ducting, filters, sensors, diffusers, and equipment layout.

Operational Qualification (OQ): Testing of airflow, pressure differentials, temperature and humidity controls, and alarm systems.

Performance Qualification (PQ): Environmental monitoring, viable/non-viable particulate testing, recovery testing, and airflow visualization.

Step-by-Step HVAC Qualification Procedure

Step 1: Review User Requirements & Design Documents (DQ)

Start with URS defining cleanroom classification (ISO 5, ISO 7, etc.), air change rates (ACR), temperature and humidity control, and contamination control strategy. DQ must verify that the HVAC system design supports these requirements. Ensure:

• Filter type and location (e.g., terminal HEPA)
• Duct material (e.g., GI ducting with insulation)
• AHU capacity and zone-wise airflow diagrams
• Integration of BMS (Building Management System)

Step 2: Conduct Installation Qualification (IQ)

Verify that all HVAC components are installed per design specs and engineering drawings. Use checklists to confirm:

• Filter certificates (HEPA, pre-filters)
• Air handling unit (AHU) installation records
• Damper locations and settings
• Sensor calibration reports (temperature, RH, DP)
• Support brackets, insulation, and drain line connections

Step 3: Execute Operational Qualification (OQ)

This stage evaluates whether the HVAC system performs consistently within specified operational limits. Key tests include:

1. Airflow Velocity Test

• Measured using a calibrated anemometer
• Typical range: 0.45 ± 0.05 m/s for unidirectional airflow
• Performed across HEPA filter face or room inlets

2. Air Changes per Hour (ACH)

• ACH = (Total Air Volume per Hour) / Room Volume
• ISO 7 requires ≥ 30–60 ACH; ISO 5 ≥ 240 ACH (typical)

3. Differential Pressure Qualification

Measured between adjacent areas (e.g., Grade B to C)

• Target differential: 10–15 Pa
• Must remain positive to prevent ingress of contamination
• Tested using manometers or magnehelic gauges

4. Temperature and Relative Humidity Mapping

Monitor temperature (20–25°C) and RH (≤60%) across multiple locations in cleanrooms using data loggers. Confirm uniformity and stability over time.

5. Alarm and Sensor Calibration Check

Test low/high temperature and pressure alarms. Ensure all HVAC monitoring instruments are within calibration limits.

Step 4: Conduct Performance Qualification (PQ)

PQ demonstrates consistent performance under simulated or actual load. This includes microbiological and particulate tests.

1. HEPA Filter Integrity Testing (PAO/DOP Test)

• Aerosol challenge with polyalphaolefin (PAO)
• Scan filter face to detect any leakage
• Acceptance: ≤ 0.01% penetration

2. Airflow Visualization (Smoke Study)

• Visualize unidirectional flow in critical areas
• Demonstrates laminarity and absence of turbulence
• Recorded and reviewed for regulatory evidence

3. Particle Count Testing (Non-Viable)

Cleanroom Grade	≥0.5 µm/m³ Limit	≥5.0 µm/m³ Limit
Grade A	3,520	20
Grade B (At rest)	35,200	2,900
Grade C	352,000	29,000

4. Recovery Test

Evaluate the time taken to return to required particle levels after contamination. Typical acceptance: recovery within 15–20 minutes.

5. Microbial Monitoring (Viable Particulate)

• Active air sampling and settle plates in critical areas
• Grade A: ≤1 cfu/m³ (air), 1 cfu/4h (surface)
• Tested during PQ and periodically during requalification

Documentation for HVAC Qualification

Each stage of qualification should be supported by approved protocols and signed reports. Include:

• HVAC Qualification Plan (linked to VMP)
• DQ/IQ/OQ/PQ Protocols
• Test data sheets, sensor calibration certificates
• Alarm test logs, airflow velocity reports, PAO integrity test results
• Deviation reports and change controls
• Final summary report and QA approvals

Common Deviations in HVAC Qualification

• Unacceptable pressure differential between rooms
• Low airflow velocity at terminal HEPA locations
• HEPA filter leakage or poor sealing
• Delayed recovery time beyond specification
• Temperature excursions outside 20–25°C
• Non-laminar smoke flow in aseptic zones

Requalification and Monitoring

HVAC systems require periodic requalification based on risk assessment and change management. WHO recommends:

• Filter integrity tests: Every 6 months
• Airflow visualization: Annually or during layout changes
• Microbial & particle monitoring: Routine as per EM program

Conclusion

HVAC qualification is a foundational element of contamination control strategy in pharmaceutical cleanrooms. Following a structured approach covering airflow, HEPA filter integrity, pressure differentials, and temperature/RH mapping is essential. Documentation, protocol adherence, and proper deviation handling ensure the system is audit-ready and GMP compliant.

To download validated HVAC qualification templates, SOPs, and airflow testing protocols, visit PharmaSOP.in. For in-depth guidance on system validation strategy, visit PharmaValidation.in.

External Reference Links

• EMA Annex 1
• FDA Guidance on Process Validation
• ICH Q9 (Quality Risk Management)
• WHO TRS 961 Annex 5 – HVAC Qualification