PHARMA DEVILS

QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

PERFORMANCE QUALIFICATION
PROTOCOL FOR
CIP-SIP MODULE
CAPACITY: 250 LITER

EQUIPMENT ID No.
LOCATION CIP/SIP ROOM
DATE OF QUALIFICATION
SUPERSEDED PROTOCOL NO. NIL
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

PROTOCOL CONTENTS

S. No. SUBJECT PAGE No.

1. PROTOCOL APPROVAL 3

2. OBJECTIVE 4

3. SCOPE 4

4. RESPONSIBILITY 5

5. EQUIPMENT DETAILS 6

6. SYSTEM DESCRIPTION 6

7. REASON FOR QUALIFICATION 8

8. SITE OF STUDY 8

9. FREQUENCY OF REQUALIFICATION 8

10. PRE-REQUALIFICATION REQUIREMENTS 9

11. TESTS AND CHECKS 12

12. CHECKLIST OF ALL TESTS AND CHECKS 24

13. REFERENCE 25

14. DOCUMENTS TO BE ATTACHED 25

15. NON-COMPLIANCE 25

16. DEVIATION FROM PRE-DEFINED SPECIFICATION 25

17. CHANGE CONTROL 25

18. ABBREVIATIONS 26
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

1.0 PROTOCOL –PRE APPROVAL:

INITIATED BY:
DESIGNATION NAME SIGNATURE DATE
OFFICER/EXECUTIVE
(QUALITY ASSURANCE)

REVIEWED BY:

DESIGNATION NAME SIGNATURE DATE

HEAD
(PRODUCTION)
HEAD
(ENGINEERING)

APPROVED BY:

DESIGNATION NAME SIGNATURE DATE

HEAD
(QUALITY ASSURANCE)
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

2.0 OBJECTIVE:
 The objective of this protocol is to establish that CIP-SIP Module meets the following criteria:
 The CIP-SIP Module is performed as per the pre-defined parameter and/ or quality attributes.
 The CIP-SIP Module unit is capable suitable for cleaning of manufacturing vessels, filtration vessels
& associated product transfer lines.

3.0 SCOPE:
 The Protocol covers all aspects of Performance Qualification for the CIP-SIP Module installed in the
CIP/SIP area.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

4.0 RESPONSIBILITY:
The Validation Group, comprising of a representative from each of the following Departments, shall be
responsible for overall compliance of this Protocol:

DEPARTMENTS RESPONSIBILITIES

 Preparation, Review Approval and Compilation of the Performance

Qualification Protocol.
 Protocol Training.
Quality Assurance
 Co-ordination with Quality Control, Production and Engineering to
carryout Performance Qualification Activity.
 Monitoring of Performance Qualification.
Quality Control  Analytical Support (Microbiological Testing / Analysis)
External Qualification
 Performance of Qualification activity as per protocol.
Agency(if Applicable )
 Review of Performance Qualification Protocol.
Production
 To co-ordinate and support Performance qualification Activity.

 Review of Performance Qualification Protocol.

Engineering
 To co-ordinate and support Validation Activity.
 Responsible for Trouble shooting during execution (If Occurs).
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

5.0 EQUIPMENT DETAILS:

Equipment Name CIP-SIP MODULE
Equipment ID.

Manufacturer’s Name

Supplier’s Name

Place of Installation CIP/SIP AREA

6.0 SYSTEM DESCRIPTION:

CIP-SIP Module 250 Ltr is fully automatic unit used for washing and Sterilizing different capacity of
vessel (Capacity from 100 to 500 Ltr), piping & inline devices.
The CIP technology involves the use of, pure steam, Water for injection high pressure pumps, tanks and
aseptic design principles to ensure that large scale process are free of dirt & organic contaminants.
The complete plant will be operated through PLC provided in the control panel. The HMI will display the
various setting for the processes programmed. The annual mode also can be run through HMI.
The sequences logic will have following control philosophy.
 Purified Water once through Pre wash cycle – Fixed
 Purified Water Recirculated wash cycle – Optional
 WFI once through rinse cycle - Fixed
The design of each and every part are carried out considering the safety, required output, optimum utility
and energy saving. The different utilities needs to be controlled as required.
The CIP-SIP Module is also used to sterilize in place Manufacturing tank, Holding tank, product
pipeline, and filter housing transfer/circulation pump by passing clean steam and connecting the outlet
valve through flexible hose by SIP system.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

