BORU

Sansheng Pharmaceutical P.L.
C
Title: Performance Qualification Protocol For Superheated Water Sterilizer
model HWSM15010
Doc. No.: Equipment ID： Page:
SS-PQ-001/SV W1501A 1 / 28
Qualification Document
Performance Qualification Protocol for
Superheated Water Sterilizer model HWSM15010
Document No.: _________
Equipment ID: ________
Manufacturer: Truking Technology Limited
Equipment location: Small Volume Parenteral Manufacturing Area
Protocol Approval Page:
Prepared by Liquid Workshop Director Signature/Date
Reviewed by Engineering Department Signature/Date
Sansheng Pharmaceutical Plc.

Sansheng Pharmaceutical P.L.C
Title: Performance Qualification Protocol For Superheated Water
Sterilizer model HWSM15010
SS-PQ-001/SV W1501A 2 / 28
Signature/Date
Production Department
Signature/Date
R& D Department
Signature/Date
Approved by QA Manger
Signature/Date
Authorized By QA Director
Location of docu- Issue date:

QA
ment

SS-PQ-001/SV W1501A 3 / 28
Table of Contents Pages
1. Objective..................................................................................................................................... 4
2. Scope______________________________________________________________________________________4
3. Concept of the Equipment Qualification___________________________________________________________5
4. Validation Team members______________________________________________________________________5
5. Responsibility________________________________________________________________________________5
6. Training of Personnel__________________________________________________________________________6
7. Installation, Operational Qualification & calibration_________________________________________________6
8. Reference___________________________________________________________________________________8
9. Description of Equipment_____________________________________________________________________10
10. Frequency of Validation______________________________________________________________________11
11.Performance Qualification Tests (PQ-Tests)_______________________________________________________11
12.Deviation List______________________________________________________________________________24
13.Deviation Table (Attach Additional page if required)_______________________________________________25
14.Attachment_________________________________________________________________________________26
15. P-Certificate_______________________________________________________________________________27

SS-PQ-001/SV W1501A 4 / 28
1. Objective
The objective of this protocol is to verify the performance qualification attributes of sterilization
and to establish sufficient data to assure that the Superheated Water Sterilizer model
HWSM15010 is suitable for sterilizing planned load and is consistently doing sterilization of
products as expected. The objectives of this qualification is to determine the process variables and
acceptable limits (process time, temperature and pressure), and to set up appropriate in process
controls.
 To ensure that heat distribution throughout the chamber is uniform and the temperature is
within the limit of 121 to 123 oC.
 To ensure that the heat is sufficiently penetrating into the innermost portions of the load
subjected for sterilization to achieve a temperature of 121 to 123 oC during the sterilization
hold period.
 To ensure that the superheated water sterilization process is, when challenged with
Geobacillus steriotherophilus biological indicator spore strips having spore population of
10 6 spores strip, should reduce the bacterial load by more than 6 log reduction.
 To verify that the computed F0 value is sufficiently greater than the Biological F0.
 To prepare master chart of sterilization cycle for reference during normal production cycle.
 To establish the Autoclave Cycle, which when operated within specified operating ranges,
helps to achieve a predetermined Sterility Assurance Level (SAL).
2. Scope
This protocol shall be applicable to the Autoclave Superheated Water Sterilizer model
HWSM15010 located at small volume Injection line of Sansheng Pharmaceuticals plc.
The study design also incorporated empty chamber heat distribution, loaded chamber heat distri-
bution &heat penetration, loaded chamber biological challenge test for maximum load.

