1.0 Objective
The objective of this protocol is to verify the performance qualification attributes i.e. sterilization and to establish sufficient data to assure that the STEAM STERILIZER (Equipment ID No.) supplied by M/s, XYZ is suitable for sterilizing planned load.- To prepare master chart of sterilization cycle for reference during normal production cycle.
- To demonstrate that Autoclave is leak proof and there is no leakage from the chamber.
- To ensure that system is capable to remove air pocket from Autoclave chamber.
- To ensure that heat distribution throughout the chamber is uniform and the temperature is within the limit of 121 to 123°C.
- To ensure that the heat is sufficiently penetrating into the innermost portions of the load subjected for sterilization to achieve a temperature of 121°C - 123°C during the Sterilization hold period.
- To ensure that the steam Sterilization process, when challenged with Geobacillus Stereothermophilus Biological indicator spore strips having spore population of 106 spores strip, should reduce the bacterial load by more than 6 log reduction.
2.0 Scope
This Protocol shall be applicable to the Autoclave (Equipment No.: ABCD), situated in the clean room no. A10 in the plant of ……………..Company, located at………………city.3.0 References
3.1 Internal References
Sr. No.
|
Reference
Detail
|
Document No.
|
01
|
Operation
of Kaye Validator
|
|
02
|
Calibration of Measuring & Testing Devices
|
|
03
|
Operation of HTR
|
|
04
|
Operation of Valprobe loggers
|
|
05
|
Handling of Biological Indicator
|
|
06
|
Risk Management
|
|
07
|
Deviation Management
|
3.2 Others
Sr. No.
|
Reference Detail
|
Document No.
|
01
|
Scottish Health Technical
Memorandum 2010, Part 3 of 6,
Validation and verification
Sterilization, June 2001
|
SHTM 2010
|
02
|
BRITISH STANDARD BS EN, Sterilization — Steam sterilizers —
Large sterilizers (The European Standard EN 285: 1996)
|
EN 285
|
03
|
Industrial Moist Heat Sterilization
In Autoclaves
PDA Technical Monograph No. 1,
2005 Revision Supplement, Volume 59, Number X
|
PDA Journal
of
Pharmaceutical
Science and
Technology
|
04
|
Sterilization of health care products — Moist heat — Part 2:
Guidance on the application of ANSI/AAMI/ISO 17665-1
|
ANSI/AAMI/ISO
17665-1
|
4.0 Responsibilities
Department
|
Responsibilities
|
Quality Assurance
|
Q.A.
Officer / Executive:
• To
prepare/review standard operating procedure/protocol as per current GMP
requirement and organization’s Quality norms.
• To ensure
& follow correct procedure written in SOP & protocol.
• Ensure the
sampling instruction written in Protocol is followed to withdraw sample at specified location in
specified time interval and witness of validation activity.
• Test the
collected product sample tested as per specification.
• To report
any abnormality to QA Manager / QA Head and take corrective and
preventive action in coordination with respective department head.
Q.A. Manager:
• Review
& Approval of Protocol
& Report.
• Ensure all
the raw data generated were in accordance with protocol & expected
results achieved.
Head - Q.A./ President-Technology:
Review and approval of protocol and validation report.
|
Technical Department
|
Executive / Manager Technical: Is
responsible for review & scheduling the planned validation activity and
to provide technical support for execution of protocol.
|
Manufacturing
|
Manufacturing
Chemist: To follow
instruction written in SOP
Production Manager/ Q.A. Manager
• Ensure implementation of BMR and protocol.
• Ensure the sample were withdrawn & sent to the
QC for testing as per specification.
• Ensure all the equipment used during Process
validation was documented in respective equipment usage log.
|
5.0 Frequency
5.1 Initial Validation
Three (3) successful runs for all planned loads.5.1.1 Shifting of the equipment from one location to another location.