Part I
Pure Steam inlet

WFI
INLET
Cooling water Tem
inlet p. H3
Displ 0.2 µ Nitrogen
ay Gas
Cooling out
let
Manufact
Raw Nitrogen purge Tube
uring
Steam ttank
Inlet TANK
HOLDING
TANK
Return to
CIP-SIP
Magnetic
Module
Stirrer
Steam Trap Valve
Temperature
Sensor H1 – HOUSING FOR (1.0 ) MICRON PRODUCT CARTRIDGE FILTER
H2 – HOUSING FOR 0.22 MICRON PRODUCT CARTRIDGE FILTER
Pressure gauge
H3 – HOUSING FOR 0.22 MICRON AIR CARTRIDGE FILTER

Diaphragm valve
Part-II

Pure Steam Air Vent

inlet Filter
WFI
Temp.
Cooling water INLET Display
inlet
H2
0.2 µ Nitrogen
Gas
Cooling out let
HOLDING
TANK Nitrogen Spurge Tube
Raw Steam
Inlet
Return to CIP-
SIP Module
Magnetic
Stirrer Steam Trap Valve

Temperature
Sensor
Pressure gauge

Diaphragm valve
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

7.0 REASON FOR QUALIFICATION:

 New equipment in CIP/SIP Room.
 After completion of the Operation Qualification of the Equipments, it is imperative to perform the
Performance Qualification. The study will establish that the parameters are followed, critical
variables are under control and the quality of the output is, as desired.

8.0 SITE OF STUDY:

CIP/SIP room.

9.0 FREQUENCY OF REQUALIFICATION :

 Half Yearly as per Validation Master Plan.
 After any major breakdown or after major modification.

10.0 PRE-QUALIFICATION REQUIREMENTS :

Verification for availability, completeness and approval status of all the required relevant documents
shall be done and observations shall be recorded in the performance qualification report

10.1 Verification of Documents

Record the observations for documents in the below mentioned table.

Checked By Verified By
Completed (Engineering)
S.No. Document Name Document / SOP No. (QA)
(Yes/No) Sign/Date Sign/Date
1. Executed and approved
Design Qualification
document
2. Executed and approved
Installation Qualification
document
3. Executed and approved
Operational Qualification
document
4. SOP for operation &
Cleaning of Laminar Air
Flow
5. SOP for Preventive
Maintenance of Laminar
Air Flow
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

10.2 TEST EQUIPMENT

S.No. Test Instrument

1. Duly Calibrated Data logger with calibrated PT-100 sensors.

2. Biological Indicator 106 spores i.e. Geobacillus stearothermophilus must be checked for
spore population.

3. Chemical Indicator (Steam Clox).

4. All parts of CIP/SIP module like temperature sensors, pressure gauges, must be calibrated.

10.3 TEST EQUIPMENT CALIBRATION:

Review the calibration status for the test equipment (Data Logger with PT-100 sensors) to be utilized
and record the calibration status Performance qualification report. All Equipment / Instrumentation must
remain within the Calibration due date for the duration of Validation Study for which the item is used. If
a due date potentially occurs during the testing period then the instrument must be recalibrated before it
is utilized. Calibration of all the instruments used for qualification should be mentioned along with
Calibration Certificates.

10.4 CALIBRATION OF TEMPERATURE SENSORS:

Pre & Post Calibration of Temperature Sensors

Pre & Post calibration shall be carried out before starting and after completion of Validation activity.

PRE & POST CALIBRATION OF TEMPERATURE SENSORS:

A) PREPARATION OF ICE BATH:
 Prepare a container with Crushed Ice and add enough Purified Water to ensure a proper Slush
Solution.
 Allow the Temperature to Stabilize. Ensure to add sufficient crushed ice to maintain the
Equilibrium State of ice and water.
 Measure the temperature by using reference digital Thermometer.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

B) PROCEDURE:
 Temperature sensors which are to be used for Qualification study shall be calibrate in Ice Bath at
approximately 0°C and in High Temperature reference block at 50°C, 100°C,121°C & 150 °C
prior to its usage in the qualification.
 Record the Temperature of all the sensors while putting them in ice bath after one minute of
temperature stabilization.
 Put individual sensor to the slot of High temperature Reference block which is stabilized at
required temperature. Record the readings at least one minute after stabilization of temperature.
 Record the Temperature for five minutes by data logger and attach the print out in Performance
Qualification Report.

