Scope

This SOP is applicable to all filters used in the sterile manufacturing of injectable products, including 0.22 µm sterilizing-grade filters utilized before aseptic filling operations.

3. Responsibilities

• Manufacturing Officer: Perform FIT and document results.
• Quality Assurance (QA): Review and verify integrity test results.
• Engineering: Maintain filtration systems and calibration of instruments.
• QC Microbiology: Evaluate microbial retention performance if required.

4. Accountability

The Head of Production is accountable for ensuring the proper execution and documentation of pre-sterile FIT as per this SOP.

5. Procedure

5.1 Types of Filter Integrity Tests

• Bubble Point Test
• Diffusion Test
• Pressure Hold Test

5.2 Pre-Test Preparations

1. Ensure all equipment is cleaned and calibrated.
2. Use sterilized 0.22 µm hydrophilic membrane filters or appropriate type.
3. Connect the filter assembly to the automated integrity tester.
4. Ensure no leaks are present in the tubing or connections.

5.3 Execution of Test

1. Wet the filter with Water for Injection (WFI) or product solution, as applicable.
2. Select the appropriate integrity test based on product compatibility.
3. For bubble point:
   • Apply pressure gradually.
   • Observe the pressure where continuous bubbling begins.
4. For diffusion:
   • Apply constant pressure (e.g., 48 psi).
   • Measure gas flow in cc/min.
5. Compare the result with manufacturer’s acceptance criteria.

5.4 Acceptance Criteria

1. The bubble point must not be lower than the minimum specified value.
2. Diffusion rate must fall within the validated range.
3. If test fails, replace the filter and repeat the test.

5.5 Documentation

1. Record all details in the Filter Integrity Test Logbook (Annexure-1).
2. Document the filter serial number, batch number, test method, date, result, and operator initials.
3. Attach the automated test printout (Annexure-2).

5.6 Troubleshooting

1. If test fails:
   • Check for wetting errors or air pockets.
   • Re-wet and re-test the filter once.
2. Replace filter if test fails again and investigate deviation.

5.7 Post-Test Activity

1. Upon successful completion, label the filter as “Tested – Ready for Use”.
2. Proceed to aseptic filling only after QA approval of test report.

6. Abbreviations

• FIT: Filter Integrity Test
• WFI: Water for Injection
• QA: Quality Assurance
• QC: Quality Control

7. Documents

1. Filter Integrity Test Logbook – Annexure-1
2. Automated Test Printout – Annexure-2
3. Filter Replacement Log – Annexure-3

8. References

• USP <1207> – Sterile Product Package Integrity Evaluation
• ICH Q7 – Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
• FDA Guidance on Sterile Drug Products Produced by Aseptic Processing

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: Filter Integrity Test Logbook

Date	Batch No.	Filter Type	Serial No.	Test Type	Result	Performed By
20/06/2025	IV-5689	0.22 µm PES	FLTR-8821	Bubble Point	Pass	Rajesh Kumar

Annexure-2: Automated Test Printout

Attach system-generated test result print showing:

• Filter Type
• Operator ID
• Date & Time
• Pass/Fail Status

Annexure-3: Filter Replacement Log

Date	Old Filter Serial No.	New Filter Serial No.	Reason	Approved By
20/06/2025	FLTR-7798	FLTR-8821	Integrity Test Failure	Sunita Reddy

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
10/01/2022	1.0	Initial Issue	New SOP	QA Head
24/06/2025	2.0	Revised acceptance criteria and added Annexure-3	Annual Review	QA Head