SS-PQ-001/SV W1501A 5 / 28
3. Concept of the Equipment Qualification
In this qualification plan all the required performance qualification tests are described, the accept-
ance criteria are mentioned and the test results will be documented.
If test results meet the acceptance criteria, or the explanation about the deviation is acceptable, it
means that the autoclave is qualified. Any deviation shall be explained clearly.
4. Validation Team members
Validation team shall comprise of representatives from the following functional units:
Quality Assurance Department, including the In-Process Quality Assurance
Production Department
Liquid Workshop
Quality Control Department
Engineering Department
R& D Department
The validation team shall be organized by QA Manager or his/her design.
The List of Validation Team Members (Attach additional page if required)
Sr. No Name Department Position Signature
1
2
3
4
5
6
7
8
9
5. Responsibility
5.1. Quality Assurance:

5.1.1. Preparation and approval of validation Protocol as well as providing training for validation
team.
SS-PQ-001/SV W1501A 6 / 28
5.1.2. Collection of samples as per the sampling plans by In-Process Quality Assurance.
5.1.3. Review and approval of the data compiled, review of deviations (if any), monitoring
the process as per the process parameters and for withdrawal of validation samples.
5.1.4. Preparation of validation summary report, review and approval.
5.1.5. Approval of the qualification report.
5.2. 5.2.1. Executing the batch.
5.2.2. Review of qualification protocol and summary report.
5.2.3. Preparation and approval of operating procedures (SOPs).
5.2.4. Providing Training.
5.3.5.3.1. Testing of samples as per the test procedures.
5.3.2. Review of validation protocol and summary report.
5.3.3. Providing Training.
5.4.
5.4.1. Providing technical support during qualification.
5.4.2. Review of validation protocol and summary report.
5.4.3. Make the machine accessible for qualification and feeding the necessary test parameter.
5.4.4. Calibration and verification of measuring devices and instruments.
6. Training of Personnel
Before validation, the related person should be trained of this validation protocol and related
SOPs. The training record shall be attached behind this validation protocol for reference.
7. Installation, Operational Qualification & calibration
7.1 Confirmation/verification
It is relevant document and other details (Attach Additional pages if required)
SN Document Name Conform / not Conform

1 User manual Yes□ No□
2 List of change parts Yes□ No□
SS-PQ-001/SV W1501A 7 / 28
SN Document Name Conform / not Conform
3 Maintenance manual Yes□ No□

4 Maintenance SOP Yes□ No□
5 Electrical drawings Yes□ No□
6 Mechanical drawings Yes□ No□
7 Verify the availability of approved purchase order Yes□ No□
8 Verify the availability of invoice Yes□ No□
9 Check the manufacturer and supplier Yes□ No□
10 Verify the model number and serial number Yes□ No□
11 Check for any physical damage Yes□ No□
12 Verify the availability of all required utilities Yes□ No□
Conﬁrm location and installation requirements per recom-
13 Yes□ No□
mendation of manufacturers
Installation conducted per the instructions provided in the
14 Yes□ No□
protocol
Conclusion:
Check by / Date: Reviewed by/Date:
7.2 Testing Instruments

All instrumentation used for testing shall be checked for calibration and verification. The results
should be recorded in the following table and assessments need to be made.
Testing
Measuring
equipment Model No. Calibration company Validity Result
range
Name

SS-PQ-001/SV W1501A 8 / 28
Checked by： Date：

Approved by： Date：
Note: Calibration certificate of testing instrument shall be used as attachment.
8. Reference
8.1.
SN Reference Document No.
1 Standard Operating Procedure for Superheated Wa-
ter Sterilizer model HWSM15010
2 Standard operating procedure for Validator
3 Standard operating procedure for calibration of
measuring and testing Devices.
4 Standard operating procedure for data loggers
5 Standard operating procedure for handling of Biolo-
gical Indicator
6 Standard operating procedure for Risk Management
7 Standard operating procedure for Deviation man-
agement
SS-PQ-001/SV W1501A 9 / 28

Title: Performance Qualification Protocol For Superheated Water Sterilizer
model HWSM15010
SS-PQ-001/SV W1501A 10 / 28
9. Description of Equipment
This sterilizer is general-purpose sterilization equipment for sterilization by high-temperature cir-

