- OBJECTIVE
- To establish documented evidence which will provide a High degree of assurance and reliability about the performance of the BUNG WASHING MACHINE.
- To verify the Rubber stopper washing process is capable of consistently and reliably removing
- Particulate matter contaminants, such as dust, lint, fibres etc.,
- Bacterial Endotoxins, from the spiked rubber stoppers, and to establish the washing and equipment operation parameters.
- SCOPE
- The scope of this protocol is limited to carry out the performance Qualification of 20mm Grey/Bromo butyl rubber stopper washing process by using Rubber stopper washer located in the Preparation and Sterilization Zone of injectable section.
- Note: The protocol is not applicable for pre-washed and/or siliconized rubber stoppers received in Ready for sterilization (RFS) bags.
- To be performed at the time of relocation or Requalification.
- To be performed after the completion and authorization of Operational Qualification.
- EQUIPMENT DESCRIPTION
- Bung washer is installed in unit preparation room.
- Purpose of the equipment:
- Purpose of this Bung washer is for washing & Siliconization of the various types of rubber stoppers.
- Basic mode of operation:
- The equipment as suggested by names, washes the bungs with detergent and rinses with Purified water & WFI automatically through PLC. There is one vessel for washing the bungs having capacity of 10,000 bungs. The entire process is time dependent and hence has to be checked the cleanliness of the bungs.
- The vessel have inputs of compressed air, Purified water & WFI inlets and heaters perforated basket which hold the bungs during the process are placed inside the vessel. The vessel is covered with transparent lids to view the bungs in washing process. The bungs have a totally enclosed environment and are controlled by a PLC automated system.
- Abbreviations and definitions
-
Abbreviation Definitions PQP Performance Qualification Protocol SOP Standard Operating Procedure Abbreviation Definitions QA Quality Assurance QC Quality Control NA Not Applicable No. Number ºC Degree Centigrade SLT Standard Laboratory Technique
- RESPONSIBILITIES AND IDENTIFICATION OF EXECUTION TEAM
- Responsibilities: The group comprising of representatives from each of the following departments shall be responsible for the overall compliance with this protocol.
| Department | Responsibility |
| Production | Execute the validation activity & provide necessary support |
| Engineering & Utility | Participate & provide necessary support for the validation activity |
| Quality Control | Testing of samples as per the test procedures |
| Quality Assurance | Monitoring, sampling & reviewing the validation activities. |
- After completion of each load wash cycle, collect the spiked red butyl rubber stoppers with the help of clean forceps in to previously cleaned stoppered conical flask and close the flask.
- Operate the bung washer as per the SOP and record the details in the annexure-1.
- Randomly add 10 nos. of dust spiked rubber stoppers for each trial of previously estimated for the quantity of the particulate matter load on each stopper and Close the drum.
- Charge cleaned bung washer with the minimum / maximum load of 20mm butyl rubber stoppers.
- Rubber Stopper Washing
- Use 60 no’s of the spiked and dried plugs to carry out performance qualification test.
- The data generated shall be used for the estimation of the washing machine capacity to wash the test load of rubber stoppers as per the standard washing cycle.
- Record the observations in the annexure-1.
- Collect the water from the conical flask into a clean beaker and send to microbiology laboratory for estimation of particulate matter present in the water.
- Add 50 ml of WFI to the stoppered conical flask and sonicate the flask for 5 minutes.
- Place 10 rubber stoppers in previously cleaned stoppered conical flask for estimation of particulate count.
- Dry the plugs at 60-700C to ensure that the spike dust is adhered to the plugs.
- Add 0.2 ml of the dust suspension to each rubber stopper on the concave portion of the rubber plug.
- Take 70 rubber stoppers with different colour of the load rubber stoppers for easy identification (for minimum and maximum loads and each load having three trials).
- Sonicate well on a sonicator.
- Add 5 gm of standard dust, which is previously passed through 100 mesh.
- Collect 100 ml of WFI in a 500 ml stoppered conical flask.
- Spiking Of Rubber Stoppers with Particulate matter
- Following test procedures are followed to qualify the equipment for its performance.
- Load details: Selected load sizes are 5000 and 10000 nos. of 20mm grey/ butyl rubber stoppers to evaluate bung washer efficiency with the minimum and maximum load sizes.
- TEST PROCEDURES
- Identification of Executors: The personnel involved in the execution of this protocol shall be recorded- Name, Designation, Signature and Date.
