in classified areas (Grade A/B/C) within the manufacturing facility. It includes routine environmental monitoring (EM) using viable and non-viable methods.

3. Responsibilities

• Microbiology Personnel: Perform routine air sampling, documentation, and trend analysis.
• Production Operators: Ensure cooperation during monitoring and report abnormalities.
• Quality Assurance (QA): Review and approve EM records.
• Engineering: Maintain AHU systems and particle counters.

4. Accountability

The QA Head is accountable for ensuring compliance to this SOP and reviewing EM data for action and compliance decisions.

5. Procedure

5.1 Classification of Areas

1. Identify and categorize filling rooms into:
   • Grade A: Laminar Air Flow (LAF) zones where open vial/syringe filling occurs
   • Grade B: Background to Grade A
   • Grade C: Preparation and gowning areas

5.2 Monitoring Parameters

1. Parameters to monitor:
   • Viable Particles (microbial contamination)
   • Non-Viable Particles (0.5 μm and 5.0 μm)
   • Temperature and Relative Humidity (RH)
   • Differential Pressure

5.3 Monitoring Frequency

1. Grade A: Continuous for non-viable particles; viable particles every shift.
2. Grade B: Once per shift (viable), twice daily (non-viable).
3. Grade C: Daily (viable), once daily (non-viable).
4. Temperature, RH, and differential pressure: Monitored continuously or at least twice per shift.

5.4 Sampling Locations and Methods

1. Define locations as per Risk Assessment and Validation Report.
2. Use the following methods:
   • Air Sampler (active sampling) – 1000 L volume
   • Settle Plates – Expose for 4 hours
   • Contact Plates – For surface checks
   • Particle Counters – Installed/portable units

5.5 Alert and Action Limits

1. Refer to Annexure-1 for limits by grade and parameter.
2. Investigate any values that exceed alert/action levels using the EM Deviation Investigation Form (Annexure-2).

5.6 Data Review and Trending

1. Microbiology to review and record results daily.
2. Compile monthly trend reports (Annexure-3).
3. QA to review and initiate corrective actions if required.

5.7 Equipment Calibration and Maintenance

1. Ensure all EM instruments are calibrated per schedule.
2. Document calibration certificates and paste copies with Annexure-4.

6. Abbreviations

• SOP: Standard Operating Procedure
• EM: Environmental Monitoring
• LAF: Laminar Air Flow
• QA: Quality Assurance
• AHU: Air Handling Unit

7. Documents

1. Environmental Monitoring Limits Table – Annexure-1
2. EM Deviation Investigation Form – Annexure-2
3. Monthly Trend Report Format – Annexure-3
4. Calibration Certificate Log – Annexure-4

8. References

• EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
• WHO Technical Report Series 961
• ISO 14644-1 and 14698 standards

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: Environmental Monitoring Limits Table

Grade	Viable (cfu/m³)	Non-Viable 0.5μm (particles/m³)	Temperature (°C)	RH (%)
A	<1	3520	20–22	≤55
B	10	35200	20–22	≤55
C	100	352000	20–23	≤60

Annexure-2: EM Deviation Investigation Form

Date	Location	Parameter	Observed Value	Investigation Outcome	Corrective Action
21/06/2025	LAF-1	Viable	3 cfu/m³	Operator-related breach	Retraining conducted

Annexure-3: Monthly Trend Report Format

Month	Location	Average Viable	Average Non-Viable	Alert/Action Events
June 2025	Filling Room	0.4	2900	2

Annexure-4: Calibration Certificate Log

Instrument	ID No.	Calibration Date	Next Due	Performed By
Particle Counter	PC-005	01/06/2025	01/12/2025	Sunil Mehta

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
15/03/2022	1.0	Initial SOP Release	New Process	QA Head
24/06/2025	2.0	Updated sampling methods, added calibration log	Annual Review	QA Head