Cleanroom Design & ISO Classification for HVAC Engineers

Cleanroom Design & ISO Classification for HVAC Engineers

Cleanroom HVAC systems maintain controlled environments with specified particle concentrations, temperature, humidity, and pressure. This guide covers ISO 14644 classifications, airflow patterns, filtration requirements, and design methodology for pharmaceutical, semiconductor, biotechnology, and medical device manufacturing facilities.

ISO 14644 Cleanroom Classification

Particle Concentration Limits

ISO 14644-1 Classification Table:

Units: Particles per cubic meter

Maximum particle concentration:

$$C_N = 10^N \times \left(0.1/D\right)^{2.08}$$

Where:

• $C_N$ = maximum permitted concentration (particles/m³)
• $N$ = ISO classification number (1-9)
• $D$ = particle size (μm), 0.1 to 5.0 μm

Example for ISO 5 at 0.5 μm: $$C_5 = 10^5 \times (0.1/0.5)^{2.08} = 100,000 \times 0.0352 = 3,520 \text{ particles/m}^3$$

Operational States

As-Built: Facility complete, all services connected, no equipment or personnel At-Rest: Equipment installed and operating, no personnel Operational: Normal production with personnel and processes active

Most stringent specification applies to operational state.

Airflow Patterns

Unidirectional (Laminar) Flow

Characteristics:

• Parallel air streams at uniform velocity (0.3-0.5 m/s = 60-100 fpm)
• Vertical downflow or horizontal crossflow
• Minimum turbulence, sweeps particles directly to return/exhaust
• Required for ISO 3-5 cleanrooms (highest cleanliness)

Design:

graph TD
    A[100% HEPA Ceiling Coverage<br/>0.45 m/s downflow] --> B[Work Zone<br/>Uniform Laminar Flow]
    B --> C[Raised Perforated Floor<br/>Return Plenum]
    C --> D[Return Air Fan]
    D --> E[Pre-filter MERV 8]
    E --> F[Final Filter MERV 14]
    F --> G[Fan Filter Unit FFU<br/>or Central AHU]
    G --> A
    
    H[Makeup Air<br/>10-20%] --> E

HEPA coverage:

• ISO 3-4: 80-100% ceiling coverage
• ISO 5: 60-80% ceiling coverage
• Remainder: non-perforated return grilles

Velocity uniformity: ±20% across work zone

Non-Unidirectional (Turbulent Mixed) Flow

Characteristics:

• HEPA diffusers supply air at high velocity (induces mixing)
• Air changes per hour (ACH) dilute particles
• Lower cost than unidirectional flow
• Suitable for ISO 6-8 cleanrooms

Design:

• HEPA filters in ceiling (15-25% coverage)
• Low sidewall or floor-level returns
• High air change rates (60-600 ACH depending on class)

Air change rates:

Filtration Requirements

Filter Cascade

Three-stage filtration (typical):

1. Pre-filter (MERV 8-10): Protect downstream filters, extend life
2. Intermediate filter (MERV 14-15): Remove majority of particles, protect HEPA
3. Final filter (HEPA H13 or ULPA U15): Terminal filtration at diffusers

HEPA filter performance (EN 1822):

MPPS = Most Penetrating Particle Size (minimum efficiency point)

Fan Filter Units (FFUs)

Components:

• HEPA or ULPA filter (2’ × 4’ or 2’ × 2’ typical)
• Integral fan (EC motor, variable speed)
• Mounting frame for grid ceiling

Advantages:

• Modular, easy to replace
• Individual flow control
• Reduced ductwork
• Lower static pressure (distributed fans)

Disadvantages:

• Higher maintenance (many motors)
• Noise (fans in occupied space)
• Heat gain from motors

Application: Common for ISO 4-6 cleanrooms in semiconductor, pharmaceutical

Pressure Cascade Design

Pressure Differential Strategy

Principles:

• Prevent contamination migration from lower to higher cleanliness areas
• Maintain positive pressure in clean areas relative to surrounding spaces
• Pressure cascade: highest pressure in cleanest room

Typical pressure differentials:

• Between cleanroom and corridor: +0.02" to +0.05" w.g. (+5 to +12.5 Pa)
• Between ISO classification levels: +0.02" to +0.03" w.g.
• Cleanroom to outdoor: +0.10" to +0.20" w.g.

Pressure cascade example:

graph LR
    A[ISO 5 Sterile Core<br/>+0.08\\" w.g.] -->|+0.02\\"| B[ISO 6 Buffer Zone<br/>+0.06\\" w.g.]
    B -->|+0.03\\"| C[ISO 7 Gowning<br/>+0.03\\" w.g.]
    C -->|+0.03\\"| D[Corridor<br/>0.00\\" w.g.]
    D -->|+0.05\\"| E[Outside<br/>-0.05\\" w.g.]

