Validation

Performance Qualification

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.

Depending on your needs and the complexity of the system, Performance Qualification can be combined with Installation Qualification or Operational Qualification.

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.

HVAC Qualification

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.

Executed Tests:

• 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.