The Guide to Cleanroom Standards

Cleanrooms are the backbone of industries where precision, sterility, and contamination control are non-negotiable. Whether you’re manufacturing pharmaceuticals, assembling microchips, or conducting biotech research, understanding cleanroom standards helps ensure regulatory compliance and operational success.

What Are Cleanroom Standards?

Cleanroom standards define the acceptable level of airborne particles and environmental control required for a space to be considered clean. These standards guide cleanroom design, construction, and operation, helping organizations minimize contamination risk while meeting regulatory and safety requirements.

Cleanroom classifications focus on:

• Maximum particle counts per cubic meter or foot

• Air changes per hour (ACH)

• Temperature and humidity control

• Pressure differentials

• Filtration systems and airflow patterns

Familiarizing yourself with cleanroom standards will help you choose the appropriate solutions for your intended use case. Here is everything you need to know before implementing a hardwall or softwall cleanroom. 

Common Cleanroom Classification Systems

Cleanroom standards ensure that sensitive work environments meet the appropriate air cleanliness standards to protect products and processes. These standards guide cleanroom design, construction, and operation, helping organizations minimize contamination risk while meeting regulatory and safety requirements. 

The three most commonly referenced cleanroom standards include:

• ISO 14644-1 (international particle count classification)

• USP 797 and USP 800 (for sterile and hazardous drug compounding)

• GMP and FDA Guidelines (for pharmaceutical and medical manufacturing)

Legacy systems like Federal Standard 209E and BS 5295 are largely retired but may still appear in historical documentation.

Meeting the appropriate cleanroom certification requirements is vital for compliance and safety. ISO cleanroom standards are used globally and have been widely adopted across most industries. However, several other cleanroom standards were used before ISO 14644-1 was adopted.

A few examples you may encounter are:

• BS 5295: A U.K. standard that has largely been replaced by ISO 14644-1

• Federal Standard 209E: A retired U.S. standard 

• GMP and FDA Guidelines: Regulatory frameworks designed to promote compliance in pharmaceutical and medical device manufacturing

These standards apply to the following industries:

• Pharmaceuticals

• Biotechnology

• Aerospace

• Semiconductors

In most cases, you will use the ISO cleanroom standards to choose the appropriate environment for your use case. However, you may see references to GMP and FDA guidelines if you work in an industry subject to those rule sets. 

ISO Standards: An Overview

ISO 14644-1 is the global benchmark for cleanroom classification. It ranks cleanrooms by the concentration of airborne particles and spans from ISO Class 1 (most stringent) to ISO Class 8 (least stringent). Here's an overview:

Here is a breakdown of each class:

ISO 1: Ultra-Clean Environments

ISO 1 allows near-zero particle counts; requires advanced HEPA/ULPA filtration, full laminar flow, and strict positive pressure zones.They are also equipped with advanced HEPA filtration and precise temperature and humidity control. ISO 1 environments use positive pressure to prevent contamination. 

Typically, a hardwall cleanroom is the best option for creating a true ISO 1 environment. These are used in:

• Semiconductor fabrication

• Aerospace

• Nanotechnology

• Best fit: Hardwall modular cleanrooms with full HVAC integration

When there is no margin for error, you need an ISO 1 cleanroom. 

ISO 2: High-Precision Environments

ISO 2 environments deliver stringent air cleanliness and high-efficiency filtration, controlling environmental factors like humidity and pressure. You should consider an ISO 2 cleanroom for applications such as biotech and pharmaceutical production when you need to control air purity and humidity to an extremely high standard.. 

ISO 3: Nano-scale and Quantum applications 

Common application in nano-scale technology. When designing an ISO 3 cleanroom, manufacturers must maintain low particle counts with laminar airflow. These spaces also use strict pressure control. Some common use cases include:

• Semiconductor fabrication

• DNA Sequencing & Synthetic Biology

• Microlithography

• Nanotechnology

ISO 3 cleanrooms can be constructed using hard walls or soft materials. The key is to choose a reputable provider that builds cleanrooms in accordance with the latest standards. 

Very rare - only used in niche semiconductor R&D ISO 5: Sterile Manufacturing and Clean Assembly

ISO 5 cleanrooms limit particles to 3,520 per cubic meter. To maintain such an environment, the cleanrooms must be protected using strict personnel protocols and advanced filtration. ISO 5 cleanrooms are best suited for:

• Medical device implantable production 

• Pharmaceutical sterile compounding 

• Biotechnology- Cell and gene therapy 

While softwall cleanrooms offer flexibility in many applications, they are not suitable for sterile manufacturing environments that require ISO 5 conditions. Sterile compounding and aseptic processes demand cleanrooms with smooth, impervious, and non-porous surfaces that can withstand frequent disinfection using sterilants. Additionally, maintaining positive pressure gradients between clean zones is critical to preventing contamination. Softwall systems lack the structural integrity to hold stable pressure and cannot be fully sealed, making them difficult to sanitize and unable to meet strict regulatory standards. For this reason, only hardwall cleanrooms—with airtight construction and durable, chemically resistant finishes—are appropriate for ISO 5 sterile manufacturing and are required to support USP 797, FDA, and cGMP compliance. 

