Maintaining proper pressure differentials is essential for meeting ISO 14644, USP 797/800, cGMP, and other regulatory requirements. Pressure control ensures that air flows in the correct direction—either to prevent external contaminants from entering the cleanroom or to keep hazardous substances from escaping. Depending on the application, a cleanroom may require positive pressure, negative pressure, or a multi-room pressure cascade.

Importance of Cleanroom Pressure Differential

Proper pressure differential control is vital for cleanroom stability, air cleanliness, and regulatory compliance. Correct pressure levels prevent external contaminants—such as dust, microbes, and chemical particles—from entering, while avoiding airflow reversal that could cause cross-contamination or product quality issues.

Since pressure determines airflow direction, it plays a key role in preventing particles and microorganisms from spreading between rooms, which is essential in pharmaceuticals, biotech, medical device manufacturing, and semiconductor production.

Pressure control is also a core requirement of ISO 14644, GMP, and USP 797/800. Even small deviations can affect cleanliness levels, increase contamination risks, or lead to compliance failures. Therefore, precise pressure control and continuous monitoring are indispensable for maintaining cleanroom performance and safety.

Positive Pressure Cleanrooms

Positive pressure is used when the goal is to keep contaminants out.
Common industries include:

• Pharmaceuticals
• Semiconductors
• Electronics manufacturing
• Aerospace
• Medical device production

When doors open, clean air flows outward, blocking contaminants from entering.

Typical pressure differential:
+0.03 to +0.05 in. w.g. (≈ +7.5 to +12.5 Pa)

Multiple rooms often use a pressure cascade, where cleaner areas maintain higher pressure.

Negative Pressure Cleanrooms

Negative pressure is used when hazardous materials must be contained to prevent their escape.

Common applications include:

• Cytotoxic drug handling areas (USP 800)
• Infectious pathogen laboratories (biosafety labs)
• Hazardous chemical processing areas

Air always flows into the room, preventing contaminants from escaping.

Typical differential:
–0.01 to –0.03 in. w.g. (≈ –2.5 to –7.5 Pa)

This ensures safe operation and regulatory compliance.

Cleanroom Pressure Differential Requirements

ISO 14644 & GMP Standards

Between clean zones of different classifications: ≥ 5 Pa

Between cleanroom and non-cleanroom areas: ≥ 10 Pa

USP 797 / USP 800 Requirements

USP 797 sterile compounding rooms: Positive pressure

USP 800 hazardous drug rooms: Negative pressure (minimum –2.5 Pa)

These standards ensure safe airflow direction and minimize cross-contamination risks.

Air Volume Calculation for Pressure Differential

To maintain stable pressure, leakage compensation airflow must be accurately calculated.

Leakage Airflow Formulas

LC = µP × AP × ΔP × ρ or LC = α × q × l

Note：

LC = required leakage compensation airflow

AP = effective gap area

ΔP = required pressure differential

q = leakage rate per meter of gap

α = safety factor

Proper airflow balancing ensures the room maintains its pressure setpoint.

Common Methods for Pressure Differential Control

Constant Air Volume (CAV) Control

Suitable for stable environments. Features:

• Fixed supply air volume
• Fresh-air ratio adjustments
• Return-air damper tuning
• Corridor pressure used as the reference baseline

Variable Air Volume (VAV) Control

Best for dynamic cleanrooms with changing load and personnel levels.

Features:

• Real-time airflow regulation
• PID-controlled dampers
• Automatic supply/exhaust adjustment
• Pressure sensor feedback (OP control mode)

VAV provides higher precision and more stable pressure control.

System Commissioning and Maintenance

• Perform air-balancing during commissioning
• Regularly inspect filters, dampers, sensors, and fans
• Verify pressure readings (e.g., Magnehelic gauge)
• Rebalance airflow after layout or equipment changes

Consistent maintenance is crucial to long-term pressure stability and regulatory compliance.

Conclusion

Proper pressure differential control is essential for cleanroom contamination prevention, regulatory compliance, and personnel safety. By selecting the appropriate pressure type, accurately calculating leakage compensation airflow, and implementing CAV or VAV systems, facilities can maintain stable and controlled airflow, protect products and operators, and consistently meet industry standards such as ISO, GMP, and USP.

FAQs：

Q: What is a pressure differential system?

A: A pressure differential system is a permanently installed setup that maintains controlled air pressure differences between areas to prevent smoke, dust, or contaminants from entering. It is commonly used in cleanrooms, laboratories, and high-rise building escape routes.

Q: What is the ideal pressure differential?

A: The ideal pressure differential depends on the application but is generally designed to maintain 10–15 Pa between adjacent rooms. This ensures proper airflow direction, prevents contamination, and maintains safety when doors are open or closed.

Q: How to reduce differential pressure?

A: Differential pressure can be reduced by adjusting valves or dampers to increase pressure drop across the system. Gradual regulation ensures the desired pressure setpoint is reached without affecting airflow stability.

Q: What is the acceptable differential pressure?

A: There is no universal value for acceptable differential pressure. It is calculated based on system design, operational requirements, and environmental conditions, and should be verified during commissioning and maintenance.

Q: What is the process of differential pressure?

A: Differential pressure is measured using devices like elastomer diaphragms that respond to pressure changes. The diaphragm’s movement is converted into readable signals, allowing continuous monitoring and control of airflow direction.