Standard Operating Procedure for Media Filtration Before Use in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/128/2025
Supersedes	SOP/BS/128/2022
Page No.	Page 1 of 11
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the procedure for sterile filtration of culture media used in upstream biosimilar processes to ensure removal of particulates and microbial contaminants prior to inoculation or cell culture applications.

2. Scope

This SOP applies to the filtration of liquid media, feeds, and supplements prepared in the media preparation area and used in biosimilar manufacturing, including cell line development and bioreactor inoculation.

3. Responsibilities

• Production: Perform filtration as per batch requirement and document process.
• Engineering: Ensure filters and filtration setups are installed and functioning properly.
• QA: Verify filter integrity test and review batch records.

4. Accountability

The Head of Manufacturing is accountable for ensuring that only sterile, filtered media is used in any cell culture-related process steps and that all filtration steps are documented and verified.

5. Procedure

5.1 Preparation for Filtration

1. Verify that the media preparation is complete, pH adjusted, and labeled properly.
2. Transfer media into a sterile container under a biosafety cabinet (Grade A/ISO 5).
3. Ensure use of 0.22 µm sterilizing-grade membrane filters with valid certificate of compliance.
4. Record filter lot number and expiry in Annexure-1.

5.2 Filtration Setup

1. Assemble filtration setup using:
   • Peristaltic pump (if applicable)
   • Pre-sanitized tubing sets
   • Sterile storage carboy or bioreactor input
2. Perform pre-use filter integrity check (Bubble Point Test or Diffusion Test).
3. Document test result in Annexure-2: Filter Integrity Record.

5.3 Execution of Filtration

1. Connect inlet tubing to media container and outlet to receiving sterile container or line.
2. Start pump or use gravity feed ensuring flowrate as per validation (typically 0.5–2.0 L/min).
3. Maintain aseptic technique throughout the process.
4. Monitor for pressure build-up or leakage.
5. Upon completion, perform post-use filter integrity test.

5.4 Labeling and Documentation

1. Label filtered media with:
   • “Sterile Filtered” status
   • Date and Time
   • Used by
   • Batch No.
2. Record details in Annexure-3: Media Filtration Log.
3. Submit completed records to QA for review.

6. Abbreviations

• µm: Micrometer
• QA: Quality Assurance
• GMP: Good Manufacturing Practice

7. Documents

1. Filter Certificate of Compliance – Annexure-1
2. Filter Integrity Test Record – Annexure-2
3. Media Filtration Log – Annexure-3

8. References

• USP <797> – Sterile Preparations
• WHO TRS 1019 – GMP for Biotech
• ISPE Baseline Guide – Sterile Manufacturing

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 Certificate Record

Date	Filter Type	Lot No.	Expiry	Verified By
04/05/2025	0.22 µm PES	FTR-2201	12/2026	Ajay Verma

Annexure-2: Filter Integrity Test Record

Date	Test Type	Result	Status	Checked By
04/05/2025	Bubble Point	Passed	Accepted	Sunita Reddy

Annexure-3: Media Filtration Log

Date	Media	Volume	Filtered By	Integrity Status	Remarks
04/05/2025	CHO Feed A	15L	Ajay Verma	Pass	Clear

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Clarified integrity test and labeling	Audit Observation