vials, ampoules, and prefilled syringes that are sealed during the filling process in Grade A/B classified environments at [Company Name].

3. Responsibilities

• Filling Machine Operator: Performs sealing operation and initial checks.
• IPQA Officer: Verifies sealing integrity and documents observations.
• Engineering Officer: Ensures machine sealing parameters are calibrated and maintained.

4. Accountability

The Head – Quality Assurance is accountable for ensuring proper implementation and compliance with this SOP.

5. Procedure

5.1 Preparation for Sealing Integrity Checks

1. Ensure that sealing equipment is cleaned and sterilized before the start of operation.
2. Verify that sealing parameters (e.g., temperature, pressure, time) are set as per the validated batch parameters.
3. Ensure the presence of IPQA personnel before sealing begins.

5.2 In-Process Sealing Integrity Check

1. Conduct sealing integrity checks at defined intervals (e.g., every 30 minutes or every 100 units).
2. Inspect for the following:
   • Uniformity of seal
   • Presence of crimping defects
   • Any signs of leakage or gaps
   • Correct positioning of aluminum cap (vials) or plunger (syringes)
3. Perform leak test using vacuum or dye ingress method where applicable (especially for ampoules).
4. Record the inspection results in the Sealing Integrity Logbook (Annexure-1).

5.3 Handling of Defects

1. Any unit failing the integrity check must be segregated and documented as rejected.
2. Investigate cause and check previous 10 sealed units if a defect is detected.
3. If a trend of rejection is observed, stop the line and inform QA and engineering.

5.4 Post-Batch Integrity Evaluation

1. IPQA to select samples from the beginning, middle, and end of the batch for final sealing integrity checks.
2. Document results and include in the Batch Manufacturing Record (BMR).

5.5 Frequency of Monitoring

1. Initial line clearance check
2. Every 30 minutes during filling
3. Post-batch summary check
4. During changeovers

6. Abbreviations

• SOP: Standard Operating Procedure
• IPQA: In-Process Quality Assurance
• BMR: Batch Manufacturing Record
• cGMP: Current Good Manufacturing Practices

7. Documents

1. Sealing Integrity Logbook – Annexure-1
2. Sealing Parameter Checklist – Annexure-2
3. Defect Observation Report – Annexure-3

8. References

• 21 CFR Part 211 – CGMP for Finished Pharmaceuticals
• ICH Q8 – Pharmaceutical Development
• WHO TRS 961 Annex 6 – GMP for Sterile Products

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: Sealing Integrity Logbook

Date	Time	Batch No.	Checked By	Observation	Remarks
18/06/2025	10:30 AM	VIAL-BT-2305	Sunita Reddy	No Defects	Complies

Annexure-2: Sealing Parameter Checklist

Parameter	Set Value	Observed Value	Status
Sealing Temperature	120°C	121°C	OK
Sealing Pressure	25 psi	25 psi	OK

Annexure-3: Defect Observation Report

Date	Batch No.	Defect Observed	Corrective Action	Performed By
18/06/2025	VIAL-BT-2305	Crimping Misalignment	Tool adjusted, 10 units rechecked	Rajesh Kumar

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial Release	New SOP	QA Head
18/06/2025	2.0	Updated frequency and annexure templates	Annual Review	QA Head