performance qualification protocol cum report...performance qualification of dry heat steriliser...

PERFORMANCE QUALIFICATION PROTOCOL CUM REPORT FOR

DEPYROGENATING & STERILIZING TUNNEL

Protocol cum Report No.: Batch Size: 250 vials Page No.: 1 of 25

PHARMA SCHOLARS MICROBIOLOGY DEPARTMENT

PERFORMANCE QUALIFICATION

PROTOCOL CUM REPORT FOR

DEPYROGENATING AND

STERILIZING TUNNEL





CONTENTS

S. No. Description

1.0 Approval of Performance Qualification Protocol

2.0 Objective

3.0 Responsibilities

4.0 Equipment Description & Identification

5.0 Methodology for Performance Qualification

6.0 Critical parameters and acceptance Criteria

7.0 Verification of reference documents

8.0 Verification of Materials Required

9.0 Training Records

10.0 Test Equipment Details

11.0 Depyrogentaing and Sterilizing Tunnel Set Parameters

12.0 Records of Observations and Results

13.0 Deviation Sheet

14.0 List of Appendix

15.0 Summary & Conclusion

16.0 Post Approval of Performance Qualification

Appendix 1: Deviation and Corrective Action Report Form





1.0 Protocol cum Report approval

Protocol Prepared BY:

Functional Area Name Signature Date

Production

Engineering

Quality Assurance

Protocol Reviewed By:


Head Production

Head Engineering

Quality Assurance

Protocol Approved By:


Head Operation

Head Quality Assurance





2.0 Objective:

The objective of this protocol is to provide an outline for the performance qualification of Depyrogentaing and

Sterilizing Tunnel installed in Washing area of Dry powder Injectables and to verify that;

➢ The Tunnel performs according to its pre-defined specifications and qualifies for its intended purpose.

➢ The performance data of the Tunnel is documented for future reference.

➢ Release of Tunnel for routine use.

2.1 Scope:

This protocol will be implemented for performance qualification of Depyrogenation and Sterilizing Tunnel

supplied by M/s. ………, in order to check whether the Machine gives required Sterilization/ depyrogenation

for Vials.

2.2 Re-qualification:

Performance Qualification of Dry Heat Steriliser shall be re-qualified in case of;

➢ Any change in the existing equipment, facility or system, which can affect the performance of the

qualified process.

➢ Once in six months ± 15 days. Only one cycle for minimum and maximum size of vials shall be

requalified.

Instructions:

1. For each data sheet, record the requested information in black ink.

2. In the "Verified" column, indicate that the item is inspected and verified according to pre-laid Specifications.

Verification can be by a visual examination referring literature and using a measuring device, etc.

3. After each data sheet is completed, put signature and date in the assigned space.

4. Where the required information is not available ‘Not Available’ shall be entered accordingly. A single diagonal line

shall be scribed through unused boxes and comments sections and “N/A” meaning “not applicable” entered, along

with initials and date of the person who enters the line.





3.0 Responsibilities:

3.1 Validation Team

(Comprising members from Production, Engineering, Validation and Quality Assurance)

• Prepares the performance qualification protocol.

• Ensures that the protocol is in compliance with current policies and procedures on equipment Qualification.

• Ensures that the content is sufficient, clearly defined, technically sound and accurate.

• Distributes the draft protocol for review and collates comments.

• Makes any necessary corrections to the protocol and answers queries from the reviewers.

• Distributes the finalized protocol for review and approval signatures.

• Execution of PQ protocol.

• Review of protocol, the completed qualification data package, and the final report.

3.2 Head – Production/Engineering/Validation/Operations

• Review and Approval of protocol, the completed qualification data package, and the final report.

• Assist in the resolution of validation deviations.

3.3 Head - Quality Assurance

• Review and Approval of protocol, the completed qualification data package, and the final report.

• Verification that the protocol test requirements are completed and properly documented for approval.

• Assist in the resolution of validation deviations.

