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.
5. Procedure
5.1 Temperature and Humidity Monitoring
- Digital sensors shall continuously record temperature and humidity via a Building Management System (BMS).
- Daily manual cross-verification shall be done using calibrated hygrometers and thermometers.
- Record values in Annexure-1: Temperature and Humidity Log.
- 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
- Magnehelic gauges or electronic sensors shall monitor pressure differentials between classified areas.
- Daily verification shall ensure pressure gradient is maintained:
- Grade B to C: +10 to +15 Pascal
- Grade C to D: +10 to +15 Pascal
- Record values in Annexure-2: Differential Pressure Log.
5.3 Particulate Monitoring (Non-Viable)
- Conduct particle count using calibrated particle counters per ISO 14644 standards.
- Frequency:
- Grade A: Daily (during operation)
- Grade B: Weekly
- Grade C/D: Monthly
- Record results in Annexure-3: Particulate Monitoring Report.
5.4 Microbiological Monitoring (Viable)
- Use settle plates, swabs, contact plates, and air samplers as per EM schedule.
- Exposure time and site numbers to follow validated protocol.
- Document all results in Annexure-4: Microbiological Monitoring Record.
5.5 Alarm and Deviation Handling
- Any out-of-specification reading must trigger a visual/auditory alarm.
- Initiate deviation as per SOP/QA/045/2025 and investigate root cause.
- Document CAPA and ensure restoration within limits.
5.6 Trend Analysis
- QA shall review environmental monitoring data monthly.
- Analyze for recurring excursions, seasonal trends, and system failures.
- 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
- Temperature and Humidity Log – Annexure-1
- Differential Pressure Log – Annexure-2
- Particulate Monitoring Report – Annexure-3
- Microbiological Monitoring Record – Annexure-4
- 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
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 |