5.1.2 If replacement of major components / Instruments.
5.1.3 Change in PLC programme.
5.2 Revalidation
One successful run once in a year for all loads at defined maximum load pattern.6.0 Rationales for Validation Study
6.1 Rationales for Probes quantity
6.1.1 Empty chamber Heat Distribution
In steam sterilization process steam is not flowing, only condensate formed in the chamber is purged out and the pressure in the chamber is maintained by further inlet of steam. Therefore uniform heat distribution is expected in the steam sterilizer chamber during sterilization hold period and probability of non-uniformity within the chamber is less.In the Autoclave steam inlet is from the both sides of the chamber through baffles, for uniform distribution of steam in the chamber. Condensate drain point is located at the bottom. Three horizontal planes of two shelves (i.e. top and bottom) are selected for temperature mapping. 4 probes to be placed in four corners of top shelves, 3 probes at corner &1 probe at centre of top selves. 3 probes at corner & 1 probe in drain point of lower shelves (attach layout)
6.1.2 Loaded chamber heat penetration
For sterilization of Rubber stoppers, Garment & Miscellaneous Load (Silicone tube) the 5 probes are placed inside the load, 1 probe in drain point and 4 probes in the chamber as per respective loading pattern diagram attached as Exhibits to this protocol for monitoring of heat penetration in loaded chamber.Once the maximum and minimum load are validated for Autoclave at defined validated Load pattern need not to qualify periodically for minimum load. Therefore only maximum loads will be periodically revalidated at defined load pattern considering it as worst case scenario.
6.2 Process Parameter
Key operating parameters as per Operational Qualification identified are as below:
Sr.
No.
|
Parameter
Details
|
Process
Parameter
|
1
|
Pure Steam Pressure
|
NLT
2.0 Bar (g)
|
2
|
Vacuum
|
NLT
–0.70 Bar (g)
|
3
|
Compressed Air
|
NLT
6.0 Bar (g)
|
6.3 Functional Risk Assessment
Function wise processes are listed and evaluated for assessment of risk to either product quality and data integrity. It involves mainly following steps.- Identifying GMP Risk
- Identifying Risk Scenarios
- Assessing the likelihood of An Adverse Event
- Assessing the severity of impact
- Detection of adverse impact
- Overall priority
6.4 Identifying GMP Risk
System function parameters are evaluated and identified whether they represent a risk when assessed against a series of GMP criteria.Following types of risks are mainly identified during risk assessment process for qualification of system as below:
- Risks towards non-availability of required documentation
- Risks towards non-availability of required SOPs
- Risks towards non-availability of system Access Control
- Risks towards abnormal user operation performed at the time of system operation
- Risks towards incorrect configuration of system
- Risks towards Improper and/or inadequate training
6.5 Identifying Risk Scenarios
Having determined that a particular function may have a GMP risk associated with it, the assessment proceeds to identify the various risk scenarios i.e. the events that identify the risks associated with use of the system.The functions identified are analyzed by considering possible hazards/adverse effects and what controls may be needed to minimize the potential harm.
6.6 Assessing the Likelihood of An Adverse Event
After identifying hazards / adverse events, determine the likelihood (frequency or probability) of it occurring. User considers the likelihood of the adverse event occurring per number of transactions, and assigns category as per estimation of risk.6.7 Assessing the Severity of Impact
After determining likelihood of adverse event, severity of its impact on process is assessed. These effects take into account impact on regulatory compliance, impact on product quality and impact on data integrity.The impact of risk occurring may be described as follows:
6.8 Ranking of Adverse Event Severity
Table - I
Value
|
(S)
Severity of Event (Consequence)
|
3
|
High(H) : Can cause serious adverse health consequences which
can threaten the life of Patient or even death
|
2
|
Medium(M) : Temporary or reversible adverse health consequences
but the life of the patient is not threatened
|
1
|
Low(L) : No effect/Impact for patients
|
6.9 Detection of Adverse Event
Next step is to identify if the adverse event can be recognized or detected by other means in the system. Adverse event having high probability of detection, may not pose a serious threat because it can be recognized quickly and suitable corrective action taken to mitigate its impact. If an adverse event has a low probability of detection, then the risk condition needs to seriously consider a review of the design or the implementation of alternative procedures to avoid the event.6.10 Ranking of Adverse Event Detection
Table - II
Value
|
(D) Level
of Detection
|
1
|
High (H): The risk can be easily detected through deployed
control measure/system and the detection system is automated.
|
2
|
Medium (M): The risk can be detected later through deployed
control measure/system and the detection is through manual method.
|
3
|
Low (L): The risk cannot be detected through deployed control
measure/system the detection is possible after longer period/interval.
|
6.11 Risk Review and Monitor Controls
After controls are implemented, they will be monitored for life cycle of the system. This will be part of performance monitoring of the system. Periodic review after the system is fully operational /validated shalla. Consider whether previously unrecognized risks are present
b. Determine if previously identified hazards are still present ( and to what level)
c. Ascertain if the estimated risk associated with a hazard is no longer acceptable
d. Evaluate whether all existing controls are still necessary
6.12 Risk Assessment & Control During Execution of study
6.12.1 Nature of Risk & its mitigation action to the risk identified
Sr.
