Sterile Injectable Manufacturing: SOP for Monitoring Manufacturing Environmental Conditions – V 2.0

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Sterile Injectable Manufacturing: SOP for Monitoring Manufacturing Environmental Conditions – V 2.0

Standard Operating Procedure for Monitoring Manufacturing Environmental Conditions


Department Sterile Injectable Manufacturing
SOP No. SOP/SIM/030/2025
Supersedes SOP/SIM/030/2022
Page No. Page 1 of 15
Issue Date 18/06/2025
Effective Date 20/06/2025
Review Date 18/06/2026

1. Purpose

To define the procedure for monitoring environmental conditions such as temperature, relative humidity, pressure differentials, particulate counts, and microbial contamination in manufacturing areas to ensure product quality and regulatory compliance.

2. Scope

This SOP applies to all controlled

environments within the sterile manufacturing facility, including aseptic filling, preparation areas, airlocks, change rooms, and support areas.

3. Responsibilities

  • Microbiology/QA Personnel: Responsible for environmental monitoring (viable and non-viable).
  • Engineering: Ensures HVAC system performance and calibration of sensors.
  • Production: Maintains cleanliness and notifies any deviation in environmental parameters.

4. Accountability

The Head – Quality Assurance is accountable for ensuring proper monitoring, data review, and compliance with environmental requirements.

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5. Procedure

5.1 Temperature and Humidity Monitoring

  1. Digital sensors shall continuously record temperature and humidity via a Building Management System (BMS).
  2. Daily manual cross-verification shall be done using calibrated hygrometers and thermometers.
  3. Record values in Annexure-1: Temperature and Humidity Log.
  4. Acceptable range: 18°C to 25°C and RH 40%–60% for manufacturing areas unless otherwise specified in product requirements.

5.2 Differential Pressure Monitoring

  1. Magnehelic gauges or electronic sensors shall monitor pressure differentials between classified areas.
  2. Daily verification shall ensure pressure gradient is maintained:
    • Grade B to C: +10 to +15 Pascal
    • Grade C to D: +10 to +15 Pascal
  3. Record values in Annexure-2: Differential Pressure Log.

5.3 Particulate Monitoring (Non-Viable)

  1. Conduct particle count using calibrated particle counters per ISO 14644 standards.
  2. Frequency:
    • Grade A: Daily (during operation)
    • Grade B: Weekly
    • Grade C/D: Monthly
  3. Record results in Annexure-3: Particulate Monitoring Report.

5.4 Microbiological Monitoring (Viable)

  1. Use settle plates, swabs, contact plates, and air samplers as per EM schedule.
  2. Exposure time and site numbers to follow validated protocol.
  3. Document all results in Annexure-4: Microbiological Monitoring Record.
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5.5 Alarm and Deviation Handling

  1. Any out-of-specification reading must trigger a visual/auditory alarm.
  2. Initiate deviation as per SOP/QA/045/2025 and investigate root cause.
  3. Document CAPA and ensure restoration within limits.

5.6 Trend Analysis

  1. QA shall review environmental monitoring data monthly.
  2. Analyze for recurring excursions, seasonal trends, and system failures.
  3. Document analysis in Annexure-5: Monthly Trend Report.

6. Abbreviations

  • SOP: Standard Operating Procedure
  • BMS: Building Management System
  • RH: Relative Humidity
  • QA: Quality Assurance
  • HVAC: Heating, Ventilation and Air Conditioning

7. Documents

  1. Temperature and Humidity Log – Annexure-1
  2. Differential Pressure Log – Annexure-2
  3. Particulate Monitoring Report – Annexure-3
  4. Microbiological Monitoring Record – Annexure-4
  5. Monthly Trend Report – Annexure-5

8. References

  • EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
  • WHO TRS 961 – Environmental Monitoring Guidelines
  • ISO 14644-1: Cleanrooms and Associated Controlled Environments

9. SOP Version

Version: 2.0

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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: Temperature and Humidity Log

Date Area Temp (°C) RH (%) Checked By
18/06/2025 Filling Room 21.5 48 Ravi Shankar

Annexure-2: Differential Pressure Log

Date From Area To Area Pressure (Pa) Checked By
18/06/2025 Grade B Grade C 14 Deepika Nair

Annexure-3: Particulate Monitoring Report

Date Area ≥0.5 µm Count ≥5.0 µm Count Status
18/06/2025 LAF Bench 200 0 Pass

Annexure-4: Microbiological Monitoring Record

Date Sample Type Area CFU Count Remarks
18/06/2025 Settle Plate Filling Area 0 Compliant

Annexure-5: Monthly Trend Report

Month Parameter No. of Excursions Action Taken Reviewed By
May 2025 RH 2 Adjusted dehumidifier settings QA Manager

Revision History

Revision Date Revision No. Details Reason Approved By
01/01/2022 1.0 Initial SOP Release New SOP QA Head
18/06/2025 2.0 Added trend analysis and BMS integration reference Annual Review QA Head
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