4.0 Equipment Description & Identification:

4.1 Equipment Description

The machine shall be used for Sterilization / depyrogenation of different size of vial i.e. 7.5 ml, 10 ml, 15 ml,

20 ml & 30 ml etc through the use of a hot-air laminar air flow sterilizing tunnel. The instrument is being

used for sterilizing of glass vials. The height of the receptacles is not exceeds 100 mm. The tunnel is made

with, both in feed and out feed conveyor for continuous line installation between washing and filling

machines. The full belt width for carrying the vials is 750 mm. The air damper plate is adjustable, which is to

be done depending on the size of the vials.

The machine is having a sterilizing zone, comprising a closed housing with built in filters, the hot air is

calculated at 350˚C / 662˚F the air heating elements are located in the hot zone and the air temperature is kept

constant by the use of regulating device the sensor needed for this are located in the direct air current beneath

the filters. The cooling zone continuous to sterilizing zone is designed as a laminar flow unit and protects vial

during transit through tunnel. When integrated with a washing machine and a filling machine the vials are

transported and controlled automatically.





4.2 Name 0f The Equipment : Dry Heat Steriliser (Tunnel)

4.3 Make : M/s…………...

4.4 Model /Serial No : ……………….

4.5 Equipment Identification No. : ……………….

4.6 Equipment Location. : Injection (Room No.: ………..)

Remarks (if any):

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

Verified By & Date:…………….





5.0 Methodology for Performance Qualification:

5.1 Parameters to be checked:

5.1.1 Air supply inspection of HEPA filters of different zones in sterilization tunnel before study of heat distribution & penetration study.

a. Integrity test of HEPA filter

b. Air velocity

c. Non viable particle count

d. Air flow pattern

5.1.2 Heat distribution studies

a. With calibrated data Logger & thermocouple.

5.1.3 Heat penetration studies

a. With calibrated data Logger & thermocouple.

b. With Endotoxin Challenge Test.

5.1.4 Data logger & thermocouple calibration (Pre calibration and Post calibration)

5.2 Process Variables:

a. Size of vial to be validated : ________________________

b. Type of Vial : ________________________

c. Conveyer speed : ________________________

5.3 Test Plan:

5.3.1 Air supply inspection of HEPA filters (Integrity Test of HEPA)

Test equipment required:

Aerosol Photometer

Aerosol Generator

Switch ON the Sterilization Tunnel to reach the operating condition for at least half an hour and then Switch

OFF the heaters to cool down and then check the integrity of HEPA filters as per respective SOP.

Scan the down streamside of HEPA filter using overlapping strokes with the photometer probe. Scan the

entire surface area and perimeter of filter including the junctions between the filter and the filter-mounting

frame.





5.3.2 Air Velocity HEPA Filters:

Test equipment required: Anemometer

Switch ON the Sterilization Tunnel to reach the operating condition allow the pressure of different zones to

get stabilize for at least half an hour and then Switch OFF the heaters to cool down.

Measure the air velocity of HEPA filters as per respective SOP & take the reading of Air Velocity under each

filter.

5.3.3 Non-viable Particle counts

Test equipment required: Particle counter

Switch ON the Sterilization Tunnel to reach the operating condition and allow the pressure of different zones

to get stabilize for at least half an hour and then Switch OFF the heaters to cool down. Take the readings of

particle count of different zone of Tunnel as per respective SOP.

5.3.4 Air flow pattern for intersection flow of Tunnel:

Switch ON the blower of Sterilization Tunnel to reach the operating condition and allow the pressure of

different zones to get stabilize for at least half an hour and then Switch OFF the heaters to cool down.

Take a smoke pencil and bring it near to the intersection of Drying-Sterilization zone, Sterilization & Cooling

zone and also do at the intersection of Vial filling room and exit of the sterilization Tunnel. Observe the

direction of smoke.

5.3.5 Heat Distribution studies of the Tunnel:

Ensure that all the process parameters are set to their respective values as being done for routine production

run. Tie 12 thermocouples with the help of Teflon tape together with S.S rod at equidistant through out the

width of the Tunnel. Care should be taken to avoid contact of the tips of the thermocouple with any solid part

of the Tunnel as well as SS rod. Put these thermocouples along width of the Sterilization Tunnel’s conveyor

belt as per Annexure-1.