culating water spray (Superheated water). The items to be sterilized will be placed on the steriliza-
tion carts divided into 6-8 layers with a total of 6 sterilization carts. The product loading capacity
of this sterilization cabinet (Sterilizer) is:
Specification loading method Full Load
1ml 5500×8×6 26.4
2ml 5500×8×6 26.4
3ml 4300×6×6 15
5ml 2800×6×6 10
10ml 2100×6×6 7.5
The sterilization procedure is divided into stages of preparation, heating, heat preservation and
sterilization, and cooling.
At the beginning of the cycle a sanitary type pump circulates the filling water through a heat that
is indirectly heated in counter-current with plant steam. The water is then sprayed onto the load
from the upper and side part of the chamber. Uniform water redistribution in the lower layers of
the load is ensured by suitable perforated racks that support the product.
The cooling phase is performed by the same circulating water, which is continuously recirculated
through the heat exchanger, in which cold/chilled water (instead of steam) now flows without
contact with the circulating water. The sterilization process of this sterilizer is controlled by com-
puter. The sterilization program is set to sterilize at 121°C for 30 minutes. The temperature con-
trol uses temperature sensors, which are installed at the circulating water inlet at the top of the
sterilizer and the drain at the bottom of the sterilizer; the temperature display Use temperature
sensors and distribute them evenly at the bottom of the sterilization chamber. An appropriate set
partial pressure of air, 3.2 bars is maintained in the chamber during hold time to compensate for
the over-pressure inside the containers. Various parameters of the sterilization process are dis-
played and recorded by the computer.

SS-PQ-001/SV W1501A 11 / 28
10. Frequency of Validation
10.1.
Three (3) successful runs for all planned loads
10.2.
One successful run in a year for all loads at defined maximum load pattern.
If the autoclave has undergone major repair or moved to a new location that has different fa-
cility supplies.
Any changes in the load size, load configuration, or container characteristics (volume, geo-
metry, etc).
If replacement of Major components /Instruments
Changing in PLC programme
11.
Operate in accordance with the "HWSM15010 Water Bath Sterilizer Operation Standard
Operating Procedures no………", confirm various parameters and operation reliability of the
water bath sterilizer during operation, and prove that it can achieve the predetermined design
capacity, meet the sterilization requirements, and make the sterilization.
The performance evaluation of the sterilizer includes: no-load (Empty chamber) heat distribution
test, half-load and full-load heat distribution test, half-load and full-load heat penetration test as
part of biological indicator challenge test, each test will be conducted three consecutive times to
confirm the reproducibility of the equipment performance.
11.1. 11.1.1 No-load (Empty chamber) heat distribution test
The intent of this study is to demonstrate the temperature uniformity and stability of the sterilizing
medium throughout the loaded sterilizer.
Procedure
 Distribute the calibrated probes evenly in the sterilizer under test, and divide them into 3
layers, upper, middle and lower, with 5 probes in each layer; the top view of the specific
placement position of the probes is shown in the schematic diagram. The probes shall not
touch the wall of the autoclave because walls will have high temperature than the chamber.
 Connect the line between the probe and the data logger.

SS-PQ-001/SV W1501A 12 / 28
 Set the sterilization program at 121°C for 30 minutes, and operate the autoclave as per SOP
…… to collect data for the processes of heating, sterilization, cooling, and drainage from
the start of sterilization.
 Turn on the two data logger and start to collect data. The frequency of data collection is
once every 30 seconds.
When the sterilization cycle completes;

 Collect thermograph from the temperature recorders of the autoclave and attach as part of
report.
 Download the data from data logger into the computer for data-analysis and printing. En-
close the data printouts as part of report.
 Compile the data generated during the test for complete evaluations of the system.
 Turn off the instrument and repeat the test three times.
Probe placement results:
 The top layer of the sterilizer is 1/2/3/4/5, the middle layer is 6/7/8/9/10, the bottom layer
is 11/12/13/14/15, and there are 1 probe for the inlet and outlet of super-heated circulating
water. There are 15 probes in the sterilizer, 17 in total.
Top view of probe distribution
.
1 4
Probe number 1 2 3 4 5
Placement
3
Placement
2 5
Placement
Probe number 16 17
Placement
Confirmed by Year Month date

