Oct 28, 2025

What Is Cleanroom Validation

Introduction: What Is Cleanroom Validation?

Cleanroom validation is the formal process of verifying that a cleanroom performs as designed, maintaining the environmental conditions required for controlled manufacturing. It confirms that the facility, systems, and equipment operate within defined parameters for particle count, airflow, pressure, temperature, and humidity.

Validation ensures that a cleanroom meets regulatory expectations, but its purpose extends beyond compliance—it protects product integrity, process reliability, and patient safety in industries like pharmaceuticals, biotechnology, semiconductors, and advanced manufacturing.

Regulatory bodies such as the FDA (21 CFR Parts 210/211), the European Medicines Agency (EU GMP Annex 1), and ISO (14644-1 and -2) require cleanrooms to be validated before they are put into use and periodically revalidated thereafter. Without proper validation, facilities risk regulatory non-compliance, operational inefficiencies, and potential contamination events that can halt production or lead to costly recalls.

Key Stages of Cleanroom Validation

The validation process typically follows a structured sequence that aligns with international standards and Good Manufacturing Practice (GMP) guidelines. Each stage is designed to verify specific aspects of the cleanroom’s design, installation, and performance.

Design Qualification (DQ)

This stage confirms that the cleanroom design meets the intended specifications and process requirements. It involves reviewing design documentation, layout drawings, and equipment specifications to ensure the environment will achieve the target cleanliness level, airflow control, and pressure differentials. DQ also confirms that materials, finishes, and systems are appropriate for the intended use.

Installation Qualification (IQ)

IQ verifies that all components—walls, ceilings, HVAC systems, filters, sensors, and monitoring devices—are installed according to approved designs and manufacturer recommendations. Documentation at this stage includes calibration certificates, wiring diagrams, equipment manuals, and installation checklists. This step ensures that every system is correctly assembled, traceable, and ready for operational testing.

Operational Qualification (OQ)

During OQ, the cleanroom’s critical systems are tested under defined conditions to confirm they perform as expected. This includes measuring air velocity, pressure differentials, temperature, humidity, and particle counts under static conditions (no personnel or materials present). OQ demonstrates that the cleanroom can consistently achieve its target ISO class and environmental parameters.

Performance Qualification (PQ)

PQ validates the cleanroom’s performance under actual operating conditions, including equipment operation and personnel activity. Testing verifies that contamination control, airflow patterns, and recovery times remain within specified limits during normal use. PQ ensures that the cleanroom supports compliant and consistent production processes over time.

Critical Parameters to Validate

Cleanroom validation involves verifying that environmental and mechanical systems function within the limits defined by ISO 14644 and GMP guidelines. These parameters determine whether the cleanroom can consistently maintain the cleanliness class required for its intended processes.

Airflow and Air Changes per Hour (ACPH)

Adequate airflow is essential to dilute and remove contaminants. Validation includes measuring air velocity and calculating ACPH to confirm that the cleanroom meets design targets. For instance, an ISO Class 7 cleanroom typically requires 60 to 90 air changes per hour, depending on its configuration and process load.

HEPA and ULPA Filter Integrity

Filter integrity testing ensures that HEPA and ULPA filters effectively remove airborne particulates. Using methods such as aerosol challenge (e.g., DOP or PAO testing), validation teams confirm that there are no leaks or compromised seals in the filter housings.

Pressure Differentials

Pressure mapping confirms that pressure cascades are maintained between clean zones—positive pressure for sterile manufacturing or negative pressure for hazardous material handling. This prevents cross-contamination and protects both products and personnel.

Temperature, Humidity, and Vibration

Environmental conditions directly affect both personnel comfort and product quality. Temperature and humidity are monitored to confirm they remain within specified ranges. In high-precision operations like microelectronics or nanotechnology, vibration levels are also validated to avoid process disruption.

Particle Counts

Airborne particle counting is the primary criterion for ISO cleanroom classification. Measurements are taken at rest and in operation, comparing results against ISO 14644-1 limits for the designated cleanroom class. This verifies that the facility meets its cleanliness standard both before and during production activities.

Acceptance Testing Strategy (ATS)

At G-CON, validation activities are structured through an internal Good Documentation Practice (GDP) framework (IMS-SOP-7.5, Documented Information). This ensures that all testing follows a consistent, traceable methodology aligned with regulatory expectations.

Factory Acceptance Testing (FAT)

Performed at G-CON’s manufacturing facility in College Station, Texas, FAT confirms that each prefabricated POD is built according to the customer’s user requirements, functional specifications, and design documents. The purpose of FAT is to verify full system functionality—excluding elements impacted by shipping—before the unit leaves the factory.

• Customers are invited to witness FAT execution and review test protocols prior to approval.
• A post-FAT punch list identifies any outstanding items for resolution before shipment.
• Once FAT is approved, documentation serves as formal release for transport to the customer’s site.

Site Acceptance Testing (SAT)

SAT occurs at the customer’s facility after installation to confirm that the POD remains compliant with design and operational specifications. The goal is to ensure that no requirements were missed during shipping or installation.

