of sensitive products.

2. Scope

This SOP applies to all sterile injectable formulations where inert gas purging is required during compounding, filtration, filling, or headspace flushing stages.

3. Responsibilities

• Manufacturing Personnel: Perform gas purging activities as per protocol and record all parameters.
• Engineering: Ensure inert gas supply systems are functioning and calibrated.
• Quality Assurance (QA): Verify compliance with purging requirements and approve documentation.
• Quality Control (QC): Monitor oxygen levels and perform gas purity tests if applicable.

4. Accountability

The Head of Manufacturing is accountable for ensuring that inert gas purging is performed under validated and approved procedures. QA is responsible for verification and compliance monitoring.

5. Procedure

5.1 Pre-Operation Checks

1. Review the Batch Manufacturing Record (BMR) and identify stages requiring inert gas purging.
2. Ensure availability of:
   • High purity nitrogen (99.999%) or argon gas cylinders
   • Gas regulators and flow meters
   • Valid calibration certificates for pressure gauges
   • Sterile filters (0.2 μm) for gas inlet line
3. Inspect gas lines and regulators for leakage using leak detector solution or soap solution.

5.2 Inert Gas Purging during Compounding

1. Connect gas inlet to the mixing vessel using sterile, validated connections under LAF.
2. Set the gas flow rate to 10–25 LPM depending on vessel volume and type of product.
3. Allow purging for a predetermined duration (e.g., 15–30 mins) to displace headspace air.
4. Monitor and record oxygen levels using inline oxygen analyzer if required (target <2% O₂).

5.3 Inert Gas Purging during Filtration

1. Apply inert gas pressure (max 1.5 bar) to drive product through filtration assembly.
2. Ensure filter integrity and backpressure limits are not exceeded.
3. Record pressure and time in the Inert Gas Filtration Log (Annexure-1).

5.4 Inert Gas Flushing during Filling

1. Use inert gas flush in vials, ampoules, or syringes to reduce residual oxygen.
2. Ensure consistency of headspace gas with each container using validated flushing nozzles.
3. Control exposure to maintain container closure integrity post-purging.

5.5 Post-Purging Activities

1. Close all valves and safely disconnect gas lines after purging completion.
2. Verify final product parameters including oxygen concentration and pressure balance.
3. Document all purging steps and operator details in the BMR and QA logbook.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• QC: Quality Control
• BMR: Batch Manufacturing Record
• LPM: Liters Per Minute

7. Documents

1. Inert Gas Filtration Log – Annexure-1
2. Batch Manufacturing Record (BMR)
3. Gas Purging Checklist – Annexure-2

8. References

• EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
• ICH Q8 – Pharmaceutical Development
• USP <823> – Oxygen Content Analysis

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Manufacturing Executive	QA Executive	Head QA
Department	Production	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Inert Gas Filtration Log

Date	Batch No.	Start Time	End Time	Gas Used	Flow Rate (LPM)	Pressure (bar)	Operator
23/06/2025	BN-2024	10:00 AM	10:40 AM	Nitrogen	15	1.2	Rajesh Kumar

Annexure-2: Gas Purging Checklist

Checklist Item	Status (Yes/No)	Remarks
Gas Cylinder Checked & Leak Tested	Yes	OK
Sterile Filter Connected	Yes	OK
Flow Rate & Pressure Recorded	Yes	As per SOP
Purging Duration Met	Yes	15 minutes
Oxygen Level Post-Purge	Yes	<2%

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
10/07/2022	1.0	Initial Release	New SOP	QA Head
24/06/2025	2.0	Expanded scope for filtration and headspace flushing	Annual Review	QA Head