SS-PQ-001/SV W1501A 13 / 28
Acceptance Criteria
 Compare the temperature measured by each probe every 2 minutes, and the difference
between the average temperature and the temperature of each probe does not exceed
±1°C.
 The temperature at each temperature mapping probe should be within the range of 120
ºC to 123ºC during the sterilization hold period.
 The difference between lowest and highest temperature shall not be more than 2°C.
 Throughout the dwell time, all temperatures measured in the chamber should not fluctu-
ate by more than 1oC.
 Throughout the dwell time, all temperatures measured in the chamber should not differ
from each other by more than 2oC.
The record and analysis of empty chamber heat distribution results are shown in the following ta-
ble:
（A） (B) (C)
（min） Maximum Minimum Average
time temperature temperature temperature A-C C-B A-B
(min) Probe Temperat- Probe Temperat- (C)
No. ure No. ure
0
2
4
6
8
10
12
14
16

SS-PQ-001/SV W1501A 14 / 28
18
20
22
24
26
28
30
Cold Spot:
Hot Spot:
Confirmed by: Year Month date

Confirmed by: Year Month date
Analysis Result
Qualification Team Leader Date Year Month date
Statistical analysis
Perform ANOVA to check the presence/absence of significant variation between sterilization tem-
peratures of the three runs at hold temperature.
Procedure
 Distribute the calibrated probes evenly in the sterilization cabinet to be tested, and divide
them into 3 upper, middle and lower layers, with 5 probes in each layer; the top view of the
specific placement of the probes is shown in the schematic diagram.

SS-PQ-001/SV W1501A 15 / 28
 Connect the line between the probe and the verification instrument, turn on the two
verification instruments, calibrate the time of the verification instrument and the sterilization
equipment, and start collecting data. The frequency of collection is once every 30 seconds.
 Set the sterilization program at 121°C for 30 minutes, and start the sterilization cabinet to
collect the processes of heating, sterilization, cooling, and drainage from the start of
sterilization.
 After the sterilization is over, keep the records. Turn off the instrument and repeat the test
three times.

Product name: ;________________________
Specification: _________________________ ;
Lot number ; __________________________
Quantity: __________plate, each plate is about ______ piece, total ___________ piece

 The top layer of the sterilizer is 18/19/20/21/22, the middle layer is 23/24/25/26/27, the bot-
tom layer is 28/29/30/31/32, and there is one probe for the inlet and outlet of high tempera-
ture circulating water. There are 15 probes in the sterilizer, 17 in total.
18 19
20
21
22

SS-PQ-001/SV W1501A 16 / 28
Prob No. 18 19 20 21 22
Placement
Prob No. 23 24 25 26 27
Placement
Prob No. 28 29 30 31 32
Placement
Prob No. 33 34
Placement

Acceptance Criteria
 Compare the temperature measured by each probe every 2 minutes, and the difference be-
tween the average temperature and the temperature of each probe does not exceed ±1°C.
 The temperature at each temperature mapping probe should be within the range of 120 ºC
to 123ºC during the sterilization hold period.
 Throughout the dwell time, all temperatures measured in the chamber should not fluctuate
by more than 1oC.
 Minimum F0 during sterilization hold period shall be more than 12 min (Which is F0 value
of biological indicator).
The record and analysis of no-load heat distribution results are shown in the following table:
（min）（A） (B) (C) A-C C-B
time Maximum Minimum Average
(min) temperature temperature temperature A-B
Probe Temperat- Probe Temperat- (C)
SS-PQ-001/SV W1501A 17 / 28
No. ure No. ure

0
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
;
Minimum F0 during sterilization hold period
First Run Second Run Third Run
Cold Spot
Hot Spot
Result Analysis

