Process Performance Qualification Protocol For Autoclave - Pharmaceutical Guidelines 2

09.06.
2016 Process Performance Qualification Protocol for Autoclave : Pharmaceutical Guidelines
Process Performance Qualification Protocol for Autoclave
Validation Protocol of Autoclave (Steam Sterilizer) Sterilization Process i.e Autoclaving
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.
Related: Low Temperature Sterilization Process ﴾115°C﴿
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 SHTM 2010
Memorandum 2010, Part 3 of 6,
Validation and verification
Sterilization, June 2001

02 BRITISH STANDARD BS EN, Sterilization — Steam EN 285
sterilizers — Large sterilizers ﴾The European Standard EN
285: 1996﴿
03 Industrial Moist Heat Sterilization PDA Journal of
In Autoclaves Pharmaceutical
PDA Technical Monograph No. 1, Science and
2005 Revision Supplement, Volume 59, Number X Technology

04 Sterilization of health care products — Moist heat — Part ANSI/AAMI/ISO
2: Guidance on the application of ANSI/AAMI/ISO 17665‐1 17665‐1
4.0 Responsibilities:
Department Responsibilities
Quality Q.A. Officer / Executive:
Assurance
• 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.

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09.06.2016 Process Performance Qualification Protocol for Autoclave : Pharmaceutical Guidelines
• 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 Executive / Manager Technical: Is responsible for review & scheduling
Department 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.
1. Identifying GMP Risk
2. Identifying Risk Scenarios
3. Assessing the likelihood of An Adverse Event
4. Assessing the severity of impact
5. Detection of adverse impact
6. Overall priority
The above risk were prioritization of risk in High/Medium/Low categories.
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﴿

High﴾H﴿ : Can cause serious adverse health consequences which can
3
threaten the life of Patient or even death
Medium﴾M﴿ : Temporary or reversible adverse health consequences but
2
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

High ﴾H﴿: The risk can be easily detected through deployed control
1
measure/system and the detection system is automated.
Medium ﴾M﴿: The risk can be detected later through deployed control
2
measure/system and the detection is through manual method.
Low ﴾L﴿: The risk cannot be detected through deployed control
3
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 shall
a. 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. Description of Risk Impact Level of Risk after Expected results Observation Tested By
No Identified mitigation plan
﴾Sign &
﴾Low / Moderate Date﴿
/ High﴿
Risk of System Access by Unauthorized/untrained personnel
1 Unauthorized Process may gets Low • Only Qualified persons
person tries to affected. are authorized to perform
conduct the the process and conduct
process. the study
Untrained operator Process may gets • Training plan, training
tries to operate affected. record and Operation SOP
2 Low
/maintenance of should be available.
the system.
Operation SOP Process may gets • System operation SOP
does not contain affected. should contain operation
3 Low
proper information. information as
recommended by QA.
Risk on account of abnormal process condition occurred at the time of system operation
Failure of Vacuum Process gets Low • Message appears on PLC
leak test affected. “Leak Test Fail”.

4
• SOP contains
information to take action
accordingly.
Failure of Bowie Process gets Low • Fail is having indication
Dick Test affected. of light color in center of
pattern
5
• SOP contains
accordingly.
Failure of Biological Process gets Low ·
6
Indicator. affected.
Risk on account of abnormality in connected utilities at the time of system operation
If Pure steam Process gets • Pressure and hence
pressure Low affected. temperature not achieve
during running in the system.
cycle.
8 Low • Result in Atypical cycle
• SOP contains
accordingly.
Low vacuum Process gets • Result in Atypical cycle
affected.
9 Low • SOP contains
accordingly.
Temperature lower Process gets Low • Temperature not achieve
during sterilization affected. in the system.
running the cycle.
• Result in Atypical cycle
10
• SOP contains
accordingly.
Temperature higher May System loss Low • Result in Atypical cycle
during sterilization or damage to
11 phase of cycle. components • SOP contains
accordingly.
Load is not placed Load may not Low • SOP contains
Load is not placed Load may not Low • SOP contains
as per defined and get sterile information to take action
validated load accordingly.
12 pattern
• Authorized and trained
person is performing the
operation.
Risk occurred in Equipment
Door gaskets Process gets Low • Chamber vacuum not
damaged affected. maintained

13
• SOP contains
accordingly.
Malfunctioning of Process gets Low • Result in Atypical cycle
pneumatic valves affected.
14 • SOP contains
accordingly.
Malfunctioning of Process gets Low • Temperature not achieve
Steam trap affected. in the system

15
• SOP contains
accordingly.
Failure of post Could not accessed Low • Result of BI will be
calibration of about product assessed for probability of
thermocouple. sterilization survival of
microorganisms.
16 • 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 consists of the following features.
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.
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:
Name of the
Study No. of trials
S. No. Recipe
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
Loaded chamber with Rubber
4 HPHV RSD One
Stoppers
Loaded chamber with garment and
5 HPHV RSD One
hand gloves
Loaded chamber with Miscellaneous
6 HPHV RSD One
items ﴾Silicone tube﴿
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.