ISO 6: Lightly Controlled Environments

ISO Class 6 cleanrooms allow up to 35,200 particles ≥ 0.5 µm per cubic meter and maintain an average of 150+ air changes per hour, making them suitable for highly controlled environments where contamination must be minimized—but full sterility is not required. These cleanrooms are commonly used in optics assembly, laser systems, wafer inspection, and microelectronics, where even submicron particles can impact performance or yield. While not as stringent as ISO 5, ISO 6 still demands robust air handling, HEPA filtration, and careful gowning procedures. Modular cleanroom systems offer an ideal platform for ISO 6 environments, allowing facilities to scale or reconfigure clean zones without compromising compliance or control. 

ISO 7: General Manufacturing Environments

ISO Class 7 cleanrooms allow up to 352,000 particles ≥ 0.5 µm per cubic meter and are widely recognized as the baseline standard for sterile compounding environments, including those required under USP 797 and USP 800. ISO 7 spaces are commonly used in pharmaceutical cleanrooms, medical device manufacturing, biotechnology, and sterile packaging, where controlled contamination levels are essential but ISO 5 conditions are only required at the point of critical operations (e.g., inside laminar flow hoods or isolators). These cleanrooms require a minimum of 60 air changes per hour, HEPA filtration, and positive pressure zones to protect cleaner adjacent spaces. ISO 7 classification supports many core cleanroom functions, including buffer rooms, prep areas, and clean staging environments for aseptic workflows.

ISO 8: Basic Cleanrooms

ISO Class 8 cleanrooms permit up to 3,520,000 particles ≥ 0.5 µm per cubic meter and are commonly used in applications where control of larger particulate matter is essential but sterility is not required. These environments support non-aseptic manufacturing, clean staging areas, pre-gowning zones, and final packaging operations where particle loads must still be managed—particularly around dust-sensitive components or equipment. ISO 8 is frequently specified for general industrial clean manufacturing, especially in sectors dealing with powders, bulk solids, or larger device assemblies where 0.5–5.0 micron particle control remains critical to product integrity. Proper airflow design, pressure zoning, and gowning protocols are still essential to maintain compliance within ISO 8 standards..

USP Standards

The United States Pharmacopeia standards apply specifically to entities that handle pharmaceuticals and hazardous drugs. These standards establish detailed requirements for air cleanliness, pressure differentials, environmental monitoring, and personnel practices to ensure product integrity, patient safety, and worker protection.

USP <797> — Sterile Compounding of Pharmaceuticals

USP <797> establishes requirements for the sterile compounding of drugs to ensure patient safety, minimize contamination risk, and maintain the integrity of compounded preparations. The standard outlines strict controls for:

• Air cleanliness in ISO 5 primary engineering controls (e.g., laminar flow hoods or isolators)

• ISO 7 buffer rooms and ISO 8 ante rooms for classified support spaces

• Personnel training, gowning, and aseptic technique

• Environmental monitoring, cleaning, and documentation protocols

USP <797> applies to a wide range of facilities, including hospital pharmacies, outpatient clinics, infusion centers, and commercial compounding pharmacies. While the core sterility requirements remain consistent, implementation may vary depending on the volume and risk level of compounded sterile preparations (CSPs). Facilities must tailor their cleanroom design and workflow controls to meet these standards and maintain compliance through routine monitoring and quality assurance practices.

USP <800> — Handling of Hazardous Drugs in Healthcare Settings

USP <800> establishes enforceable standards for the safe handling, storage, compounding, and disposal of hazardous drugs (HDs) to protect healthcare personnel, patients, and the environment. It applies to any facility that receives, prepares, administers, or transports hazardous medications—including hospital pharmacies, outpatient clinics, infusion centers, and retail or compounding pharmacies.

Key requirements include:

• Use of containment primary engineering controls (C-PECs) such as biological safety cabinets or compounding aseptic containment isolators (CACIs)

• Placement of C-PECs within negative pressure ISO 7 buffer rooms

• Use of appropriate personal protective equipment (PPE) and spill control procedures

• Proper ventilation, exhaust systems, and segregated storage of HDs

• Detailed protocols for waste handling, decontamination, and staff training

USP <800> is particularly critical for facilities handling chemotherapy agents, antineoplastic drugs, and reproductive risk medications. While the exact infrastructure may vary depending on the facility type and drug volume, the goal remains the same: to reduce occupational exposure and ensure a safe compounding and administration environment.

Other Notable Cleanroom Standards and Guidelines

The FDA’s Good Manufacturing Practices (GMP) guidelines outline key requirements for cleanroom design, operation, and maintenance. ISO 5 or ISO 7 (or better) cleanrooms are the minimum requirement for most pharmaceutical applications. 

The National Institute for Occupational Safety and Health (NIOSH) also issues guidelines focused on worker safety and contamination control. These guidelines are often complementary to USP 800.

Consult With Our Compliance Experts Today

Maintaining proper cleanroom classifications is critical for product quality, worker safety, and regulatory compliance. When you need a reliable and compliant environment, CleanAir Solutions can help. 

We design and install clean environments to align with the latest cleanroom standards. Our offerings include both softwall and hardwall options, which can be customized to your space.

Ready to build a cleanroom that meets your industry’s standards? Contact CleanAir Solutions today to talk to an expert.