grade A areas, aligns with ISO Class 5 at rest and ISO Class 7 in operation. Grades C and D, used for less critical stages such as solution preparation or handling of non-sterile components, correspond approximately to ISO Classes 7 and 8, respectively.

Industries and Applications by ISO Classification

Each ISO cleanroom class is tailored to support specific types of products, processes, and risk profiles. Selecting the appropriate ISO classification depends on the sensitivity of the product, the potential consequences of contamination, and the regulatory expectations of the industry in which the cleanroom operates. Below are common industries and the ISO classifications typically associated with their manufacturing processes.

Pharmaceutical and Biopharmaceutical Manufacturing
This sector frequently requires ISO Class 5 to ISO Class 8 environments depending on the production stage. ISO Class 5 is used in critical operations such as aseptic filling, compounding of sterile products, and open product exposure. ISO Class 7 and 8 are used as background environments for staging, formulation, and packaging. Regulatory expectations from the FDA, EMA, and WHO dictate cleanroom design, gowning protocols, and environmental monitoring based on these classifications.

Cell and Gene Therapy (ATMPs)
Due to the high sensitivity and personalized nature of these therapies, ISO Class 5 zones are required for most manipulation steps involving patient material. Class 7 background environments are typically used for staging and storage. Modular PODs are especially effective in this space, allowing for isolated, segregated ISO Class 5 cleanrooms with dedicated HVAC and monitoring systems to prevent cross-contamination.

Semiconductors and Microelectronics
Ultra-clean environments are critical in semiconductor fabrication, where a single particle can destroy a microchip. These applications may require ISO Class 3 to ISO Class 5 cleanrooms, with specialized airflow designs, anti-static finishes, and stringent particle control. ISO Class 1 and 2 environments are extremely rare and typically reserved for nanotechnology or photolithography applications.

Aerospace and Optics
Precision assembly of optical lenses, satellites, and navigation systems often takes place in ISO Class 5 to 7 environments. These cleanrooms must minimize both particulate and molecular contamination. In addition to standard HVAC controls, designs may incorporate outgassing mitigation, vibration control, and static shielding.

Compounding Pharmacies and Hospital Labs
Facilities compounding sterile medications must comply with ISO Class 5, 7, and 8 requirements as outlined in USP <797> and <800>. ISO Class 5 is required for direct compounding under laminar flow hoods or isolators, with ISO 7 and 8 used for buffer and ante rooms. These standards ensure protection for both the patient and compounding personnel.

Medical Device Manufacturing
Devices that come into contact with human tissue must be manufactured in controlled environments to prevent contamination and ensure biocompatibility. ISO Class 7 and 8 cleanrooms are standard in this sector, supported by ISO 13485 quality systems. Applications include catheter manufacturing, implantable devices, and diagnostic kits.

Selecting the right ISO class is not about choosing the “cleanest” environment possible—it’s about aligning cleanliness levels with product risk, process sensitivity, and regulatory mandates. Overdesigning a facility can lead to excessive costs, while underdesigning creates compliance vulnerabilities. Working with a knowledgeable supplier ensures that the ISO classification selected is both appropriate and sustainable.

Monitoring and Maintaining ISO Cleanroom Classification

Achieving an ISO cleanroom classification is only the beginning. Sustaining that classification over time requires continuous monitoring, disciplined operational practices, and rigorous maintenance. Regulatory agencies expect cleanrooms to remain in a state of control not just at certification, but throughout the lifecycle of the facility. Failure to maintain ISO classification can lead to audit findings, product contamination, or regulatory sanctions.

Environmental monitoring (EM) is the frontline defense in preserving ISO class conditions. This includes real-time or periodic measurement of airborne particulate levels, temperature, humidity, pressure differentials, and in pharmaceutical environments, microbial contamination. The frequency and intensity of monitoring depend on the cleanroom’s ISO class and its criticality to the manufacturing process. For example, ISO Class 5 zones typically require continuous particle monitoring during operation, while ISO Class 8 spaces may be monitored at scheduled intervals.

Particle counters are used to sample air at specified locations within the cleanroom. These locations are identified during risk assessments and validation and include points of greatest risk—such as near open product, doors, or HEPA filter outlets. Results must be compared against the limits defined in ISO 14644-1 for the corresponding class. Deviations require investigation and, if necessary, corrective and preventive actions (CAPA).

