Cleanroom: A Comprehensive Guide to Design, Standards, and Applications

Introduction

Cleanrooms are controlled environments designed to minimize the presence of contaminants, such as dust, airborne microbes, and chemical vapors. They are crucial in various industries, including pharmaceuticals, biotechnology, electronics, and aerospace. 

This article will explore the fundamentals of cleanrooms, their design principles, components, and applications in different industries. We will also discuss the importance of maintaining cleanroom standards and the various protocols and procedures involved in cleanroom operations.

What are Cleanrooms?

A cleanroom is a specially designed and controlled environment where the concentration of airborne particles is minimized. The primary purpose of a cleanroom is to prevent contamination of sensitive processes or products, ensuring their quality and safety. 

While there are many improvised airborne pathogen purification systems, cleanrooms remain the primary requirement in industries where even the smallest amount of contamination can have significant consequences, such as pharmaceutical manufacturing, semiconductor fabrication, and biotechnology research.

Purpose of Cleanrooms

The purpose of cleanrooms is to control contaminants, which involves regulating various factors such as 

• Air filtration - The use of HEPA and ULPA filters to remove particles to protect sensitive products in critical areas.
• Temperature and Humidity Control - Maintaining a consistent environment for optimal product quality and safety.
• Pressure - Maintaining a positive pressure to keep contaminants out, ensuring a safe and sterile environment.

The level of cleanliness required in a cleanroom depends on the specific industry and application. For example, in the pharmaceutical industry, cleanrooms prevent contamination of drugs and medical devices, ensuring their sterility and patient safety. Since cleanliness is a critical regulatory requirement as well, it’s appropriately addressed in the process of a medical device design.

Recommended Reading: Stages of Medical Device Development: A Comprehensive Guide (wevolver.com)

In the semiconductor industry, cleanrooms are essential for maintaining the integrity of microelectronic components, as even a single dust particle can cause defects in the semiconductor manufacturing process.

Classifications of Cleanrooms

Cleanrooms are classified based on the number and size of airborne particles allowed per unit volume of air. The ISO 14644-1 standard defines cleanroom classifications and provides guidelines for measuring and testing cleanroom performance. The standard there are 1 standard classifies cleanrooms into nine classes, ranging from ISO Class 1 (the cleanest) to ISO Class 9 (the least clean).

Each ISO class has specific limits for the maximum concentration of particles of various sizes. For example, an ISO Class 5 cleanroom must have no more than 3,520 particles of 0.5 micrometers or larger per cubic meter of air, while an ISO Class 7 cleanroom can have up to 352,000 particles of the same size per cubic meter of air. The classification system helps industries determine the appropriate level of cleanliness required for their specific applications and processes.

The following table shows the ISO 14644-1 cleanroom classifications, along with the maximum number of particles permitted per cubic meter of air:

Before ISO 14644-1, the United States Federal Standard 209E (FS 209E)was widely used. It classifies cleanrooms into six classes, ranging from Class 1 (the cleanest) to Class 100,000 (the least clean). Although the FS 209E standard has been officially replaced by ISO 14644-1, it is still used as a reference in some industries and regions.

The ISO 14644-1 is one of the most important standards in the modern industries. Therefore, it’s implemented in Industry 4.0. as it provides a framework for ensuring the cleanliness of manufacturing environments.

Further Reading: Benefits of Industry 4.0

The cleanroom classifications help in the effective designing, construction, and maintenance of cleanrooms that meet the specific requirements of various industries and applications. Proper classification ensures that cleanrooms provide the necessary level of cleanliness and contamination control, ultimately contributing to the quality and safety of products and processes.

Cleanroom Design Principles

Several key design principles contribute to the effectiveness of a cleanroom in controlling contaminants. These principles include air filtration, air pressure control, and temperature and humidity control.

Air Filtration - One of the most critical aspects of cleanroom design is the air filtration system. High-efficiency particulate air (HEPA) filters and ultra-low particulate air (ULPA) filters are commonly used to remove particles. 