No
|
Description
of Risk Identified
|
Impact
|
Level
of Risk after mitigation plan
(Low
/ Moderate / High)
|
Expected
results
|
Observation
|
Tested
By
(Sign
& Date)
|
|
Risk of System Access by Unauthorized/untrained
personnel
|
|||||||
1
|
Unauthorized person tries to conduct the process.
|
Process may gets affected.
|
Low
|
• Only
Qualified persons are authorized to perform the process and conduct the study
|
|||
2
|
Untrained operator tries to operate /maintenance of the system.
|
Process may gets affected.
|
Low
|
• Training
plan, training record and Operation SOP should be available.
|
|||
3
|
Operation SOP does not contain proper information.
|
Process may gets affected.
|
Low
|
• System
operation SOP should contain operation information as recommended by QA.
|
|||
Risk on account of abnormal process condition
occurred at the time of system operation
|
|||||||
4
|
Failure of Vacuum leak test
|
Process gets affected.
|
Low
|
• Message
appears on PLC “Leak Test Fail”.
• SOP
contains information to take action accordingly.
|
|||
5
|
Failure of Bowie Dick Test
|
Process gets affected.
|
Low
|
• Fail is
having indication of light color in center of pattern
• SOP
contains information to take action accordingly.
|
|||
6
|
Failure of Biological Indicator.
|
Process gets affected.
|
Low
|
·
|
|||
Risk on account of abnormality in connected
utilities at the time of system operation
|
|||||||
8
|
If Pure steam pressure Low during running cycle.
|
Process gets affected.
|
Low
|
• Pressure
and hence temperature not achieve in the system.
• Result in
Atypical cycle
• SOP
contains information to take action accordingly.
|
|||
9
|
Low vacuum
|
Process gets affected.
|
Low
|
• Result in
Atypical cycle
• SOP
contains information to take action accordingly.
|
|||
10
|
Temperature lower during sterilization running the
cycle.
|
Process gets affected.
|
Low
|
• Temperature
not achieve in the system.
• Result in
Atypical cycle
• SOP
contains information to take action accordingly.
|
|||
11
|
Temperature higher during sterilization phase of
cycle.
|
May System loss or damage to components
|
Low
|
• Result in
Atypical cycle
• SOP
contains information to take action accordingly.
|
|||
12
|
Load is not placed as per defined and validated load
pattern
|
Load may not get sterile
|
Low
|
• SOP
contains information to take action accordingly.
• Authorized
and trained person is performing the operation.
|
|||
Risk occurred in Equipment
|
|||||||
13
|
Door gaskets damaged
|
Process gets affected.
|
Low
|
• Chamber
vacuum not maintained
• Result in
Atypical cycle
• SOP
contains information to take action accordingly.
|
|||
14
|
Malfunctioning of pneumatic valves
|
Process gets affected.
|
Low
|
• Result in
Atypical cycle
• SOP
contains information to take action accordingly.
|
|||
15
|
Malfunctioning of Steam trap
|
Process gets affected.
|
Low
|
• Temperature
not achieve in the system
• Result in
Atypical cycle
• SOP
contains information to take action accordingly.
|
|||
16
|
Failure of post calibration of thermocouple.
|
Could not accessed about product sterilization
|
Low
|
• Result of
BI will be assessed for probability of survival of microorganisms.
• Check
physical condition of thermocouples if found damage, white proper
justification.
