Standard Operating Procedure for Inert Gas Purging (Nitrogen Blanketing) in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/032/2025 |
| Supersedes | SOP/API/032/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To define a standard and safe procedure for performing inert gas purging using nitrogen in API manufacturing processes to protect reactive or moisture/oxygen-sensitive compounds and ensure operator and product safety.
2. Scope
This SOP is applicable to all nitrogen purging operations during synthesis, transfer, storage, or packaging of intermediates and APIs within the API manufacturing facility.
3. Responsibilities
- Production Operator: Perform nitrogen purging as per defined instructions in the BMR.
- Engineering Department: Ensure availability and maintenance of nitrogen supply lines, valves, and regulators.
- QA Officer: Review and approve nitrogen purging procedures and verify completion of relevant documentation.
4. Accountability
The Production Manager is accountable for compliance with this SOP. The QA Manager is responsible for reviewing logs and ensuring alignment with GMP and safety guidelines.
5. Procedure
5.1 Prerequisites
- Ensure nitrogen cylinder/bulk supply is connected to the distribution manifold.
- Check:
- Pressure gauge (input and output)
- Flow meter calibration
- Integrity of hoses and valves
- Verify nitrogen purity ≥ 99.5% and ensure the cylinder label is valid.
- Ensure all equipment to be purged is clean, closed, and ready for operation.
5.2 Inert Gas Purging Procedure
- Open the main nitrogen cylinder valve slowly to pressurize the line.
- Adjust the pressure regulator to the required setting (typically 1.5–2.0 kg/cm² or as per BMR).
- Start purging through the designated gas inlet line at the bottom or side of the vessel.
- Allow venting from the top vent port to displace air or undesired gases (air sweep method).
- Continue purging for the specified time (e.g., 20–30 minutes) or until oxygen analyzer shows < 2% oxygen (if applicable).
- Once complete, close inlet and vent valves and maintain a positive nitrogen pressure inside the vessel.
- Record the duration, flow rate, pressure, and purge completion time in the “Nitrogen Purging Log” (Annexure-1).
5.3 Maintenance of Nitrogen Blanket
- Maintain nitrogen pressure inside sealed reactors or vessels by using back-pressure regulators or surge tanks.
- In the case of storage tanks, apply periodic nitrogen top-up based on pressure drops.
- Ensure “Nitrogen Blanketed” tags are fixed on relevant equipment.
5.4 Safety Precautions
- Always handle nitrogen in well-ventilated areas.
- Wear safety goggles, gloves, and masks during purging operations.
- Ensure no open flames or reactive materials are nearby.
- Confirm purging is complete before any sampling or further processing.
6. Abbreviations
- SOP: Standard Operating Procedure
- API: Active Pharmaceutical Ingredient
- BMR: Batch Manufacturing Record
- QA: Quality Assurance
- kg/cm²: Kilogram per square centimeter
7. Documents
- Nitrogen Purging Log (Annexure-1)
- Nitrogen Cylinder Usage Record (Annexure-2)
- Equipment Pressure Check Sheet (Annexure-3)
8. References
- ICH Q7 – Good Manufacturing Practice for Active Pharmaceutical Ingredients
- Compressed Gas Association (CGA) Guidelines
- 21 CFR Part 211 – GMP Regulations
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Nitrogen Purging Log
| Date | Batch No. | Equipment ID | Start Time | End Time | Pressure (kg/cm²) | Flow Rate (L/min) |
|---|---|---|---|---|---|---|
| 13/04/2025 | API-202504 | R-101 | 09:00 | 09:30 | 1.8 | 40 |
Annexure-2: Nitrogen Cylinder Usage Record
| Cylinder No. | Date | Start Pressure (kg/cm²) | End Pressure (kg/cm²) | Used For | Operator |
|---|---|---|---|---|---|
| NC-1145 | 13/04/2025 | 140 | 100 | Pilot Batch Purge |
Annexure-3: Equipment Pressure Check Sheet
| Date | Equipment ID | Pre-Purge Pressure | Post-Purge Pressure | Leak Observed | Remarks |
|---|---|---|---|---|---|
| 13/04/2025 | R-101 | 0.0 | 1.6 | No | OK |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial Version | New SOP Creation | QA Head |
| 13/04/2025 | 2.0 | Added Cylinder Record and Safety Controls | Regulatory Compliance | QA Head |