A Cleanroom is an operating space in which particulate concentration is controlled within defined parameters. Cleanroom design is governed by GMP (Good Manufacturing Practice). GMP regulations ensure that cleanrooms are designed, maintained, and operated in a way that minimises contamination risks and ensures product quality. There is a sliding scale of cleanliness to a cleanroom, and these range from “clean and controlled” up to “Sterile” The level of cleanliness will be determined by the operation taking place within. Below is a summary of the different levels of GMP classifications.

 

ISO Class	Particles per cubic meter (≥0.5µm)	EU GMP Equivalent	Typical Use Case
ISO 1	N/A	No Equivalent	Sampling and statistical limitations for particles in low concentrations make classification inappropriate.
ISO 2	N/A	No Equivalent	Sampling and statistical limitations for particles in low concentrations make classification inappropriate.
ISO 3	35	No Equivalent	High-end microelectronics.
ISO 4	352	No Equivalent	Some pharmaceutical applications.
ISO 5	3,520	Grade A	Sterile filling of medicines, surgical implants.
ISO 6	35,200	Grade B	Background area for Grade A clean zones.
ISO 7	352,000	Grade C	Non-sterile medicine production.
ISO 8	3,520,000	Grade D	General pharmaceutical manufacturing.

 

ISO standard 14644-1, provides the following definition:

‘A room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation and retention of particles inside the room and in which other relevant parameters, e.g. temperature, humidity and pressure are controlled as necessary’.

While this is a clear and precise definition which guides us to design finishes and services that can meet the stringent requirements, there is of course much more to consider. A Clean room is also a place of work and while the processes undertaken within it may dictate layout, finishes and environmental controls, the needs of the occupants and the activities they are carrying out are also of paramount importance within the design solution. Safe access and workspaces, comfortable environmental conditions, the ergonomics of the space and adequate access for equipment installation and removal, and maintenance, are all important factors to be incorporated, as is the overall budget allowed for the project.

Nevertheless, the process for which the area is designed will inevitably require stringent adherence to the relevant regulations and the design must fundamentally ensure that all aspects of the facility and its environment are in full compliance with the required standards.

Several key considerations will therefore be required, as outlined below:

1. Understanding the Process

This is a crucial step in the development of the design brief, to ensure that the facility can ultimately meet the requirements of the processes to be undertaken.

The stage of development or manufacture is critical to determining the grade of cleanroom required. The type of product, its potency and sensitivity to environmental conditions, how it will ultimately be administered and its level of exposure to the environment during the process, will all be factors in determining the grade of cleanroom required and hence, the design principles to be followed.

Process Equipment specifications, Material handling and occupancy levels need to be established to determine the space requirements within the area and to optimise the ergonomic design of the accommodation.

Our understanding of the process is fundamental to ensuring that we provide the optimum room layout, with spaces maintained within the required environmental conditions.

2. Material and Personnel flows – Room adjacencies

A Process Map should be constructed to clarify the operational process flow.

This will highlight the process steps from receipt of incoming materials, through to the despatch of product from the facility.

Similarly, personnel movement through the facility, including any changing and gowning requirements, should be thoroughly reviewed to ensure that it aligns with the flow of the process and allows the optimal room layout to be established, taking account of access routes through the facility, waste management and maintenance access.

Routine maintenance should be able to be performed without compromising the room classification wherever possible, and this can only be achieved by gaining a detailed understanding of these requirements at this early stage.

3. Particulate and Contamination Control

To meet the established cleanroom standard, we must focus on minimizing contamination risk (cross contamination from lower grade areas; airborne contamination; contamination brought in by personnel or equipment).

The facility layout will again be affected by the addition of airlocks between areas of differing classification. The room finishes must ensure that it is fully sealed to its adjacent environment using smooth, non-porous and easy-to-clean surfaces which are resistant to chemical exposure relating to cleaning agents or manufacturing processes.

Airflow is critical to minimizing particulates and in the prevention of airborne contamination.

The airflow solution will be determined firstly by the required grade of cleanroom. For example, an ISO 5 area, which may be required for aseptic production, would typically require unidirectional airflow, HEPA filtered at the point of supply. ISO 14644-3 recommends an air velocity (measured 150mm to 300mm below the plenum) of between 0.36 m/s to 0.54 m/s, with low level return air paths incorporated into the room fabric, to ensure that the air remains unidirectional throughout its travel through the space.

Typically, ISO 6,7 and 8 cleanrooms may be designed using non-unidirectional airflow in combination with filtered point of supply and low-level return paths.

Air Change Rates should be calculated to maintain the specified maximum particulate concentration while taking into account the occupancy and levels of gowning. The traditionally specified air change rates, which prescribe a fixed rate to meet a specified grade, take no account of the specific operation of individual facilities, and generally result in higher than required airflows with resultant energy waste and increased capital expenditure.