- NOTE: The particulate count of the dust spiked rubber stoppers shall be estimated prior to conducting the study.
- The above procedure shall be performed for each load size.
- Repeat the above procedure for another two runs.
- Record the observations in the annexure-1.
- Raise the sample request form for the estimation of bio burden level of washed rubber stoppers.
- Collect the water from the conical flask into a clean beaker and send to microbiology laboratory for estimation of particulate matter present in the water.
- Add 50 ml of WFI water to the stoppered conical flask and sonicate the flask for 5 minutes.
- Acceptance Criteria
- The rubber stoppers after the standard washing cycle should not show any visible particles.
- ≥10 µm size particles should not exceed 25 per ml and ≥25 µm size particles should not exceed 3 per ml. (or) As per In-house specifications.
- Bioburden level is for information.
- RECORDING OF OBSERVATIONS
- Record the observations of after execution of each test procedures, in the annexure –1 (Recording of Observations For Performance Qualification).
- DISCREPANCY AND CORRECTIVE ACTION REPORT
- Document any discrepancies observed during the Performance qualification of the equipment in annexure -1. Include the corrective actions of the same. When all the discrepancies are satisfactorily resolved or an approved action plan is developed which ensures that the discrepancy will be resolved.
- COMPILATION, REVIEW AND SUMMARY REPORT
- Compile and review that all test functions have been completed, reconciled and attached to this protocol. Verify that the approvals for deviations have been taken and are resolved appropriately to the satisfaction.
- Performance Qualification shall be considered acceptable when all the conditions specified in the test procedures have been met.
- Prepare the summary report in the annexure –2 (Performance Qualification Report) and submit this for review, approval and authorisation to Validation Core Team.
- Annexures
- Annexure – 1 (Recording Of Observations For Performance Qualification)
Annexure – 1 (Recording Of Observations For Performance Qualification)
| Details Of Operational Qualification Report | |||
| Report No. | Â | Date Of Authorisation | Â |
|
| S. No. | Name | Designation & Department | Sign & Date | Training Details |
| Â | Â | Â | Â |
- Reviewed by:Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Date:
| Spiking of Rubber Stoppers |
- Â Date of spiking:Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Done by:
- Â Date of testing for particulate matter:
| Results of Particulate count | |
| Particle size | Count |
| Â | Â |
Test Done by:
 Reviewed by:                                                                                        Date:
| Washing of Rubber Stoppers |
- Load Size: (Minimum)_____________Nos Rubber stoppers         Â
| S. No. | Operation | Time | Done by
Sign & Date |
Supervised by
Sign & Date |
|
| From | To | ||||
| 1 | Load Rubber stoppers into bung washer. Randomly add 10 nos. of dust spiked rubber stoppers in to the load. Start the operation as per the SOP.
Record the quantity:________Nos. |
 | |||
| 2 | First wash:
Wash the rubber stoppers with detergent solution (______ ml) and purified water for 30 minutes. Record the temperature of Purified water: __________ºC. |
 | |||
| 3 | Second wash:
Wash the rubber stoppers with Purified water for 30 minutes. Check the clarity of rinse water as per the SOP. Clarity: OK / Not OK |
 | |||
| 4 | Third wash:
Wash the rubber stoppers with water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 4 | Check the clarity of rinse water.
Clarity: OK / Not OK |
 | |||
| 6 | Fourth wash:
Wash the rubber stoppers with Silicone oil (_______ ml) and Water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 7 | Check the clarity of rinse water as per the SOP.
Clarity: OK / Not OK |
 | |||
| 8 | If clarity is not achieved, repeat the cycle and check the clarity. | Â | |||
| 9 | Unload the rubber stoppers in to baskets after completion of all washings. | Â | |||
| 10 | Follow as per the step No. 6.2.4 to 6.2.8 in the protocol. | Â | |||
- Load Size: (Minimum)_____________Nos Rubber stoppers                 Run No. 2 of 3
| S. No. | Operation | Time | Done by
Sign & Date |
Supervised by
Sign & Date |
|
| From | To | ||||
| 1 | Load Rubber stoppers into bung washer. Randomly add 10 nos. of dust spiked rubber stoppers in to the load. Start the operation as per the SOP.
