Hygienic and controlled environments for critical activities
Cleanrooms are highly controlled spaces designed to maintain a hygienic environment with low levels of contaminants and specific temperature, humidity and pressure conditions.
These specialized areas are essential in industries such as pharmaceuticals, biotechnology, electronics and aerospace, where product quality and process safety are crucial.
There are different types of cleanrooms, classified according to ISO 14644 and GMP (Good Manufacturing Practices) guidelines, which determine the acceptable limits of particles and contaminants in the air. These classifications range from ISO Class 1, where extremely stringent control is required, to ISO Class 9, with less stringent but still controlled requirements.
Cleanrooms are critical in applications such as sterile drug production, sensitive electronics manufacturing, scientific research and development, and medical device assembly.
By ensuring a controlled, contaminant-free environment, cleanrooms contribute to the quality and safety of products and processes in these critical industries.
Construction elements, systems and protocols
Components of a clean room
The key elements for a clean room and to ensure a controlled and safe environment are:
- Modular systems for sanitary architecture: sandwich panels, doors, viewers, profiles…
- Inlet and outlet devices: material feed-throughs, air showers, interlocks…
- Heating, Ventilation and Air Conditioning (HVAC) System.
- HEPA/ULPA filters.
- Changing rooms and changing areas.
- Hand washing and disinfection stations.
- Processing equipment, furniture and work surfaces.
- Specialized lighting.
- Electrical and critical fluids installations.
- Differential pressure control.
- Particulate monitoring system.
- Humidity and temperature control.
- Alarm and security systems.
- Cleaning and disinfection protocols and procedures.
Key aspects to define the characteristics of a clean room
Sizing and optimization
When defining the layout and features of a cleanroom or classified space, it is crucial to analyze these key aspects to ensure an optimal and functional design:
- The purpose and specific requirements of the process.
- The required cleaning classification.
- Workflow and equipment layout.
- The capacity for future expansion.
- The need for support zones and changing areas.
- The type of HVAC and filtration systems required.
- The lighting design and location of electrical outlets.
- Requirements for construction materials and surface finishes.
- Monitoring and quality control systems.
phases of the design, installation and maintenance process of a cleanroom
From design to commissioning
The steps to follow to design and install a clean room are as follows:
- Definition of project requirements and objectives.
- Conceptual design, covering cleaning classification, space layout and system integration.
- Detailed design, including material selection, HVAC systems, lighting and other technical aspects.
- Construction and installation, which involves building the structure, installing systems and equipment, and conducting performance tests.
- Validation and qualification, which consists of ensuring that the cleanroom complies with design requirements and applicable standards.
- Ongoing maintenance and monitoring to ensure the integrity and performance of the cleanroom over time.
Questions and answers about Clean Rooms
A cleanroom is a controlled environment in which low levels of contaminants, such as suspended particles, microorganisms and chemical compounds are maintained. They are used in multiple sectors, such as pharmaceutical manufacturing, medical devices, microelectronics, semiconductors, aerospace, and life sciences, among others.
The ISO (International Organization for Standardization) classification is based on the ISO 14644 standard and establishes different levels of cleanliness according to the size and concentration of particles allowed. The GMP (Good Manufacturing Practices) categories follow the Good Manufacturing Practice guidelines and are mainly applied in the pharmaceutical and medical device industry. GMP classifications are based on classes A, B, C and D, with class A being the most stringent and class D the least stringent.
EPA (Efficiency Particulate Air) and ULPA (Ultra Low Penetration Air), which retain particles of different sizes and ensure air quality in the controlled environment.
Temperature and humidity in a clean room are controlled by specific air conditioning systems, such as air handling units (AHUs) and HVAC systems, which ensure stable and uniform conditions according to process and product requirements.
ISO standards divide cleanrooms into nine classes, from ISO Class 1 to ISO Class 9, where Class 1 is the cleanest and Class 9 represents a controlled environment similar to ambient air. On the other hand, GMP standards are divided into five grades (A, B, C and D), with Grade A being the most controlled and Grade D the least controlled. Both classifications are based on particle counts and, in certain cases, on the presence of microorganisms.
Cleanroom decontamination techniques vary depending on the application and specific requirements. Some of the most common techniques are:
- Hydrogen peroxide (H2O2) biodecontamination: Uses hydrogen peroxide vapor to eliminate microorganisms on surfaces and equipment. The H2O2 solution is converted into vapor and dispersed into the environment, penetrating hard-to-reach areas and providing effective disinfection.
- Decontamination by ultraviolet (UV) light: UV light, specifically in the 254 nm range, is effective in inactivating microorganisms by degrading nucleic acids and forming thymine dimers. UV decontamination is commonly used in air flow systems and exposed surfaces.
