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Performance Qualification Protocol for Sterilization and Depyrogenating Tunnel


Validation Protocol for Sterilization and Depyrogenating Tunnel used in sterile production.

1.0  PERFORMANCE QUALIFICATION TEST

Following Performance Qualification studies shall be carried out to ensure the equipment for proper operation and its ability to sterilize and depyrogenate the washed vials at the set parameters, repeatedly & consistently.
·  Air Velocity measurement.
·  HEPA FILTER Integrity test by DOP / PAO Aerosol test.
·  Air flow pattern test.
·  Non-viable airborne particle count test.
·  Heat Distribution studies.
·  Heat Penetration studies.
·  Endotoxin Challenge study.

To qualify the test the equipment should fulfill the acceptance criteria described in the individual test procedures. All instruments shall be calibrated before starting and after completion of validation studies.
After completion of the qualification tests all the data generated will be compiled to evaluate ability of the sterilization and depyrogenation tunnel to sterilize & depyrogenate different articles at the set operating parameters.

2.0  TEST CALIBRATION EQUIPMENTS

S. No
Equipment Name
Equipment I.D
Calibration on
Calibration Due on
Verified By
2.1  QUALIFICATION OF THE EXECUTION TEAM:
The execution team should be trained for execution of operation Qualification of the equipment & Record should be maintained in Annexure 1
2.2.1  AIR VELOCITY MEASUREMENT
2.2.1.1  OBJECTIVE
To demonstrate that the system is capable of delivering air velocities, as per the Requirement, to maintain continuous laminarity of HEPA Filter installed in tunnel.
2.2.1.2  EQUIPMENT USED
Digital Anemometer
2.2.1.3   METHOD
A)  This test shall be performed by a trained personal and training record shall be attached with report.
B)  This test shall be performed at least 30 minute after the tunnel has been Started Heater should be off.
C)  Measure Air velocity 6 inches below the filter at 5 locations (four corner filter and one center), calculate the average velocity of air coming from supply.                               
D)  Calculate the velocity of air coming from supply filter should be measured in Feet/min.
E)  Record the Data in Annexure II.

  V1                                         V2
                      
                                                                                 V3               


 V                                         V5








Average velocity (A) = V1+V2+V3+V4+V5/5
                            A  = Average     
2.2.1.4  ACCEPTANCE CRITERIA
Average velocity across HEPA Filter should be within the range of 90±20 Feet/min
Average velocity across HEPA Filter in sterilization zone should be within the range of 150-200Feet/min
2.2.2  HEPA FILTERS LEAKAGE TEST (DOP/PAO TEST)
2.2.2.1  OBJECTIVE
To verify the integrity of HEPA FILTERS installed in the sterilization and depyrogenation tunnel.
2.2.2.2  TEST APPARATUS                                         
•  Aerosol Generator
•  Aerosol photometer
•  Compressed Air

