The ISO 14644 Series Explained

ISO Cleanroom Certification at a Glance

ISO cleanroom certification is the benchmark that proves your environment is built and controlled to global expectations. For biotech, pharma, device, and aerospace teams, the standard framework is the ISO 14644 series.

At its core:

• ISO 14644-1 defines air cleanliness classes.
• ISO 14644-2 requires a monitoring plan that shows ongoing control.
• ISO 14644-3 lays out the test methods certifiers use to measure and confirm performance.

From there, the series expands—covering design (Part 4), operations (Part 5), and specialized risks like surface contamination, nanoscale particles, chemical residues, energy efficiency, equipment suitability, and consumables. Together, these parts create the common language that regulators, auditors, and quality leaders expect to see in reports.

This guide distills the essentials for QA managers, facility directors, and process engineers—anyone who needs clear standards mapped to real-world cleanroom work.

​​Note: This guide focuses on the ISO 14644 parts most relevant to certification programs. Supporting documents like Part 6 (terminology), Part 7 (separative devices), Part 8 (airborne molecular contamination), and Part 11 (surface cleanability) are not covered in depth here, as they apply to narrower use cases or early design considerations.)

ISO 14644-1 — Classification of Air Cleanliness (ISO Classes 1–9)

What the ISO classes mean

ISO 14644-1 sets particle concentration limits for each class (ISO 1 through ISO 9) and defines how to apply those limits at designated sampling locations. The standard focuses on particle sizes between 0.1 μm and 5 μm using light-scattering airborne particle counters. In practice, many pharma and device rooms target ISO 5 at the critical work zone and ISO 7 or 8 for surrounding areas.

Sampling locations and occupancy states

The number and placement of locations follow a defined calculation, so your sampling grid represents the room, not just convenient corners. Classification can be checked as-built, at-rest, or operational—terms that tie back to the methods in Part 3—so your plan stays consistent end-to-end.

ISO 14644-2 — Monitoring to Show Continued Control

Certification is a point-in-time check. ISO 14644-2 requires a risk-based monitoring plan that shows your cleanroom stays within control between certifications. The plan defines:

• What you measure (e.g., airborne particles, differential pressure, temperature, humidity)
• How you respond to drift or excursions
• Expectations for trending, alerts, and review so you can demonstrate control during inspections and investigations

A solid monitoring plan ties directly to the cleanroom’s ISO class and process risks. Many facilities route critical parameters into a facility monitoring system (FMS), which consolidates particle counts, pressure, temperature, and humidity into a single dashboard with alarms and audit trails. This approach makes trends visible and provides context during reviews. Choices around energy efficiency (Part 16) and consumables (Part 18) further shape long-term stability and cost of control.

ISO 14644-3 — Test Methods

ISO 14644-3 establishes the test methods that form the backbone of a certification report. These methods provide a standardized approach for measuring performance and verifying compliance across different states of occupancy. Common elements include:

• Airborne particle counting against your ISO class
• Airflow volume/velocity and air changes per hour to check dilution and directionality
• Pressure differentials across boundaries to protect high-grade rooms
• HEPA filter integrity (scan) tests to catch leaks at filters and seals
• Recovery testing to gauge how quickly the room returns to target levels
• Airflow visualization (“smoke studies”) around critical work to expose recirculation or backflow
• Supporting conditions like temperature and humidity for context

Part 3 also defines occupancy states—as-built, at-rest, operational—so methods and acceptance criteria line up with how you’re using the space. Map test points on the room drawing, list instruments with calibration dates, and spell out acceptance limits for each method for a clean, defensible report.

ISO 14644-4 and 14644-5 — Design and Operations Across the Lifecycle

ISO 14644-4 links airflow schemes, pressure cascades, zoning, and commissioning steps directly to the ISO class a space is expected to achieve. Referencing ISO 14644-4 early in a project reduces the risk of misalignment between design intent and measured performance and helps avoid costly rework when certification results don’t match the target class.

ISO 14644-5 formalizes an operations control programme (OCP) that defines personnel practices, material flow, cleaning, maintenance, training, and monitoring. By grounding daily routines in ISO 14644-5, organizations create the operational discipline needed to keep cleanrooms performing at their assigned ISO class between certification events.

Beyond Airborne Particles: Surfaces, Chemical Residues, and Nanoscale Concerns

When product risk is tied to settled or contact-transferred particles, ISO 14644-9 offers a procedure to assess particle cleanliness levels on solid surfaces. It’s not a cleaning procedure; it’s a framework for measuring and classifying surface particle levels when that matters to yield or safety.

