Standard Operating Procedure for Integrity Testing of Viral Filters in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/175/2025
Supersedes	SOP/BS/175/2022
Page No.	Page 1 of 9
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define a validated procedure for performing integrity testing on viral filtration units using bubble point or gas diffusion methods before and after filtration to confirm filter performance and compliance with GMP standards.

2. Scope

This SOP applies to all viral filters (20 nm-rated) used in downstream processing of biosimilar products, ensuring sterility assurance through integrity verification.

3. Responsibilities

• Production: Perform pre-use and post-use filter integrity testing and record data.
• Engineering: Calibrate integrity testers and support troubleshooting.
• QA: Review test reports and approve filter status for batch release.

4. Accountability

The Downstream Process Head is accountable for ensuring filters used in viral clearance steps meet predefined integrity testing criteria before batch approval.

5. Procedure

5.1 Equipment and Materials

1. Integrity Tester (automated or manual)
2. 20 nm-rated virus filters (e.g., Viresolve®, Virosart®)
3. WFI or buffer solution (pre-wetting agent)
4. Pressure source and validated tubing

5.2 Pre-Use Integrity Test

1. Install and connect the filter securely in the integrity test manifold.
2. Pre-wet the membrane using WFI or compatible buffer as per manufacturer’s instructions.
3. Run the integrity test:
   • Bubble Point Test: Gradually increase gas pressure and observe for the first bubble formation.
   • Diffusion Test: Apply constant pressure and measure steady-state gas flow across the wetted membrane.
4. Record results in Annexure-1. Test must be within manufacturer’s acceptance range.

5.3 Filtration Process

1. If pre-use test passes, proceed with viral filtration of the product as per applicable SOP.

5.4 Post-Use Integrity Test

1. Immediately after filtration, reconnect the filter setup and perform the same integrity test (bubble point or diffusion).
2. Ensure test conditions (temperature, pressure) are within specified range.
3. Record test values in Annexure-2. If post-use test fails, initiate deviation and quarantine product.

5.5 Test Result Interpretation

1. Compare test results with validated filter specifications.
2. Any deviation requires investigation, repeat test (if applicable), and QA disposition.

5.6 Documentation and Traceability

1. Ensure all test reports are signed, dated, and traceable to:
   • Filter lot number
   • Batch ID
   • Product name

6. Abbreviations

• WFI: Water for Injection
• GMP: Good Manufacturing Practice
• SIP: Steam in Place
• EU: Endotoxin Units

7. Documents

1. Pre-Use Integrity Test Log – Annexure-1
2. Post-Use Integrity Test Log – Annexure-2

8. References

• USP <1035> – Biological Indicator for Sterility Assurance
• ICH Q5A – Viral Safety Evaluation of Biotechnology Products
• WHO TRS 1004 – GMP for Biologicals

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Pre-Use Integrity Test Log

Date	Batch ID	Filter ID	Method	Result	Pass/Fail	Performed By
04/05/2025	BS-VF-023	VF20NM-11	Bubble Point	2.45 bar	Pass	Ajay Verma

Annexure-2: Post-Use Integrity Test Log

Date	Batch ID	Filter ID	Method	Result	Pass/Fail	Performed By
04/05/2025	BS-VF-023	VF20NM-11	Bubble Point	2.41 bar	Pass	Ajay Verma

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Included automated testing procedures and result documentation formats	Regulatory update