Follow the standard operating procedure for the operation of Sterilization Tunnel and allow these

thermocouples to travel the tunnel. Switch ON the Data logger. Observe the temperature profile being

achieved for each thermocouple. Take out the Temperature profile of data logger & from temperature

recorder of Tunnel. Check the FH value for each probe of data logger.

Calculate FH value based on the given formula and check the results against the acceptance criteria for

compliance.

Formula: FH = dt 10(Ta- Tb)/Z

Tb =250oC, Z= 46.4

Ta = Actual temperature

dt: Interval between two successive measurement.





5.3.6 Heat Penetration Studies of the Tunnel:

Ensure that all the process parameters are set to their respective values as being done for routine production

run. Put 12 thermocouple of Data logger into individual vial and tie it with Teflon tape in such a way that it

touches the inside bottom of the vial. Distribute these vials at equidistant through out the width of the

Tunnel’s conveyor belt as per Annexure - 1. Take run for the START of the load, in the MIDDLE of the load

and at the END of the load (i.e. three sub-runs for each individual run). Follow the standard operating

procedure for the operation of Vial Washing and Sterilization Tunnel and allow these Vials to travel the

tunnel. Switch ON the Data logger. Observe the temperature profile being achieved for each thermocouple.

Allow the thermocouple implanted with vials to travel the sterilization zone along with other vials. Check the

FH value for each probe of data logger.

Calculate FH value based on the given formula and check the results against the acceptance criteria for

compliance.

5.3.7 Endotoxin Challenge Test:

Spike 10 vials of required capacity, with 104 Endotoxin units each and dry the vials at 50 - 60°C. Ensure that

all the process parameters of tunnel are set as being done during routine production run. Distribute nine

spiked vials (properly numbered and identified) at equidistant through out the width of conveyor belt as per

Annexure-3. Take run for the START of the load, in the MIDDLE of the load and at the END of the load.

Keep one spiked vial as Positive control.

Follow the standard operating procedure for the operation of the Tunnel. Allow the spiked vials to travel the

sterilization zone along with other vials. Remove the identified numbered vials from the other end of tunnel

in the aseptic area aseptically. Collect these vials aseptically and send them to microbiological lab for

analysis of Endotoxin and check the results against the acceptance criteria for compliance and attached the

report to the validation reports.





5.3.8 Data logger & Thermocouple calibration

Data logger and thermocouple should be pre & post calibrated to ensure that the temperature measurement

system is accurate and precise. It should cover entire range of temperature (100°C, 200°C, 300°C & 350°C),

which is subjected for the validation of Tunnel.

Remarks (if any):

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

Verified By & Date:……………





6.0 Critical parameters and acceptance Criteria:

6.1 Heat distribution & penetration:

6.1.1 The FH value of each channel should be at least 30 minutes, during the sterilization and

Depyrogenation cycle. (Reference: PDA technical Report No: 03)

6.1.2 Sterilization temperature shall not be less than 300°C

6.1.3 Sterilization hold during heat distribution shall not less than 5 minutes.

6.1.4 Sterilization hold during heat penetration shall not be less than 3 minute.

6.1.5 The deviation in temperature from average is not more than ±12.5°C for each channel during

Sterilization hold period.

6.1.6 The Data logger & thermocouple is accurate to within ± 0.5°C.

6.2 Endotoxin Challenge test:

6.2.1 There should be minimum 3-log reduction of the initial Endotoxin units present for the de-

pyrogenation of Vials.

6.3 Air supply inspection:

6.3.1 Photometer readings down stream of HEPA filtration unit should be less than 0.01%.

6.3.2 Air Velocity at each point HEPA filter should not be less than 0.45 meter/second.

6.3.3 The particle count reading of each zone should comply with class 100 areas (Particles of size >

0.5µm Not more than: 100 and > 5.0µm Not more than: 01 per feet3).

6.3.4 The direction of smoke should be from Sterilization Drying zone and also from

Sterilization zone Cooling zone. Also the direction of smoke should be from vial filling

depyrogenating Tunnel.

