Standard Operating Procedure for Temperature Control in Bioreactor Operations for Biosimilar Manufacturing
| Department | Biosimilars |
|---|---|
| SOP No. | SOP/BS/068/2025 |
| Supersedes | SOP/BS/068/2022 |
| 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 controlling, monitoring, and documenting temperature parameters in bioreactors used for upstream biosimilar manufacturing to ensure optimal cell culture conditions and regulatory compliance.
2. Scope
This SOP applies to all stainless steel and single-use bioreactors (1L to 2000L capacity) operated in the upstream process areas for biosimilar production at [Insert Facility Name].
3. Responsibilities
- Upstream Operator: Monitors temperature, verifies alarms, and records observations in logs.
- Engineering Team: Calibrates sensors and maintains heating/cooling jackets and control systems.
- QA Officer: Reviews temperature trends and verifies compliance with validated ranges.
4. Accountability
The Head of Bioprocess Operations is accountable for ensuring adherence to temperature control procedures and reporting any deviations or equipment malfunctions.
5. Procedure
5.1 Pre-Operation Verification
- Ensure bioreactor temperature sensor is calibrated within the last 6 months (Annexure-1).
- Verify setpoint and deadband settings as per batch record: typically 36.5°C–37.5°C.
- Confirm that the control unit (PID controller or PLC) is operational and shows no prior faults.
5.2 Temperature Setpoint Configuration
- Set temperature on the bioreactor control panel as per process requirement (e.g., 37.0°C).
- Input control parameters (P, I, D values) based on system tuning documentation.
- Start temperature control loop, allowing jacket fluid to circulate.
5.3 Monitoring During Operation
- Monitor bioreactor display panel for live temperature and jacket temperature every 2 hours.
- Record actual temperature in the Bioreactor Monitoring Log (Annexure-2).
- If deviation > ±0.5°C from setpoint, initiate deviation handling (SOP/BS/050/2025).
5.4 Alarm Response and Troubleshooting
- In case of temperature alarm:
- Verify probe immersion and function.
- Check jacket chiller or heating system for blockages or leaks.
- Escalate unresolved issues to maintenance.
5.5 Post-Run Shutdown
- Turn off temperature control loop.
- Inspect and clean jacket circulation system if required.
- Document final reading and post-run status in Annexure-3.
6. Abbreviations
- PID: Proportional-Integral-Derivative
- PLC: Programmable Logic Controller
- QA: Quality Assurance
7. Documents
- Temperature Calibration Certificate – Annexure-1
- Bioreactor Temperature Monitoring Log – Annexure-2
- Final Temperature Shutdown Log – Annexure-3
8. References
- WHO TRS 999 – Biotechnological Manufacturing
- ICH Q8(R2) – Pharmaceutical Development
- SOP/BS/050/2025 – Deviation Handling
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Temperature Calibration Certificate
| Instrument ID | Calibration Date | Next Due Date | Calibrated By |
|---|---|---|---|
| TRX-07 | 15/02/2025 | 15/08/2025 | Sunita Reddy |
Annexure-2: Bioreactor Temperature Monitoring Log
| Date | Time | Setpoint (°C) | Actual Temp (°C) | Remarks |
|---|---|---|---|---|
| 04/05/2025 | 10:00 | 37.0 | 37.1 | Within range |
Annexure-3: Final Temperature Shutdown Log
| Batch ID | Final Temp (°C) | Time of Shutdown | Operator |
|---|---|---|---|
| BR-105 | 36.9 | 19:30 | Ajay Verma |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 04/05/2025 | 2.0 | Alarm handling and PID setpoint steps added | GMP Compliance |