Qualification and Validation Matrix Single slider On Depyrogenation and Sterilization Tunnel Palash Chandra Das. (palash.ds@gmail.

Single slider On Depyrogenation and Sterilization Tunnel Palash Chandra Das. ([email protected] and [email protected])

What will be the potential cause for

Study Name Pictorial demonstration Why to perform ? What to verify ? What will be the Test Frequency ? Test Methodology
failure ?

Airflow Velocity The purpose of this test is to measure airflow velocity and uniformity, Air velocity should be maintained within 90 fpm ± 20% of mean unit velocity for even 6 Monthly considering a critical attribute to determine the tunnel HEPA filter integrity failure
Follow the standard ISO 14644-3
Test and supply airflow rates through the HEPA filter. distribution of temperature. performance Adjustment for air supply damper

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The standard ISO 14644-3 suggests a penetration of 0.01% of the test challenge concentration but
allows alternative criteria to be agreed between customer and supplier. The FDA Guidance, however,
Physical damage of filter media
Photometer reading downstream of the HEPA filtration unit caused by the leakage should indicates that 0.01% penetration is a leak.
Filter system The purpose of this test is to confirm that the filter system is properly 6 Monthly considering a critical attribute to determine the tunnel Ageing/ replacement frequency
be less than0.01% of the upstream challenge concentration of the aerosol 100% The ISO 14644-3 standard suggests a concentration ranging 10µg/l and 100µg/l should be used for
leakage Test installed and that leaks have not developed during use performance Improper installation /or alignment or/ potential
the photometry test method. It also suggests that concentrations lower than 20µg/l reduces sensitivity,
gaps between filters
and concentrations over 80µg/l give filter fouling. It is best to use the lower recommended
concentration to minimize the potential for blockage or a bleed-through event.

Failure in Filter integrity will be the potential cause

Differential The Tunnel zones are balanced per the manufacturer specifications. Individual differential pressure of individual zone are maintain with in predefined Can be monitor Daily during the batch processing with certain
Pressure balance in between Clean room/or N/A
pressure Air does not move from dirty to clean. operational limit /or design limit logical frequency /or interval
isolator adjacent to preheating and cool zone

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Place smoke generator near pre heating zone to visualize the flow from preheating to washing area.
During Initial qualification Place smoke generator near cool zone to visualize the flow from filling to cool zone area.
To review and visualize the pressure cascade in washing to preheating , heating to After major modification or breakdown e.g. HEPA replace , Blower Consider all the elements mentioned under Air Hot zone or/ sterilization zone is more pressurized than pre heating and cool zone , therefore the
Air flow
To understand and verify the uniformity and pressure cascading preheating and cool zone and filling to cool zone malfunction velocity, Filter integrity and Differential pressure smoke flow will be both the side during entering or exit from sterilization zone
visualization The entry hot and cooling zones demonstrate laminar air flow. Periodic verification after 2-3 year , based on the risk retirement category Pressure cascade will be follows,
plan Washing Area <Preheating zone <Sterilization zone >Cool Zone <Filling area

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Tunnel Belt / To ensure the tunnel conveyor belt speed meets the requirements as specified by OEM Mark the conveyer belt and run the tunnel conveyer belt for 30 second to 1 min (check with calibrated
Tunnel conveyor speed will help to establish a desire exposure time
(original equipment manufacturer) design qualification, installation qualification, During Initial Qualification and periodic qualification Conveyer motor change or frequent trip / over load stop watch)
Conveyor speed under the high temperature. Both will help to achieve predefine
operational qualification, and performance qualification, as well as annular- and damage Stop the conveyor and measure with calibrated measuring scale. Perform 3 time and consider the
verification Depyrogenation effect.
qualifications. . Conveyor speed shall not vary more than 3% of the set speed mean for final value

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The oven must meet specifications for total particulates, . less than The particle count test should be performed by qualified or trained person. Start blower of the sterilizing
Consider all the elements mentioned under Air
Nonviable Particle The particle counts taken under the HEPA filter in the different zones of sterilizing tunnel or equal to 100 for less than 0.5 micron per ft3 or less than or tunnel. Calculate the number of location need to be tested. Switch on particle counter and place the iso-
The purpose of this test is to provide a cleanliness in the supplied air. velocity, Filter integrity and Differential pressure
Count (NVPC) Test should meet the requirement of ISO 5/class A. equal to 3,500 for less than 0.5 micron per m3 and 0 for 5 micron
category
kinetic suction probes at specified location under the filter of conveyor belt of tunnel and observe the
per m3 reading, record in reports.