Air Pressure Control - Maintaining positive air pressure within the cleanroom is essential to prevent the infiltration of contaminants from the surrounding environment. Positive air pressure means that the air pressure inside the cleanroom is higher than the pressure outside, causing air to flow outward when doors or other openings are present. This outward flow of air helps prevent unfiltered air from entering the cleanroom and reduces the risk of contamination.

Temperature and Humidity Control - Controlling temperature and humidity is crucial for maintaining the stability of processes and products within the cleanroom. Excessive temperature or humidity can lead to condensation, corrosion, or other issues that can compromise the cleanliness of the environment. 

Cleanroom Components and Equipment

Air Filtration Systems

Air filtration systems remove particles and contaminants from the air. There are several types of air filtration systems used in cleanrooms, such as: 

HEPA Filters - High-efficiency particulate air (HEPA) filters are widely used in cleanrooms as they can capture 99.97% of particles 0.3 micrometers in size. HEPA filters are made from a dense network of randomly arranged fibers, typically composed of glass or synthetic materials. 

Fig 1: HEPA Filter for Air Purifier

ULPA Filters - Ultra-low particulate air (ULPA) filters provide an even higher level of filtration than HEPA filters, capturing 99.999% of particles 0.12 micrometers in size. ULPA filters are used in cleanrooms with more stringent cleanliness requirements, such as those found in semiconductor manufacturing or pharmaceutical production. 

Air Handling Units (AHUs) - AHUs are used in cleanroom air filtration systems to condition and distribute the filtered air throughout the cleanroom. AHUs typically consist of a fan, filter, cooling coil, and heating coil, all housed within a single unit. The AHU draws in air from the surrounding environment, filters it through the HEPA or ULPA filter, and then conditions the air by adjusting its temperature and humidity before distributing it throughout the cleanroom. AHUs can be configured in various ways, such as single-pass or recirculating systems, depending on the specific requirements of the cleanroom.

HVAC Systems

Heating, ventilation, and air conditioning (HVAC) systems play a crucial role in maintaining the controlled environment of a cleanroom. HVAC systems regulate temperature, humidity, and air pressure to ensure optimal conditions for the specific industry and application.

Fig 2: A heating and ventilation system in a factory setup

Here is a quick look at the main components of an HVAC system

Temperature Control - Just as valuable as it is in process control, precise temperature control is essential in cleanrooms, as fluctuations in temperature can affect the stability of processes and products. HVAC systems use cooling and heating coils to maintain the desired temperature within the cleanroom, ensuring consistent conditions for sensitive processes.

Humidity Control -  HVAC systems use humidifiers and dehumidifiers to regulate humidity levels, providing the optimal balance for the specific application. They prevent excessive humidity build-up that can cause condensation or corrosion, as well as low-humidity that can lead to static electricity build-up. 

Air Pressure Control - HVAC systems maintain positive air pressure by controlling the volume and velocity of air entering and exiting the cleanroom. This is achieved through the use of fans, dampers, and other components that regulate airflow and pressure.

Air Distribution - HVAC systems use a combination of ductwork, diffusers, and return air grilles to distribute filtered and conditioned air evenly across the cleanroom. This helps maintain consistent cleanliness levels and prevents the buildup of contaminants in specific areas.

Cleanroom Construction and Design

The structure and constructional design of cleanrooms directly impact the ability of the cleanroom to meet its intended purpose. Cleanrooms are designed to control contamination, and the structure and construction of the room play a vital role in this.

A well-designed cleanroom will have the following features:

• Airtight Enclosure - The cleanroom must be an airtight enclosure to prevent the ingress of contaminated air. 

• HEPA filtration - The cleanroom must be equipped with high-efficiency particulate air (HEPA) filters to remove airborne contaminants. 

• Positive Pressurization - The cleanroom must be maintained at a positive pressure relative to the surrounding environment. 

• Unidirectional Airflow - The cleanroom must have unidirectional airflow, which means that the air flows in one direction only. 

Modular vs. Conventional Cleanrooms

There are two primary types of cleanroom construction: modular and conventional. Each type has its advantages and disadvantages, depending on the specific requirements of the industry and application.

