Performance Qualification (PQ) Protocol for Sterilizing and Depyrogenating Tunnel is to verify that the equipment produces the desired output. Performance qualification (PQ) of the equipment is planned after the successful completion of the installation and operational qualification.
PQ Protocol – Sterilizing and Depyrogenating Tunnel
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Sr. No. |
ITEM DESCRIPTION |
PAGE NO. |
| 1.0 | PROTOCOLAPPROVAL | |
| 2.0 | OVERVIEW: | |
| 2.1 | Objective | |
| 2.2 | Purpose | |
| 2.3 | Scope | |
| 2.4 | Responsibility | |
| 2.5 | Execution Team | |
| 3.0 | GENERAL CONSIDERATION/PREREQUISITE | |
| 4.0 | REVALIDATION CRITERIA | |
| 5.0 | PERFORMANCE QUALIFICATION PROCEDURE | |
| 5.1 | BRIEF DESCRIPTION OF EQUIPMENT | |
| 5.2 | VALIDATION PLAN AND METHODOLOGY | |
| 5.2.1 | Empty Chamber heat distribution study | |
| 5.2.1.1 | Diagram Of Empty Chamber With Empty Chamber | |
| 5.2.1.2 | Observation Of Empty Heat Distribution Study | |
| 5.2.2 | Heat Penetration Study with loaded chamber | |
| 5.2.2.1 | Diagram of loaded chamber with sensors, B.I. Units & Endotoxin | |
| 5.2.2.2 | Observation Of Heat Penetration Study | |
| 5.2.2.3 | Observation Of Biological Indicators And Endotoxin | |
| 6.0 | ACCEPTANCE CRITERIA | |
| 7.0 | DEFICIENCY AND CORRECTIVE ACTIONS | |
| 8.0 | Annexure (s) | |
| 9.0 | PERFORMANCE QUALIFICATION FINAL REPORT | |
| 9.1 | Summary | |
| 9.2 | Conclusion | |
| 9.3 | Final report approval |
1.0 |
PROTOCOL APPROVAL: |
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- Signing of this Approval page of Performance qualification Protocol No. _________________ indicates agreement that the Performance Qualification approaches describe in this document.
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- If any modifications to the Performance Qualification be required an addendum shall be prepared and approved.
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- This protocol can not be used for execution unless approved by of following authorities.
| FUNCTION | NAME | DEPARTMENT | SIGNATURE | DATE |
| PREPARED BY | QUALITY ASSURANCE | |||
| REVIEWED BY | PROJECT/ ENGINEERING | |||
| REVIEWED BY | PRODUCTION | |||
| REVIEWED BY | QUALITY CONTROL | |||
| APPROVED BY | QUALITY ASSURANCE |
2.0 |
OVERVIEW: Sterilizing and Depyrogenating Tunnel |
2.1 |
OBJECTIVE: |
The objective of developing and executing this protocol is to
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2.2 |
PURPOSE: |
| The purpose of this protocol is to verify that the equipment produces the desired output. Performance qualification of the equipment is planned after the successful completion of the installation and operational qualification.
While performing the qualification runs it will be ensured that there will be no gaps between the vials and the tunnel is running with maximum in feed, to simulate the worst case with maximum load. The tunnel is designed to achieve 03-log reduction of the Endotoxin level in the containers of 7.5 and 30 ml . |
2.3 |
SCOPE: |
| The protocol shall define the test procedures, documentation, references and acceptance criteria to establish that the performance of the equipment shall meet the predetermined acceptance criteria.
