Standard Operating Procedure for Tank-to-Tank Transfer of Cultures in Biosimilar Manufacturing
| Department | Biosimilars |
|---|---|
| SOP No. | SOP/BS/109/2025 |
| Supersedes | SOP/BS/109/2022 |
| Page No. | Page 1 of 12 |
| Issue Date | 04/05/2025 |
| Effective Date | 06/05/2025 |
| Review Date | 04/05/2026 |
1. Purpose
To define the procedure for aseptic and controlled transfer of cell culture from one tank to another (e.g., seed to seed, or seed to production bioreactor) during upstream biosimilar manufacturing, ensuring sterility and product integrity.
2. Scope
This SOP applies to all tank-to-tank culture transfers within the biosimilar upstream suite using peristaltic pumps, transfer bags, or direct sterile tubing connections.
3. Responsibilities
- Production Operator: Execute tank transfer as per protocol and document operations in real time.
- Production Supervisor: Review and approve transfer setup and monitor transfer completion.
- Engineering: Ensure pump calibration and tubing integrity prior to transfer.
4. Accountability
The Head of Production is accountable for ensuring sterile and efficient transfer of culture material without contamination risk or product loss.
5. Procedure
5.1 Pre-Transfer Preparation
- Verify source and destination tanks are labeled, cleaned, sterilized, and pressure tested.
- Ensure pre-use integrity of the seed and recipient bioreactor (temperature, DO, pressure).
- Check seed culture viability (≥ 90%) and log in Annexure-1.
5.2 Connection Setup
- Use sterile single-use transfer tubing or sanitized stainless-steel transfer lines.
- Secure all tubing with clamps and aseptic connectors (e.g., AseptiQuik, CPC fittings).
- Confirm pump type (peristaltic recommended) is cleaned and tubing loaded correctly.
5.3 Transfer Execution
- Start peristaltic pump at a flow rate suitable for vessel size (e.g., 1 L/min for 200 L).
- Monitor for:
- Air entrapment
- Foaming
- Backflow
- Adjust speed and pause if needed to prevent culture shearing or foam overflow.
- Complete transfer within 30–60 minutes for standard batches.
5.4 Post-Transfer Actions
- Clamp off tubing, disconnect using sterile scissors or welders.
- Flush lines with sterile WFI or air if protocol requires.
- Start mixing, temperature ramping, and DO stabilization in recipient tank.
5.5 Documentation
- Complete Annexure-2: Transfer Log Sheet with volume, timings, and signatures.
- Notify QA and submit transfer batch record for review.
6. Abbreviations
- DO: Dissolved Oxygen
- WFI: Water for Injection
- QA: Quality Assurance
7. Documents
- Tank Transfer Pre-Check Record – Annexure-1
- Transfer Log Sheet – Annexure-2
8. References
- WHO TRS 999 – Guidelines on Biopharmaceutical Manufacturing
- FDA Guidance on Aseptic Processing (2004)
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Tank Transfer Pre-Check Record
| Parameter | Status | Checked By | Date |
|---|---|---|---|
| Source Tank Sanitized | Yes | Sunita Reddy | 04/05/2025 |
| Recipient Tank Calibrated | Yes | Ajay Verma | 04/05/2025 |
Annexure-2: Transfer Log Sheet
| Date | From Tank | To Tank | Volume Transferred (L) | Start–End Time | Performed By |
|---|---|---|---|---|---|
| 04/05/2025 | Seed-BR-02 | Prod-BR-10 | 100 | 10:00–10:50 | Sunita Reddy |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 04/05/2025 | 2.0 | Included closed-loop transfer precautions and line flushing protocol | Process improvement |