Performance Qualification of Isolator Systems
PROCEDURE
Validation Test Procedure:
- Air velocity measurement studies
- Integrity testing of HEPA filters
- Differential pressure monitoring
- Non-viable particulate monitoring
- Power failure recovery study
- Airflow direction
- Microbial monitoring
- Lighting and sound level monitoring
- Temperature and RH monitoring
- Bio-decontamination study
- Chamber leak test
Chamber and Glove Leak Test:
Objective:
To demonstrate that the isolator leak rate meets class-IV containment enclosure as per ISO 10648-2:1994(E)
To demonstrate that the there is no leakage in the gloves attached to the isolator.
Test Requirements:
- Calibrated digital thermometer
- Calibrated thermometer
- Calibrated Differential pressure gauge
- Compressed air
The room temperature and barometric pressure shall be measured during the test with the thermometer and barometer set up close to the isolator.
Before starting the leak test, the temperature and pressure in the containment enclosure to be tested and the test room shall be allowed to stabilize.
Set up the containment enclosure positive pressure to the required value of 250 Pa and then close the extract valve.
When the pressure and the temperature are stabilized, isolate the containment enclosure by shutting the valves, and measure the temperature and pressure in the containment enclosure for an hour at 15-minute intervals, together with the ambient pressure.
The first and last readings are used for the evaluation; the intermediate readings are used to control the test conditions.
During the test (duration 1 h) the following conditions should be fulfilled:
- Internal enclosure relative pressure Variation shall be lower than 30 % of the initial value.
- Internal temperature variations shall be lower than ± 0.3 °C.
- Atmospheric pressure variations shall be lower than 100 Pa.
Air velocity measurement studies:
HEPA
Filters Integrity Test
[DOP (Di-Octyl Phthalate) POA (Poly alfa olefin)]:
Test Requirements:
- Calibrated Aerosol
photometer
- Calibrated
DOP
PAO generator - Compressed
air/Nitrogen
Procedure:
Differential Pressure Monitoring:
Test Requirements:
Procedure:
Acceptance Criteria:
Filtration isolator pressure should be 60-80 Pascal
Manufacturing and External washing isolator pressure should be not less than -40 to -60 pascals when compared with an adjacent room. Pressure drop across BIBO filters should be in the range of 50 to 200 Pascals.
Temperature & Relative Humidity Monitoring:
Test Requirements:
- Calibrated Datalogger
- Calibrated temperature and RH transmitters
Procedure:
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.
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.
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.
Temperature and relative humidity study shall be conducted with extended hour’s production run to establish the maximum heat load during operation.
Acceptance Criteria:
Temperature inside the isolators should be not more than 23+ 2 °C.
Relative Humidity inside the isolators should be not more than 55 + 5 %.
Non Viable Particulate Monitoring:
Objective: The objective of this test is to verify that the concentration of airborne particles inside isolators meets the ISO class requirements.
Test requirements: Calibrated non viable particle counter
Procedure: Switch on the isolators in process mode. Verify the set values for inlet air speeds and differential pressure across HEPA filters of all isolators.
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.
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.
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.
Connect the probe to the sampling port. Position the sampling probe vertically upward. For operational condition, all the machine should run at optimum speed.
Acceptance criteria:
> 0.5 micron particles - NMT 3520
> 5.0 micron particles - NMT 29
Power failure Recovery Study:
Objective: The objective of this test is to verify that the effect of the power failure on the concentration of airborne particles inside isolators.
Test Requirements: Calibrated Non - viable particle counter
Procedure: Ensure that the entire isolators are clean.
Ensure that the Non - viable particle counter is in a valid state with valid calibration certificate.
Set up the particle counter at the center of the isolator.
The sampling rate should be one minute and set the delay time of the particle counter to not more than 10 seconds.
Switch ON the isolators.
After about 30 minutes start the airborne particle counter in auto mode at rest state.
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.
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.
Acceptance Criteria:
Isolator should maintain the class limits minimum two minutes during the power failure.
Time taken to recover almost all equal to initial count should not be more than 5 minutes for all filling line isolators.
Lighting and Sound level monitoring:
Objective: The objective of this test is to verify that the lighting inside isolators and sound levels from isolators.
Test Requirements:
Calibrated Light intensity meter
Calibrated sound level meter
Procedure:
Ensure that the entire isolators are clean.
Switch “ON” the isolators. Let the blowers run for 30 minutes for stabilization.
Set the light intensity meter in the range of 0-1999 LUX and take the readings from the workplace.
Set the sound level meter weighting in A-level, range in 50~80 and response in Full scale.
Take the sound level readings from the distance of one meter and record the details.