C) ACCEPTANCE CRITERIA:
 No temperature sensor should vary by 1°C in Ice Bath from the mean of temperatures shown by
the calibrated thermometer during the data-logging period.
 No temperature sensor should vary by 1°C in High temperature reference block from the mean of
temperatures shown by calibrated thermometer during data- logging period.

10.5 Training Record of Validation Team:

 All the persons involved in the execution of qualification activity must be trained in all aspects of
the qualification activity including the test methodology, acceptance criteria and safety
precautions to be followed during working.
 Training record shall be attached with qualification report.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

11.0 TESTS AND CHECKS:

11.1 EFFICIENCY OF WASHING CYCLE FOR (500 L & 400 L) MANUFACTURING TANK &
CONNECTED LOOP:
A) OBJECTIVE:
To demonstrate that the system is to ensure that, the washing cycles are sufficient to remove
residual impurities of previously manufactured product from inner surface of the Manufacturing
Vessel.

B) PROCEDURE
 Collect 490 Liter water for injection in 500 Litr. Mfg. tank or collect 390 Litr. water for injection
in 400 Litr Mfg Tank.
 Add 10 Liters 5 % NaOH solution in the tank and start stirring for 10 min.
 After completion of stirring drain the solution from Mfg. tank.
 Start CIP cycle as per SOP.
 After completion of CIP cycle, immediately collect Sample from drain and send to QC
For pH Checking. All parameters should meet with acceptance criteria.
 Repeat the cycle three times.
 Take print out from the CIP system for each cycle.
 Repeat all steps with 10 % & 15 % NaOH solution Also.
 Repeat above procedure for all manufacturing tank having different capacity.

C) RESULT RECORDING:
 Record the results in Performance Qualification Report

D) ACCEPTANCE CRITERIA:
 Finally rinsed WFI should meet the WFI specification for pH (Limit 5-7) and Conductivity
(Limit: less than 1.3 µs).
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

11.2 TEST FOR EFFICIENCY OF WASHING CYCLE FOR (500 L & 400 L) HOLDING TANK &
CONNECTED LOOP:

A) OBJECTIVE:
To ensure that, the washing cycles are sufficient to remove residual impurities of previously
manufactured product from inner surface of the Holding Vessel.

B) PROCEDURE :
 Collect 490 Liter water for injection in 500 Litr. holding tank or collect 390 Litr. water for
injection in 400 Litr holding Tank.
 Add 10 Liters 5 % NaOH solution in the tank and start stirring for 10 min
 After completion of stirring drain the solution from holding tank.
 Start CIP cycle as per SOP.
 After completion of CIP cycle, immediately collect Sample from drain and send to QC for pH
Checking. All parameters should meet with acceptance criteria.
 Repeat the cycle three times.
 Take print out from the CIP system for each cycle.
 Repeat all steps with 10 % & 15 % NaOH solution Also.
 Repeat above procedure for all holding tank having different capacity

C) RESULT RECORDING:
 Record the results in Performance Qualification report

D) ACCEPTANCE CRITERIA:
 Finally rinsed WFI should meet the WFI specification for pH (Limit 5-7) and Conductivity
(Limit: less than 1.3 µs).
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

11.3 HEAT DISTRIBUTION STUDY FOR MANUFACTURING TANK & CONNECTED LOOP
A) OBJECTIVE:
 The Objective of heat distribution study is to provide a documentary evidence for a uniform
temperature distribution in Equipment train Connected with Manufacturing Tank by using 7 Nos.
of temperature probes.

B) EQUIPMENT / INSTRUMENTS
 Duly Calibrated Data logger with calibrated PT-100 sensors
 Biological Indicator 106 spores i.e. Geobacillus stearothermophilus)

C) PROCEDURE:
 Check the master data logger and probes are calibrated and which is traceable to national
standards
 Insert 7 nos. of Temperature probes in following locations, as schematically shown in system
drawing for Manufacturing tank through ……………..(Part I).
 Seal the port with clamp to ensure no steam leakage during operation.
 Set the following parameters in PLC & operate CIP/SIP module as per SOP and also start the data
logger to record actual temperatures at every 1 Minute.
S.No. Location No. of Probes No. of BI. Probe. ID
1. Manufacturing tank 5 5 2,34,5,6,