• SAT testing requires site readiness, including power, utilities, and facility integration.
• Customers review and pre-approve the SAT protocol before execution.
• Upon completion, customer sign-off confirms that the POD is fit for its intended use and ready for qualification activities.

Together, FAT and SAT provide an end-to-end verification process that minimizes project risk and accelerates commissioning while maintaining full traceability.

Validation Testing Procedures

Validation testing confirms that the cleanroom’s design, construction, and operational systems meet the required standards for cleanliness and performance. Each test is conducted under controlled conditions and documented in accordance with the facility’s validation master plan (VMP).

Air Velocity and Volume Measurements

Air velocity testing ensures that laminar and turbulent airflow patterns align with the design intent. Measurements are taken at multiple grid points using anemometers to confirm uniform air distribution across critical zones. Air volume readings are compared to design specifications to verify that the required air changes per hour are achieved.

Smoke Visualization

Smoke studies (airflow visualization) are performed to observe the movement of air within the cleanroom. This test confirms unidirectional airflow in laminar zones and verifies that no turbulence or backflow occurs near sensitive process areas. The test also helps assess the effectiveness of air return placements and the overall pressure cascade design.

Recovery Time Testing

This test determines how quickly a cleanroom can return to its specified cleanliness level after a temporary contamination event, such as personnel movement or door openings. Shorter recovery times indicate efficient airflow design and adequate filtration capacity.

Particle Counting

Particle counting, governed by ISO 14644-1, measures airborne particulate concentration at defined sampling points. Tests are conducted both at rest (no activity) and in operation (under normal working conditions). These measurements validate that the cleanroom maintains its assigned ISO classification.

Microbial Testing

For GMP-grade cleanrooms, microbial testing complements particle counting to ensure biological contamination is controlled. Contact plates, settle plates, and active air samplers are used to detect viable microorganisms in the environment. This testing verifies that aseptic conditions are maintained during operation.

Documentation and Reporting

Cleanroom validation requires meticulous documentation to demonstrate traceability and regulatory compliance. Each stage of testing is supported by structured protocols, standardized forms, and sign-offs.

Validation Master Plan (VMP)

The VMP outlines the overall strategy for qualification and validation activities, including objectives, responsibilities, schedules, and acceptance criteria. It acts as a roadmap that ensures consistency and accountability throughout the validation process.

Test Protocols and Forms

Each qualification stage—DQ, IQ, OQ, and PQ—has its own test protocols and forms detailing methods, test locations, instruments used, and acceptance criteria. These documents are reviewed and approved prior to execution.

Discrepancies and Remediation Plans

Any deviations or out-of-specification results identified during testing must be documented, investigated, and resolved. Corrective and preventive action (CAPA) reports are generated to address root causes and ensure future reliability.

Validation Summary and Approval Sign-offs

Once all tests are completed, results are compiled into a final validation report. The document summarizes testing outcomes, deviations, and corrective actions, concluding with formal approval sign-offs from engineering, quality assurance, and regulatory teams. This approval certifies that the cleanroom is validated and ready for use.

Revalidation Requirements

Validation is not a one-time activity. Cleanrooms must be periodically revalidated to ensure that performance remains within defined parameters and continues to meet ISO and GMP standards.

Frequency of Revalidation

Most facilities perform full or partial revalidation annually or biannually, depending on the classification level and regulatory requirements. High-grade aseptic areas may require more frequent checks.

Trigger Events

Revalidation is also required whenever significant changes occur that could affect airflow, filtration, or cleanliness. Common triggers include:

• Renovations or structural modifications
• Installation or replacement of major equipment
• Changes to HVAC systems or HEPA filters
• Process modifications that alter environmental conditions

Ongoing Monitoring

Between scheduled revalidations, continuous environmental monitoring (EMS) provides real-time data on temperature, humidity, pressure, and particle counts. Trends in this data can indicate performance drift and prompt corrective maintenance before compliance is compromised.

Routine monitoring also supports data-driven decision-making for predictive maintenance and operational improvements, ensuring that facilities stay audit-ready at all times.

Who Performs Validation?

Cleanroom validation can be executed by internal quality and engineering teams or outsourced to specialized third-party validation providers. The choice depends on facility size, available expertise, and regulatory requirements.

Internal Validation Teams

Organizations with in-house validation departments often handle routine monitoring, documentation, and minor requalification activities. Internal teams typically have detailed knowledge of the facility layout and operational processes, which helps streamline ongoing compliance efforts.

Third-Party Validation Providers

Independent validation specialists are often engaged for initial commissioning, major revalidations, or regulatory audits. These providers offer:

• Certified equipment and calibrated instruments
• Independent verification of performance data
• Documentation packages aligned with FDA, EMA, and ISO standards

Selecting a qualified validation partner with experience across ISO 14644, GMP, and 21 CFR Part 11 compliance ensures objective testing and traceable results.

Importance of Independence and Traceability

Whether performed internally or externally, validation must adhere to Good Documentation Practices (GDP). Each test result should be traceable, signed, and archived to provide verifiable evidence of compliance. This traceability is critical during inspections and regulatory reviews.