Design Principles for Negative Pressure Cleanrooms

Negative pressure cleanrooms are engineered to contain hazardous particles, contaminants, or pathogens by ensuring that air always flows into the controlled space—never out. They are widely used in pharmaceutical production, BSL laboratories, infectious disease labs, cytotoxic drug compounding, and specialized manufacturing where contamination must be prevented from escaping.

Below are the core design principles that govern a safe and effective negative pressure cleanroom.

1. Airflow Balance: Exhaust > Supply

The fundamental rule of negative pressure environments:

Exhaust Air Volume (CFM) > Supply Air Volume (CFM)

• 1.The room exhausts more air than it receives.

• 2.This creates a pressure differential, typically –2.5 Pa to –15 Pa, depending on the application.

• 3.Air from adjacent cleaner spaces is drawn inward, acting as a “containment barrier.”

Outcome:
Contaminants inside the room cannot flow into other areas.

2. Multi-Level Pressure Cascades

A single negative pressure room is often part of a pressure cascade, such as:

• 1.Corridor (neutral or slightly positive)

• 2.Anteroom (slightly negative)

• 3.Cleanroom / processing room (most negative)

Purpose of the cascade

• 1.Provides layered protection.

• 2.Minimizes risk of sudden air reversal if a door opens.

• 3.Ensures controlled movement of personnel and materials.

3. HEPA / ULPA Filtration

Negative pressure cleanrooms must ensure that exhausted air is fully filtered before discharge.

Standard requirements

• 1.HEPA (H13/H14) or ULPA filtration on exhaust.

• 2.In some high-risk labs (BSL-3/BSL-4), filters are installed in series for redundancy.

Benefits

• 1.Prevents contaminated particles, viruses, or biological material from entering the environment.

• 2.Ensures compliance with FDA, WHO, EU GMP, USP <797>/<800>, and ISO standards.

4. Dedicated Exhaust System

Negative pressure rooms cannot share exhaust systems with non-controlled spaces.

Key design rules:

• 1.Independent ducting.

• 2.Stack exhaust high above the building.

• 3.Prevent recirculation into rooftop HVAC intakes.

• 4.Use corrosion-resistant duct materials when handling chemicals or biological aerosols.

5. Room Envelope Integrity

To maintain pressure stability, the room must be airtight.

Requirements:

• 1.Fully sealed ceilings, wall panels, corners, and cable penetrations.

• 2.Widely used materials: coated steel panels, insulated modular cleanroom panels.

• 3.Airtight doors with automatic closer systems.

• 1.Pressure-resistant viewing windows.

Why it matters:
Even a small air leak can collapse the pressure differential.

6. Real-Time Pressure Monitoring

Negative pressure cleanrooms must have live pressure monitoring with alarms.

Monitoring devices:

• 1.Differential pressure gauges

• 2.Magnehelic meters

• 3.Digital monitoring panels

• 4.BMS / HVAC automation with alarm logging

Alarm conditions:

• 1.Insufficient pressure (leak, fan issue, door left open)

• 2.Excessive pressure (may strain HVAC or cause turbulence)

7. Controlled User Workflow

Personnel and material flow must follow the direction of airflow.

Includes:

• 1.Airlocks and anterooms

• 2.Gowning rooms

• 3.Pass-through boxes (with UV or interlock)

• 4.Door interlock systems to prevent both doors from opening simultaneously

This prevents turbulence and pressure loss.

8. Compatibility With Modular Cleanroom Systems

Modern cleanroom designs, including Dersion modular systems, support:

• 1.Quick installation

• 2.High airtightness

• 3.Easy expansion or relocation

• 4.Integrated HEPA housings and duct connections

• 5.Seamless pressure control through built-in HVAC channels

Modular designs significantly improve pressure stability compared to traditional civil construction.

9. Energy-Efficient Negative Pressure Management

Because negative pressure rooms require continuous exhaust:

Solutions include:

• 1.VFD-controlled fans

• 2.Smart pressure control algorithms

• 3.High-efficiency HEPA housings

• 4.Heat recovery ventilators (HRV) to reduce energy loss

This ensures stable containment while reducing operational costs.

10. Compliance with Relevant Standards

Design must comply with the following depending on application:

Biological & Pharma:

• 1.WHO TRS 961

• 2.EU GMP Annex 1

• 3.FDA CFR Parts 210/211

• 4.USP <797> / <800>

• 5.ISO 14644 series

Hazardous materials:

• 1.NFPA standards

• 2.OSHA guidelines

• 3.BSL-2/3/4 requirements