for operating prefilled syringe filling machines used in the sterile injectable manufacturing area.

3. Responsibilities

• Machine Operator: Performs setup, operation, and in-process checks during filling.
• Line Supervisor: Reviews setup, ensures area clearance, and supervises production activities.
• Engineering Technician: Assists in machine setup, troubleshooting, and maintenance.
• QA Officer: Conducts in-process verification and ensures compliance.

4. Accountability

The Production Manager is accountable for compliance with this SOP and ensuring safe and efficient machine operations.

5. Procedure

5.1 Pre-Operation Checks

1. Verify the room clearance as per Area Line Clearance SOP.
2. Confirm the availability of batch documents, materials, and sterilized syringes.
3. Ensure machine cleaning and maintenance have been completed and logged.
4. Ensure all safety guards and sensors are functional.

5.2 Machine Setup

1. Switch ON the machine and log in using operator credentials.
2. Set the following machine parameters:
   • Filling volume: (e.g., 1.0 mL ± 0.05 mL)
   • Plunger insertion force and depth
   • Vacuum settings if applicable
   • Speed: Based on batch size and output requirement
3. Install pre-sterilized syringe tubs onto the infeed station.
4. Check nozzle alignment and perform a dummy run using WFI (Water for Injection).

5.3 Start of Batch Operation

1. QA to verify and sign off machine settings before commencing batch.
2. Initiate filling under LAF (Laminar Air Flow) with batch BMR open and entries ready.
3. Perform fill volume checks every 15 minutes and record in Annexure-1.
4. Check plunger position and insertion using visual and weight verification.

5.4 In-Process Monitoring

1. Continuously observe:
   • Nozzle dripping
   • Stop-start delays
   • Jammed plungers or misalignment
2. Any deviations to be recorded and investigated per Deviation SOP.
3. Perform cleaning of the nozzle tip every hour using lint-free swabs and IPA.

5.5 End of Operation

1. Shut down the filling machine after batch completion.
2. Record end time, machine parameters, and lot-wise reconciliation data.
3. Disassemble parts requiring cleaning and submit to washing area.
4. Perform machine cleaning as per SOP/SIM/056/2025 and record in Annexure-2.

5.6 Documentation

1. Ensure all entries in the BMR are complete and countersigned.
2. QA to review Annexure-1 and Annexure-2 for correctness.
3. Submit batch documentation for QA review and archival.

6. Abbreviations

• SOP: Standard Operating Procedure
• BMR: Batch Manufacturing Record
• LAF: Laminar Air Flow
• WFI: Water for Injection

7. Documents

1. Prefilled Syringe Fill Volume Log – Annexure-1
2. Cleaning Record for Filling Machine – Annexure-2

8. References

• WHO TRS 961 Annex 6: GMP for Sterile Pharmaceutical Products
• EU GMP Annex 1: Manufacture of Sterile Medicinal Products
• ICH Q9: Quality Risk Management

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Manufacturing Executive	QA Executive	Head QA
Department	Production	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Prefilled Syringe Fill Volume Log

Date	Batch No.	Volume Set	Avg Volume	Checked By
18/06/2025	PFS2025IV05	1.0 mL	0.99 mL	Rajesh Kumar

Annexure-2: Cleaning Record for Filling Machine

Date	Time	Cleaned By	Verified By (QA)	Remarks
18/06/2025	18:30	Sunita Reddy	Ajay Verma	Machine cleaned and dried

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/02/2022	1.0	Initial Release	New SOP	QA Head
18/06/2025	2.0	Updated for machine parameter optimization	Annual Review	QA Head