vial filling operations for sterile injectable products across all filling lines equipped with online vision systems, electronic sensors, or gravimetric monitoring systems used at [Insert Company Name]’s sterile manufacturing facility.

3. Responsibilities

• Machine Operator: To continuously observe the vial fill levels via HMI and visual inspection. Promptly report discrepancies to the Production Supervisor.
• In-Process Quality Assurance (IPQA) Officer: To verify fill level compliance, review alerts and rejection trends, and record real-time checks.
• Production Supervisor: To assess machine performance, authorize interventions, and coordinate with engineering when variances occur.
• Engineering/Maintenance: To calibrate, maintain, and troubleshoot vial fill level detection systems and associated hardware.
• QA Manager: To review the monitoring records and ensure procedural compliance during audits.

4. Accountability

The Production Head is accountable for the effective implementation of this SOP and ensuring appropriate corrective actions in case of anomalies in vial fill levels.

5. Procedure

5.1 System Setup and Verification

1. Ensure the vial filling line is prepared, and all cleaning and line clearance activities are completed and documented.
2. Verify that the vial fill level monitoring system is active, clean, calibrated, and functional. This includes:
   • Camera lenses or sensors (capacitive, gravimetric, or infrared)
   • Associated software and rejection mechanisms
   • Alarms and interface displays
3. Initiate a dry run with empty or filled test vials to confirm alignment and sensitivity of the monitoring system.

5.2 Monitoring During Filling

1. Begin batch filling after receiving QA clearance.
2. The real-time vial fill level detection system shall evaluate each vial after it passes the filling station and before sealing.
3. Set acceptable fill limits as per the validated batch manufacturing record (e.g., 5.0 ± 0.1 mL).
4. The system shall automatically:
   • Accept correctly filled vials
   • Reject underfilled or overfilled vials
   • Log data for each rejection
5. Rejected vials must be collected in the designated rejection bin and recorded in the Fill Volume Rejection Log (Annexure-1).

5.3 Manual Checks

1. Every 30 minutes, IPQA must collect 5 vials for manual verification using a calibrated analytical balance or visual comparator.
2. Record each observation in the Manual Fill Check Log (Annexure-2).
3. If deviation is observed beyond acceptance criteria, stop the line and inform QA and maintenance for investigation.

5.4 Rejection Limits and Alerts

1. System shall trigger an alert if:
   • More than 3 consecutive fill rejections occur
   • Total rejections exceed 2% of batch size
   • Sensor or system malfunction is detected
2. Immediately pause the machine on alert and initiate deviation documentation (Annexure-3).
3. Engineering and QA shall jointly assess root cause and implement CAPA if needed.

5.5 Data Logging and Batch Summary

1. The system shall generate continuous logs of:
   • Each vial’s fill level
   • Time of rejection
   • Batch number and operator ID
2. Post batch completion, export and attach the electronic summary report to the BMR.
3. Ensure backups are maintained for a minimum of 5 years.

5.6 Equipment Calibration and Maintenance

1. Monthly calibration of sensors and cameras must be performed and documented (refer SOP/ENG/045).
2. Corrective adjustments and preventive maintenance schedules shall be defined based on equipment manuals.
3. Calibration certificates and maintenance logs must be available during audits.

5.7 Deviation Handling

1. All fill volume deviations, equipment malfunctions, or procedural lapses must be captured in deviation form (Annexure-3).
2. QA must investigate the incident, determine impact on batch quality, and recommend batch disposition.
3. CAPA shall be closed within 30 days and reviewed during internal quality audits.

6. Abbreviations

• SOP: Standard Operating Procedure
• IPQA: In-Process Quality Assurance
• BMR: Batch Manufacturing Record
• CAPA: Corrective and Preventive Action

7. Documents

1. Fill Volume Rejection Log – Annexure-1
2. Manual Fill Check Log – Annexure-2
3. Deviation Form – Annexure-3

8. References

• 21 CFR Part 211 – CGMP for Finished Pharmaceuticals
• 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	Production Executive	QA Executive	Head QA
Department	Production	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Fill Volume Rejection Log

Date	Batch No.	Vial No.	Fill Volume (mL)	Rejection Type	Operator
24/06/2025	VIAL0625-03	105	4.8	Underfill	Rajesh Kumar

Annexure-2: Manual Fill Check Log

Date	Batch No.	Vial No.	Observed Volume	Result	Checked By
24/06/2025	VIAL0625-03	3	5.05 mL	Acceptable	Sunita Reddy

Annexure-3: Deviation Form

Deviation No.	DEV/IPC/067
Date	24/06/2025
Observed By	Rajesh Kumar
Description	Increased underfill rate detected after 11:45 AM
Immediate Action	Machine stopped, maintenance informed
Root Cause	Pressure fluctuation in fill nozzle
CAPA	Replaced pneumatic valve, calibrated sensor

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
15/04/2022	1.0	Initial Release	New SOP	QA Head
24/06/2025	2.0	Updated with electronic monitoring and annexures	Periodic Review	QA Head