ISO 14644-10 defines how to assess surface chemical cleanliness in processes where molecular residues or elemental deposits pose a risk, providing methods to detect and characterize those contaminants.

Some cleanrooms and mini-environments require attention to nanoscale particle behavior. ISO 14644-12 sets specifications for monitoring air cleanliness at that scale and provides guidance on interpreting the results.

Equipment, Materials, Energy, Deposition, & Consumables

ISO 14644-14 provides the framework for qualifying tools, instruments, and machines for cleanroom use, limiting hidden particle sources that could compromise certification. The original 2016 edition remains the baseline while a revision is underway in 2025.

ISO 14644-15 defines how to assess the suitability of equipment and materials for cleanroom use when airborne chemical release or off-gassing presents a risk. The 2017 edition is current, with a revision in progress.

Cleanrooms are energy-intensive environments, and ISO 14644-16 provides guidance for reducing consumption while maintaining control, linking energy use back to design, commissioning, and operational practices.

Airborne particle counts don’t capture the full contamination picture, and ISO 14644-17 explains how to interpret deposition data and apply it within a contamination control program.

ISO 14644-18 defines how to assess wipes, swabs, garments, and other cleanroom consumables for suitability, focusing on particle release, chemical cleanliness, and functional performance.

How ISO 14644 Maps to a Real Certification Program

Certification programs typically align across four areas:

• Scope and acceptance criteria: ISO 14644-1 assigns classes to each space, with limits that carry into user requirements and SOPs. Clear definitions at this stage reduce ambiguity and prevent disputes during review.
• Test plan and execution: ISO 14644-3 provides the methods used by certifiers, from sampling locations to occupancy states. Well-documented test points, calibrated instruments, and consistent data capture form the backbone of a defensible report.
• Monitoring and requalification: ISO 14644-2 frames monitoring as a continuous activity. Trend data, alert levels, and triggers for requalification (such as nearby construction or equipment changes) keep performance visible between certification events.
• Lifecycle controls: ISO 14644-4 and -5 extend the program into design and operations, stabilizing cleanrooms across their lifespan. Additional parts (9, 10, 14, 15, and 18) become relevant when issues with surfaces, chemical residues, equipment, or consumables enter the picture.

Quick reference (what each part delivers):

• 1: Classes and limits (what “ISO Class 7” means for particles)
• 2: Monitoring plan and review (showing control over time)
• 3: Methods used by certifiers (what gets tested and how)
• 4/5: Design and operations (practices that keep rooms stable)
• 9/10/12: Surfaces, chemistry, nanoscale topics (beyond airborne counts)
• 14/15/16/17/18: Equipment, materials, energy, deposition, consumables (supporting choices that prevent surprises)

Where ISO Lines Up with USP and cGMP

ISO gives you the how—classes, methods, and monitoring. U.S. frameworks like USP <797> and FDA cGMP define expectations for sterile compounding and drug manufacturing. For compounding pharmacies, USP <797> became official on November 1, 2023, and spells out facilities, environmental monitoring, and documentation. For manufacturers, the FDA’s guidance in Aseptic Processing — Current Good Manufacturing Practice (2004) remains a key reference. Your ISO evidence plugs into those systems so auditors can see both performance and control. 

How VaLogic Bio Supports ISO Cleanroom Certification

At VaLogic Bio, certification is never just a checkbox. Every program we deliver is mapped directly to ISO 14644: scoping acceptance criteria against Part 1, structuring test plans with Part 3 methods, and producing reports that stand up to inspection. 

The work doesn’t stop once a room passes. By tying design reviews to ISO 14644-4 and embedding operational discipline from ISO 14644-5, we help facilities hold their class over time rather than slip between recertifications. 

Monitoring fits the same pattern—our systems reflect the principles of ISO 14644-2, consolidating particle counts, pressure, temperature, and humidity into a single dashboard that makes control visible day to day. 

Whether it’s a baseline certification, a targeted re-test after a change, or a complete monitoring strategy, the approach stays consistent: align every step with the standard, reduce points of debate, and give QA leaders defensible results they can trust.

Ready to align your cleanroom program with ISO 14644 from design through daily monitoring? Connect with VaLogic Bio to schedule certification, request a targeted re-test, or see how an integrated monitoring plan can keep your rooms at class — and inspection-ready.