• Recalibration
to be done.
|
|||
7.0 Equipments/ Material to be used for Validation Study:
- Calibrated Valprobe loggers/ Thermocouples
- Kaye Valprobe/Kaye Validator
- Calibration Unit
- Biological Indicator
- Media to incubate
- Chart paper (Yokogawa)
- Bowie Dick Pack
7.1 Technical Data
Mfg. By:
|
|
Installed
on:
|
|
Model no.:
|
|
Size:
|
|
Working
Pressure:
|
|
Volume:
|
|
Door:
|
|
Hydraulic
test Pressure:
|
|
Construction:
|
- The Autoclave Chamber is made up of Stainless Steel sheet, which is welded with a U-Profile Stainless Steel Jacket. The Autoclave Chamber is provided with two sliding doors, which are also made up of Stainless Steel reinforced with mild steel support structure. The door is operated with the help of pneumatic cylinder, when the door reaches the end position gaskets are pushed out automatically with help of compressed air for sealing similarly to open the door gasket is retracted by vacuum. When the gasket is retracted the door slides automatically. The Door sealing is done with the help of tubular, silicone rubber gasket. To ensure proper sealing the gaskets are activated with compressed air and retracted with the help of vacuum.
- Door interlocks are provided to prevent simultaneous opening of both the doors of critical area side (sterile area side) and controlled area side (non- sterile area side) and process lock to prevent opening of the door during the operation.
- The Autoclave chamber is insulated with resin-bonded glass wool, which helps in reducing the heat loss to the environment and ensuring uniform distribution of temperature inside the chamber. This insulation is covered with stainless steel cover plate.
- A Stainless steel pipe stand support is provided for the equipment thus requiring no special foundation. For ensuring leak tight partition between the Controlled area (Non-Sterile area side) and Clean area (Sterile area side), a Stainless steel flush paneling is provided on the partitioning wall and the outer cover of Autoclave. All Joints, Crevices are filled with Silicon sealant to prevent any leakage.
The Autoclave is
provided with the following systems and accessories for proper functioning.
- Water-ring type vacuum pump with suitable electric motor.
- Vacuum break filter on the clean area side. One pair of removable Stainless Steel railings inside the sterilization chamber for smooth and easy operation of the load article.
- Loading tray constructed of Stainless steel SS316.
- Chamber Compound gauge on sterile and Controlled area side, Jacket pressure gauge of the Controlled area side, Gasket compound gauge for both the doors on the Controlled area side and critical area side, Safety valve for jacket and chamber, Steam trap with strainer and NRV for chamber.
- Pure steam is supplied through SS-316 piping from generation center installed at WFI generation room.
- Control panel consisting of PLC, Digital Temperature input to the microprocessor from a 5 No’s of Temperature transmitters, one Pressure transmitter, Pressure and vacuum switches for giving digital pressure/vacuum signals to the microprocessor, Manual backup system for operation in case of microprocessor failure.
- Stainless steel Internal Piping, Ball valves with rotary actuators for all the process lines with solenoid valves to regulate air supply to the pneumatic rotary actuators.
7.2 Monitoring and Controlling of the sterilization cycle
7.2.1 Two PT-100 probes, inserted in Chamber to monitor temperature on yokogawa recorder.7.2.2 One similar PT-100 probe is left in the drain by which cycle is controlled by PLC. Temperature of drain shall be monitored on PLC and at yokogawa recorder.
7.3 Study Design
S. No.
|
Study
|
Name of the Recipe
|
No. of
trials to be taken
|
1
|
Vacuum leak test
|
Leak
Test
|
One
|
2
|
Bowie – Dick Cycle
|
Bowie-Dick
|
One
|
3
|
Empty chamber Heat Distribution
|
HPHV
RSD
|
One
|
4
|
Loaded chamber with Rubber Stoppers
|
HPHV
RSD
|
One
|
5
|
Loaded chamber with garment and hand gloves
|
HPHV
RSD
|
One
|
6
|
Loaded chamber with Miscellaneous items (Silicone
tube)
|
HPHV
RSD
|
One
|
Note:
- New load may be introduce in loading pattern in between two
scheduled re- qualification study after three successful validation run and
report of same shall be attached as addendum to last validation report.*
Reference
cycle detail (Initial validation with Protocol No)
Sr. No.
|
Protocol No.
|
Protocol No.
|
1
|
Heat Penetration study in Rubber closure RFS (Ready For
Sterilization) bag (Applicable for 20 mm rubber stopper)
|
|
2
|
Heat Penetration study for Garment Sterilization
|
|
3
|
Heat Penetration study for Miscellaneous Load
|
7.4 Sterilization Cycle Parameters
Sr.