The Scope of this protocol is limited to the performance qualification of Sterilizing and depyrogenating tunnel installed in the Dry powder Injectable facility. Once the performance qualification of Sterilizing and depyrogenating tunnel has been completed successfully, the equipment shall be released for production. |
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2.4 |
RESPONSIBILITY: |
The following shall be responsible;
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2.5 |
EXECUTION TEAM: |
| Execution team is responsible for the execution of performance qualification of Sterilizing and depyrogenating tunnel. |
| DEPARTMENT | DESIGNATION | NAME | SIGNATURE | DATE |
| PRODUCTION | ||||
| PROJECT/ ENGINEERING | ||||
| QC | ||||
| QA |
3.0 |
GENERAL CONSIDERATION/PREREQUISITE |
| 3.1 | Approved Standard operating procedure of the equipment shall be available |
| 3.2 | Approved analytical methods for testing the samples collected during the processing |
| 3.3 | The installation and operational qualification of the equipment shall be successfully completed before the execution of the performance qualification. |
| 3.4 | All the deficiencies and discrepancies related to the equipment which affect the product quality and corrective action taken shall be recorded in the appropriate section of the protocol. |
| 3.5 | The analytical test results and other reports related with the equipment shall be attached with the performance qualification of the equipment and finally verified. |
| 3.6 | After successful completion of PQ activities, equipment shall be cleaned as per respective cleaning SOP’s and released for manufacturing. |
4.0 |
Revalidation Criteria: Sterilizing and Depyrogenating Tunnel |
| The Sterilizing and Depyrogenating Tunnel shall be revalidated if | |
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5.0 |
PERFORMANCE QUALIFICATION PROCEDURE |
5.1 BRIEF DESCRIPTION OF EQUIPMENT:
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- The Tunnel sterilizer is located in the Sterilization and depyrogenating tunnel area.
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- The tunnel is designed to achieve 03-log reduction of the Endotoxin level in the containers of 7.5 and 30 ml.
5.2 VALIDATION PLAN AND METHODOLOGY:
5.2.1 Empty Chamber heat distribution study:
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- The performance of the tunnel will be checked first by Empty Chamber Heat Distribution study.
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- 16 RTDs sensors will be used for heat distribution study and placed as per sensor location diagram.
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- A metal frame will be prepared to hold the sensors without letting them touch the conveyor or any other metal surface during the run and which will not obstruct the airflow during the empty camber run significantly.
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- 16 Number of RTDs will be tied to the metal strip/ frame so as to maintain a level of 50 mm from the conveyor level and should not touch each other as well as any metal or other surface during the run.
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- Set the control temperature of tunnel to 350 °C and the conveyor speed at the highest i.e. 150 mm/ min.
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- Start the tunnel and leave it to stabilize for approx. 15 minutes after achieving of set temperature.
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- The frame will be then put into the tunnel in feed and should be locked to the conveyor belt so as not to slip during the run while carrying the RTDs.
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- Log the data by data logger with scan interval time of 60 seconds.
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- If first run found ok then further take three consecutive such empty chamber heat distribution run is to be taken with at least 30 minutes interval.
5.2.1.1 Diagram Of Empty Chamber With Sensor Location:
5.2.1.2 Observation of Empty Chamber heat distribution study:
1st Run Date : Process started at:
Description of Load : Empty chamber
| Sensor ID | Sterilization temp. Achieved at | Sterilization Completed at | Total Exposure time | Maximum Temperature during sterilization | Minimum Temperature during sterilization | Remarks |
| Mean temperature during the sterilization cycle | |||
| Maximum variation from the mean temperature | |||
| Minimum variation from the mean temperature |
| Temperature of Controlling Sensors of Tunnel | Reading of temperature of the reference RTDs | ||
| Sterilizing zone Entry Control Temperature | Sterilizing zone Exit Control temperature | Reference RTD towards right side | Reference RTD towards left side |
FH Value:————————
| FH = Δt x Lethality Rate | Lethality Rate: 10 (T-Tb)/Z |
Δt : Cycle time
T : Actual Cycle temperature
