sterile manufacturing facility.

3. Responsibilities

• QC Analyst: Conducts CCIT and records the results.
• QC Reviewer: Reviews data for compliance and correctness.
• QA Officer: Verifies integrity test results prior to batch release.

4. Accountability

The Head of Quality Control is accountable for ensuring the integrity of the container closure system through validated CCIT methods.

5. Procedure

5.1 Sampling

1. Collect samples from each batch as per sampling plan (refer Annexure-1: Sample Log).
2. Include samples from the beginning, middle, and end of the filling process.

5.2 Test Methods

1. Use any of the following validated techniques based on product and packaging type:
   • Vacuum Decay Method
   • Helium Leak Detection
   • High Voltage Leak Detection (HVLD)
   • Dye Ingress Test
2. Ensure all equipment used is calibrated and validated before use (see Annexure-2: Equipment Calibration Log).

5.3 Execution of CCIT

1. Inspect each sample using the chosen method according to the validated SOPs.
2. For HVLD:
   • Connect the syringe/vial to the HVLD system.
   • Apply voltage and record any current leakage.
   • A value above set threshold indicates failure.
3. For dye ingress:
   • Submerge samples in 0.1% methylene blue solution and apply vacuum.
   • Inspect for dye penetration after specified hold time.
4. Document all observations in Annexure-3: CCIT Results Sheet.

5.4 Acceptance Criteria

1. All samples must pass CCIT without leak detection, dye ingress, or voltage current beyond limit.
2. If any sample fails, follow deviation and batch investigation procedures.

5.5 Handling Failures

1. Isolate failed sample and inform QA.
2. Initiate root cause investigation and evaluate impact on batch disposition.
3. Record investigation in Annexure-4: CCIT Failure Report.

6. Abbreviations

• CCIT: Container Closure Integrity Testing
• HVLD: High Voltage Leak Detection
• QA: Quality Assurance
• QC: Quality Control
• SOP: Standard Operating Procedure

7. Documents

1. Sample Log – Annexure-1
2. Equipment Calibration Log – Annexure-2
3. CCIT Results Sheet – Annexure-3
4. CCIT Failure Report – Annexure-4

8. References

• USP <1207> Container Closure Integrity Testing
• ICH Q8 – Pharmaceutical Development
• WHO TRS 996 – Annex 6

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	QC Analyst	QA Executive	Head QA
Department	Quality Control	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Sample Log

Date	Product	Batch No.	Sampled By	Remarks
17/06/2025	Diclofenac Injection	DFC-0625-B	Anil Sharma	Start, mid, end samples

Annexure-2: Equipment Calibration Log

Equipment ID	Type	Calibration Date	Calibrated By	Remarks
HVLD-01	HV Leak Detector	01/06/2025	Rajesh Kumar	Calibrated

Annexure-3: CCIT Results Sheet

Sample ID	Method	Result	Tested By	Remarks
DFC-0625-B-01	HVLD	Pass	Sunita Reddy	—

Annexure-4: CCIT Failure Report

Sample ID	Failed Method	Description	Action Taken	Reported By
DFC-0625-B-07	Dye Ingress	Blue dye detected	Sample quarantined	Vinay Pawar

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial issue	New SOP	QA Head
18/06/2025	2.0	Added HVLD protocol and updated annexures	Annual Review	QA Head