- Pharmaceutical Equipment
- Lab Equipment
- Air Handling Units
- Pharmaceutical Equipment
- Lab Equipment
- Air Handling Units
- Thermal Mapping
- Stores Mapping
- High-rise Warehouse
- Cold Stores
- Pharmaceutical Equipment Mapping
- Stability Walk-in Chambers
- Stability Chambers
- Hot Air Ovens
- Steam Sterilizers
- Depyrogenation Tunnels
- HVAC Qualification
- Air Velocity and Air Changes
- Differential Pressure Test
- HEPA Filter Leakage Test
- Air Flow Visualization (Non‐unidirectional flow)
- Airborne Particle Count
- Environmental Conditions – Temperature and Relative Humidity
The Installation Qualification Protocol verifies the proper installation and configuration of a System. This can include ensuring that necessary files have been loaded, equipment has been installed, the necessary procedures have been approved, or the appropriate personnel have been trained. The requirements to properly install the system were defined in the Design Specification. Installation Qualification must be performed before completing the Operational Qualification or Performance Qualification.
Depending on your needs and the complexity of the system, Installation Qualification can be combined with Operational Qualification or Performance Qualification.
Installation Qualification protocols should be approved before protocol execution. A copy of the unexecuted protocol should be kept in the validation package. The unexecuted protocol should be approved by the System Owner and Quality Assurance. The executed protocol should be signed by the tester and reviewed by the system owner and Quality.
What is the definition of Installation Qualification?
The FDA definition of installation qualification is: Establishing confidence that process equipment and ancillary systems are compliant with appropriate codes and approved design intentions, and that manufacturer recommendations are suitably considered. In practice, the installation qualification is the executed test protocol documenting that a system has the necessary prerequisite conditions to function as expected.
The Operational Qualification Protocol is a collection of test cases used to verify the proper functioning of a system. The operational qualification test requirements are defined in the Functional Requirements Specification. Operational Qualification is usually performed before the system is released for use.
Depending on your needs and the complexity of the system, Operation Qualification can be combined with Installation Qualification or Performance Qualification.
Operational Qualifications should be approved before protocol execution. A copy of the unexecuted protocol should be kept in the validation package. The unexecuted protocol should be approved by the System Owner and Quality Assurance. The executed protocol should be signed by the tester and reviewed by the system owner and Quality.
What is the definition of Operational Qualification?
The FDA definition of operational qualification is: Establishing confidence that process equipment and sub-systems are capable of consistently operating within stated limits and tolerances. In practice, the operational qualification is the executed test protocol documenting that a system meets the defined functional requirements, or that the system does what it’s supposed to do.
Performance Qualifications are a collection of test cases used to verify that a system performs as expected under simulated real-world conditions. The performance qualification tests requirements defined in the User Requirements Specification (or possibly the Functional Requirements Specification). Sometimes the performance qualification is performed by power users as the system is being released.
Performance Qualifications should be approved before protocol execution. A copy of the unexecuted protocol should be kept in the validation package. The unexecuted protocol should be approved by the System Owner and Quality Assurance. The executed protocol should be signed by the tester and reviewed by the system owner and Quality.
What is the definition of Performance Qualification?
The FDA definition of performance qualification is: Establishing confidence through appropriate testing that the finished product or process produced by a specified process meets all release requirements for functionality and safety and that procedures are effective and reproducible. In practice, the performance qualification is the executed test protocol documenting that a system meets the defined requirements to function in the production environment.
Temperature Mapping is performed to determine if a storage area can maintain temperature within defined limits (Fridges, Freezers, Rooms, Warehouses and Incubators etc.). Sensors are distributed throughout the unit/room in pre-defined locations to confirm it performs within pre-defined set points.
The storage area is further challenged with additional tests such as empty mapping, loaded mapping, door open, power failure, pull down tests, fan failure etc. which are all performed to demonstrate the unit controls within pre-defined parameters and to determine the position of permanent monitoring/alarm probes.
We perform humidity mapping on storage areas that contain product which may be impacted by a change in humidity, stability cabinets and humidity chambers. Humidity should form a part of the risk assessment to determine if monitoring and mapping is required.