In addition to air sampling, pressure differentials between adjacent rooms must be continuously monitored. Cleanrooms rely on pressure cascades to prevent the backflow of contaminants, with higher-class areas held at a higher pressure than their surroundings. Automated systems with visual and audible alarms alert operators when pressures deviate from setpoints, allowing rapid response before product safety is compromised.

HVAC systems must be inspected and maintained regularly. This includes filter integrity testing (e.g., HEPA leak testing), airflow velocity checks, temperature and humidity calibration, and inspection of ductwork and dampers. All results should be documented and made readily available for audits. Filters should be replaced according to manufacturer recommendations or if performance falls outside acceptable limits.

Personnel and material flow protocols also play a major role in maintaining ISO classification. Improper gowning, unauthorized entry, and poor cleaning practices are frequent causes of particulate spikes. Standard Operating Procedures (SOPs), training, and compliance audits ensure that cleanroom behaviors align with ISO expectations. Cleaning and disinfection schedules must be followed precisely, using agents compatible with the room’s classification and surface finishes.

By combining robust EM programs, preventative maintenance, validated HVAC systems, and disciplined operational controls, facilities can preserve their cleanroom classification and ensure long-term compliance. These practices are not only regulatory requirements—they are essential for protecting product quality and manufacturing continuity.

Modular Cleanrooms and ISO Classification Compliance

Modular cleanrooms offer a transformative approach to achieving and maintaining ISO cleanroom classifications. Unlike traditional stick-built construction, modular cleanrooms are prefabricated in controlled environments, factory-tested, and delivered with pre-engineered systems that are optimized for compliance. This model dramatically shortens the time from design to operation and provides greater consistency in performance across facilities.

Each POD from G-CON, for example, is built to meet specific ISO 14644 classifications, typically ISO Class 5 through 8. The classification is embedded into the POD’s design: air handling units, HEPA filtration layouts, airflow patterns, lighting, pressure balancing, and cleanable finishes are all engineered and validated to support the desired classification. Because these components are assembled and tested off-site, the POD arrives at the client’s location with proven performance characteristics.

Factory Acceptance Testing (FAT) is conducted before shipment, confirming that each POD meets required airflow velocity, pressure differentials, and particulate control specifications for its ISO class. This prevalidation reduces the time and effort required during Site Acceptance Testing (SAT) and accelerates the Installation Qualification (IQ) and Operational Qualification (OQ) processes.

G-CON’s modular cleanrooms are also equipped with integrated Environmental Monitoring Systems (EMS) and optional Building Management Systems (BMS) that support ISO compliance. These systems provide continuous data on temperature, humidity, particle levels, and pressure, and are Part 11–compliant for use in regulated environments. Alerts and trend reporting help teams maintain control and proactively manage deviations.

Another major advantage of modular cleanrooms is repeatability. Facilities that require multiple cleanrooms—either in the same site or across global locations—can deploy identical PODs with identical ISO classifications and performance profiles. This uniformity simplifies validation, training, SOP development, and regulatory inspections. It also enables more agile expansion when production capacity increases or new therapies are brought to market.

POD(r) cleanrooms are also easier to maintain than traditional builds. Components such as filters, ductwork, and air handling units are accessible through integrated service corridors or panels. Their predictable layouts and documentation simplify maintenance protocols and reduce downtime during service.

By choosing modular cleanrooms, organizations gain speed, scalability, and certainty in achieving ISO classification. Whether for a single ISO Class 5 aseptic suite or an ISO Class 8 compounding environment, modular solutions deliver compliance by design—backed by documentation, validation, and post-installation support that meets the most demanding global standards.

Common Mistakes and Misconceptions About ISO Classifications

While ISO cleanroom classifications provide a clear framework for designing and maintaining controlled environments, many organizations make critical errors in applying or interpreting these standards. These missteps can lead to compliance failures, unnecessary costs, and operational inefficiencies. Recognizing common pitfalls helps organizations plan more effectively and avoid costly rework.

