Cleanroom Validation Protocols in a Nutshell

Validation is of vital importance for any cleanroom. Its goal is to make sure the cleanroom is designed and installed according to its designated ISO classification, and all its components meet the necessary regulations and standards.

Cleanroom validation is often done by third-party agencies, and it requires a comprehensive inspection and a couple of tests. After the assessment is done, the cleanroom is certified to a particular class that indicates the control levels inside the area. Clean room validation is a multiphase process that begins with design qualification and finishes with final certification.

When the initial certification process is done, you need to ensure your cleanroom keeps operating the way it did when it was established. As a rule of thumb, cleanrooms should pass annual, semi-annual or quarterly certification, depending on the industry.

4 Phases of Cleanroom Validation Process

Cleanroom validation consists of several phases and different tests to determine the area’s cleanliness levels. Some of the evaluations included in these phases refer to airflow volume, velocity tests, HEPA/ULPA filter leak tests, smoke testing, airborne particle count tests, humidity, pressure, and temperature testing.

There are four main phases in clean room protocol:

What Tests Does Cleanroom Validation Process Include?

The following evaluations are commonly performed during the cleanroom certification process:

Airflow/Smoke Pattern

A smoke pattern or smoke study is one of the most important qualification parameters. It involves a smoke generator device that adds a visible fume in front of the HEPA or ULPA filters or in the area where the product should be exposed.

The main goal of the smoke study is to observe the airflow pattern and prove that the smoke has a similar density as the air. Namely, inadequate airflow might put your products at risk of damage.

Since the physical properties of the smoke play a vital role in the overall qualification process, this testing should be conducted by professionals using proper safety equipment.

Airflow Velocity/Changes per Hour

Another qualification test includes airflow velocity and changes per hour, which is performed on the HVAC system. This test uses a simple formula to calculate the average air velocity (V). The HEPA filter inlet area (A) is calculated in feet, while the total air volume (T) is calculated by multiplying the average velocity of the air and the inlet area (T=AxV).

To obtain the changes per hour rate, divide the total air change by the room’s volume.

Filter Integrity Testing

Filter integrity testing, also known as the HEPA filter leak test, is an obligatory part of cleanroom validation. During this testing, it is necessary to introduce particulates to challenge the filter and measure the output. The air velocity should be within the HEPA filter’s higher limit to meet the most common cleanroom requirements.

Viable Particle Monitoring

Viable monitoring is employed daily by using the swab test and nutrient agar medium for the microorganism incubation. The number of microorganisms should be according to standards and regulations. Otherwise, the investigation must be done to determine the root cause and preventive actions.

Non-Viable Particle Test

Particle count is performed at static conditions before the cleanroom has established operational working conditions. The particle count should be in the range of a specific cleanroom classification – ISO Class 1 – ISO Class 9.

Pressure Difference

The pressure difference is evaluated by using the manometer attached to the walls of the area. The pressure difference is typically kept positive from the cleanest site to the less clean zone, ranging from 1 and 20 mmHg pressure.

Temperature and Humidity Uniformity Test

The purpose of the temperature and humidity uniformity test is to prove that the cleanroom HVAC system is able to maintain the temperature and certain humidity levels within the recommended limits. The uniformity of humidity and temperature inside the cleanroom can be measured and monitored using a chart recorder, calibrated data logger, thermocouple, thermometer, manometer, etc.

Recovery Test

The principle goal of the cleanroom recovery test is to check the amount of time necessary for the environmental conditions in the cleanroom to return to a regular state of control after a specific particle generation event.

Potential Cleanroom Test Failure

All test failures will be recorded in the test documents and reports, which must be submitted to the management team for further investigation and assessment. The quality team will later identify the course of action and determine whether any additional testing is needed. Besides, the team can order some preventive measures to tackle the deviation.

Once the cleanroom has passed all the evaluations and the issues have been solved, the cleanroom is ready to continue the validation process.

FDA Clean Room Requirements

According to the FDA (Food and Drug Administration), a cleanroom is an isolated environment, strictly controlled in terms of temperature, humidity, air pressure, airflow, air motion, lighting, and particles of viable and non-viable nature.

The FDA has set specific regulations regarding pharmaceutical cleanrooms and facilities that handle food and drug production. These regulations aim to prevent contamination and reduce the risk of incidents involving food or drug damage.

For that reason, all industries involving pharmaceuticals, foods, and drugs must abide by the FDA standards that refer to the following:

• Cleanroom planning and construction
• Clean air standards
• Humidity, air pressure, temperature, and dust control
• Air filtration system
• Cleaning and sanitizing surfaces and equipment

ISO Cleanroom Specifications

The ISO 14644 standards determine the classification of air cleanliness based on the concentration of airborne particles in cleanroom environments. ISO classifications range from 1 to 9, where ISO Class 1 is considered the cleanest while ISO Class 9 is the “dirtiest.” Most industries require ISO 5 – ISO 8 cleanrooms for their daily operations.

Look at the chart below to understand ISO regulations better:

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Cleanroom Classification Grades

While the ISO classification system is broadly used in the US and Canada, cleanrooms across Europe, Australia, and Asia abide by the grading system. While grade A refers to the cleanest cleanrooms and sterile operations, grade D is suitable for packing or support applications in the pharmaceutical industry.