Elixir Department: SOP for Use of Controlled Atmosphere During Mixing – V 2.0

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Elixir Department: SOP for Use of Controlled Atmosphere During Mixing – V 2.0

Standard Operating Procedure for Use of Controlled Atmosphere During Mixing in Elixir Manufacturing

Department Elixir Department
SOP No. SOP/ELX/120/2025
Supersedes SOP/ELX/120/2022
Page No. Page 1 of 10
Issue Date 11/04/2025
Effective Date 15/04/2025
Review Date 11/04/2026

1. Purpose

To establish a standardized procedure for maintaining a controlled atmosphere (such as nitrogen blanketing or inert gas environment) during the mixing of sensitive elixir formulations to ensure product stability, prevent oxidation, and enhance safety.

2. Scope

This SOP is applicable to all mixing operations involving oxidation-sensitive, volatile, or alcohol-based elixir products where a controlled atmosphere is required to maintain product quality and reduce risks of degradation or flammability.

3. Responsibilities

  • Production Operator:
    • Ensure proper setup of inert gas supply and monitor parameters during mixing.
  • Production Supervisor:
    • Verify gas purity, equipment readiness, and record all operating parameters.
  • Engineering Department:
    • Maintain and calibrate gas control systems and safety interlocks.
  • QA Department:
    • Approve controlled environment settings before start and review batch documentation post-operation.
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4. Accountability

The Head of Production and the Engineering Head are jointly accountable for ensuring compliance with this SOP and

proper documentation of controlled atmosphere mixing operations.

5. Procedure

5.1 Preparation and System Checks

  1. Verify that the product to be manufactured requires a controlled atmosphere as per the Master Formula Record (MFR).
  2. Ensure that the mixing vessel is equipped with:
    • Gas inlet and outlet ports
    • Pressure relief valve
    • Oxygen sensor or gas concentration display
  3. Check that nitrogen or inert gas cylinder is properly connected and leak tested.
  4. Confirm gas purity is ≥99.5% (unless otherwise specified).

5.2 Establishing Controlled Atmosphere

  1. Purge the mixing vessel with nitrogen for a minimum of 10–15 minutes or until oxygen level drops below 5% (or as per protocol).
  2. Close the outlet valve to maintain pressure slightly above atmospheric (typically 1.05–1.1 atm).
  3. Initiate mixing only after confirming stable pressure and oxygen levels.

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5.3 Mixing Under Inert Conditions

  1. Start mixer at defined RPM and record values in the BMR.
  2. Continuously monitor gas pressure, flow rate, and oxygen level using installed gauges or data loggers.
  3. If oxygen level rises above acceptable limits, stop mixing and reinitiate purging.

5.4 Post-Mixing and Transfer

  1. Maintain positive pressure of nitrogen until bulk is transferred to the next stage (filtration/storage/filling).
  2. Flush transfer lines with nitrogen prior to use if applicable.
  3. Record total mixing time and gas usage in the Controlled Atmosphere Log (Annexure-1).

5.5 Equipment Cleaning

  1. Shut off gas supply and depressurize vessel before opening.
  2. Label the vessel as “TO BE CLEANED.”
  3. Follow standard cleaning procedures as per relevant SOP for cleaning of mixing vessels.

5.6 Deviation Handling

  1. If gas supply is interrupted, oxygen levels rise, or pressure drops unexpectedly:
    • Stop processing and initiate deviation report.
    • Quarantine batch for QA decision.
    • Document all observations and corrective actions taken.

6. Abbreviations

  • SOP: Standard Operating Procedure
  • QA: Quality Assurance
  • RPM: Revolutions Per Minute
  • MFR: Master Formula Record
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7. Documents

  1. Controlled Atmosphere Log (Annexure-1)
  2. Batch Manufacturing Record (BMR)
  3. Deviation Form (if applicable)

8. References

  • 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals
  • ICH Q8 – Pharmaceutical Development
  • WHO TRS 986 – GMP Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

Prepared By Checked By Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Controlled Atmosphere Log

Date Batch No. Equipment ID Gas Used Purge Duration Final O₂ Level Mixing Time Verified By (QA)
11/04/2025 ELX-1053 MIX-205 Nitrogen 15 min 3.2% 45 min Sunita Reddy

Revision History:

Revision Date Revision No. Revision Details Reason for Revision Approved By
01/01/2024 1.0 Initial SOP Release New SOP QA Head
11/04/2025 2.0 Expanded safety interlock and deviation handling steps GMP Update QA Head
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