1. Purpose

To describe the procedure for monitoring non-viable particulate matter in controlled manufacturing areas to ensure compliance with GMP, ISO 14644, and regulatory requirements.

2. Scope

This SOP is applicable to all classified areas (Grade A, B, C, and D) within the manufacturing facility where sterile or critical operations are performed.

3. Responsibility

• Microbiologist/Analyst: Perform monitoring, record and report results.

• QC/QA: Review data, evaluate excursions, and ensure compliance.

• Engineering: Support with HVAC system checks and corrective actions.

4. Materials & Equipment

• Calibrated Airborne Particle Counter (capable of detecting ≥0.5 µm and ≥5.0 µm particles).

• Sampling probe, tubing, and tripod (as required).

• Data recording sheets or electronic data capture system.

• Cleanroom garments and PPE.

5. Procedure

5.1 Preparation

1. Verify calibration status of particle counter.

2. Ensure cleanliness and sanitization of equipment before entry.

3. Transport equipment into classified areas through proper airlocks.

5.2 Sampling Locations & Frequency

• Grade A/B: During each critical operation (continuous or at defined intervals).

• Grade C/D: At defined frequencies (e.g., weekly/monthly or per qualification plan).

• Locations: Critical zones (filling, compounding, aseptic connections), background areas, gowning rooms, and airlocks.

• Number of locations: As per ISO 14644-1 Annex B or facility risk assessment.

5.3 Sampling Procedure

1. Place sampling probe at working height (~0.8–1.2 m above the floor, near operational area).

2. Set sample volume as per ISO 14644 (minimum 1 m³ per location, or as validated).

3. Record particle counts for ≥0.5 µm and ≥5.0 µm channels.

4. Avoid obstruction of airflow during monitoring.

5. After completion, remove particle counter following gowning/exit procedure.

5.4 Acceptance Criteria (as per ISO 14644-1 / EU GMP Annex 1)

Note: In Grade A, during operations, the limit for ≥5.0 µm is considered zero (action level) as per EU GMP Annex 1 (2022).

5.5 Post-Monitoring

1. Save/record results electronically or in logbook.

2. Compare results against defined alert/action limits.

3. Report any excursion immediately to QA and initiate investigation.

4. Clean and store the particle counter in designated storage area.

6. Precautions

• Ensure equipment is calibrated and handled aseptically.

• Do not block unidirectional airflow during sampling.

• Avoid movement or personnel interference during measurement.

• Use validated sampling volumes and positions.

7. Documentation

• Record location, date, time, equipment ID, sample volume, and results.

• Maintain trending data for periodic review (monthly/quarterly).

• Attach particle counter printouts (if available) to EM records.

8. References

• ISO 14644-1: Cleanrooms and Associated Controlled Environments

• EU GMP Annex 1: Manufacture of Sterile Medicinal Products (2022)

• USP <1116>: Microbiological Control and Monitoring of Aseptic Processing Environments

• WHO TRS