HVAC / Cleanrooms Qualification

An integral component of any pharmaceutical production is cleanrooms, which enable the manufacturing of medicinal products in an air environment of a specified quality according to the selected cleanliness grade. The quality parameters of the air in a cleanroom depend on a number of factors determined by different systems/structural elements/design aspects:

Heating, Ventilation & Air Conditioning system (HVAC – Heating, Ventilation & Air Conditioning, air treatment in a central air conditioning unit/air handling unit/AHU).
Air duct distribution system, through which air is supplied and removed from the rooms.
Terminal filtration system using HEPA filters for air supply into the room.
Location of air supply and exhaust grilles in the room, airflow patterns, and air mixing efficiency.
Materials used for the internal finishing of the cleanroom (surfaces).
The presence of dead zones, gaps, or recesses where dust can accumulate.
The airtightness of the cleanroom structures.
Electrical conductivity (static charge) on the elements of the cleanroom's enclosing structures.

To ensure a holistic risk-based approach, all these factors must be considered and, depending on the cleanliness class and risk level, tested during validation activities. The scope of validation activities for cleanrooms generally includes:

Installation Qualification (IQ)
Operational Qualification (OQ)
Regular requalification, which can also be regarded as Performance Qualification (PQ)

Since one air handling unit typically services a group of rooms, and the scope of qualification tests is quite large, it is practical to separate the qualification activities into protocols for the qualification of individual air handling units (and associated ductwork systems) and protocols for the qualification of individual cleanrooms.

For air handling units and associated ductwork systems, isolated IQ and OQ tests are performed in a similar manner to technological equipment and clean utilities systems.

IQ and OQ tests for cleanrooms are also carried out individually for each room, based on a general protocol template for rooms of a given cleanliness class. The tests performed differ significantly from other validated equipment. Furthermore, when conducting the OQ of cleanrooms, it is assumed that the ventilation (HVAC) systems are operational and functioning correctly.

The Operational Qualification (OQ) of cleanrooms is performed according to the standard ISO 14644-3 “Cleanrooms and associated controlled environments. Part 3: Test Methods.”

As a rule, the scope of OQ for cleanrooms includes the following tests:

Measurement of static differential pressure
Temperature
Relative humidity
Determination of air supply volume/velocity (calculation of air exchange rate)
Integrity testing of the installed filtration system
Confirmation of cleanliness class based on the concentration of airborne particulate matter

In special cases, including higher cleanliness classes, the following additional tests may be conducted:

Airtightness testing of the enclosing structures
Determination of recovery time (based on particulate matter concentration)
Airflow visualization
Measurement of static electricity
Determination of lighting levels

The qualification of cleanrooms requires specialized measuring equipment, including:

Differential pressure manometer
Thermohygrometer
Balometer/anemometer
Discrete laser particle counter for airborne particulates
Aerosol particle generator with calibrated particle size (for HEPA filter integrity testing)
Aerosol diluter (for HEPA filter testing)

Cleanroom qualification is a labor-intensive and time-consuming process. In addition to measuring equipment, at least two specialists and ladders/elevating equipment are required to access ceiling air supply grilles. Additionally, supply grille filter holders must be equipped with special ports for aerosol injection and concentration measurement above the filter. Considering the significant time required to move and connect the equipment in each room and to each grille, conducting OQ for a single room takes an average of 1–2 hours or more.

The specialists at Tarqvara Pharma Technologies have years of experience in conducting qualification, validation, and acceptance tests within the pharmaceutical industry, in full compliance with international, European, and national GMP/GxP regulations and standards.