SS-PQ-001/SV W1501A 18 / 28

peratures of the three runs at hold temperature
11.1.3. Fo value for biological indicators (minimum Fo )
The biological Fo value for biological indicator exposed during the sterilization can be cal-
culated as follows.
Fo = D121 (log A – log B)
Where,
D121 = D Value of the biological indicator at 121OC
A =experimental biological indicator concentration or spore population
B =desired level of sterility (SAL of 10-6).
Acceptance Criteria
The minimum Fo value shall not be less than 12 min
11.1.4
 Distribute the calibrated probes evenly in the sterilization cabinet to be tested, and divide
them into three layers: upper, middle and lower layers, with 5 probes on each layer; the
top view of the specific placement of the probes is shown in the schematic diagram.
 Connect the line between the probe and the verification instrument, turn on the two
verification instruments, calibrate the time of the verification instrument and the
sterilization equipment, and start collecting data, and the collection frequency is once
every 30 seconds.
 Set the sterilization program at 121°C for 15 minutes, and start the sterilization cabinet to
collect the processes of heating, sterilization, cooling, and drainage from the start of
sterilization.
 After the sterilization is over, keep the records. Turn off the instrument and repeat the test
three times.
SS-PQ-001/SV W1501A 19 / 28
 The top layer of the sterilizer is 35/36/37/38/39, the middle layer is 40/41/42/43/44, the
bottom layer is 45/46/47/48/49, and there is one probe for the inlet and outlet of high
temperature circulating water. There are 15 probes in the sterilizer, 17 in total.
35
36
37
38
39
Probe No. 35 36 37 38 39
Placement
Probe No. 40 41 42 43 44
Placement
Probe No. 45 46 47 48 49
Placement
Probe No. 50 51
Placement

Acceptance Criteria
 Compare the temperature measured by each probe every 2 minutes, and the difference be-
tween the average temperature and the temperature of each probe does not exceed ±1°C.
 The temperature at each temperature mapping probe should be within the range of 120 ºC
to 123ºC during the sterilization hold period.

SS-PQ-001/SV W1501A 20 / 28
 Throughout the dwell time, all temperatures measured in the chamber should not fluctuate
by more than 1oC.
 Minimum F0 during sterilization hold period shall be more than 12 min (Which is F 0 value
of biological indicator).
The record and analysis of no-load heat distribution results are shown in the following table:
（A） (B) (C)
（min） Maximum Minimum Average
time temperature temperature temperature A-C C-B A-B
(min) Probe Temperat- Probe Temperat- (C)
No. ure No. ure
0

SS-PQ-001/SV W1501A 21 / 28
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
Minimum F0 during sterilization hold period

First Run Second Run Third Run
Product name: ;________________________

Specification: _________________________ ;
Lot number: ; __________________________
Quantity: __________plate, each plate is about ______ piece, total ___________ piece;
Cold Spot
Hot Spot


SS-PQ-001/SV W1501A 22 / 28
Result Analysis
peratures of the three runs at hold temperature
11.1.5.
 This test is carried out along with the full load heat distribution test, repeated three times.
 This challenge test serves as heat penetration study confirmation test.
 Place 15 Bacillus stearothermophilus biological indicators (packed in vials/Ampules along
with the product as per layout of probe distribution and put them into different positions in
the sterilization cabinet to ensure that a bacterial tube is placed in the cold spot area of the
sterilizer. After the sterilization is completed, take out the biological indicator, and operate
together with a control tube according to the incubation temperature (56-60°C) and
incubation time (24-48 hours) specified in the instruction manual of the biological indicator.
After incubation, if the sterilization tube does not change color (purple), it means that the
biological indicator test has passed, and the sterilization tube changes color (yellow),
indicating that the biological indicator test fails, and the cultured control tube should be
positive, that is, it will change color (yellow). Otherwise, the test is invalid. The above test
should be carried out three times in a row to confirm the reproducibility of the sterilization
process.
Biological indicator name: Bacillus stearothermophilus ATCC7953
Acceptable Criteria
6-log reduction should be observed in any exposed biological indicators on complete incubation.
Biological Indicators and Heat Penetration Testing record
Validation results Control bacteria
label Location Remark
Negative Positive Negative Positive
SS-PQ-001/SV W1501A 23 / 28

Biological indicator test results and evaluation:

SS-PQ-001/SV W1501A 24 / 28
Reviewer Date Year month date
PQ1 Action to be taken in case of failure

 If the Heat penetration or Heat Distribution cycle fails in any respect, deviation should be
raised as per SOP and 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.
12.Deviation List
SN Deviation name Deviation No.