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During Initial Qualification and periodic qualification ( Industry

practice is once 2 yearly frequency)
Failure in the heater blank
To understand the uniformity of empty tunnel heat distribution pattern Distribution in the tunnel less uniform than autoclave. Therefore distribution thermocouples After major breakdown or/ maintenance activity of heating and Use zig plate to hold vial with the probes (sensor) in place as it help smooth travel through the tunnel.
Empty Heat Variation/or misalignment in individual pressure
in empty condition. It gives confidence on the over all design and are within a range of ± 15.0°C or more can be appropriate consideration based on the conveyor system based on the risked based approach Attach the connecting cable of probes (sensor) to data logger, which can scan the date, time and
distribution study control philosophy and shows how healthy is your tunnel. OEM (original equipment manufacturer) specification in design document. Apart from the Qualification in alternate way this test can be
Improper air flow
temperature of probes at every 10 seconds.
Air floe within tunnel and adjoining area
considered as maintenance check during preventive maintenance.

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Study Approach 1:
Heat penetration/load mapping study:
All the container configuration must be evaluated initially but later on container
configuration shows least FH value can be consider as worst one to challenge for periodic
qualification.
Confirmatory study for Depyrogenation: At least one heat penetration study using thermocouples will be Container enters to tunnel are wet therefore must The temperature sensor should to be place into direct contact with the glass item at the bottom-most
To ensure that heat is sufficiently penetrating into the inner most
Endotoxin study to be considered for the lowest FH configuration with least time- performed for complex load configuration. (6 monthly/or NMT 1 be evaluated for uniformity based on the drying the container.
Heat penetration portion of the vial subjected for sterilization and Depyrogenation to
temperature condition from the nominal (routine) cycle. Required to demonstrate minimum year) efficiency at washing machine by purging Sensor should to be placed to cover the tunnel width extreme right/ left corner and middle (highest
achieve desired heat Penetration and endotoxin log reduction
and Endotoxin efficiency of the Tunnel Sterilizer
3 log reduction. This is considered as worst case challenge to confirm Depyrogenation Temperature uniformity and delivery of heat will be documented. compressed air to get uniform thermal input. density) to get temperature measurement across width of conveyor belt.
challenge study efficiency. These studies can be combine with endotoxin challenge or Container complexity must be evaluated based on Get the spiked vials with approx. 10,000 EU/vial of bacterial endotoxin from microbiology. The recovery
Note: Challenge thermal probe and endotoxin unit should not less than
Performance Qualification: individual endotoxin studies can be performed with different the load mass and type of container (tubular or of endotoxin concentration after exposing to Depyrogenation tunnel should show more than 3 log
5 unit.
If time and temperature criteria is consistently meeting the require FH, then endotoxin frequency identified with risk based approach. molded). reduction.
challenge may be leverage considering confirmatory study out come.
Study Approach 2:
All temperature measured in the chamber is ≥ 300°C. Minimum cumulative FH
location will be determined for informational purposes only. The recovery of endotoxin
concentration after in sterilization and Depyrogenation should at least 3 log reductions.

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Cool Zone sterilization cycle provides better sterility assurance to avoid

the microbial contamination after sudden stoppage of machine or Firm should look into all the element which can
breakdown /or routine maintenance program . Temperature not less than 170 °C for 1 hr. to be observed. The most common time- impact the heating. Dry heat sterilization typically done in 160-190 °C where objective is sterilization rather than
In routine it is recommended to switch on the tunnel in Blower temperature relationships for sterilization with hot air sterilizers are 170 °C (340 F) for 60 Options include a sterilizable cool zone for improved sterility Ensure adequate closure of cool zone from Depyrogenation. It will perform in empty condition only as expectation to sterilize the zone not the
Cool Zone On/Night mode to maintain the Grade A (ISO 5) condition after minutes, 160 °C (320 F) for 120 minutes, and 150 °C (300 F) for 150 minutes. assurance. Industry practice for requalification is NMT 2 yr. but can sterilization zone and filling area to reduce potential containers.
sterilization completion of batch activity. When machine is completely stopped for Bacillus atrophaeus spores should be used to monitor the sterilization process for dry heat be different based on the practices and procedure followed by heat loss. Distribute sufficient numbers of thermocouples and Bacillus atrophaeus (ATCC No. 9372) biological
performing preventive maintenance or sudden break down because they are more resistant to dry heat than are G. stearothermophilus spores. individual firm. Calibration of sensors and data logger. indicators throughout the conveyor in the cool zone.
maintenance cool zone sterilization cycle need to be considered. Minimum 6 log reduction of biological indicator Bacillus atrophaeus. Selection , qualification and validity of biological Review temperature data after completion of cycle, collect the BI’s and submit the BI’s to micro for
Irrespective of maintenance a periodic qualification can be a way to indicators. incubation.
review and understand the reproducibility.

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Revision 01 , typographical correction , dated 16 Dec 2020

Prepared by Das, Palash Chandra 12/16/2020 Page 1