Modular Cleanrooms - These are pre-fabricated, self-contained units that can be easily assembled, disassembled, and reconfigured. They are typically constructed from lightweight materials, such as aluminum, steel, or plastic, and are designed to be easily transported and installed. Some of the advantages of modular cleanrooms include:

• Flexibility - Modular cleanrooms can be easily expanded, downsized, or reconfigured to accommodate changing needs or requirements.

• Construction Speed - Modular cleanrooms can be assembled more quickly than conventional cleanrooms, reducing downtime and allowing for faster project completion.

• Cost-effectiveness - Modular cleanrooms often have lower construction costs compared to conventional cleanrooms, as they require less labor and materials.

Disadvantage of Modular Cleanrooms - These rooms offer reduced structural stability and a potentially shorter lifespan compared to conventional cleanrooms.

Conventional Cleanrooms - These are built using traditional construction methods and materials, such as concrete, steel, and drywall. They are typically more permanent structures and are designed to meet specific industry standards and requirements. Some advantages of conventional cleanrooms include:

• Durability - Conventional cleanrooms are generally more robust and have a longer lifespan than modular cleanrooms.

• Customization - Conventional cleanrooms can be designed and built to meet the unique requirements of a specific industry or application, allowing for greater customization and optimization.

Disadvantage of Conventional Cleanrooms - These rooms can be more expensive and time-consuming to construct compared to modular cleanrooms, and they may be less flexible in terms of expansion or reconfiguration.

Cleanroom Flooring and Wall Systems

Cleanroom flooring and wall systems are essential components of cleanroom design, as they contribute to maintaining cleanliness and preventing contamination. The choice of materials and construction methods for flooring and wall systems can significantly impact the overall performance and effectiveness of a cleanroom.

Flooring Systems - Cleanroom flooring must be durable, easy to clean, and resistant to chemicals and abrasion. Common flooring materials used in cleanrooms include:

• Epoxy - Epoxy flooring is a popular choice for cleanrooms due to its seamless, non-porous surface, which is easy to clean and resistant to chemicals. Epoxy flooring can also be formulated with anti-static properties to reduce the risk of electrostatic discharge (ESD) in sensitive environments.

Fig 3: A cleanroom featuring an Epoxy System Flooring and double glass windows

• Vinyl - Vinyl flooring is another common option for cleanrooms, as it is cost-effective, easy to maintain, and available in a variety of colors and finishes. Vinyl flooring can also be made with anti-static properties for ESD-sensitive applications.
• Raised access flooring - Raised access flooring systems consist of modular panels supported by adjustable pedestals, creating a space beneath the floor for routing utilities, such as electrical and HVAC systems. 

Wall Systems - Cleanroom walls must be constructed from materials that are easy to clean, resistant to chemicals, and capable of maintaining airtight seals. Common wall systems used in cleanrooms include:

• Modular Wall Panels - Modular wall panels are pre-fabricated, interlocking panels made from materials such as aluminum, steel, or plastic. They are easy to install, reconfigure, and maintain, making them a popular choice for cleanroom construction. Modular wall panels can also be designed with integrated windows, doors, and utility ports for added convenience.
• Gypsum Board - Gypsum board, also known as drywall, is a conventional wall construction material that can be used in cleanrooms when properly sealed and finished. Gypsum board walls must be coated with a suitable paint or sealant to create a smooth, non-porous surface that is easy to clean and resistant to chemicals.
• Glass or acrylic walls - Glass or acrylic walls can be used in cleanrooms to create a visually open environment while maintaining airtight seals and cleanliness. Glass and acrylic walls are easy to clean and resistant to chemicals, making them suitable for cleanroom applications.

Cleanroom Operations and Maintenance

Cleanroom Protocols and Procedures

Maintaining the cleanliness and integrity of a cleanroom environment requires strict adherence to protocols and procedures. These guidelines help ensure that cleanroom personnel, equipment, and processes do not introduce contaminants that could compromise product quality or safety. 