No
|
Name of
Parameter
|
|
Leak
test
|
||
1.
|
Programme
Name
|
Vacuum
Leak Test
|
2.
|
Select
Cycle (Recipe No)
|
4
|
3.
|
Leak
Vacuum on
|
-0.7
kg/cm2
|
4.
|
Vacuum
Hold
|
15
min
|
7.5 Recipe For Bowie Dick Cycle
Sr.
No
|
Name of
Parameter
|
Bowie
– Dick Test
|
1.
|
Select
Cycle (Recipe No)
|
5
|
2.
|
Initial
vacuum time
|
2
min
|
3.
|
Pulsation
|
3
|
4.
|
Preheating
Temperature
|
95ºC
|
5.
|
Preheating
Time
|
1
min
|
6.
|
Sterile
Temperature
|
121.0
ºC
|
7.
|
Sterile
Time
|
10
min
|
8.
|
Sterile
Print Time
|
1
min
|
9.
|
Dry
Vacuum Time
|
0
min
|
10.
|
Dry
Vacuum Value
|
-0.700
Kg/cm2
|
11.
|
Door
Open Temperature
|
90
deg
|
7.6 Recipe For HPHV RSD cycle
Sr.
No
|
Name of
Parameter
|
Value
|
1.
|
Select
Cycle (Recipe No)
|
7
|
2.
|
Initial
Vacuum Pulse
|
3
|
3.
|
Initial
Vacuum Value
|
500
mm of Hg
|
4.
|
Initial
vacuum time
|
2
min
|
5.
|
Preheating
Temperature
|
95
ºC
|
6.
|
Preheating
Time
|
1
min
|
7.
|
Sterile
Temperature
|
121.0
ºC
|
8.
|
Sterile
Time
|
15
min
|
9.
|
Sterile
Hold Print Time
|
60
sec
|
10.
|
Dry
Vacuum Pulse
|
3
|
11.
|
Dry
Vacuum Value
|
600
mm of Hg
|
12.
|
Dry
Vacuum Time
|
20
min
|
13.
|
JKT
STM PRE REL
|
2
min
|
14.
|
Cool
Vacuum Value
|
600
mm of Hg
|
15.
|
Cool
Vacuum Time
|
5
min
|
16.
|
Jacket
Air vent ON
|
5
sec
|
17.
|
Jacket
Air vent OFF
|
12
sec
|
18.
|
Jacket
Air Pressure Rel
|
1
min
|
19.
|
Door
Open Temperature
|
90
deg
|
8.0 Procedure
8.1 Vacuum leak test Procedure
8.1.1 Put the flexible probes inside the chamber through the validation port provided for the validation cycles prior to start of Vacuum leak test.8.1.2 Ensure that Autoclave is empty and chamber is at ambient temperature.
8.1.3 Ensure compressed air is ‘ON’ at required pressure of 6 bar.
8.1.4 Ensure sufficient water supply is available for seal of vacuum pump
8.1.5 Ensure gasket lubrication is proper
8.1.6 Switch ‘ON Main’ switch provided on panel board.
8.1.7 Close loading side door by pressing “Door 1 close” Push button provided on main panel board.
8.1.8 Ensure chart recorder is ‘ON’ & graph is properly loaded.
8.1.9 Check the programme from control panel.
8.1.10 Enter the Operator level password & enter the programme as per requirement.
8.1.11 Select programme by pressing ‘Enter’ Key F1 once.
8.1.12 All parameter will start on displaying on screen one by one.
8.1.13 Enter F1 button and select programme, the display will show YES-1 NO-2.
8.1.14 Checks the online printer attached to PLC & then select 1 and press Enter.
8.1.15 Cycle will start in automatic mode as per set parameter as PLC will show “Leak Test Vac ON” and vacuum will be created in chamber.
8.1.16 After completion of hold period, vacuum release valve will open and message will display “Leak Test Vac Release” and continue till the chamber pressure comes to atmospheric pressure.
8.1.17 At the end of the cycle, if the leak rate is more than 1 mm of Hg/ min during hold period, then message will display “Leak Test Fail” & if it is less than 1 mm of Hg/min during hold period, then message will display “Leak Test Pass”.
8.1.18 If cycle fails, initiate work request form for rectification of problem.
8.1.19 After rectification of problem fresh cycle to be run. Upon completion of cycle screen will display “Cycle Over”.
8.1.20 Continue to run for next cycle of Bowie-Dick test.
8.2 Bowie Dick test Procedure
8.2.1 Load the tray in the autoclave chamber.8.2.2 Place the Bowie-Dick test pack on the bottom shelf of the sterilizer just above the drain point (Nearly 100 mm over the drain).
8.2.3 Selected the recipe Bowie-Dick test cycle from MMI/HMI display as per point no 8.1.10 to 8.1.12. Ensure that sterilization hold time is 10 minutes, at 121°C. (Manufacturer’s recommendation).
8.2.4 Start the cycle by pressing Enter key.
8.2.5 After the cycle is over, open the door from control area side & take the sterilized test pack from the Autoclave and check the indicator paper/strip for uniform color change.
8.2.6 Observation should be recorded in test data sheet no 05 (Exhibit II).
8.2.7 A Fail is indicated by light color in the center of the pattern than around the edges when compared with control.
8.2.8 Failure of the pattern to change completely black or dark brown at 121 °C when compared with control.
8.3 Procedure For Empty Chamber Heat Distribution Study
8.3.1 Connect the calibrated thermocouples with SIM to the Kaye Validator and distribute these thermocouple through out chamber as per Exhibit-III.8.3.2 Operate Kaye Validator as per SOP or Val probe logger as per SOP.
8.3.3 Run HPHV RSD cycle as per SOP with recipe defined in point 7.6.
8.3.4 Select the cycle from the MMI/ HMI panel as per point no.8.1.10 to 8.1.12 & start HPHV RSD cycle as well as start Kaye Validator at same time. Scan data at every 10 sec interval in Validator.
8.3.5 After completion of the cycle take the printout of report generated through Kaye Validator. Evaluate the report as per acceptance criteria.
8.3.6 Attach the report generated through Kaye Validator and PLC print out & graph from chart less recorder to the report.
8.4 HEAT PENETRATION STUDIES
8.4.1 Procedure For Loaded chamber heat penetration study:8.4.1.1 Load the articles into Double door Autoclave as per their respective loading diagram attached as exhibit to this protocol.
8.4.1.2 Place heat penetration probes inside the loaded articles and select the positions where heat penetration is difficult.
8.4.1.3 Connect the Thermocouple with SIM to Kaye Validator as per SOP or Val probe logger as per SOP, which senses the temperature.
8.4.1.4 Place biological indicator folded with aluminum foil strips of Geobacillus Stereothermophilus containing 106 spores along with flexible probes.
8.4.1.5 Select the HPHV RSD cycle as per point no. 8.1.10 to 8.1.12.
8.4.1.6 Start the cycle by pressing Enter key from the MMI / HMI panel as well as start Kaye Validator at same time. Scan data at every 10 sec interval in Validator.
8.4.1.7 After completion of the cycle take the printout of report generated through Kaye Validator. Evaluate the report as per acceptance criteria
8.4.1.8 Carry out total three replicate runs with loaded chamber for newly introduced load (first time study).
8.4.1.9 Take out all exposed biological indicator strips & send the biological indicator to microbiological lab for testing as per SOP of handling of biological indicators and recording the results in observation sheet.
8.4.2 Heat Penetration Study: Maximum Load of 20mm Rubber Stopper in RFS Bag (Ready For Sterilization)
8.4.2.1 Load the 20 mm rubber stopper [(1) 5000 Nos. x 5 bags = 25,000 nos. OR (2) 2500 nos. x 10 bags = 25,000 nos.] packed in Rexam pack ready for sterilization in the chamber of autoclave in two trays as per defined loading diagram attached with this protocol.
8.4.3 Heat Penetration Study: Minimum Load of 20mm Rubber Stopper in RFS Bag
8.4.3.1 Load the 20 mm rubber stopper (2500 nos. x 1 bags = 2,500 nos.) packed in Rexam pack ready for sterilization in the chamber of autoclave in two trays as per defined loading diagram attached with this protocol.
8.4.4 Heat Penetration Study: Garment Sterilization with Maximum Load
8.4.4.1 Load the 32 numbers of garment packed in baby bag & 32 goggle for sterilization in the chamber of autoclave in two trays as per defined loading diagram attached (Exhibit VIII) with this protocol.