Record the quantity:________Nos. |
 | |||
| 2 | First wash:
Wash the rubber stoppers with detergent solution (______ ml) and purified water for 30 minutes. Record the temperature of Purified water: __________ºC. |
 | |||
| 3 | Second wash:
Wash the rubber stoppers with Purified water for 30 minutes. Check the clarity of rinse water as per the SOP. Clarity: OK / Not OK |
 | |||
| 4 | Third wash:
Wash the rubber stoppers with water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 4 | Check the clarity of rinse water.
Clarity: OK / Not OK |
 | |||
| 6 | Fourth wash:
Wash the rubber stoppers with Silicone oil (_______ ml) and Water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 7 | Check the clarity of rinse water as per the SOP.
Clarity: OK / Not OK |
 | |||
| 8 | If clarity is not achieved, repeat the cycle and check the clarity. | Â | |||
| 9 | Unload the rubber stoppers in to baskets after completion of all washings. | Â | |||
| 10 | Follow as per the step No. 6.2.4 to 6.2.8 in the protocol. | Â | |||
- Load Size: (Minimum)_____________Nos Rubber stoppers                 Run No. 3 of 3
| S. No. | Operation | Time | Done by
Sign & Date |
Supervised by
Sign & Date |
|
| From | To | ||||
| 1 | Load Rubber stoppers into bung washer. Randomly add 10 nos. of dust spiked rubber stoppers in to the load. Start the operation as per the SOP.
Record the quantity:________Nos. |
 | |||
| 2 | First wash:
Wash the rubber stoppers with detergent solution (______ ml) and purified water for 30 minutes. Record the temperature of Purified water: __________ºC. |
 | |||
| 3 | Second wash:
Wash the rubber stoppers with Purified water for 30 minutes. Check the clarity of rinse water as per the SOP. Clarity: OK / Not OK |
 | |||
| 4 | Third wash:
Wash the rubber stoppers with water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 4 | Check the clarity of rinse water.
Clarity: OK / Not OK |
 | |||
| 6 | Fourth wash:
Wash the rubber stoppers with Silicone oil (_______ ml) and Water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 7 | Check the clarity of rinse water as per the SOP.
Clarity: OK / Not OK |
 | |||
| 8 | If clarity is not achieved, repeat the cycle and check the clarity. | Â | |||
| 9 | Unload the rubber stoppers in to baskets after completion of all washings. | Â | |||
| 10 | Follow as per the step No. 6.2.4 to 6.2.8 in the protocol. | Â | |||
-  Load Size: (Maximum)_____________Nos Rubber stoppers                Run No. 1 of 3
| S. No. | Operation | Time | Done by
Sign & Date |
Supervised by
Sign & Date |
|
| From | To | ||||
| 1 | Load Rubber stoppers into bung washer. Randomly add 10 nos. of dust spiked rubber stoppers in to the load. Start the operation as per the SOP.
Record the quantity:________Nos. |
 | |||
| 2 | First wash:
Wash the rubber stoppers with detergent solution (______ ml) and purified water for 30 minutes. Record the temperature of Purified water: __________ºC. |
 | |||
| 3 | Second wash:
Wash the rubber stoppers with Purified water for 30 minutes. Check the clarity of rinse water as per the SOP. Clarity: OK / Not OK |
 | |||
| 4 | Third wash:
Wash the rubber stoppers with water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 4 | Check the clarity of rinse water.
Clarity: OK / Not OK |
 | |||
| 6 | Fourth wash:
Wash the rubber stoppers with Silicone oil (_______ ml) and Water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 7 | Check the clarity of rinse water as per the SOP.
Clarity: OK / Not OK |
 | |||
| 8 | If clarity is not achieved, repeat the cycle and check the clarity. | Â | |||
| 9 | Unload the rubber stoppers in to baskets after completion of all washings. | Â | |||
| 10 | Follow as per the step No. 6.2.4 to 6.2.8 in the protocol. | Â | |||
-  Load Size: (Maximum)_____________Nos Rubber stoppers                Run No. 2 of 3
| S. No. | Operation | Time | Done by
Sign & Date |
Supervised by
Sign & Date |
|
| From | To | ||||
| 1 | Load Rubber stoppers into bung washer. Randomly add 10 nos. of dust spiked rubber stoppers in to the load. Start the operation as per the SOP.
Record the quantity:________Nos. |
 | |||
| 2 | First wash:
Wash the rubber stoppers with detergent solution (______ ml) and purified water for 30 minutes. Record the temperature of Purified water: __________ºC. |
 | |||
| 3 | Second wash:
Wash the rubber stoppers with Purified water for 30 minutes. Check the clarity of rinse water as per the SOP. Clarity: OK / Not OK |
 | |||
| 4 | Third wash:
Wash the rubber stoppers with water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 4 | Check the clarity of rinse water.
