Standard Operating Procedure for Primary Clarification Using Depth Filters in Bioreactor Operations for Biosimilars
| Department | Biosimilars |
|---|---|
| SOP No. | SOP/BS/088/2025 |
| Supersedes | SOP/BS/088/2022 |
| Page No. | Page 1 of 11 |
| Issue Date | 04/05/2025 |
| Effective Date | 06/05/2025 |
| Review Date | 04/05/2026 |
1. Purpose
To describe the standardized procedure for primary clarification of harvested cell culture broth using depth filtration systems to remove cell debris and insoluble impurities prior to downstream purification in biosimilar manufacturing.
2. Scope
This SOP is applicable to all harvested mammalian cell culture broths within the biosimilar production facility undergoing depth filtration as the first clarification step post-centrifugation.
3. Responsibilities
- Production Operator: Perform filter assembly, operation, and integrity checks.
- Engineering Personnel: Calibrate and maintain filtration system hardware.
- QA Officer: Review filter logs and validate compliance with GMP standards.
4. Accountability
The Production Manager is accountable for execution and verification of depth filtration operations and ensuring product is clarified as per specifications.
5. Procedure
5.1 Pre-Filtration Setup
- Ensure centrifuged harvest is transferred to the holding tank connected to the depth filter setup.
- Verify cleaning status of filtration skid and mark it “Cleaned and Ready.”
- Use pre-validated filter cartridges (e.g., Millistak+ HC or equivalent) based on process compatibility.
5.2 Filter Assembly and Integrity Check
- Install depth filter capsules into the housing with inlet/outlet direction as per flow arrow.
- Tighten housing clamps and check for leaks.
- Conduct pre-use water flush and integrity test as per manufacturer instructions.
5.3 Filtration Operation
- Start the peristaltic or diaphragm pump at low flow rate (~50 L/hr) and gradually increase to process rate (~200–500 L/hr).
- Maintain differential pressure within allowable range (e.g., <1.5 bar).
- Monitor turbidity of filtrate at periodic intervals using portable turbidimeter.
- Collect filtrate in pre-labeled clarified harvest tank.
5.4 Filter Changeover
- If differential pressure exceeds limit or flow drops significantly, initiate changeover.
- Record filter lot number, run time, volume processed, and reason for replacement in Annexure-1.
- Restart with new pre-sterilized filter module.
5.5 Post-Operation
- Perform post-use water flush and inspect filter housing for retained debris.
- Label used filters and dispose according to biohazard waste procedure (refer SOP/BS/048/2025).
- Record total volume filtered, filtrate turbidity, and final pressure in Annexure-1.
6. Abbreviations
- GMP: Good Manufacturing Practice
- QC: Quality Control
- L/hr: Liters per Hour
- µm: Micron
7. Documents
- Depth Filtration Log – Annexure-1
8. References
- ICH Q7 – GMP for APIs
- WHO TRS 999 – Biotech Production
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Depth Filtration Log
| Date | Batch No. | Filter Lot No. | Volume (L) | Start Pressure (bar) | End Pressure (bar) | Remarks | Operator |
|---|---|---|---|---|---|---|---|
| 04/05/2025 | BS-088-B03 | DF-5247 | 480 | 0.4 | 1.3 | Filter replaced after 480L | Ajay Verma |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 04/05/2025 | 2.0 | Incorporated filter integrity testing and turbidity monitoring steps | Compliance with updated WHO GMP guidance |