There are four parts to the qualification process that need to be completed for using a cleanroom for its intended purpose:
• Design Qualification (DQ)
• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)
Performance qualification is one of the key steps in the process. Performance qualification focuses on confirming that the facility and process equipment perform as intended and meet predetermined acceptance criteria over a specified period. Performance qualification refers to the activities undertaken to demonstrate that facilities, building systems, and process equipment are suitable and perform as specified in project design documents.
Any system parameters that could directly impact the quality of the product being manufactured or filled in that cleanroom should undergo testing
In PQ, there are a series of tests that must be conducted to confirm that a cleanroom performs as it is intended. These are generally written as separate test cases. Each test case will have a title, a document number, and a version number. Each test case will have:
1. An objective specific to that test case
2. A procedure for executing that test case
3. The acceptance criteria for each instruction in the test case
The purpose of this article will be to provide a general overview of the testing procedures associated with the performance qualification process.
Any system parameters that could directly impact the quality of the product being manufactured or filled in that cleanroom should undergo testing. The environmental parameters to be tested will include room pressurisation, air purity, temperature, and relative humidity.
Room Pressurisation
Test and balance verification – Confirmation that all HVAC systems are installed and set up to generate the proper supply and exhaust air volumes to meet the desired air change rate and cooling requirements of the equipment.
Room air pressurisation testing confirmation – In a cleanroom, the room pressurisation should minimise the introduction of uncontrolled air supply with an undefined number of particles into the space. The cleanroom is maintained at a higher pressure to protect the cleanroom from contamination from adjacent less clean spaces. Without the proper levels of differential air pressure between spaces, contaminates could pass from a lower-pressure to a higher-pressure space and contaminate cleaner areas. Also, control of these differential air pressures is essential and must be tested over a specified time period to ensure proper function. Controlling pressure during a 24-hour test is an example of a test case commonly used for certifying cleanrooms. A guideline of 15 Pa (or .06” w.c.) is used as a target differential pressure between spaces.
Room airflow confirmation – Without the proper pressurisation, the room airflow confirmation would not be possible. Cleanroom tests that are part of the performance qualification test cases will confirm that the air moves in the correct direction between areas. The air direction through doorways, hatches, etc., should be from clean to less clean.
Air Purity
HEPA air volume and air change rate verification (including air velocity) – This test will confirm that the air volume and speed are within the specified ranges for the filters being tested. With a volume that is too low, the system might fail the particulate test due to the lack of air changes (ACH) required to meet the room classification. The air velocity test will ensure that the velocity is uniform across the filter, which could create turbulent air or airflow patterns in the clean space. Air velocities between 90—100 fpm are a generally accepted target velocity for most filter manufacturers. Velocities higher than a manufacturer’s recommendations might damage the filter due to the speed at which the air passes through the filter.
HEPA filter integrity testing and verification – This testing procedure is conducted by introducing an aerosol upstream of the filter and then measuring with a scan detector the amount of the aerosol that penetrates the filter. The test will confirm that the filters have an efficiency of 99.99% for particulate sizes greater than 0.3 microns or larger while operating at normal conditions.
The quality team will determine the course of action and whether additional testing or data is required
Particle count verification – After a risk assessment is performed to determine critical areas in the cleanroom where an exposed product might be vulnerable to contamination, someone qualified to perform the test will conduct a non-viable particle count test. The tests can be performed in one of two states or possibly both states. The first state is an “at rest” state. The second state is an “in operation” state. The test will collect samples of particulates to determine the size and concentration of the particulate matter in the space. The International Standards Organization (ISO) has published the 14644-1:2015 document which specifies the maximum concentration limits for each classification. After the initial commissioning of the classified space, a monitoring program will be implemented to confirm that the particle counts remain at the appropriate levels.
Room classification verification – Each cleanroom is certified for the intended classification requirements of each space. Each cleanroom will be certified to perform at a level that is commensurate with the work that is being conducted in that space. For example, in a fill finish operation, the classification for the space might be an ISO class 5. For this classification, the maximum number of particles is 3,520 particles/cubic meter for airborne particulate in the “in operation” state.
Temperature and Humidity
The process being performed within each cleanroom will determine the allowable ranges of temperature and humidity, which are established by the manufacturing and the quality teams. These ranges will be specified in the User Requirement Specification (URS) and subsequent project engineering documents such as the functional specification. Each cleanroom will need to demonstrate the ability to control the temperature and humidity within the ranges over a period of time.
Additional Testing
In addition to environmental control there are other tests that will need to be performed as well. These tests are:
• Recovery Test
• Ambient Light Verification
• Sound Level Verification
• Vibration Level Verification
• Security Testing
• System start up and shut down verification
• Alarm function testing
• Automation software and HMI testing
• Fault condition testing
• Smoke Study Testing
• Software Validation
For the tests performed, all test failures will be noted in the test documents and in a deviation report. All deviations must be submitted to the site quality team or a member of the senior management team for review, investigation, and assessment. The quality team will determine the course of action and whether additional testing or data is required. The quality team might also assign corrective and preventative actions to address the deviation.
When all corrective and preventive actions are complete, the site quality team shall perform the final close-out of the deviation report. Once the cleanroom has passed all test cases and all deviations have been resolved, the cleanroom is ready for the next phase of the validation process.