Clarity: OK / Not OK |
 | |||
| 6 | Fourth wash:
Wash the rubber stoppers with Silicone oil (_______ ml) and Water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 7 | Check the clarity of rinse water as per the SOP.
Clarity: OK / Not OK |
 | |||
| 8 | If clarity is not achieved, repeat the cycle and check the clarity. | Â | |||
| 9 | Unload the rubber stoppers in to baskets after completion of all washings. | Â | |||
| 10 | Follow as per the step No. 6.2.4 to 6.2.8 in the protocol. | Â | |||
-  Load Size: (Maximum)_____________Nos Rubber stoppers                Run No. 3 of 3
| S. No. | Operation | Time | Done by
Sign & Date |
Supervised by
Sign & Date |
|
| From | To | ||||
| 1 | Load Rubber stoppers into bung washer. Randomly add 10 nos. of dust spiked rubber stoppers in to the load. Start the operation as per the SOP.
Record the quantity:________Nos. |
 | |||
| 2 | First wash:
Wash the rubber stoppers with detergent solution (______ ml) and purified water for 30 minutes. Record the temperature of Purified water: __________ºC. |
 | |||
| 3 | Second wash:
Wash the rubber stoppers with Purified water for 30 minutes. Check the clarity of rinse water as per the SOP. Clarity: OK / Not OK |
 | |||
| 4 | Third wash:
Wash the rubber stoppers with water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 4 | Check the clarity of rinse water.
Clarity: OK / Not OK |
 | |||
| 6 | Fourth wash:
Wash the rubber stoppers with Silicone oil (_______ ml) and Water for injection for 30 minutes. Record the temperature of the WFI: __________ºC. |
 | |||
| 7 | Check the clarity of rinse water as per the SOP.
Clarity: OK / Not OK |
 | |||
| 8 | If clarity is not achieved, repeat the cycle and check the clarity. | Â | |||
| 9 | Unload the rubber stoppers in to baskets after completion of all washings. | Â | |||
| 10 | Follow as per the step No. 6.2.4 to 6.2.8 in the protocol. | Â | |||
- OBSERVATIONS
- Particulate MatterÂ
| Load Size | Run No. | Particulate matter | Done by
Sign & Date |
Verified by
Sign & Date |
|
| ≥10 µm particles | ≥25 µm particles |  |  | ||
| Minimum | 1 of 3 | Â | Â | ||
| 2 of 3 | Â | Â | |||
| 3 of 3 | Â | Â | |||
| Maximum | 1 of 3 | Â | Â | ||
| 2 of 3 | Â | Â | |||
| 3 of 3 | Â | Â | |||
- Bio burden results
- Date of test: Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Date of Report:
- Media used for TABC:Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Auto clave Load No.:
- Media used for Fungi:Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Auto clave Load No.:
| Load Size | Run No. | Cfu/10 rubber stoppers | Done by
Sign & Date |
Verified by
Sign & Date |
|
| TABC | Fungi | Â | Â | ||
| Minimum | 1 of 3 | Â | Â | ||
| 2 of 3 | Â | Â | |||
| 3 of 3 | Â | Â | |||
| Maximum | 1 of 3 | Â | Â | ||
| 2 of 3 | Â | Â | |||
| 3 of 3 | Â | Â | |||
- Remarks:
| Discrepancy And Corrective Action Report |
| Reference :
Discrepancy : Corrective Action     : Satisfactorily completed? [Yes / No]: Checked by / date:                                                 Reviewed and approved by / date: |
| Reference :
Discrepancy : Corrective Action : Satisfactorily completed? [Yes / No]: Checked by / date:Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Reviewed and approved by / date: |
| Reference :
Discrepancy : Corrective Action : Satisfactorily completed? [Yes / No]: Checked by / date:Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Â Reviewed and approved by / date: |
- REQUALIFICATION CRITERIA
- Requalification criteria is as follows
- If the machine is subjected for any major maintenance, up-gradation and/or modification that could directly or indirectly affect equipment performance and product quality.
- Any change in the cleaning procedure and/or washing cycle.
- Any change in the rubber stopper specification.
- Major change/ modification in the facility
- Relocation of the equipment.