2.2.2.3  METHOD
a)  Filter testing shall be performed only after operational air velocities have been verified and adjust wherever necessary.
b)  Position the smoke generator and introduce (DOP/PAO) smoke into the stream of the HEPA Filter. The concentration of (DOP/PAO) aerosol is 80-120µg per liter of air.
c)  Programme the instrument at 100% concentration for upstream.
d)  Scan the downstream side of the HEPA with an appropriate photometer probe.
e)  The probe shall scan the entire filter face and frame at a position about 1 inch from the face of the filter.
f)  Scanning shall be done at the rate of 2 feet/minute.
g)  Record the observation in Annexure III
2.2.2.4  ACCEPTANCE CRITERIA
During scanning percentage of DOP or PAO penetration shown by photometer should not be more than 0.01% of the upstream concentration through the filter media and should be zero through mounting joints.
2.2.3  AIR FLOW LAMINARITY:
2.2.3.1  OBJECTIVE
To determine the air flow pattern of HEPA Filter installed in sterilization and depyrogenation tunnel
2.2.3.2  EQUIPMENT USED
Titanium Tetra Chloride (Chemical Used).
 Video Camera. 
2.2.3.3   METHOD
TITANIUM TETRA CHLORIDE
a)  Take the glass rod with cotton or sponge tied to it.
b)  Dip the rod in Titanium Tetra Chloride solution and place the stick at Downstream of HEPA Filter.
c)  Check the air flow direction at the Downstream of the filter face.
d)  Observe & record the same with video camera.
2.2.3.4  ACCEPTANCE CRITERIA
The stream of air should be unidirectional and non-turbulent upto working zone.
2.2.3.5  Record the result in Annexure V
2.2.4  AIR BORNE NON-VIABLE PARTICLE COUNT TEST
2.2.4.1  OBJECTIVE
To establish that at different locations within the tunnel, a count size of particles per cubic meter is within the limit.
2.2.4.2  EQUIPMENT USED
Air Borne Particulate Counter, duly calibrated with traceability certificate.
2.2.4.3  METHOD
a)  The test should be perform only when the earlier test have been performed (air velocity, filter integrity, air laminarity) and found to be conforming to the requirement. The particle count test should be performed by qualified and/ or trained personnel only.
b)  Calculate the number of location by the following formula
No. of sampling location: NL=√A
Where:
NL=The minimum number of sampling locations (Rounded up to a whole number)
A=The area of the HEPA Filter installed in tunnel in m2
c)  Use calibrated particle analyzer for non viable particle count and consider 0.5µ and 5.0 µ
d)  Perform 3 consecutive cycles.
e)  Record the data in Annexure VIII
2.2.4.4  ACCEPTANCE CRITERIA    
The system shall capable of achieving the desired cleanliness grade in the subjected critical work locations in the tunnel as per the designed specified limit                   
                 CRITERIA
ACCEPTANCE

 Non viable Air particle count test
Maximum number of permitted particles per cubic meter equal to or above
          GRADE
≥ 0.5 µm
 ≥5.0 µm
GRADE A
3520
29
2.2.5  HEAT DISTRIBUTION STUDY
2.2.5.1  OBJECTIVE
The objective of the test is to ensure that:
The Sterilizing & Depyrogenating Tunnel when operated with Empty Chamber is capable of producing the temperature profiles as per the temperature set points set in the PLC of the equipment. The temperature distribution is uniform throughout the sterilization period.
Three run to be performed to qualify the measurement of the temperature throughout the chamber during the sterilization cycle.
2.2.5.2  Equipment Used
Data Logger with Minimum 12 Probes duly calibrated.
2.2.5.3  METHOD
Record the set parameters of the sterilization cycle to be operated during the test. Suspend the probe in the chamber in different position in such a way that probes don’t touch any metallic surface. Record the position of the probe in a representative schematic manner.
Connect the probes to suitable data logger, which can scan and print the actual temperature observed at different locations with respect to time.
Operate the Sterilizing & Depyrogenation Tunnel Also start the data logger to record the actual temperatures with respect to time.
After completion of sterilization cycle switch off the data logger.
Collect print out from the printer of Sterilizing & Depyrogenation Tunnel.
Download the data from the data logger in the computer for the data analysis and printing enclosed the printout obtained from the data logger.
2.2.5.4  ACCEPTANCE CRITERIA:
The Temperature at each Temperature probe should be ≥300°C during the cycle.
2.2.5.5 Observations and Results In Annexure VI
Record the temperature at various locations
2.2.6  HEAT PENETRATION STUDY
2.2.6.1  OBJECTIVE
Objective of this test is to ensure that, heat is sufficiently penetrating into the innermost  portion of the Vial subjected for sterilization & Depyrogenation to achieve desired temperature during the sterilization & Depyrogenation cycle.
Loaded chamber Heat penetration studies must be conducted for three consecutive cycles with temperature probes.
The recovery of Endotoxin Concentration after exposing to Depyrogenation tunnel should show more than 3 log reduction.
Three run to be performed to qualify the measurement of the temperature throughout the tunnel by seven (during the sterilization cycle).
2.2.6.2  EQUIPMENT USED
Data Logger with 12 Probes duly calibrated.
2.2.6.3  METHOD
Conduct the study with loaded chamber for three consecutive cycles with temperature probes and Endotoxin vials.
Suspend the 12 probes inside the vial and put into tunnel for Heat Penetration Study.
Record the position of the probes in a representative schematic form.
Insert 9 Endotoxin Vials (Marked vials) having 10000 EU each along with the temperature sensors.
Connect the probes to suitable data logger, which can scan and print the actual temperature observed at different locations with respect to time.
Operate the Sterilizing & Depyrogenating Tunnel  also start the data logger to record the actual temperatures within the Sterilizing & Depyrogenating Tunnel with respect to time.    
BELT SPEED CAN BE CALCULATED BY USING THE FOLLOWING FORMULA:

      (Vial diameter)2 × cos30o × washing machine output
                          Tunnel conveyor width

 STERILIZATION HOLD TIME:            Length of sterilizing zone
                                                                            Conveyor speed

2.2.6.4  ACCEPTANCE CRITERIA
Throughout the dwell time, all temperature measured in the chamber is ≥ 300°C. The recovery of endotoxin concentration after exposing in sterilization and depyrogenation should show at least 3 log reduction.
3.0  ACCEPTANCE CRITERIA
 S.No.
TEST  PERFORMED
ACCEPTANCE CRITERIA
1.
Air velocity test
Average velocity across the HEPA filter should be within the range of 90 ± 20% FPM.
2.
HEPA Filter integrity testing
Leakage in the filter should not be more than 0.01% and should be zero through mounting joints.
3.
Air flow pattern
Air flow pattern should be unidirectional and non turbulent.
4.
Non Viable particle counter
Acceptable limit of
0.5µ Particles is 3520  and 5.0µ is 29 in 1M3 of air.
5.
Heat distribution studies
Temperature should be uniform throughout the cycle
6.
Heat penetration studies
Should show at least 3 log reduction after exposing
Sterilization temperature

4.0  RESULT:

The results obtained after execution of the protocol, will be presented in the validation report.  All results will be compared against the acceptance criteria. Any deviation failure to meet these specifications will be duly documented. A deviation indicates variance from the acceptance criteria however, does not necessarily mean that the qualification as unacceptable. During execution of this protocol, if any deviation is noticed, the person executing the protocol initiates a deviation report and provides the detail description of the deviation. Investigation may be performed to identify root cause for the deviations or failures and corrective action will be taken to minimize such deviations or failures in the future.

5.0  CONCLUSION:

Conclusion will be drawn after compilation and evaluation of result.


ANNEXURE 1
Training for Performance Qualification of sterilization and depyrogenating Tunnel
Name of the trainer  :       
Designation              :
Date of training        :
Duration                  :
Sr. No.
Name of Trainee
Department
Signature

Comments  _____________________________________________________________
                     
Training given by     _______________           _______________      
                                       Name                                 Sign/Date

ANNEXURE II
AIR VELOCITY MEASUREMENT TEST
Date of Test         : __________________
Equipment ID:
Name of testing instrument Digital Anemometer
Calibrated on    : ____________________        Calibration due: ___________

HEPA
FILTER No.
Velocity [FPM]
Average
Velocity
[FPM]
Location 1    (V1)
Location 2
(V2)
Location 3
( V3)
Location 4
(V4)
Location 5
(V5)
1
2
3
4
5
6

Checked by
(Production)   _________________   _________________    ____________
                               (Name)                       (Signature)                      (Date)
Verified by
(QA)               _________________   _________________    ____________
                               (Name)                       (Signature)                      (Date)


ANNEXURE III
          HEPA FILTER INTEGRITY TESTING
Date of Test  : ________________                                   
Equipment ID :
Name of Testing Instrument: Aerosol Photometer 
Calibrated on : ________________ Calibration due: _______________

HEPA Filter No.