Airflow Balance Method

Supply - Return - Exhaust = Positive Pressure:

$$CFM_{supply} = CFM_{return} + CFM_{exhaust} + CFM_{leakage}$$

Where $CFM_{leakage}$ creates positive pressure

Leakage estimation:

$$CFM_{leakage} = C \cdot A \cdot \sqrt{\Delta P}$$

Where:

• $C$ = flow coefficient (depends on leakage path)
• $A$ = leakage area (ft²)
• $\Delta P$ = pressure differential (in w.g.)

Typical design: 5-10% excess supply over return/exhaust

Temperature and Humidity Control

Typical requirements:

Humidity control importance:

• Low humidity (< 30% RH): Electrostatic discharge (ESD) risk, product drying
• High humidity (> 60% RH): Condensation, microbial growth, corrosion

Control strategy:

• Cooling coil + reheat for dehumidification
• Steam humidifier (cleanest, no particles)
• ±2°F temperature stability
• ±5% RH humidity stability

Cleanroom HVAC System Design

Recirculation Air Handling Unit (RAHU)

Components:

graph LR
    A[Return Air<br/>from Cleanroom] --> B[Pre-filter<br/>MERV 8]
    B --> C[Cooling Coil<br/>Dehumidification]
    C --> D[Reheat Coil<br/>Temperature Control]
    D --> E[Supply Fan<br/>VFD]
    E --> F[Final Filter<br/>MERV 14]
    F --> G[Ductwork to<br/>HEPA Diffusers/FFUs]
    
    H[Makeup Air 10-20%] --> B
    I[Exhaust 5-10%] -.->|from cleanroom| A

Makeup air (outdoor air):

• 10-20% of supply to maintain positive pressure
• Compensate for exhaust (fume hoods, process equipment)
• Pre-conditioned by dedicated makeup air unit (MAU)

Exhaust:

• Local exhaust for hazardous processes (fume hoods, biosafety cabinets)
• General room exhaust (5-10% of supply)
• HEPA filtration on exhaust if biohazard or toxic materials

Control Sequences

Pressure control:

1. Measure room pressure relative to reference (corridor)
2. Modulate supply or exhaust airflow to maintain setpoint
3. Typical: modulate exhaust damper, supply constant

Temperature control:

1. Measure room temperature
2. Modulate cooling/reheat valves
3. Supply fan maintains constant airflow (pressure independent)

Humidity control:

1. Measure room humidity
2. Cooling coil for dehumidification (condensate removal)
3. Steam humidifier for humidification

Design Methodology

Step-by-step cleanroom HVAC design:

1. Define cleanliness class (ISO 5-8 typical)
2. Select airflow pattern (unidirectional or turbulent)
3. Calculate air changes (table lookup or particle generation model)
4. Size supply airflow (ACH × volume / 60)
5. Calculate cooling load (envelope, lights, equipment, people, ventilation)
6. Verify supply airflow (max of ACH or cooling requirement)
7. Design pressure cascade (supply = return + exhaust + leakage)
8. Select filtration (three-stage: pre, intermediate, HEPA/ULPA)
9. Layout diffusers/returns (ensure uniform airflow)
10. Size ductwork and AHU (low velocity to reduce noise)
11. Design controls (pressure, temperature, humidity)
12. Specify testing and commissioning (particle count, airflow, pressure)

Commissioning and Testing

ISO 14644-3 Test Methods:

1. Particle count test: Confirm classification with optical particle counter
2. Airflow velocity/volume: Verify ACH or unidirectional velocity
3. Pressure differential: Confirm cascade between rooms
4. HEPA filter leak test: DOP or PAO challenge (99.99% minimum)
5. Air pattern visualization: Smoke test to confirm airflow direction
6. Recovery test: Time to return to specified cleanliness after contamination
7. Temperature and humidity: Verify control ranges

Acceptance criteria:

• Particle counts ≤ ISO class limits (at 95% confidence)
• Airflow uniformity ±20% of average
• Pressure differentials ±0.01" w.g. of setpoint
• HEPA integrity: zero leaks > 0.01% of upstream concentration

Related Technical Guides:

• Air Filtration Design
• Building Pressurization Control
• Ventilation Rate Calculations
• HVAC Control Strategies
• Healthcare HVAC Design

References:

• ISO 14644-1: Classification of Air Cleanliness by Particle Concentration
• ISO 14644-3: Test Methods
• ASHRAE Applications Handbook, Chapter 18: Clean Spaces
• IEST-RP-CC006: Testing Cleanrooms
• FDA Guidance: Sterile Drug Products Produced by Aseptic Processing