- Chemical decontamination: This involves the use of chemical disinfectants, such as alcohols, quaternary chlorides, sodium hypochlorite, among others, to eliminate microorganisms on surfaces and equipment. Chemical agent selection depends on the type of contaminant and compatibility with cleanroom materials.
- Autoclave decontamination: Autoclave sterilization uses high pressure steam and temperature to eliminate microorganisms on equipment and materials. It is an effective technique for decontamination
Lighting in clean rooms must meet the requirements of brightness, uniformity and quality, avoiding the generation of particles. Energy-efficient and watertight LED luminaires are commonly used, specifically designed for controlled environments, complying with applicable regulations and standards.
The qualification process includes tests and verifications to ensure that the cleanroom meets specific standards and requirements. It involves validation of the design (DQ), installation (IQ), operation (OQ) and performance (PQ) of systems and equipment, ensuring compliance with applicable regulations and best practices.
Regular maintenance is essential to ensure that systems and equipment operate efficiently and reliably, maintaining environmental quality and compliance with applicable regulations. This includes inspection, calibration, adjustment and repair of critical equipment such as HVAC systems, HEPA/ULPA filters, monitoring and control systems.
Specific protocols and procedures are established to control the flow of people and materials. This includes the use of changing areas and locker rooms, decontamination of materials prior to entering the room, and strict adherence to circulation guidelines to minimize cross-contamination.
Clean rooms emerged in the 1960s, driven by the aerospace industry and semiconductor manufacturing. Since then, they have evolved and adapted to various industries, such as pharmaceuticals, biotechnology and medical devices, keeping pace with regulatory developments and technological advances.
Vocabulary RELATING TO CLEAN ROOMS
- Airlock: Intermediate chamber between two areas of different cleanliness levels, used to control particle transfer and maintain differential pressure.
- Anteroom: Space prior to the entrance of a clean room, where workers dress in appropriate clothing and follow hygiene protocols.
- Air barrier: Technique used to separate two environments and prevent the transfer of particles, usually by means of an air curtain or a pressure difference.
- Containment barrier: A system or device that prevents the release of particles, chemical or biological agents into the surrounding environment, providing additional protection in critical areas of a cleanroom.
- Laminar flow cabinet: Filtration unit that provides a clean working area, protected by a clean, unidirectional air flow.
- Qualification: Process of verification and documentation to demonstrate that a cleanroom meets established design and performance requirements.
- Bioburden: Total number of viable microorganisms present in a sample, usually expressed as Colony Forming Units (CFU) per unit volume or surface area.
- ISO classification: Categorization of cleanrooms according to ISO 14644, based on the concentration of particles in the air.
- Contamination: Undesirable presence of particles, chemical or biological agents in a cleanroom environment.
- Disinfection: The process of reducing the number of viable microorganisms on an object or surface to a safe level.
- Sterilization: The process of eliminating or inactivating all viable microorganisms, including bacterial spores, on an object or surface.
- HEPA Filtration: High Efficiency Particulate Air Filtration, used to remove airborne particles from the air.
- ULPA Filtration: Ultra Low Penetration Air Filtration, a more advanced air filtration than HEPA, used to capture extremely small particles.
- Laminar flow: Unidirectional air flow at constant and parallel velocity, minimizing turbulence and reducing the risk of contamination.
- Turbulent flow: Air flow that does not follow a defined pattern and can cause the dispersion of particles and contaminants.
- Quality assurance: A system of procedures, tests and preventive actions designed to ensure that a product, process or service meets specified quality requirements.
- GMP: Good Manufacturing Practices, a set of regulations governing production and quality control in the manufacture of pharmaceutical, cosmetic and food products.
- HVAC: Heating, Ventilation and Air Conditioning, a system that controls the temperature and humidity in a clean room.
- ISO 14644: International standard that establishes requirements and classifications for cleanrooms and controlled environments, including the measurement and monitoring of particulates and environmental parameters.
- Particulate Matter Monitoring: The process of measuring and monitoring the concentration of particulate matter in the air to ensure compliance with cleanliness requirements.
- Particulates: Microscopic solids or liquids suspended in the air, which can carry contamination in a cleanroom.
- Pass-boxes: (Passthrough or SAS) Device for transferring materials between areas of different classification, minimizing exposure to the external environment.
- Differential pressure: The difference in pressure between two adjacent areas, used to control air flow and prevent cross-contamination.
- Modular Cleanroom: Cleanrooms of modular construction, allowing for easy installation, expansion and reconfiguration.
- Cleanroom: Environmentally controlled space designed to minimize contamination and maintain a specific level of cleanliness.
- Validation: The process of ensuring and documenting that a system or process in a cleanroom works consistently and produces the expected results.
- Cleanroom clothing: Special clothing designed to minimize particle release and protect the worker and the cleanroom environment.