Acceptance Criteria:
Lighting levels inside the isolators should not less than 500 LUX.
Sound levels from the distance of one meter should not more than 90 dB.
Air Flow Direction (Smoke Test):
Objective:
To verify the unidirectional parallel airflow throughout the positive isolators and the capability of the HEPA filter unit to limit the dispersion and turbulence of air so as to maintain ISO - 5 environmental conditions.
To verify the negative air flow through the negative isolators so as to maintain the negative pressure inside the isolator.
Test Requirements: Fog generator (Glycerin) and Digital camera
Procedure: Switch “ON” the isolators. Let the blowers run for 30 minutes for stabilization.
Hold the smoke generator pointing in the direction of airflow below the HEPA filter.
Verify that the path of smoke is parallel to the airflow direction.
Take video at each point. Ensure that the installed equipment is cleaned and sanitized immediately after performing the test.
Acceptance Criteria: The Smoke Flow Pattern should coincide with the designed specifications laid down in the isolators manual and should maintain
- The unidirectional air flow up to the working height
- The flow from the HEPA to the Exhaust Cut out
Microbiological Environmental Monitoring:
Objective: The objective of this test is to verify that the isolators can maintain the required cleanliness with respect to microbiological contamination as defined in international Standards.
Test Method: Three types of tests shall be carried out under microbial monitoring i.e. Active Sampling, Passive Sampling and surface monitoring.
Passive Air Sampling (Settle plate method):
Switch “ON” the isolators. Let the blowers run for 30 minutes for stabilization. Expose the labeled plates at the designated locations inside the Isolators listed in Appendix-3.
Ensure that the surface of the agar is open to the environment by removing the lid of the Petri plate and placing it in the adjacent position.
After completion of the exposure period of for 4 hrs and note the time for exposure, close the lid and transfer the closed plate to the stainless steel container. Bring the container back to the Laboratory.
Keep one un-exposed plate from a lot of plates carried into the manufacturing areas as negative control and label it accordingly.
Incubate all the exposed SCDA plates along with the negative control at 20 -25°C for 3 days, followed by 30-35°C for 2 days.
Perform passive sampling under the Filling line isolators daily for a period of 03 days.
Active Air Sampling: Switch “ON” the isolators. Let the blowers run for 30 minutes for stabilization.
Keep the air sampler at the designated location, place the labeled plate in the aspirating head and open the Petri plate cover.
Take care not to touch the inside of the Petri plate cover and the sieve during this operation.
Close the aspirating head with the sieve and start the air sampler to sample 1000 liters (1 m3) of air.
Expose the labeled plates at the designated locations inside the Isolators listed.
Incubate all the SCDA plates at 20–25°C for 3 days, followed by 30-35°C for 2 days.
Perform Active air sampling under the isolators daily for a period of 03 days.
Surface monitoring (Swab method):
Switch “ON” the isolators. Let the blowers run for 30 minutes for stabilization.
Identify the locations which are to be sampled by swab.
Wet swab by dipping in sterile saline and swab the surface of 25 cm2.
Transfer the swab into the sterilized saline tubes and transfer to laboratory but do not store exceeding the swab hold time period.
Incubate the media Petri plates contains filter after completion of filtration at 20–25°C for 3 days, followed by 30-35°C for 2 days.
Perform surface monitoring under the isolators daily for a period of 03 days.
Acceptance Criteria:
Grade |
Air
Sample (Cfu/m3) |
Settle
plate (cfu/
Plate) |
Surface
monitoring (cfu/swab) |
A |
<1 |
<1 |
<1 |
C |
100 |
50 |
25 |
- VHP Generator (Fogstar Power Jet)
- Hydrogen Peroxide (15%) + Peroxyacid (0.2%)
- Active air sampling (Volumetric air sampling)
- Passive air sampling (Settle plate method)
- Surface monitoring (Swab method)
- Change of location.
- Break down of Critical parts.
S.NO. |
TESTS
TO BE CARRIED OUT |
FREQUENCY |
1. |
Air velocity measurement studies |
6 months + 2 weeks |
2. |
Integrity testing of HEPA filters |
6 months + 2 weeks |
3. |
Differential pressures monitoring |
During operation |
4. |
Temperature and Relative humidity monitoring |
During operation |
5. |
Non-viable particulate monitoring |
During operation |
6. |
Power failure recovery study |
Annually + month |
7. |
Airflow direction |
Annually + month |
8. |
Microbial monitoring |
During operation |
9. |
Bio-Decontamination |
6 months + 2 weeks |
10. |
Chamber and gloves Leak test |
6 months + 2 weeks |
11. |
Lighting and sound levels |
Annually + month |
0 Comments
If you have any doubts, please let me know
Emoji