Tb: Base temperature
Z : Microbial Death Rate Constant = 46.4oc
– Slide: 13/51
Lethality Rate = 10 ( – ) /46.4
Lethality Rate =
FH = x
FH =
2nd Run : Date : Process started at:
Description of Load : Empty chamber
| Sensor ID | Sterilization temp. Achieved at | Sterilization Completed at | Total Exposure time | Maximum Temperature during sterilization | Minimum Temperature during sterilization | Remarks |
| Mean temperature during the sterilization cycle | |||
| Maximum variation from the mean temperature | |||
| Minimum variation from the mean temperature |
| Temperature of Controlling Sensors of Tunnel | Reading of temperature of the reference RTDs | ||
| Sterilizing zone Entry Control Temperature | Sterilizing zone Exit Control temperature | Reference RTD towards right side | Reference RTD towards left side |
FH Value:————————
| FH = Δt x Lethality Rate | Lethality Rate : 10 (T-Tb)/Z |
Δt : Cycle time
T : Actual Cycle temperature
Tb: Base temperature
Z : Microbial Death Rate Constant = 46.4oc
– Slide: 13/51
Lethality Rate = 10 ( – ) /46.4
Lethality Rate =
FH = x
FH =
3rd Run : Date : Process started at:
Description of Load : Empty chamber
| Sensor ID | Sterilization temp. Achieved at | Sterilization Completed at | Total Exposure time | Maximum Temperature during sterilization | Minimum Temperature during sterilization | Remarks |
| Mean temperature during the sterilization cycle | |||
| Maximum variation from the mean temperature | |||
| Minimum variation from the mean temperature |
| Temperature of Controlling Sensors of Tunnel | Reading of temperature of the reference RTDs | ||
| Sterilizing zone Entry Control Temperature | Sterilizing zone Exit Control temperature | Reference RTD towards right side | Reference RTD towards left side |
FH Value:————————
| FH = Δt x Lethality Rate | Lethality Rate : 10 (T-Tb)/Z |
Δt : Cycle time
T : Actual Cycle temperature
Tb: Base temperature
Z : Microbial Death Rate Constant = 46.4oc
– Slide: 13/51
Lethality Rate = 10 ( – ) /46.4
Lethality Rate =
FH = x
FH =
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Acceptance Criteria – Sterilizing and Depyrogenating Tunnel
- No sensor should vary by more than 10 °C from the mean of the readings of all the sensors during the total period of sterilization.
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- At the mid point of Sterilizing zone the readings of the individual sensors should not vary by more than 10°C from the reading of the controlling sensors of the tunnel.
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- The FH value of each cycle should be more than 30 min. at 250 oC (The Z value for Endotoxin destruction at 250 0 C is 46.40 C)
5.2.2 Heat Penetration Study with loaded chamber
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- For the performance qualification 3 consecutive penetration study to be taken for each types of vials (i.e. 7.5 & 30ml.)
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- In all the run temperature will be logged through 16 RTDs as well as min. 08 Bioindicators including cold spot identified during the heat distribution at entry & exist position and min. 10 Endotoxin source vials will be placed besides the sensor respectively for each run for 7.5ml and 30ml vials.
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- In the tunnel in a single row, 36 numbers of 7.5 ml tubular vials and 23 numbers of 30 ml tubular vials can be accommodated.
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- For qualification study during performance qualification, 16 thermocouples will be placed. For 7.5 ml vials in single lines of vials.
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- Temperature logging is done by data logger from the in feed to the out feed and when the vials comes out after sterilization the vials are collected and the vials as well as the indicators are sampled to QC (Micro) for incubation and LAL test (BET).
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- If first run completed successfully then further consecutive three such exercises will be performed with these vials with time intervals not less than 20 minutes.
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- The tunnel will run idle without any load for first approx 15 minutes after achieving of set temperature to allow the tunnel to stabilize in order to avoid the fluctuation of temperature.
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- Always it will be ensured that after stabilization the tunnel is fully loaded from in feed to out feed before putting in the vials and sensors meant for qualification.
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- Record the data of temperature logging as well as LAL test and incubation results at the respective tables and attach the data sheets / graphs with report. Attach the data printed by the printer attached with the tunnel during the period.
