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
V4
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.
Related: How to Write a Validation Protocol?
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
+C2 +--
+Cn )/n
|
Average
In
M3
(Am =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
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