Some of the key aspects of cleanroom protocols and procedures include:

Personnel Training - Cleanroom personnel must be trained in proper cleanroom etiquette, including gowning procedures, hygiene practices, and the handling of materials and equipment to reduce the risk of contamination introduced by human activity.

Gowning Procedures - Cleanroom personnel must wear specialized clothing, such as coveralls, gloves, face masks, and shoe covers, to minimize the release of particles from their bodies and clothing. Gowning procedures typically involve donning cleanroom garments in a designated gowning area, following a specific sequence to minimize contamination.

Material and Equipment Handling - Materials and equipment entering the cleanroom must be carefully handled to prevent contamination. This may involve cleaning or sterilizing items before they enter the cleanroom, using specialized containers or packaging, and following specific procedures for moving items within the cleanroom.

Access Control - Access to cleanrooms should be restricted to authorized personnel who have received proper training in cleanroom protocols and procedures. Access control measures, such as keycards or biometric systems, can help ensure that only trained personnel enter the cleanroom, reducing the risk of contamination.

Cleanroom Cleaning and Disinfection

Regular cleaning and disinfection of cleanroom surfaces, equipment, and tools are essential for maintaining cleanliness and preventing the buildup of contaminants. Effective cleaning and disinfection procedures involve the use of specialized cleaning agents, equipment, and techniques tailored to the specific requirements of the cleanroom environment.

Cleaning Agents - Cleanroom-grade cleaning agents are designed to remove particles, residues, and contaminants from surfaces without introducing additional contaminants. These cleaning agents may include detergents, disinfectants, and sterilants, depending on the specific needs of the cleanroom. It is crucial to select cleaning agents that are compatible with the materials and surfaces found in the cleanroom to avoid damage or degradation.

Cleaning Techniques - Effective cleanroom cleaning and disinfection procedures involve specific techniques to ensure thorough removal of contaminants. Some common cleanroom cleaning techniques include:

• Wiping - Wiping surfaces with cleanroom-grade wipes, using a systematic and consistent pattern, helps ensure that contaminants are effectively removed. Wipes should be folded and rotated to expose a clean surface as they become soiled, minimizing the risk of recontamination.
• Mopping - Mopping cleanroom floors, walls, and ceilings should follow a specific pattern, such as starting from the cleanest area and moving towards the dirtiest, to prevent the spread of contaminants. Mop heads should be changed regularly to maintain cleanliness.
• Vacuuming - Vacuuming should be performed using cleanroom-grade vacuum cleaners with HEPA or ULPA filters, ensuring that particles are captured and not released back into the environment. Vacuuming should be done systematically, covering all surfaces and areas within the cleanroom.

By implementing effective cleaning and disinfection procedures, cleanrooms can maintain the required level of cleanliness and contamination control, ensuring the quality and safety of products and processes.

Cleanroom Monitoring and Validation

Monitoring and validation are essential aspects of cleanroom operations and maintenance, as they help ensure that the cleanroom is performing as intended and meeting the required cleanliness standards. Regular testing and certification are necessary to maintain compliance with industry regulations and guidelines.

Particle Count Monitoring - Particle count monitoring measures the concentration of airborne particles within the cleanroom environment. Particle counters are used to sample the air at various locations within the cleanroom, providing real-time data on particle concentrations which directly indicates the cleanroom performance.

Airflow and Pressure Monitoring - Sensors and gauges are used to measure air velocity, pressure differentials, and other parameters, ensuring that the cleanroom's HVAC system is functioning correctly and maintaining the required conditions.

Temperature and Humidity Monitoring - Temperature and humidity sensors are used to continuously monitor the environmental conditions within the cleanroom. This data is essential for maintaining the stability of processes and products and preventing issues related to condensation, corrosion, or static electricity.

Recommended Reading: How to Select the Best Temperature Sensors for Your Smart Project (wevolver.com)

Microbiological Monitoring - In cleanrooms used for pharmaceutical, biotechnology, or other life science applications, microbiological monitoring is necessary to detect the presence of microorganisms, such as bacteria, fungi, or viruses. It typically involves the use of air samplers, surface swabs, or contact plates to collect samples, which are then analyzed in a laboratory to identify and quantify any microbial contaminants.