Pressure gradients should be designed to provide airflow cascades from higher to lower grades, in order to prevent airborne contamination ingress, or to provide containment where cross contamination is deemed a risk.

4. Environmental Control

Achieving the required temperature and humidity, and maintain stable control over these parameters, will usually be critical to the process. Every product or procedure will have unique requirements, and our air system design must provide the capability of meeting these conditions, while the associated control system will be designed to ensure that the required stability of conditions is maintained.

The processes being undertaken will also dictate airflow control requirements within the facility. Cleanliness levels will be maintained by a carefully designed positive pressure regime design, allowing air to flow from higher to lower grade rooms, through door interlocked airlocks where required. Similarly, potent products or hazardous environments will require a negative pressure regime to be implemented to ensure that surrounding areas cannot be contaminated.

All of these parameters will be controlled and monitored by the centralised Building Management System, for the facility. Depending on the dictates of the qualification requirements, an independent Environmental Monitoring System may also be utilised to continuously measure and record Temperature, Humidity, Pressure and Particle Concentrations, thus providing full traceability throughout the process cycle.

5. Integration of Utilities and Services

The operation of the room and incorporated equipment is reliant on carefully designed power and water and gas utilities, accurately sized to provide the necessary flow rates, pressures and power requirement to ensure uninterrupted operation.

All of these services should ideally be concealed within the fabric of the ceilings and walls, to maintain a smooth, crevice free finish to the internal faces, to aid cleaning and prevent the trapping of particulates.

Maintenance is also a key consideration. Wherever possible, maintainable items (such as dampers or valves) should be located within the designated plant spaces to allow repairs and adjustments to be carried out without contamination risk to the controlled space.

Where local isolation or equipment maintenance is required, then purpose designed access panels should be provided, which can be sealed to prevent air leakage or particle ingress.

Where sockets, screens or HMI panels are recessed into partitions, they should (where heat gain is not an issue) be enclosed within a mounting box manufacture from non-porous, non-shedding material, with any entry ports fitted with grommets and well-sealed.

6. Energy Efficiency

As can be seen from the previous points, Cleanrooms are inherently energy hungry to maintain the closely controlled environment required and are constructed from high quality materials which themselves require high energy input to facilitate their manufacture.

Our design must seek to reduce the energy input, without compromising the classification and functionality of the space, thus increasing energy efficiency.

Offsite pre-fabrication of construction elements such as partition walls, or engineering plant including pump and fan skids, can help to reduce material wastage while local sourcing of products wherever possible can significantly reduce transportation.

A well-sealed space is required to achieve the required air pressures and to prevent contamination by particle or air ingress. Conversely, a poorly sealed space will require greater quantities of air to provide this pressurisation. Exacting quality inspections during construction are of paramount importance to ensure that supply and extract airflows can be utilised at their designed values.

Air Change Rates should be optimized by calculation, with knowledge of the gowning protocols that will be in place in operation. This prevents the use of unnecessarily high air change rates based on historical norms. Any reduction will result in smaller plant and distribution systems and lower power input requirements.

More well-established principles should also be considered, e.g., Variable volume/flow systems, heat recovery systems, high-efficiency motors, LED lighting, etc. All will help minimize energy requirements and, in many cases, will be fundamentally necessary to comply with the Building Regulations.

7. Qualification

All GMP facilities will be required to be qualified and validated as part of the process. A qualification master plan (QMP) would be produced outlining the overall strategy for qualification. This would include timelines, roles and responsibilities and acceptance criteria.

The different stages of qualification are as follows:

Design Qualification (DQ)

• Confirm that the design of the facility, systems, and equipment meets GMP requirements.
• Ensure alignment with process and product specifications.
• Review engineering drawings, specifications, and material compatibility.

Installation Qualification (IQ)

• Verify that equipment, utilities, and systems are installed as per design specifications.
• Document the installation details (e.g., location, materials, connections).
• Check compliance with applicable engineering standards.

Operational Qualification (OQ)

• Test systems and equipment to ensure they operate within specified parameters.
• Verify controls, alarms, and interlocks function correctly.
• Perform environmental qualification (e.g., HVAC systems) to ensure required conditions (e.g., temperature, humidity) are met.

Performance Qualification (PQ)

• Demonstrate that systems and equipment consistently perform as intended under real-world conditions.
• Validate processes with simulated production runs or actual products.
• Conduct environmental monitoring to confirm compliance with cleanliness standards.

Follow on works from the qualification process is validation, Documentation and training

A Final Word

Closely controlled environments are essential to our modern lifestyles in relation to health, food production, electronics as well as manufacture and research and development projects throughout many of our industries. Our cleanroom designs will need to meet regulatory standards, while also being tailored to the industry / process for which they are to be employed. Close collaboration between architects, services designers and construction teams is essential to providing a fully coordinated solution, which will meet the specific requirements of the processes and products involved.