1. Purpose

To establish a procedure for environmental monitoring of the manufacturing area to ensure controlled conditions and compliance with cGMP requirements.

2. Scope

This SOP applies to all classified manufacturing areas (Grade A, B, C, and D) where sterile or critical operations are carried out.

3. Responsibility

• Microbiology Analyst: Perform monitoring, record results, and report deviations.

• QC Supervisor/QA: Review monitoring data and ensure corrective actions.

• Production/Engineering: Support during monitoring and implement corrective measures.

4. Materials & Equipment

• Settle plates (SCDA, SDA, TSA as required)

• Contact plates (RODAC plates)

• Active air sampler

• Particle counter (0.5 µm & 5.0 µm)

• Swabs (sterile)

• Incubators (20–25°C & 30–35°C)

• Disinfectants (validated)

• Data recording sheets/EM logbook

5. Procedure

5.1 Sampling Plan

• Grade A/B: Daily during each production activity.

• Grade C/D: At defined frequency (e.g., weekly/monthly).

• Locations: Critical zones, background areas, gowning rooms, airlocks, and utilities.

• Parameters monitored: Viable particles, non-viable particles, surface contamination, personnel monitoring.

5.2 Methods of Monitoring

1. Settle Plates – Expose for 4 hours at critical and non-critical locations.

2. Active Air Sampling – Use calibrated air sampler, as per volume requirement.

3. Contact Plates (Surface Monitoring) – Press RODAC plates onto equipment, walls, and working surfaces.

4. Swab Test – For irregular surfaces.

5. Personnel Monitoring – Finger dab plates and gown monitoring post-operation.

6. Non-Viable Particulate Monitoring – Use calibrated particle counter for 0.5 µm and 5.0 µm.

5.3 Incubation & Reading

• Bacterial plates: 30–35°C for 48–72 hours.

• Fungal plates: 20–25°C for 5–7 days.

• Record colony forming units (CFU) and identify isolates if limits exceeded.

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

• Follow established alert and action limits for each grade (A, B, C, D).

• Example: Grade A should have 0 CFU for both air and surfaces.

5.5 Documentation & Reporting

• Record results in EM logbook or electronic system.

• Report excursions/deviations immediately.

• Trend data monthly/quarterly to assess environmental control.

6. Precautions

• Perform monitoring aseptically to avoid contamination.

• Use sterile, validated media.

• Ensure instruments are calibrated.

• Do not obstruct manufacturing activity during sampling.

7. References

• ISO 14644-1

• EU GMP Annex 1

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

• WHO TRS Guidelines