Remarks (if any):

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

____________________________________________________________________________________________________

Verified By & Date:………………………..





7.0 Verification of Reference Documents:

S.No. Subject/Title of Document Document No. Verified by

1. SOP for Operation & Cleaning of Depyrogenating & Sterilization

Tunnel

2. SOP for Preventive Maintenance of Tunnel

3. SOP for Integrity testing of HEPA filters

4. SOP for Particulate matter count monitoring

5. SOP for Air velocity measurement

6. SOP for Endotoxin challenge test

8.0 Verification of Materials required:

S.No. Item/Reagent required Manufacturer/

Supplier

Batch No./AR

No. Expiry Date

Location of

Certificate Of

Analysis

Verified By

1. Smoke generating agent

(Titanium tetrachloride)

2.

Vials Type:

___________

Size : ____________

3. LAL

4. Endotoxin 10,000

5. LAL Reagent Water

Remarks (if any):

________________________________________________________________________________________________________

________________________________________________________________________________________________________

________________________________________________________________________________________________________

Verified By & Date:…………………….





9.0 Training Records:

SUPERVISORY STAFF

S.No Area of training Name of trainee Training on protocol is given*?

(Yes/ No) Checked by

1.0 Vial Sterilization &

De-pyrogenation

2.0 Engineering

3.0 Production

4.0 Validation

5.0 Quality Assurance

6.0 Microbiological

7.0 Others (Specify):

OPERATORS

8.0 Tunnel Operation

9.0 Vial washing Machine

10.0 Others (Specify):

Name of the Trainer: ______________

Remarks (if any):

_______________________________________________________________________________________________________

_______________________________________________________________________________________________________

_______________________________________________________________________________________________________

Verified By & Date:……………





10.0 Test Equipment Details:

Review the calibration status of the test equipment including the temperature probes of the data logger to be utilized in

performance qualification testing and record the calibration due dates in the table below. All equipment / instrumentation

must remain within the calibration due date for the duration of PQ test for which the item is used. If a due date potentially

occurs during the testing period then the instrument must be recalibrated before it can be utilized.

S.No. Test Instrument ID Calibration

Certificate No. Calibration Date Next Calibration Due

Checked

By & Date

1. Aerosol Photometer

2. Anemometer

3. Particle Counter

4. Channel – 1

Temperature Sensor-1

5. Channel – 2


6. Channel – 3


7. Channel – 4


8. Channel – 5


9. Channel – 6


10. Channel – 7


11. Channel – 8


12. Channel – 9


13. Channel – 10


14. Channel – 11


15. Channel – 12


Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

Verified By & Date:……………………..





11.0 Dry Heat Steriliser (Tunnel) Test Details:

S.No. Details Observation

1. Previous Qualification Details

(Date, Vial Size, etc.)

2. Pressure differential of zones in tunnel

3. Pressure differential of Filling and

Washing Area

4. Temperature of washing and filling area

before start of study

5. Duration of study (hours)

6. Machine set parameters

6.1 Control probe of tunnel

6.2 Set temperature of Heater – 1




6.6 Conveyor start temperature

6.7 Conveyor Stop temperature

6.8 Too high temperature

6.9 Conveyor speed

Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………






12.0 Records of Observations and Results:

12.1 Observations of Study of HEPA integrity, Air velocity of HEPA filters, particle count and air flow pattern test.

Test Parameter Observations Verified

by/Date Location Acceptance criteria Result

HEPA integrity

Drying zone

Filter –1

Penetration should be less than

0.01%

Sterilization zone

Filter – 01

Filter – 02

Filter – 03

Filter – 04

Cooling zone

Filter – 01

Filter – 02

Average Air

velocity

Drying zone

Note less than 0.45 m/s (89 feet /

minute)

Sterilization zone

Cooling zone

Particle count

Drying zone

Location –1

Location –2

Location –3

Location –4

Particles of

≥0.5µm: Not more than 100

particles/ ft3.

Particles of

≥5.0µm: Not more than 1

particle/ ft3.