8.5 Heat Penetration Study: Garment Sterilization with Minimum Load
8.5.1 Load the 5 numbers of garment packed in baby bag & 5 goggle for sterilization in the chamber of autoclave in two trays as per defined loading diagram attached (Exhibit IX) with this protocol.8.6 Heat Penetration Study: Miscellaneous Load (Silicone Tube)
8.6.1 Ensure cleaning of Silicone tube before packing in Rexam bag.8.6.2 Keep the silicone pipe (Approx 2 meter long) in Rexam bag by folding in circular way, keeping both end open.
8.6.3 Insert the biological Indicator folded with aluminum foil along with Thermocouple in both end of silicone tube. Insert the probe as long as it goes inside the tube. Care should be taken when insertion that after sterilization the biological indicator should be removed easily.
8.6.4 Load the 4 number of silicone tube packed in Rexam pack ready for sterilization in the chamber of autoclave in two trays as per defined loading diagram attached with this protocol.
8.7 Load Configuration
Sr. No
|
Load No
|
Name of the
Load
|
Load Pattern
|
Load Type
|
No of
Articles
|
01
|
NA
|
Leak Test
|
NA
|
NA
|
NA
|
02
|
NA
|
Bowie Dick
Test
|
Bowie Dick
|
NA
|
1 No
|
03
|
1
|
Rubber
Stopper
|
20 mm
Rubber Stopper
(5000 nos x
05 bags)
or (2500
nos x 10 bags)
|
Maximum
|
25,000 Nos
|
04
|
3
|
Rubber
Stopper
|
20 mm
Rubber Stopper
(2500 nos x
1 bag)
|
Minimum
|
2,500 Nos
|
05
|
10
|
Garment Load
|
Garment Bags
|
Maximum
|
32
|
Goggle
|
32
|
||||
06
|
11
|
Garment Load
|
Garment Bags
|
Minimum
|
5
|
Goggle
|
5
|
||||
07
|
12
|
Miscellaneous
Load
|
Silicon tube
|
NA
|
4
|
8.8 Attachments to Report
8.8.1 Attachment 01: Common for all tests- Calibration Report of Thermocouples
- Calibration Verification Report of Thermocouples
- Yokogawa Graph
- PLC print
- Test Indicator Paper
- Yokogawa Graph
- PLC print
- Standard Format: VAL/STR/1.4
- Yokogawa Graph
- PLC print
- Thermocouples set up Report
- Thermocouples Qualification Report
- Standard Format: for logging data
- Yokogawa Graph
- PLC print
- Thermocouples set up Report
- Thermocouples Qualification Report
- Attachment 06: For Heat Penetration Study for 20mm Rubber Stopper Minimum Load
- Attachment 07: For Heat Penetration Study for Garment Sterilization Maximum Load
- Attachment 8: For Heat Penetration Study for Garment Sterilization Minimum Load
- Attachment 9: For Heat Penetration Study for Miscellaneous Load
9.0 Sampling Procedure
- Scan data at every 10 sec interval in Validator/Valprobe.
- Minimum 10 nos. of temperature sensors placed in the chamber geometrically for temperature monitoring study.
- Minimum 10 nos. of Biological Indicator placed in the chamber next to the temperature sensors for temperature monitoring study.
10.0 Acceptance Criteria
10.1 Vacuum Leak Test
10.1.1 The vacuum drop should not be more than 1mm Hg/ 1 min of vacuum hold.10.2 Bowie-Dick Test
10.2.1 The indicator paper / sheet should be uniform change in color (Brown) over the entire pattern of indicator sheet when compared with control.10.3 Heat Distribution Study
10.3.1 Temperature distribution within the chamber must be between 121°C to 123°C at all location during the sterilization period (dwell time).10.3.2 There should not be any slowest heating point (Cold Spot) in the Autoclave chamber.
10.3.3 The equilibrium time should not be more than 30 sec.
10.4 Heat Penetration Study
10.4.1 Temperature distribution within the chamber must be between 121°C to 123°C at all location during the sterilization period (dwell time).10.4.2 Sterilization temperature should be maintained for NLT 15 min for minimum 10 thermocouple during hold period.
10.4.3 6-log reduction should be observed in any exposed biological indicators on complete incubation period.