When performing humidity mapping it is important to ensure the humidity data loggers are calibrated for the range you are testing.
The duration of temperature map should show the stability of the unit and identify any routine changes within the use for example a defrost cycle. Your site may already have a Validation Master Plan (VMP) or procedure with the mapping durations detailed. The table below shows some typical examples for temperature mapping durations:
|Fridge, Freezer, Incubator
|24 Hours to 7 Days
For warehouses it is important to consider the movement of people, fans, doors opening and closing, seasonal variations. It is important to consider the impact of these variations including changes in shift patterns or the week and weekend. It is also important to understand the temperature distribution during seasonal variations by performing winter and summer maps.
In the pharmaceutical industry qualification of HVAC systems is done by using a risk based approach. Failure mode effect analysis (FMEA) concepts were used for risk assessment of a HVAC system to determine the scope and extent of qualification and validation in this present work. The HVAC is the “direct impact” system in the aseptic practice which directly affects the product quality and regulatory compliance. The level of risk associated with the HVAC system was assessed based on the impact and severity of the probable risk in aseptic practice in sterile manufacturing. On completion of the risk assessment, control and measures developed and recommended actions for unacceptable risk were identified for improved cGMP compliance and qualification of the system upgrades. After completion of the risk assessment the recommended actions were extended and verified against the qualification stages of the HVAC system. Finally, the HVAC system was subjected to a performance qualification (PQ) study. All of the tests were performed and a report was generated. On evaluation of the data collected during PQ, it was found that the HVAC system met all the specified design criteria and complied with the entire cGMP requirement. Hence the system stands validated for PQ.
Air Velocity and Air Changes
- Velocity at the inlet air grills was measured at 5 points in a plane parallel to filter face plane and at a distance of about 6 inches (~ 150mm) from the filter/opening face. The velocity was measured for at least 10 seconds from each point. It is performed by thermal anemometer and vane type anemometer and calculated by formula where, D is no. of air changes, B is air supply volume (CFM), R is volume of the room (ft3), 60 is factor (for air change per hour).
Differential Pressure Test
- Measure and record the pressure difference between the room to be tested and any surrounding ancillary environment.
HEPA Filter Leakage Test
- Position the aerosol generator to introduce an aerosol challenge upstream of the HEPA filter to a concentration of 20‐100mg/m³ (20–100 µg/lit.) of air by opening appropriate number of nozzles. Measure upstream concentration of aerosol by using upstream port. Adjust the photometer’s gain / span control for a full‐scale deflection on 100% range. Scan the downstream side of the HEPA filter. The photometer probe should be about 1 inch from the surface and at a transverse rate not more than 10ft/minute with a sample flow rate of 1cft/min ± 10%
Air Flow Visualization (Non‐unidirectional flow)
- Generate the tracer particles by water for injection (WFI) fogger. Position the tracer at the appropriate place, such as at the downstream of supply air and the return air risers as well as at the doors opening and check for the indication of the airflow direction. Record the airflow pattern using photography/videography
Airborne Particle Count
- Derive the number of sampling point locations by using the equation where, NL is the minimum number of sampling locations and √A is Area of the room in square meter.
- Volume of sample (for grade A at rest and operation, grade B at rest) ‐1m3 equivalent to 35.3 ft3
- Volume of sample (for grade B at operation and other grades at both conditions) ‐1 ft3
Recovery/decontamination rate test
- Take the particle count in the area before aerosol generation under resting conditions. The sampling rate should be 1 CFM. Artificially generate DOP/PAO aerosol in the classified area and check the count (1000 times more than classified area “at rest”). Record the particle count and time. Stop the aerosol generator. The time at which the aerosol generator is stopped should be the starting time for establishing the recovery rate. Start the particle counting at the specified location at a sampling rate of 1 CFM. Establish the time required for attaining the “at rest” condition
Environmental Conditions – Temperature and Relative Humidity
- Digital hygrometers and a Sling hygrometer were used to perform the test for 5 consecutive days for category A1 AHUs and for 3 consecutive days for AHUs of other categories.