2. Manufacturing tank condensate drain (at 1 1 7

the point of )
3. SIP module Drainage - 1 -

4. Manufacturing tank steam inlet 1 1 1

 Perform three consecutive SIP cycle for Manufacturing tank & Connected Loop (Part I) as per
respective SOP at 122.00C and 1.5 bar pressure for 30 minutes.
 Monitor the temperature and pressure throughout the sterilization cycle. Check Temperature on
display of data logger at different locations and also as being plotted on the graph. Check and
record pressure differentials on the pressure gauges installed at various locations.
 Repeat above procedure for all manufacturing tank having different capacity
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

D) RESULTS:
 Record the observations in Performance Qualification Report

E) ACCEPTANCE CRITERIA:
 There should be uniform distribution of heat through Equipment train Connected with
manufacturing tank during the sterilization hold period and the temperature at each temperature
mapping probe should be within the limit of 122.0°C during the Sterilization Hold Period.
 Temperature Uniformity at a given time of Temperature recording between all probes during hold
period should not be more than ± 1°C.
 Following parameter should meets for successful Performance qualification of CIP/SIP module.
Test Parameter Acceptance Criteria
Description A Clear colorless liquid
PH Between 5.0 to 7.0
Bacterial Endotoxin NMT 0.25 EU/ml
Conductivity (at 250C) NMT 1.3 µ s/cm
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

Temperature Sensor & BI’s Location for Manufacturing tank with Connected Loop
Probe 1 Part-I
Steam
Air Vent
Inlet Filter

Probe 3 Probe6
Manufact
uring Probe5
TANK
Probe 2
Probe 4 BI Indicator
SIP Drainage

Probe 7

BI-
D BI
Indicator
Temperature Sensor
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

11.4 HEAT DISTRIBUTION STUDY FOR HOLDING TANK & CONNECTED LOOP

A) OBJECTIVE:
 The Objective of heat distribution study is to provide a documentary evidence for a uniform
temperature distribution in Equipment train Connected with Holding Tank by using 5 Nos. of
temperature probes.

B) EQUIPMENT / INSTRUMENTS
 Duly Calibrated Data logger with calibrated PT-100 sensors
 Biological Indicator 106 spores i.e. Geobacillus stearothermophilus)

C) PROCEDURE:
 Check the master data logger and probes are calibrated and which is traceable to national
standards
 Insert 4 nos. of Temperature probes in following locations, as schematically shown in system
drawing for Manufacturing tank
 Seal the port with clamp to ensure no steam leakage during operation.
 Set the following parameters in PLC & operate CIP/SIP module as per SOP and also start the data
logger to record actual temperatures at every 1 Minute.

S.No. Location No. of Probes No. BI Probe I.D.

1 Holding tank 5 5 2, 3 4,5,6,

2 Holding tank condensate drain 1 1 7

3 SIP In let 1 1 1

4 SIP Module Drainage - 1 -

 Perform three consecutive SIP cycle for Holding tank & Connected Loop (Part II) as per
respective SOP at 122.0C and 1.5 bar pressure for 30 minutes.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

 Monitor the temperature and pressure throughout the sterilization cycle. Check Temperature on
the temperature gauge at different locations and also as being plotted on the graph. Check and
record pressure differentials on the pressure gauges installed at various locations.
 After completion of each sterilization cycle, start drying of product line by selecting filter drying
program on the machine and passing sterile filtered air for 30 minutes.
 At the initial stages of the filter drying process, collect steam condensate samples aseptically from
the sampling points specified in System drawing and test for the following parameters.
 Take the printout from data logger & CIP/SIP Module
 Repeat above procedure for all Holding tank having different capacity

D) RESULTS:
 Record the observations in of Performance Qualification Report.

F) ACCEPTANCE CRITERIA:
 There should be uniform distribution of heat through Equipment train Connected with
manufacturing tank during the sterilization hold period and the temperature at each temperature
mapping probe should be within the limit of 122.6°C during the Sterilization Hold Period.
 Temperature Uniformity at a given time of Temperature recording between all probes during hold
period should not be more than ± 1°C.
 Following parameter should meets for successful Performance qualification of CIP/SIP module.
Test Parameter Acceptance Criteria
Description A Clear colorless liquid
PH Between 5.0 to 7.0
Bacterial Endotoxin NMT 0.25 EU/ml
Conductivity (at 250C) NMT 1.3 µ s/cm
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

TEMPERATURE SENSOR & BI’S LOCATION FOR HOLDING TANK WITH CONNECTED
LOOP (Part II)

Steam
Inlet Air Vent
Filter
Probe 1
BI Indicator

Probe 2 Probe 5

Probe 4 Probe 3
HOLDING
TANK
Probe 6 SIP Drainage
BI Indicator

Probe 7

Pressure Gauge
D

Temperature Sensor

Temperature Gauge
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

11.5 BIO-CHALLENGE STUDY FOR MANUFACTURING TANK& CONNECTED LOOP

A) OBJECTIVE:
The purpose of Bio-challenge study is to provide documentary evidence that the SIP cycle is
capable to achieve microbial inactivation, by using Geobacillus stearothermophilus ATCC 7953.

B) PROCEDURE:

 Biological challenge study concurrently carried out with heat distribution study,
 Place the biological indicator in a horizontal position in the following locations as specified in
system drawing part I.

S.No. Location No. of BI

1 Manufacturing tank 5
2 Manufacturing tank condensate drain 1
3 SIP Module Drainage 1
4 SIP Inlet IN Tank 1

 After completion of sterilization cycle remove the biological indicator with the help of safety
gloves. Content of the ampoule are hot and under pressure. Allow to cool at room temperature for
10 to 15 minutes.
 Sent the exposed biological indicator to microbiology laboratory for incubation.
 After incubation observe the indicator for growth. (+ve when purple color change to yellow color,
- ve when purple color remain as such).
 Place the processed units and one unprocessed unit (control) in a vertical position in an incubator
at 55 -600C for 48 hours.
 Observe the incubated units after each 24 hrs and record the observation in respective format
 If exposed indicator shows positive results increase holding time and validate the cycle for this
period to get minimum Sterility Assurance Level (SAL) 10 -6.Run three consecutive cycles.
 After 2 days incubation, all positive units should be discarded as per SOP.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

C) ACCEPTANCE CRITERIA:

 If positive control unit does not show sign of growth consider the test invalid.
 A negative control unit should not show any growth during incubation .
 A failed sterilization cycle is indicated by turbidity or color change toward yellow in exposed
biological indicator.
 Test unit that retains its purple color after sterilization indicates that sterilization parameters have
been met.

11.6 BIO-CHALLENGE STUDY FOR HOLDING TANK & CONNECTED LOOP

A) OBJECTIVE:
The purpose of Bio-challenge study is to provide documentary evidence that the SIP cycle is
capable to achieve microbial inactivation, to an SAL 10-6 by using Geobacillus Stearothermophilus
ATCC 7953.

B) PROCEDURE

 During the heat distribution study, place the biological indicator in a horizontal position in the
following locations as specified in system drawing part II.

S.No Location No. of BI

1 Holding tank 5
2 Holding tank Condensate drain 1

3. SIP Module 1
4 SIP Inlet IN Tank 1

 After completion of sterilization cycle remove the biological indicator with the help of safety
gloves. Content of the ampoule are hot and under pressure. Allow to cool at room temperature for
10 to 15 minutes.
 Sent the exposed biological indicator to microbiology laboratory for incubation.
 After incubation observe the indicator for growth. (+ve when purple color change to yellow color,
- ve when purple color remain as such).
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

 Place the processed units and one unprocessed unit (control) in a vertical position in an incubator
at 55 -600C for 48 hours.
 Observe the incubated units after each 24 hrs and record the observation in respective format
 If exposed indicator shows positive results increase holding time and validate the cycle for this
period to get minimum Sterility Assurance Level (SAL) 10 -6.Run three consecutive cycles.
 After 2 days incubation, all positive units should be discarded as per SOP.

D) ACCEPTANCE CRITERIA:

 If positive control unit does not show sign of growth consider the test invalid.
 A negative control unit should not show any growth during incubation .
 A failed sterilization cycle is indicated by turbidity or color change toward yellow in exposed
biological indicator.
 Test unit that retains its purple color after sterilization indicates that sterilization parameters have
been met.

11.7 F0 CALCULATION
A) Numerical F0 Value:
The actual observations obtained during the heat distribution study at different temperature sensing
locations are complied in the table and the observed temperature shell be subjected for calculation
of F0 values at that particular location. The lethality factor calculations are done by using the
following formula and the computed (during the sterilization period) are given in the following
table.
F0=dt ∑ 10(T-121)/Z __________ (a)

F0=dt ∑ (Sum of lethality factors)

Where,

dt : Time interval between successive temperature measurements (in min).

T : Observed temperature at that particular time (as per the actual temperatures recorded)
Z = change in the heat resistance of Geobacillus stearothermophilus spores as temperature is
changed (100C or as mentioned in COA).
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

B) F0 Value for Biological Indicators:

The biological Fo value for biological indicator strip exposed during the sterilization can be
calculated as follows.
Fo = D121 (log A – log B) ……… (b)
Where,

D121 D value of the biological indicator at 1210C

A Experimental Biological indicator concentration or spore population
B Desired level of sterility (SAL- 10-6)

C) Desired Spore log reduction:

Calculate the desired reduction in spore population by using the formula-
SLR desired =log A- log SAL desired ---------------(c)
Where,

A Experimental population of Biological Indicator

:

SAL desired Desired level of sterility (10 -6)

:
D) Actual Spore log reduction:
Calculate actual reduction in spore population by using the formula-
SLR Actual = F0 / D121------------------------------ (d)
Where,

F0 : Minimum calculated F0 value

D121 : D value of the biological indicator at 1210C.

E) ACCEPTANCE CRITERIA:
The calculated numerical Fo value of SIP cycle should be more than the biological indicator value,
which is exposed in SIP validation.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

12.0 CHECKLIST OF ALL TESTS AND CHECKS:

This checklist is provided to ensure that all tests or checks required for this protocol to be executed and
consisting of following tests.

S.No. Name of Test or Check Acceptance Criteria

1. Test for Efficiency of washing Cycle for PH : Between 5.0 to 7.0
Manufacturing tank& Connected Loop Conductivity :NMT 1.3 µ s/cm
2. Test for Efficiency of washing Cycle for PH : Between 5.0 to 7.0
Holding tank & Connected Loop Conductivity :NMT 1.3 µ s/cm
3. Heat distribution study for Manufacturing Description : A Clear colorless liquid
tank& Connected Loop PH : Between 5.0 to 7.0
Bacterial endotoxin :NMT 0.25 EU/ml
Conductivity :NMT 1.3 µ s/cm
4. Heat Distribution Study For Holding Tank& Description : A Clear colorless liquid
Connected Loop PH : Between 5.0 to 7.0
Bacterial endotoxin :NMT 0.25 EU/ml
Conductivity :NMT 1.3 µ s/cm
5. Biological challenge Study Test unit that retains its purple color after
sterilization indicates that sterilization
parameters have been met.

6. F0 value Calculation The calculated numerical Fo value of SIP cycle

should be more than the biological indicator
value, which is exposed in SIP validation.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

13.0 REFERENCES:
 Validation Master Plan.
 Schedule – M “Good Manufacturing Practices and Requirements of Premises, Plant and
Equipment for Pharmaceutical Products.”
 WHO Essential Drugs and Medicines Policy, QA of Pharmaceuticals, Vol-2.Good
Manufacturing Practices and Inspection.
 “Operation and Cleaning of Clean In Place (CIP) Module”.

14.0 DOCUMENTS TO BE ATTACHED:

 Raw data of Chemical Analysis
 Calibration Certificates for pH Meter.
 Calibration Certificates for Conductivity Meter.
 Raw data of Microbiological Analysis.

15.0 NON COMPLIANCE:

 In case of any Non-Compliance observed during performance qualification test, inform to head
QA for required action.
 All the required action should be addressed in the report and justified

16.0 DEVIATION FROM PRE-DEFINED SPECIFICATION, IF ANY:

 In case of any deviation observed during PQ, inform to Head QA for necessary action.
 Document the deviation detail in observed deviation section.
 The Head QA will study the impact of deviation. If deviation is acceptable and it does not have an
Impact on properties of product & prepare final conclusion.

17.0 CHANGE CONTROL, IF ANY:

 If any change control is required during PQ, inform to Head QA for necessary action.
 Document the details observed.
 The Head QA will study the impact of change. If change is acceptable and it does not have an
Impact on properties of product & prepare final conclusion.
 PHARMA DEVILS
QUALITY ASSURANCE DEPARTMENT

PERFORMANCE QUALIFICATION PROTOCOL FOR CIP-SIP MODULE (250 LITER)

18.0 ABBREVIATIONS:
No. : Number
Ltd. : Limited
ID No. : Identification Number
ml : Milliliter
CIP : Clean In place
SIP : Sterilization in place
SOP : Standard operating procedure
PPQ : Protocol performance qualification
FDA : Food & drug administration
ID. : Identification
Ltd : Limited
No. : Number
% : Percent