Overdesigning the Cleanroom
One of the most frequent mistakes is specifying a lower ISO class than necessary. While ISO Class 5 environments provide high levels of particulate control, they are expensive to build and operate due to higher air change rates, stricter gowning, and increased energy demands. Applying ISO Class 5 conditions to non-critical operations—where ISO Class 7 or 8 would suffice—results in wasted capital and maintenance resources without improving product quality.

Assuming ISO Compliance Equals GMP Compliance
ISO 14644 addresses airborne particle control but does not address broader GMP requirements such as material segregation, personnel flow, microbial contamination, or documentation. A cleanroom may meet ISO Class 7 particle limits and still fall short of FDA or EU GMP requirements. Manufacturers must understand that ISO classification is only one part of regulatory compliance and design accordingly.

Neglecting Zone Segregation and Flow Design
Failing to properly separate cleanroom zones of different ISO classifications can lead to cross-contamination and loss of control. Airflow should always move from cleaner to less clean areas, and personnel and materials should follow unidirectional paths. Interlocked doors, pressure differentials, and well-defined procedures are critical to maintaining segregation.

Inadequate Monitoring and Maintenance
ISO classification must be maintained over time—not just demonstrated at startup. Some facilities underinvest in monitoring systems or delay routine maintenance, leading to gradual degradation in performance. Without continuous oversight, filter failures, HVAC imbalances, or personnel errors can result in undetected noncompliance.

Confusing “At Rest” with “In Operation” Standards
Many companies mistakenly believe a cleanroom that meets ISO limits during commissioning will remain compliant during production. Particle counts often rise significantly when personnel are present and processes are active. ISO certification should reflect “in operation” conditions for regulated manufacturing—not just “at rest” baselines.

By understanding these misconceptions and proactively addressing them during design, validation, and operation, manufacturers can build cleanrooms that not only meet ISO classification but also perform reliably under real-world production conditions.

ISO Classification as a Foundation for Compliance and Control

ISO cleanroom classifications provide the essential framework for designing and managing controlled environments across regulated industries. From pharmaceuticals to microelectronics, these classifications define the maximum allowable airborne particles and inform every element of cleanroom architecture, from HVAC design to zoning and environmental monitoring.

But ISO compliance is more than a certification step—it’s a foundational strategy for achieving product quality, regulatory readiness, and operational excellence. By selecting the appropriate ISO class for each process, aligning facility design with airflow and pressure requirements, and implementing robust monitoring and maintenance systems, companies can build facilities that are not only compliant but also efficient, scalable, and audit-ready.

Modular cleanrooms like those offered by G-CON deliver ISO-classified environments with precision, speed, and repeatability. Engineered and validated off-site, these PODs streamline the path to ISO certification and enable companies to meet demanding timelines without compromising compliance. Whether you’re launching a new therapy, scaling manufacturing, or entering global markets, ISO-compliant modular cleanrooms provide the infrastructure you need to succeed—faster, smarter, and more confidently.

Frequently Asked Questions About ISO Cleanroom Classifications

What is the difference between ISO Class 5 and ISO Class 7?
ISO Class 5 environments allow up to 3,520 particles ≥0.5 µm per cubic meter, while ISO Class 7 allows up to 352,000. Class 5 is used for aseptic fill-finish and sterile processing; Class 7 serves as a background for those zones or is used in non-aseptic production.

How often must a cleanroom be requalified to maintain ISO classification?
ISO 14644-2 recommends requalification at least every 6 months for ISO Class 5 and annually for Class 6–8, or more frequently based on risk and regulatory requirements. Requalification includes particle counts, airflow testing, and pressure verification.

Can modular cleanrooms meet ISO Class 5 requirements?
Yes.Prefabricated PODs from G-CON are engineered for ISO Class 5–8 compliance and are tested via Factory Acceptance Testing (FAT) before delivery. These systems can maintain ISO Class 5 conditions with integrated HEPA filtration, pressure control, and validated airflow.

Does ISO classification guarantee GMP compliance?
No. ISO classification addresses airborne particle concentration. GMP compliance includes documentation, SOPs, environmental monitoring, personnel behavior, and microbial control. ISO compliance is part of GMP readiness—but not the whole picture.

Do all cleanrooms need to be ISO classified?
No. Only environments that must control airborne particulate matter to specific limits require ISO classification. The need depends on product risk, regulatory expectations, and process sensitivity. Some supporting spaces may fall outside formal classification.