5.2.2.1 DIAGRAM OF LOADED CHAMBER WITH SENSORS, B.I. UNITS & ENDOTOXIN
5.2.2.2 Observation of Loaded Chamber heat Penetration study:
1st Run DATE : Process started at:
Description of Load : Loaded Chamber Size of vials : 7.5 ml
| Sensor ID | Sterilization temp. Achieved at | Sterilization Completed at | Total Exposure time | Maximum Temperature during sterilization | Minimum Temperature during sterilization | Remarks |
| Mean temperature during the sterilization cycle | |||
| Maximum variation from the mean temperature | |||
| Minimum variation from the mean temperature |
| Temperature of Controlling Sensors of Tunnel | Reading of temperature of the reference RTDs | ||
| Sterilizing zone Entry Control Temperature | Sterilizing zone Exit Control temperature | Reference RTD towards right side | Reference RTD towards left side |
5.2.2.3 OBSERVATION OF BIOLOGICAL INDICATORS AND ENDOTOXIN
Run No. : 1st Date:
Description of Load:
| Bio Indicators | |||
| Description | 7.5 ml vial | 30 ml vial | |
| Make | |||
| Lot No | |||
| Expiry | |||
| D Value | |||
| Spore concentration | |||
| Endotoxin source vials (Dried to inner surface) | |||
| Description | 7.5 ml vial | 30 ml vial | |
| Endotoxin Make | |||
| Lot No | |||
| Vial Endotoxin Concentration | |||
| Results from microbiology | |||
Run No. : 2nd Date:
Description of Load :
| Bio Indicators | |||
| Description | 7.5 ml vial | 30 ml vial | |
| Make | |||
| Lot No | |||
| Expiry | |||
| D Value | |||
| Spore concentration | |||
| Endotoxin source vials (Dried to inner surface) | |||
| Description | 7.5 ml vial | 30 ml vial | |
| Endotoxin Make | |||
| Lot No | |||
| Vial Endotoxin Concentration | |||
| Results from microbiology | |||
Run No. : 3 rd Date:
Description of Load :
| Bio Indicators | |||
| Description | 7.5 ml vial | 30 ml vial | |
| Make | |||
| Lot No | |||
| Expiry | |||
| D Value | |||
| Spore concentration | |||
| Endotoxin source vials (Dried to inner surface) | |||
| Description | 7.5 ml vial | 30 ml vial | |
| Endotoxin Make | |||
| Lot No | |||
| Vial Endotoxin Concentration | |||
| Results from microbiology | |||
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Acceptance Criteria
- During the Final PQ runs of the tunnels all the RTDs should achieve the expected sterilization temperature for the expected time period with a maximum excess of 10°C and 30
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- During the sterilization period the reference RTDs should not differ by more than 10 °C from the reading of the controlling sensors of the tunnel.
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- The vials inner surface should be in contact with thermocouple tip. Because the objective is to sterilize the inner wall of the container as well as inner space.
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- In each run the biological indicators placed should show nil growth after incubation. At least 6-log reduction of the spores should be achieved.
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- Dry Heat Sterilization should provide at least 3-log reduction of Endotoxin.
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- The FH value of each cycle should be more than 30 min. ( Considering the Z – Value for Endotoxin destruction rate at 2500 C is 46.4 min
6.0 |
ACCEPTANCE CRITERIA |
| 6.1 | The sterilizer tunnel being operated in high heat, adequate precaution is to be taken during qualification purpose to avoid burn injury due to touching of any heated part or materials that has been heated by the tunnel like thermocouple wires, metal frame etc. |
| 6.2 | During the operation of tunnel for qualification, the tunnel will be allowed to stabilize for at least 15 minutes after reaching the set temperature so as to avoid the unnecessary temperature fluctuation. |
| 6.3 | Biological indicators with spores of Bacillus subtilis/Bacillus at rophae us, not less than 106 spores / strip. |
| 6.4 | Endotoxin source vials in which at least 1000 EU/ml Endotoxin dried to the inner surface of the vial. |
| 6.5 | Performance Qualification shall be considered acceptable when all the conditions specified in respective data sheets are completed and optimum process conditions are finalised, with simulation of worse case situations. |
| 6.6 | Any deviation from the acceptance criteria of the specific check point shall be reported and decision shall be taken for the rejection, replacement or rectification of the equipment/component. |
| 7.0 | DEFICIENCY AND CORRECTIVE ACTIONS |
| Following deficiency was verified and corrective actions taken in consultation with the validation team. |
| Description of deficiency: |
| Corrective action(s) taken: |
8.0 Annexure (s):
| Sr.No. | Annexure No. | Title of Annexure |
9.0 |
PERFORMANCE QUALIFICATION FINAL REPORT: |
| 9.1 | SUMMARY: |
| 9.2 | CONCLUSION: |
9.3 FINAL REPORT APPROVAL:
- It has been verified that all tests required by this report are completed, reconciled and attached to this protocol or included in the qualification summary report.
- Verified that all amendments and discrepancies are documented, approved and attached to this protocol.
- Signature in the block below indicate that all items in this qualification report of Sterilizing and depyrogenating tunnel have been reviewed and found acceptable and that all variations or discrepancies have been satisfactorily resolved. The equipment can be taken for production trial.
| NAME | DESIGNATION | DEPARTMENT | SIGNATURE | DATE |
| PRODUCTION | ||||
| PROJECT/ENGINEERING | ||||
| QUALITY CONTROL | ||||
| QUALITY ASSURANCE |
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