Sterilization zone

Location –1

Location –2

Location –3

Location –4

Cooling zone

Location –1

Location –2

Location –3

Location –4

Air flow pattern

Sterilizing zone, drying

zone, cooling zone and

filling area

Sterilization zone to drying zone

Sterilization zone to cooling zone

Vial filling to sterilizing zone Drying zone

Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………






12.2 Observations of Heat Distribution Study (Type _________________)

Process Parameter Observations Verified by/Date

Start Time

Stop Time

Differential pressure of washing and filling area.

Differential Pressure drying zone

Differential Pressure sterilizing zone

Differential Pressure cooling zone

Speed Of Tunnel During Sterilization Hold (Min &

Max)

Sterilization Hold Time started at

Sterilization Hold Time ended at

Sterilization Hold Time

Limit: Not less than 5 Minutes

Complies /Not complies

Maximum Temperature deviation in positive side from

average for all probes

Limit: Not more than +12.5°C


Maximum Temperature Deviation in negative side

from average for all probes

Limit: Not less than -12.5°C


Maximum temperature (From all probes)

Not less than 300°C and not more than 350°C.


Minimum temperature (From all probes)

Not less than 300°C


Minimum FH value (Compare all probes)

Limit: Not less than 30


Maximum FH value (Compare all probes)



Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………






12.3 Observations of Heat Penetration Study [(Type ____________________ (Run 1)]:

Process Parameter Observations

Verified by/Date Initial Middle End

Start Time

Stop Time

Differential pressure of washing and filling

area.




Speed Of Tunnel During Sterilization Hold

(Min & Max)






Maximum Temperature deviation in positive

side from average for all probes



Maximum Temperature deviation in negative

side from average for all probes

Limit: Not more than -12.5°C



Not less than 300°C and not more than 350°C.











Endotoxin test

Limit: 3 log reduction

Complies / Not complies

Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………









Start Time

Stop Time

Differential pressure of washing and

filling area.




Speed Of Tunnel During Sterilization

Hold (Min & Max)






Maximum Temperature deviation in

positive side from average for all probes




negative side from average for all probes




Not less than 300°C and not more than

350°C.











Endotoxin test



Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………









Start Time

Stop Time

Differential pressure of washing and

filling area.




Speed Of Tunnel During Sterilization

Hold (Min & Max)







positive side from average for all probes




negative side from average for all probes




Not less than 300°C and not more than

350°C.











Endotoxin test



Post calibration of data logger Channels

and temperature probes


Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………






13.0 Deviation Sheet:

Report any deviation from the acceptance criteria or from protocol instructions in the Deviation report form of

Appendix 1. Record the total number of deviations reported during the performance qualification activities of this

Protocol. Record the Deviation number and Title in the Table below. Include all Deviation Report Forms in

Appendix 1. Indicate the status of each variance as ‘Closed’ only when the Deviation is resolved.

Deviation No. Deviation Title Status

Total No. of Deviations: ___________

Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………






14.0 List of Annexures:

Annexure No. Document Title

Remarks (if any):

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………






15.0 Summary & Conclusion:

16.0 Post Approval of Performance Qualification:


Head Engineering

Head Production

Head Operation

Head Quality Assurance





Appendix 1: Deviation and Corrective Action Report Form

This Deviation and Corrective Action Report Form shall be completed for each result that does not meet the expected or as

designed condition encountered during the execution of the protocol. Each form shall be numbered sequentially and tracked

on the Deviation Sheet within the protocol.

Deviation Report Number:

Protocol Section No.: Date of Test:

Description Of Test Result:

Immediate Action Taken:

Corrective Action Taken/ Planned:

Deviation Reported By:

Name: Signature: Date:

Corrective action must be taken prior to approval of PQ:

Head-Engg. Signature

Date:

Head-User dept. signature Date:

QA Signature: Date:

Corrective Action Implemented:

Corrective Action Implemented By:

Name: Signature: Date:

(Attach comments and supporting documentation as necessary)

Was a re-test or amendment necessary due to the Deviation? Date of re-test:

Is Deviation Closed (Yes/No):

QA Signature: Date: