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1.0 PROCEDURE
1.1 Validation Test Procedure:
The HVAC system will be considered qualified for consistent and reliable performance (Validated) on successful completion of the following tests.
1.1.1 Air velocity measurement studies
1.1.2 Integrity testing of HEPA filters
1.1.3 Differential pressure monitoring
1.1.4 Non-viable particulate monitoring
1.1.5 Power failure recovery study
1.1.6 Airflow direction
1.1.7 Microbial monitoring
1.1.8 Lighting and sound level monitoring
1.1.9 Temperature and RH monitoring
1.1.10 Bio-decontamination study
1.1.11 Chamber leak test
To qualify the System, above tests should fulfill the acceptance criteria described in the individual test procedures. After completion of the
qualification tests, all the data generated will be compiled together to evaluate the ability of the isolator system to maintain the designed conditions.
To demonstrate that the air system is capable to balance and delivering sufficient air volumes to maintain a minimum cross-sectional velocity under
the HEPA filter should be 0.45 m/s + 20% measured 6 inches downstream of the HEPA filter of Filling line isolator.
1.3.3 Procedure:
1.3.3.1 Switch “ON” the Blowers of the isolators; let the blowers run for 15 minutes for stabilization.
1.3.3.2 Measure the Air Velocity of HEPA filter in Feet per Minute for each filter by placing the sensor of the instrument at approximately 6 inches
below the grill and 6 inches away from the edge of filter grill. Take 5 readings as shown in the figure and average the 5 readings.
1.3.3.3 Multiply the result by 60 to determine the throughput per hour.
1.3.3.4 If there is more than one filter in the room, add the volume of air (throughput per hour) of each filter.
1.3.3.5 Divide the total air volume delivered (throughput per hour) into the room by room volume to get air changes per hour.
1.3.3.6 Multiply the average velocity by the calibration factor of the instrument and record the readings.
1.3.3.7 Measurement should be taken for a minimum of 15 seconds.
1.3.4 Acceptance Criteria: A minimum cross-sectional velocity under the HEPA filter should be 0.45 m/s + 20% or 90 FPM+ 20%.
1.4 HEPA Filters Integrity Test [DOP (Di-Octyl Phthalate) POA (Poly alfa olefin)]:
1.4.1 Objective: To establish the integrity of the HEPA filters installed in the isolators.
1.4.3 Procedure:
1.4.3.1 Switch “ON” the Blowers of the isolators. Let the blowers run for 15 minutes for stabilization.
1.4.3.2 Directly test aerosol at the DOP PAO port by giving adequate pressure using nitrogen or compressed air at test pressure not less than 1.5
kg/cm2.
1.4.3.3 Switch “ON” Aerosol Photometer and allow for stabilization for five minutes.
1.4.3.4 DOP upstream concentration should be 20 to 80 mg/liter of air. Adjust baseline concentration as 100 % and check for detection in the
photometer.
1.4.3.5 Scan the HEPA Filter surfaces and periphery at a traverse rate of not more than approximately 10 ft/min by passing the receptor probe 1 inch
from the filter surface, in overlapping strokes for any leakage.
1.4.3.6 Any leakage greater the acceptance criteria observed during scanning shall be identified and recorded.
1.4.4 Acceptance Criteria: During scanning percentage of the DOP PAO penetration shown by photometer should be less than 0.01% through the
filter media and should be “zero” through mounting joints.
1.6.3 Procedure:
1.6.3.1 Before starting the study ensure that Air conditioning system of isolators is in continuous operation for at least one hour prior to performing
these tests.
1.6.3.2 Ensure that the measuring instrument is in the calibrated state with a valid calibration certificate. Place the temperature and RH transmitters
as per the location mentioned in the Appendix-1.
1.6.3.3 Distribution studies shall be performed at working height level. Monitor the temperature and relative humidity inside the isolators for a
minimum of 24 hours with an interval of 5 minutes.
1.6.3.4 Temperature and relative humidity study shall be conducted with extended hour’s production run to establish the maximum heat load during
operation.
1.7.3 Procedure:
1.7.3.1 Switch on the isolators in process mode. Verify the set values for inlet air speeds and differential pressure across HEPA filters of all isolators.