Certification and Compliance - Cleanrooms must undergo regular testing and certification to ensure compliance with industry standards and regulations, such as ISO 14644-1 or the United States Federal Standard 209E.

Leakage Detection - Leaks can allow contaminated air to enter the cleanroom, compromising product quality and putting employees at risk. Therefore, cleanroom maintenance personnel regularly inspect the cleanroom for leaks and perform leakage detection tests on key areasFig 4: Leakage Scan on a HEPA filter in a cleanroomLeakage detection in cleanrooms can be conducted using a variety of methods, depending on the specific application and the type of leak being detected. Some of the most common methods include:

• Aerosol photometer - This device measures the concentration of airborne particles in the air. An increase in particle concentration can indicate a leak. 

• Sniffer probe -  This device is used to detect the presence of tracer gas released into the cleanroom. 

• Ionization chamber - This device detects the presence of ions in the air. An increase in ion concentration can indicate a leak. Ionization chambers are typically used to detect leaks in vacuum systems and other high-purity environments.

• Pressure decay test -  This test measures the rate at which the pressure in a sealed enclosure decreases over time. These tests are typically used to detect leaks in large enclosures, such as cleanroom chambers and gloveboxes.

• Bubble leak test -  This test uses a soapy solution to identify leaks in pressurized systems. If the soapy solution bubbles when applied to a joint or fitting, it indicates a leak. Bubble leak tests detect leaks in plumbing, gas lines, and other pressurized systems.

Cleanroom Applications in Various Industries

Pharmaceutical and Biotechnology

Cleanrooms play a vital role in the pharmaceutical and biotechnology industries, where maintaining a contamination-free environment is crucial for ensuring quality, safety, and efficacy of products. In these industries, cleanrooms serve various purposes, such as research and development, manufacturing, and quality control.

Research and Development - In pharmaceutical and biotechnology research, cleanrooms provide a controlled environment for conducting experiments and studies involving sensitive biological materials, such as cells, tissues, or microorganisms. Maintaining a clean and sterile environment is essential for preventing contamination and ensuring the accuracy and reliability of research results.

Manufacturing - Cleanrooms are used in the manufacturing of pharmaceutical products, such as drugs, vaccines, and medical devices, to ensure their sterility and safety for patients. The manufacturing process often involves the handling of active pharmaceutical ingredients (APIs), which must be protected from contamination to maintain their potency and effectiveness. Cleanrooms in pharmaceutical manufacturing are typically designed to meet stringent cleanliness standards, such as ISO Class 5 or higher, depending on the specific product and process requirements.

Quality Control - Cleanrooms are used for various quality control activities, such as microbiological testing, environmental monitoring, and product inspection. These activities require a controlled environment to prevent contamination and ensure the accuracy and reliability of test results.

Electronics and Semiconductor Manufacturing

Cleanrooms are essential in the electronics and semiconductor manufacturing industries, where even the smallest amount of contamination can have significant consequences on product quality and performance. In these industries, cleanrooms are used for various processes, such as wafer fabrication, assembly, and testing.

Fig 5: A view of a Bright Advanced Semiconductor Production Fab Cleanroom with Working Overhead Wafer Transfer System

Wafer Fabrication - Cleanrooms used in wafer fabrication are typically designed to meet stringent cleanliness standards, such as ISO Class 3 or higher, to minimize the risk of defects caused by particles or contaminants.

Assembly and Packaging - Cleanrooms used in assembly and packaging processes must maintain a controlled environment to prevent contamination that could compromise the performance or reliability of the devices. These cleanrooms are typically designed to meet cleanliness standards such as ISO Class 5 or higher, depending on the specific requirements of the product and process.

Testing and Quality Control - Semiconductor devices undergo various testing and quality control procedures to ensure their performance, reliability, and compliance with industry standards. Cleanrooms used for testing and quality control must provide a controlled environment that minimizes contamination risk, ensuring the accuracy and reliability of test results. 

