Design-Based Differential Pressure in Cleanroom Spaces Ⅰ

1. Background of Differential Pressure Issues

In pharmaceutical facility design, room differential pressure is critical for maintaining air quality and preventing cross-contamination.

2. Regulatory Guidelines

U.S. FDA Requirements:

Operational zones must be rationally divided to ensure airflow from high to low cleanliness areas.

Adjacent rooms must maintain a positive pressure of 10–15 Pascals (Pa) when doors are closed; outward airflow must be ensured when doors are open to prevent contamination, with strict control over door opening time.

Aseptic processing rooms adjacent to non-classified areas must maintain at least 12.5 Pa positive pressure at all times.

Cleanroom differential pressure must be continuously monitored, recorded frequently, and alarms documented with deviations investigated.

Annex 1 of EudraLex:

Cleanrooms must be supplied with filtered air, maintaining positive pressure or directional airflow (e.g., flushing zones).

Adjacent rooms of different grades must have at least 10 Pa pressure difference, with critical zones requiring special protection.

Positive or negative pressure airlocks may be used for pathogenic or highly toxic materials.

Pressure indicators must be installed between cleanrooms and background environments. Critical pressures require continuous monitoring and recording with immediate alarm systems, while non-critical pressures may be monitored periodically.

3. HVAC System Design Options

HVAC system balance is key to maintaining cleanroom differential pressure. Supply airflow must offset heat/humidity changes, dilute particles, and provide pressurization. Six basic designs include:

• Fixed Balance System: Air balancers manually set supply and return/exhaust airflow per design drawings, stable but inflexible to unexpected changes; mechanical variable air volume control boxes can be added.
• Fixed Offset System: Electronic setting of supply and return/exhaust airflow, with controllers maintaining set values; stable and adaptable to operational changes, requiring regular calibration.
• Tracking System: Electronic setting of supply airflow, with controllers adjusting return/exhaust to maintain offset; stable and adaptable, requiring calibration.
• Direct Pressure Control System: Electronic setting of supply airflow, directly controlling return/exhaust to achieve target pressurization; adaptable to system and adjacent space changes, but inactive during door openings.
• Nested Loop System: Electronic setting of supply airflow, with controllers adjusting return/exhaust and continuously regulating offset for target pressurization; stable and adaptable, with adjustments inactive during door openings.
• Hybrid System: Combines the above (e.g., 95% fixed recirculation with variable exhaust fans for pressure control in classified corridors), balancing simplicity and cost-effectiveness.