Heat Penetration study in Rubber closure RFS
1 ﴾Ready For Sterilization﴿ bag ﴾Applicable for 20
mm rubber stopper﴿
Heat Penetration study for Garment
2
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 Bowie – Dick

Name of Parameter
Test
2. Initial vacuum time 2 min
3. Pulsation 3
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
Door Open 90 deg
11.
Temperature
7.6 Recipe For HPHV RSD cycle:
Sr. No Name of Parameter Value

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”.
8.1.19 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:
Load Name of the No of

Sr. No Load Pattern Load Type
No Load Articles
01 NA Leak Test NA NA NA
Bowie Dick
02 NA Bowie Dick NA 1 No
Test
20 mm Rubber
Stopper
Rubber ﴾5000 nos x 05

03 1 Maximum 25,000 Nos
Stopper bags﴿
or ﴾2500 nos x 10
bags﴿
20 mm Rubber
Stopper
Rubber
04 3 Minimum 2,500 Nos
Stopper
﴾2500 nos x 1
bag﴿
Garment Bags 32
05 10 Garment Load Maximum
Goggle 32
Garment Bags 5
06 11 Garment Load Minimum
Goggle 5
Miscellaneous
07 12 Silicon tube NA 4
Load
Note:
1. During validation study, if there is any change required in the type and/ number of articles to be loaded, loading diagram will be changed. As per the
validation result the diagrams will be established for routine cycles and accordingly SOP will be established. In this case protocol will not be revised, as
validation method will remain same.
8.8 Attachments to Report:
8.8.1 Attachment 01: Common for all tests
• Calibration Report of Thermocouples
• Calibration Verification Report of Thermocouples
8.8.2 Attachment 02: For Leak Test Cycle
• Yokogawa Graph
• PLC print
8.8.3 Attachment 03: For Bowie‐Dick Test
• Test Indicator Paper
• Yokogawa Graph
• PLC print
8.8.4 Attachment 04: For Heat Distribution Study
• Standard Format: VAL/STR/1.4
• Yokogawa Graph
• PLC print
• Thermocouples set up Report
• Thermocouples Qualification Report
8.8.5 Attachment 05: For Heat Penetration Study for 20mm Rubber Stopper Maximum Load
8.8.5 Attachment 05: For Heat Penetration Study for 20mm Rubber Stopper Maximum Load
• Standard Format: for logging data
• Yokogawa Graph
• PLC print
• Thermocouples set up Report
• Thermocouples Qualification Report
All above documents are required for below attachments as per respective studies:
• 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. SOP title SOP No. Issue No. / Revision

No.
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 Issue No. :
devices
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. Name of Equipment Last Next Remarks

Equipment No. / ID No. Calibration / Calibration /
No. Validation Validation
done on due on
1. Kaye Validator
2000
2. Val Probe logger
11.0 New risk observed if any During the process:

Pl. mention as it is report part
12.0 Discussion:
12.1 Procedure: To mention, how conducted the study. Pl. mention as it is report part
12.2 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
Stopper Minimum Load
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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Process Performance Qualification Protocol For Autoclave - Pharmaceutical Guidelines 2

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09.06.

Related: Low Temperature Sterilization Process ﴾115°C﴿

Sr. No. Reference Detail Document No.

Sr. No. Reference Detail Document No.

Memorandum 2010, Part 3 of 6,

Validation and verification

Sterilization, June 2001

PDA Technical Monograph No. 1, Science and

2005 Revision Supplement, Volume 59, Number X Technology

• To ensure & follow correct procedure written in SOP & protocol.

• Ensure the sampling instruction written in Protocol is followed to

• Test the collected product sample tested as per specification.

• To report any abnormality to QA Manager / QA Head and take

• Review & Approval of Protocol & Report.

Head ‐ Q.A./ President‐Technology:

Review and approval of protocol and validation report.

Production Manager/ Q.A. Manager

• Ensure implementation of BMR and protocol.

• Ensure all the equipment used during Process validation was

5.1 Initial Validation:

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.

6.0 Rationales for Validation Study:

6.1 Rationales for Probes quantity

6.1.1 Empty chamber Heat Distribution:

6.1.2 Loaded chamber heat penetration:

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﴿

6.3 Functional Risk Assessment

1. Identifying GMP Risk

2. Identifying Risk Scenarios

3. Assessing the likelihood of An Adverse Event

4. Assessing the severity of impact

5. Detection of adverse impact

6. Overall priority

The above risk were prioritization of risk in High/Medium/Low categories.

6.4 Identifying GMP Risk

• Risks towards non‐availability of required documentation

• Risks towards non‐availability of required SOPs

• Risks towards non‐availability of system Access Control

• Risks towards incorrect configuration of system

• Risks towards Improper and/or inadequate training

6.5 Identifying Risk Scenarios

6.6 Assessing the Likelihood of An Adverse Event

6.7 Assessing the Severity of Impact

The impact of risk occurring may be described as follows:

6.8 Ranking of Adverse Event Severity

Value ﴾S﴿ Severity of Event ﴾Consequence﴿

6.9 Detection of Adverse Event

6.10 Ranking of Adverse Event Detection

Value ﴾D﴿ Level of Detection

6.11 Risk Review and Monitor Controls

a. Consider whether previously unrecognized risks are present

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:

leak test affected. “Leak Test Fail”.

• Result in Atypical cycle

• Result in Atypical cycle

16 • Check physical condition