Aerospace and Defense

Cleanrooms play a critical role in the aerospace and defence industries, where maintaining a contamination-free environment is essential for ensuring the quality, reliability, and safety of products and systems. 

In these industries, cleanrooms are used for various purposes, such as the manufacturing of sensitive components, assembly of spacecraft and satellites, and testing of advanced technologies.

Sensitive Component Manufacturing - Aerospace and defense applications often involve the use of sensitive components, such as sensors, optics, and microelectronic devices, which require a controlled environment during manufacturing to prevent contamination and ensure their performance and reliability. Cleanrooms used in the manufacturing of sensitive components must meet specific cleanliness standards, such as ISO Class 5 or higher.

Recommended Reading: https://www.wevolver.com/article/aerospace-manufacturing-in-2023 

Spacecraft and Satellite Assembly - The assembly of spacecraft and satellites involves the integration of various components and systems, which must be protected from contamination to ensure their functionality and longevity in the harsh conditions of space. Cleanrooms used for spacecraft and satellite assembly must maintain a controlled environment that minimizes the risk of contamination, typically meeting cleanliness standards such as ISO Class 6 or higher.

Testing and Quality Control -  Aerospace and defense products and systems undergo rigorous testing and quality control procedures to ensure their performance, reliability, and compliance with industry standards and regulations. Cleanrooms used for testing and quality control must provide a controlled environment that minimizes the risk of contamination, ensuring the accuracy and reliability of test results. The cleanliness standards for these cleanrooms depend on the specific testing procedures and product requirements.

Conclusion

Cleanrooms are essential in various industries, including pharmaceuticals, biotechnology, electronics, and aerospace, where maintaining a contamination-free environment is crucial for ensuring product quality, safety, and reliability. By adhering to strict design principles, using appropriate components and equipment, and following rigorous protocols and procedures, cleanrooms can effectively control contaminants and provide the necessary level of cleanliness for diverse applications. Regular monitoring and validation are vital for maintaining compliance with industry standards and regulations, ensuring the ongoing performance and effectiveness of cleanroom environments.

Frequently Asked Questions (FAQs)

1. What is a cleanroom? 

A cleanroom is a controlled environment designed to minimize the presence of contaminants, such as dust, airborne microbes, and chemical vapors. Cleanrooms are essential in industries where even the smallest amount of contamination can have significant consequences, such as pharmaceutical manufacturing, semiconductor fabrication, and biotechnology research.

2. How are cleanrooms classified? 

Cleanrooms are classified based on the number and size of airborne particles allowed per unit volume of air. The International Organization for Standardization (ISO) developed the ISO 14644-1 standard, which defines cleanroom classifications and provides guidelines for measuring and testing cleanroom performance.

3. What are the key design principles of cleanrooms? 

The key design principles of cleanrooms include air filtration, air pressure control, and temperature and humidity control. These principles help maintain a controlled environment that minimizes the risk of contamination.

4. What are the main components of a cleanroom? 

The main components of a cleanroom include air filtration systems, HVAC systems, and cleanroom furniture and fixtures. These components work together to maintain the required level of cleanliness and contamination control.

5. Why is monitoring and validation important in cleanrooms? 

Monitoring and validation are essential aspects of cleanroom operations and maintenance, as they help ensure that the cleanroom performs as intended and meets the required cleanliness standards. Regular testing and certification are necessary to maintain compliance with industry regulations and guidelines.

References

1. Scott D. Lowther, Wei Deng b, Zheng Fang, Douglas Booker, Duncan J. Whyatt, Oliver Wild, Xinming Wang, Kevin C. Jones, (2020). “How efficiently can HEPA purifiers remove priority fine and ultrafine particles from indoor air?”, https://www.sciencedirect.com/science/article/pii/S0160412020319565 

2. US EPA, (2023). “What is a HEPA filter?”

3. ISO, (2015), “ISO 14644-1:2015(en), Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness by particle concentration”

4. Labcompare, (2022), “EPA vs ULPA: What's the Difference?”

5. Cleanroom Technology, (2006). “Integrity testing of HEPA filters”

6. R&D World, (2017), “HVAC Design for Cleanrooms”