Standard Operating Procedure for Use of Jacketed Reactors with Temperature Control in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/023/2025 |
| Supersedes | SOP/API/023/2022 |
| Page No. | Page 1 of 11 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To define the procedure for the safe, efficient, and compliant operation of jacketed reactors equipped with temperature control systems to maintain desired thermal conditions during API manufacturing processes.
2. Scope
This SOP applies to all jacketed glass-lined and stainless-steel reactors in the API plant that utilize temperature control units (TCUs), heating/cooling baths, or circulating oil systems for regulated temperature conditions during chemical synthesis.
3. Responsibilities
- Production Operator: Set and monitor temperature parameters as per BMR and operate the reactor as per instructions.
- Shift Supervisor: Ensure equipment functionality and safety checks are conducted before use.
- Engineering Personnel: Maintain the jacket, temperature probes, and fluid circulation system.
- QA Officer: Verify operating conditions and review associated records during batch review.
4. Accountability
The Production Manager and Maintenance Head are accountable for ensuring the equipment is operated, maintained, and monitored per validated procedures and GMP expectations.
5. Procedure
5.1 Equipment Pre-Check
- Ensure reactor jacket is clean, intact, and free from visible leaks or corrosion.
- Verify that temperature sensors (RTD or thermocouples) are calibrated (refer to Annexure-1).
- Check TCU oil/water level and circulation pump functionality.
- Ensure control panel is functional and set to manual or DCS mode as applicable.
- Verify availability of backup cooling and heating fluids (glycol, oil, chilled water).
5.2 Reactor Startup and Setpoint Adjustment
- Turn ON the temperature control system from the main panel.
- Set the desired setpoint temperature as per BMR instructions.
- Allow temperature to reach equilibrium and stabilize before charging reagents.
- Record the ramp-up time, hold temperature, and observed deviations (Annexure-2).
5.3 Monitoring and Control During Reaction
- Record temperature at 15-minute intervals or as specified in BMR.
- Observe for anomalies in temperature fluctuation, flow rate, and pressure build-up.
- If fluctuation exceeds ±2°C from setpoint, inform engineering and record deviation.
- Monitor jacket return temperature and inlet temperature to confirm circulation efficiency.
5.4 Safety Guidelines
- Ensure temperature is within safe operating range of reactor and product chemistry.
- Do not operate the jacketed reactor with low oil or water level in the bath unit.
- Wear heat-resistant gloves and PPE while handling heating media or working near hot surfaces.
- Shut down immediately in case of:
- Jacket rupture
- TCU pump failure
- Sensor malfunction
5.5 Shutdown and Cleaning
- After the process, allow the temperature to return to ambient conditions.
- Shut off the circulation pump and temperature control unit.
- Clean reactor jacket externally with lint-free cloth and inspect for residue buildup.
- Document shutdown and cleaning status in the equipment logbook.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- TCU: Temperature Control Unit
- BMR: Batch Manufacturing Record
- DCS: Distributed Control System
- RTD: Resistance Temperature Detector
7. Documents
- Temperature Probe Calibration Record (Annexure-1)
- Temperature Monitoring Log (Annexure-2)
- Equipment Cleaning and Shutdown Checklist (Annexure-3)
8. References
- ICH Q7 – GMP for Active Pharmaceutical Ingredients
- 21 CFR Part 211.63 – Equipment Design, Size, and Location
- WHO GMP Guidelines for Chemical APIs
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 Probe Calibration Record
| Probe ID | Calibrated On | Next Due | Status | Verified By |
|---|---|---|---|---|
| RTD-01 | 01/04/2025 | 01/10/2025 | Pass |
Annexure-2: Temperature Monitoring Log
| Time | Setpoint (°C) | Observed Temp (°C) | Inlet Temp (°C) | Return Temp (°C) | Operator |
|---|---|---|---|---|---|
| 09:00 | 65 | 64.8 | 66 | 64.5 |
Annexure-3: Equipment Cleaning and Shutdown Checklist
| Date | Reactor ID | Shutdown Performed By | Jacket Cleaned | Remarks |
|---|---|---|---|---|
| 13/04/2025 | R-103 | Yes | Ready for next batch |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Release | New Equipment Installation | QA Head |
| 13/04/2025 | 2.0 | Included Oil Circulation and Shutdown Guidelines | Operational Enhancement | QA Head |