Standard Operating Procedure for Pre-Filter and Sterile Filter Use in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/153/2025
Supersedes	SOP/BS/153/2022
Page No.	Page 1 of 10
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the procedure for installation, use, and integrity testing of pre-filters and sterile-grade filters in biosimilar manufacturing processes to ensure product sterility and compliance with GMP standards.

2. Scope

This SOP applies to filtration systems used for media, buffer, product intermediates, and bulk drug substances in upstream and downstream processing at biosimilar production sites.

3. Responsibilities

• Production: Install filters, perform filtration, document parameters.
• QA: Review filter integrity results, approve usage logs and deviation reports.
• Engineering: Ensure calibration of integrity test instruments and support troubleshooting.

4. Accountability

The Manufacturing Head is accountable for ensuring GMP-compliant operation of all sterile and pre-filter systems used in biosimilar processing.

5. Procedure

5.1 Filter Selection and Verification

1. Select pre-filters (e.g., 0.45 µm) for particulate removal and sterile filters (0.22 µm or 0.1 µm) for microbial retention.
2. Verify:
   • Filter type and pore size
   • Manufacturer, lot number, expiry date
   • Integrity test certification (COC)
3. Document in Annexure-1: Filter Traceability Log.

5.2 Installation of Filters

1. Install filters aseptically in Grade A/B area using sanitized gloved hands.
2. Ensure correct orientation as per flow direction marked on the housing.
3. Tighten securely and verify no bypass/leakage.

5.3 Filter Integrity Testing

1. Pre-use integrity test is mandatory for sterile filters using validated methods:
   • Bubble Point
   • Diffusion Test
   • Pressure Hold Test
2. Use automated integrity test unit and input:
   • Product type
   • Filter surface area
   • Test parameters
3. Record results in Annexure-2: Filter Integrity Test Report.

5.4 Filtration Procedure

1. Flush filter (if required) with WFI or buffer as specified in the batch record.
2. Start filtration ensuring pressure remains between 1–3 bar and flow rate is consistent.
3. Do not exceed manufacturer’s maximum pressure rating.

5.5 Post-Use Integrity Testing

1. Immediately after use, perform post-use integrity test using same method as pre-use.
2. If filter fails, quarantine product and initiate deviation as per SOP.

5.6 Deviation and Replacement

1. If filter integrity test fails:
   • Stop filtration
   • Notify QA
   • Use reserve validated filter if authorized
2. Document in Annexure-3: Filter Failure & Replacement Log.

6. Abbreviations

• WFI: Water for Injection
• QA: Quality Assurance
• COC: Certificate of Compliance

7. Documents

1. Filter Traceability Log – Annexure-1
2. Filter Integrity Test Report – Annexure-2
3. Filter Failure & Replacement Log – Annexure-3

8. References

• ICH Q7 – GMP for APIs
• EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
• WHO TRS 999 – Biotherapeutic Products Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Filter Traceability Log

Date	Filter Type	Lot No.	Pore Size	Used In Batch	Installed By
04/05/2025	Sterile 0.22 µm	SF-2204	0.22 µm	BS-DP-082	Ajay Verma

Annexure-2: Filter Integrity Test Report

Date	Filter ID	Test Type	Result	Pass/Fail	Tested By
04/05/2025	SF-2204	Bubble Point	3.4 bar	Pass	Sunita Reddy

Annexure-3: Filter Failure & Replacement Log

Date	Filter ID	Failure Type	Action Taken	Reviewed By (QA)
04/05/2025	SF-2201	Failed Integrity	Replaced with SF-2204	QA Officer

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added post-use testing and failure handling flow	GMP improvement