SS-PQ-001/SV W1501A 25 / 28
13.Deviation Table (Attach Additional page if required)

The deviations which exist in the execution process of protocol will be recorded.
Inspection report Deviation No.
Description of deviation and corrective action
Approval of corrective action

SS-PQ-001/SV W1501A 26 / 28
Corrective Action Result
Liquid Workshop Signature : Date:

Production Department Signature : Date:
Engineering and Utility Signature : Date:
Quality Control Department Signature : Date:
QA Department Signature : Date:
14.Attachment
 In the table all the attachments which are used for the Qualification, have to be mentioned.
 Of the attachments, which are not attached to the Qualification protocol, from where it
comes has to be mentioned clearly.
 Attachment 01: Common for all tests
 Calibration Report of Thermocouples
 Verification Report of Thermocouples
 Attachment 02: For Heat Distribution Study
 Standard Format: for logging data
 Yokogawa Graph
SS-PQ-001/SV W1501A 27 / 28
 PLC print
 Attachment 03: For Heat Penetration Study /Biological Challenge test
 Pictures showing Color of Biological indicator before and after incubation
 Standard Format: for logging data
 Yokogawa Graph
 PLC print

SN. Appendix File Name
15. P-Certificate
The persons, who have signed the document, confirm the completeness of the test documentation
and the execution of the tests.
The execution and the results fulfil the requirements. No deviation is applicable. The equipment
has been released for the PQ activities and contract requirement.
The execution and the results do not fulfil the requirements. Critical deviations are not noticed.
The equipment has been released for the PQ activities and contract requirement.
The execution and the results do not fulfil the requirements. Critical deviations are noticed. The
equipment has not been released for the PQ activities and contract requirement. Further measures
have to be done. Corrections have to be documented separately.
SS-PQ-001/SV W1501A 28 / 28
Conclusion
Final Approval
QA Director Signature /Date

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Sansheng Pharmaceutical P.L.

Performance Qualification Protocol for

Superheated Water Sterilizer model HWSM15010

Document No.: _________

Equipment ID: ________

Manufacturer: Truking Technology Limited

Equipment location: Small Volume Parenteral Manufacturing Area

Protocol Approval Page:

Prepared by Liquid Workshop Director Signature/Date

Reviewed by Engineering Department Signature/Date

Sansheng Pharmaceutical Plc.

Location of docu- Issue date:

Sansheng Pharmaceutical Plc.

Table of Contents Pages

Sansheng Pharmaceutical Plc.

Sansheng Pharmaceutical Plc.

3. Concept of the Equipment Qualification

4. Validation Team members

5.1. Quality Assurance:

SN Document Name Conform / not Conform

SN Document Name Conform / not Conform

3 Maintenance manual Yes□ No□

7.2 Testing Instruments

Sansheng Pharmaceutical Plc.

Checked by： Date：

Note: Calibration certificate of testing instrument shall be used as attachment.

Sansheng Pharmaceutical Plc.

This sterilizer is general-purpose sterilization equipment for sterilization by high-temperature cir-

Sansheng Pharmaceutical Plc.

10. Frequency of Validation

Sansheng Pharmaceutical Plc.

When the sterilization cycle completes;

Confirmed by Year Month date

Sansheng Pharmaceutical Plc.

Confirmed by: Year Month date

Qualification Team Leader Date Year Month date

Sansheng Pharmaceutical Plc.

Probe placement results:

Sansheng Pharmaceutical Plc.

Confirmed by Year Month date

No. ure No. ure

Sansheng Pharmaceutical Plc.

Qualification Team Leader Date Year Month date

Confirmed by Year Month date

Sansheng Pharmaceutical Plc.

Sansheng Pharmaceutical Plc.

Minimum F0 during sterilization hold period

Product name: ;________________________

Confirmed by Year Month date

Sansheng Pharmaceutical Plc.

Qualification Team Leader Date Year Month date

Confirmed by Year Month date

Biological indicator test results and evaluation:

Sansheng Pharmaceutical Plc.

Reviewer Date Year month date

PQ1 Action to be taken in case of failure

Sansheng Pharmaceutical Plc.

13.Deviation Table (Attach Additional page if required)

Approval of corrective action

Sansheng Pharmaceutical Plc.

Corrective Action Result

Liquid Workshop Signature : Date:

SN. Appendix File Name

Sansheng Pharmaceutical Plc.