10.4.4 The equilibrium time should not be more than 30 sec.
10.5 Action to be taken in case of failure
10.5.1 If the vacuum leak test fail, this may be due to insertion of thermocouple, initiate the work request for the maintenance of autoclave leakage.10.5.2 If the Bowie-Dick test fails, this may be due to gasket leakage of leakage due to insertion of thermocouple. Initiate the work request for the maintenance leakage of autoclave.
10.5.3 If the Heat penetration or Heat Distribution cycle fails in any respect, raised the deviation as per SOP. Discard the cycle, investigate the cause of failure. Make the required corrections / modifications by initiate the work request for the maintenance of equipment prior to carrying out three additional sterilization cycles.
10.5.4 During the revalidation if any load configuration fails in any respect a deviation should log & load configuration should be invalidated. After through investigation, three runs of same load / modified load configuration to be validated with proper justification.
List of Standard Operating Procedure involved during validation study:
Sr.
No.
|
SOP title
|
SOP No.
|
Issue No. /
Revision No.
|
1.
|
Sterilization Procedure
|
Issue No. :
Rev. No. :
|
|
2.
|
Handling of biological Indicator
|
Issue No. :
Rev. No. :
|
|
3.
|
Operation of Kaye Validator 2000
|
Issue No. :
Rev. No. :
|
|
4.
|
Calibration of Measuring & testing devices
|
Issue No. :
Rev. No. :
|
|
5.
|
Operation of Val probe logger
|
Issue No. :
Rev. No. :
|
|
6.
|
Operation of HTR-400
|
Issue No. :
Rev. No. :
|
|
7.
|
Sterilization Procedure
|
Issue No. :
Rev. No. :
|
Details of Equipment used for analysis
Sr.
No.
|
Name of
Equipment
|
Equipment
No. / ID No.
|
Last
Calibration / Validation done on
|
Next
Calibration / Validation due on
|
Remarks
|
1.
|
Kaye
Validator 2000
|
||||
2.
|
Val Probe
logger
|
11.0 New risk observed if any During the process
Pl. mention as it is report part12.0 Discussion
12.1 Procedure: To mention, how conducted the study. Pl. mention as it is report part12.2 Acceptance Criteria: Pl. mention as it is report part
12.3 Change Control Note: Study is conducted under any change control system , if yes, pl. mention.
12.4 Deviation: Pl. mention for deviation, if any.
12.5 Out of Specification: Pl. mention for OOS, if any.
12.6 Within Date:
12.6.1 Last Validation performed on: _________________12.6.2 Current Validation performed on: _________________
Remarks (if any):
12.7 Training: Pl. mention about training details given for protocol execution to team members.
13.0 Modifications Suggested
After execution of protocol, if any modification is suggested to get the desired results.
14.0 Conclusion
Conclude the report for acceptance or non acceptance of equipment as per protocol acceptance criteria.
15.0 Records
15.1 Standard Formats
Sr. No.
|
Format
Detail
|
Document No.
|
15.1.1
|
Records of All The Cycles/ Runs With Relevant Calculations
|
|
15.1.2
|
Bacterial Challenge Test Report For Heat Penetration Study
|
15.2 Exhibits
Sr. No.
|
Exhibit
Detail
|
Exhibit No.
|
15.2.1
|
Front View Of Sterilizer
|
|
15.2.2
|
Bowie-Dick Test Load
|
|
15.2.3
|
Temperature sensor distribution in Empty Chamber Heat
Distribution Cycle
|
|
15.2.4
|
Temperature sensor & BI distribution For 20mm Rubber Stopper Maximum Load
|
|
15.2.5
|
Temperature sensor & BI distribution For 20mm Rubber Stopper Minimum Load
|
|
15.2.6
|
Temperature sensor & BI distribution For 32mm Rubber Stopper Maximum Load
|
|
15.2.7
|
Temperature sensor & BI distribution For 32mm Rubber Stopper Minimum Load
|
|
15.2.8
|
Temperature sensor & BI distribution For Garment Maximum Load
|
|
15.2.9
|
Temperature sensor & BI distribution For Garment Minimum Load
|
|
15.2.10
|
Temperature sensor & BI distribution in Miscellaneous Load
|
Exhibit-X
|
Also see: Autoclave Validation in Pharmaceuticals
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