1.7.3.2 Allow the isolators stabilize at this operating condition for approximately 30 minutes. Record the actual values of inlet air speeds and
differential pressure across HEPA filters of all isolators.
1.7.3.3 Connect the measuring probe with silicon hose to the particle counter. Set the particle counter according to appropriate test equipment
operating procedures at different sampling locations mentioned in the attached drawing of Location mentioned in Appendix-2 of Non-Viable Particle
Count Monitoring in the isolators at the working height.
1.7.3.4 The air sample volume from each location shall be 1 m3. Run the counter using 0.2-micron purge filter to purge the sampling port. Perform
this test during start-up of the test.
1.7.3.5 Connect the probe to the sampling port. Position the sampling probe vertically upward. For operational condition, all the machine should run
at optimum speed.
1.8.3 Procedure:
1.8.3.1 Ensure that the entire isolators are clean.
1.8.3.2 Ensure that the Non - viable particle counter is in a valid state with valid calibration certificate.
1.8.3.3 Set up the particle counter at the center of the isolator.
1.8.3.4 The sampling rate should be one minute and set the delay time of the particle counter to not more than 10 seconds.
1.8.3.5 Switch ON the isolators.
1.8.3.6 After about 30 minutes start the airborne particle counter in auto mode at rest state.
1.8.3.7 Switch OFF the isolators after about one minute sample to simulate the power failure condition and check the time at which the cumulative
count of either 0.5 or 5m particle exceeds the limit.
1.8.3.8 Switch ON the isolators and check the time at which the cumulative count of both 0.5m or 5m particles are almost equal to the initial counts.
1.9.3 Procedure:
1.9.3.1 Ensure that the entire isolators are clean.
1.9.3.2 Switch “ON” the isolators. Let the blowers run for 30 minutes for stabilization.
1.9.3.3 Set the light intensity meter in the range of 0-1999 LUX and take the readings from the workplace.
1.9.3.4 Set the sound level meter weighting in A-level, range in 50~80 and response in Full scale.
1.9.3.5 Take the sound level readings from the distance of one meter and record the details.
1.10.3 Procedure:
1.10.3.1 Switch “ON” the isolators. Let the blowers run for 30 minutes for stabilization.
1.10.3.2 Hold the smoke generator pointing in the direction of airflow below the HEPA filter.
1.10.3.3 Verify that the path of smoke is parallel to the airflow direction.
1.10.3.4 Take video at each point. Ensure that the installed equipment is cleaned and sanitized immediately after performing the test.
1.10.4 Acceptance Criteria: The Smoke Flow Pattern should coincide with the designed specifications laid down in the isolators manual and should
maintain
1.10.4.1 The unidirectional air flow up to the working height
1.10.4.2 The flow from the HEPA to the Exhaust Cut out
2.0 RE-QUALIFICATION:
2.1 Un Scheduled Revalidation:
Revalidate the equipment in the following cases:
2.1.1 Change of location.
2.1.2 Break down of Critical parts.
3.0 RECORDING:
3.1 Record the observation after the execution of each test procedures in the performance qualification record.
3.2 Compile and review that all test functions have been completed, reconciled and attached to this protocol. Verify that the approvals for deviations
have been taken and are resolved appropriately to the satisfaction.
3.3 Prepare the summary report and submit this for approval and authorization to Validation Core Team.
3.4 Document the discrepancies observed during the Performance qualification of the equipment in performance qualification record.
3.5 When all the discrepancies are satisfactorily resolved or an approved action plan is developed which ensures that the discrepancy will be
resolved.
3.6 Training shall be conducted before commencing the validation studies and record the same in training format.
4.0 REFERENCES:
4.1 ISO 10648-2, Classification according to leak tightness and associated checking methods.
4.2 ISO 13408-6, Aseptic processing of health care products-Isolators.
4.3 Area fumigation with Hydrogen peroxide vapor, Steris Corporation, Mentor, Ohio
4.4 VHP cycle development report for a 6 glove isolator, Walker barrier system
Submitted By:
Alluri Sitaramaraju
Estima Pharma Solutions
E-mail - alluri2025@estimapharma.com
Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read
pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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