Upstream
Concentration
%age
Downstream
Concentration
%age (NMT 0.01%)
Remarks
1
100%
2
100%
3
100%
4
100%
5
100%
6
100%
Checked by
(Production)  _________________   _________________    ____________
                               (Name)                       (Signature)                      (Date)
Verified by
(QA)              _________________   _________________    ____________
                               (Name)                       (Signature)                      (Date)


ANNEXURE IV
AIR FLOW PATTERN TEST

Date of Test                              :
Equipment ID                             :
Teat Conditions                          :  Static
Name of the Testing Chemical    :   Titanium Tetra Chloride
CONDITION
CRITERIA
YES/NO
STATIC
Whether the fumes of the titanium tetra chloride follow unidirectional path

Checked by
(Production)   _________________   _________________    ____________
                               (Name)                       (Signature)                      (Date)
Verified by
(QA)              _________________   _________________    ____________
                               (Name)                       (Signature)                      (Date)


ANNEXURE V
NON VIABLE PARTICLE COUNT TEST

Date of Test              : ____________                         Equipment ID:
HEPA Filter No           :
Test Conditions         : Static                                                                     
Name of Instrument  : Air Borne Particulate Counter
Calibrated on            : ________________                                                          
Calibration due          : ________________
Location
   No.
Particle
 Size
Particulate Count
Average
(A=C1
+C+--
+Cn )/n
Average
In M3
(A=A*
35.2)
Count 1
(C1)
Count 2
(C2)
Count3
(C3)
Count 4
(C4)
Count 5
(C5)
L 1
≥ 0.5µ
≥ 5.0µ
L 2
≥ 0.5µ
≥ 5.0µ
L 3
≥ 0.5µ
≥ 5.0µ
L 4
≥ 0.5µ
≥ 5.0µ
L 5
≥ 0.5µ
≥ 5.0µ

ANNEXURE VI
HEAT DISTRIBUTION STUDY
TEST INSTRUMENT DETAILS TO BE USED FOR VALIDATION
Test instrument name
Model no
Calibration done date
Sensor type
& quantity
Make
Calibration due date

CYCLE NO
Equipment name
Date of experiment
Equipment id no
Equipment make
Cycle start
Cycle end
Equipment location

STERILIZATION CYCLE PARAMETERS









Conveyor
Start temperature
Sterilization Hold time
Conveyor
Stop temperature
Belt speed   in mm
Sterilization temperature

                              STERILIZATION CYCLE OBSERVATION

TIME
TEMPERATURE SENSORS
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
MEAN
Ple. Refer temp mapping date and print out of reading & temperature mapping data as attachment
   
 Inference __________________________________________________
__________________________________________________
     

 Reviewed By                               Reviewed By                                  Approved By       Head Engineering                        Head Production                               Head -QA
                                                     
ANNEXURE VII 
HEAT PENETRATION STUDY
TEST INSTRUMENT DETAILS TO BE USED FOR VALIDATION
Test instrument name
Model no
Calibration done date
Sensor type
& quantity
Make
Calibration due date

CYCLE NO
Equipment name
Date of experiment
Equipment id no
Equipment make
Cycle start
Cycle end
Equipment location

STERILIZATION CYCLE PARAMETERS
Conveyor
Start temperature
Sterilization Hold time
      -----
Conveyor
Stop temperature
Belt speed   in mm
      -----
Sterilization temperature
        -----
      -----

STERILIZATION CYCLE OBSERVATION
TIME
TEMPERATURE SENSORS
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
MEAN
Ple. Refer temp mapping date and print out of reading & temperature mapping data as attachment
     Inference_________________________________________________________________________________________________________________________________________________________
      Reviewed By                               Reviewed By                                  Approved By 
Head Engineering                        Head Production                                   Head -QA
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.
Email: .moc.enilediugamrahp@ofni Need Help: Ask Question


1 Comment so far : Add yours...

sohel shaikh said...

dear sir,
i want to know about air velocity of HEPA in sterilization zone in sterilization and depyrozination tunnel it 150-200 FPM. it obey which guideline?

hope you reply me soon

regards,

sohel

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