Detailed Explanation of Modular Cleanroom Cleaning Procedures

modular cleanrooms are widely used in pharmaceutical, biotechnology, medical device, semiconductor, and precision manufacturing environments. Their construction may include prefabricated panels, ceilings, flooring systems, and integrated utilities. While the controlled environment is modular, the cleaning program should be defined, documented, and aligned with the facility's contamination-control needs, approved procedures, and applicable requirements.

This article explains how to approACH modular cleanroom cleaning procedures, from preparation and sequencing to tools, disinfection, verification, and maintenance.

Why Modular Cleanroom Cleaning Requires a Defined Procedure

cleanrooms Control Contamination, Not Simply Visible Dirt

A cleanroom is designed to control airborne particle concentration and, where required, other contamination risks. ISO 14644-1:2015 specifies the classification of air cleanliness by airborne particle concentration. It does not classify surface cleanliness or characterize the chemical or viable nature of airborne particles.

Cleaning therefore addresses soil, residue, and contamination on surfaces and equipment. It is separate from airborne particle classification and should not be assumed to achieve a given microbiological state unless validated for that purpose.

How Modular Construction Changes the Cleaning Assessment

Modular construction can introduce seams, joints, penetrations, and interfaces between panels, ceilings, floors, doors, and service connections. These features are not identical in every modular room, but they may create areas where soil or residue can accumulate or where access for cleaning is limited.

A cleaning procedure should identify accessible surfaces, defined interfaces, and any areas that require planned access or removal of components. Material compatibility with panels, sealants, coving, and flooring should be confirmed with the supplier or through facility testing.

Cleaning, Disinfection, Sanitization and Decontamination: Know the Difference

Cleaning

Cleaning removes visible and non-visible soil, residue, and contaminants from surfaces. Prior cleaning is commonly part of an approved procedure where disinfection is required. In EU GMP Annex 1 sterile-manufacturing environments, cleaning before effective disinfection is explicitly required.

Disinfection

Disinfection is a separate controlled step intended to reduce or inactivate microorganisms to a defined level. It is not sterilization. The selection of a disinfectant, its preparation, and its application should follow the facility's approved procedure, with validation where required by the applicable regulatory or quality system. Manufacturer instructions should also be followed.

Sanitization

Sanitization generally refers to reducing microbial contamination to a level considered acceptable for a defined purpose. In cleanroom operations, the term may be used differently across industries, so the SOP should define what the activity includes and how it is controlled.

Decontamination

Decontamination is a broader term for reducing or removing contamination, which may include particles, chemicals, or biological agents depending on context. IEST-RP-CC018.6:2026 includes a section on decontamination for planned or unplanned disruptions and recovery planning.

What Determines a Modular Cleanroom Cleaning Procedure?

1. cleanroom classification

The classified air cleanliness level informs the Contamination Control Strategy but does not by itself dictate cleaning frequency or disinfectant choice. ISO 14644-5:2025 addresses operations control, including personnel, entry and exit of personnel and materials, cleaning, maintenance, and monitoring.

2. Process and Product Risk

The product, process, and patient or end-user risk influence cleaning requirements. For sterile drug and biological products manufactured using aseptic processing in the U.S., FDA aseptic-processing guidance provides additional recommendations.

3. Contamination Type

Particles, chemical residues, and microbiological contamination require different assessment methods and cleaning approaches. ISO 14644-13:2026 can support assessment of surface cleanliness by particle and chemical concentration, but it does not prescribe pharmaceutical residue acceptance limits, microbiological disinfection requirements, or detailed site-specific procedures.

4. Surface and Material Compatibility

Cleaning agents and tools must be compatible with panels, sealants, flooring, coving, and equipment surfaces. Compatibility should be verified with suppliers and through facility evaluation before routine use.

5. Environmental Monitoring and Historical Data

Monitoring data can help identify trends, recurring contamination, or areas requiring additional attention. However, airborne particle monitoring, surface particle assessment, chemical residue evaluation, and microbiological monitoring are not interchangeable.

6. Regulatory and Quality-System Requirements

FDA 21 CFR 211.56 requires written sanitation procedures covering buildings and facilities, cleaning schedules, methods, equipment, and materials. FDA 21 CFR 211.67 specifically addresses equipment and utensil cleaning and maintenance. The specific methods and frequencies must be appropriate to the facility and product.

How to Build a Cleanroom Cleaning SOP

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SOP Scope

Define the areas, surfaces, equipment, and activities covered. State what is excluded and how adjacent or supporting areas are handled.

Responsibilities

Assign responsibilities for preparation, cleaning, disinfection, inspection, documentation, and approval. Training requirements should be defined.

Approved Cleaning Materials and Tools

List approved wipes, mops, vacuums, buckets, cleaning agents, and disinfectants. Include preparation instructions where applicable.

Cleaning Method

Describe the accepted technique for each surface type. This may include wiping direction, overlapping strokes, and tool change frequency.

Cleaning Sequence

No single universal sequence applies. The sequence should be determined through risk assessment and the approved SOP, considering airflow, zoning, contamination sources, surface layout, personnel and material routes, and waste removal. Directional principles may be used only where justified by the specific facility and process.

Frequency

Frequency should be determined by risk assessment, monitoring data, process activity, and facility requirements. IEST-RP-CC018.6:2026 provides guidance for establishing appropriate housekeeping frequency and monitoring effectiveness, without prescribing a universal schedule.

Risk-Based Modular Cleanroom Cleaning Procedure: Step-by-Step Framework

Step 1: Confirm Area Status and Cleaning Authorization

Verify that the area is available for cleaning and that production activities have stopped or are appropriately controlled. Confirm any required gowning, access, and safety precautions.

Step 2: Prepare and Verify Cleaning Tools and Materials

Prepare approved cleaning agents, disinfectants, wipes, mops, and containers. Verify that agents are within their approved use period and that tools are clean and appropriate for the area.

Step 3: Transfer Cleaning Materials Into the Controlled Area

Transfer materials using the facility's approved entry procedure. Avoid introducing contamination through packaging, containers, or transfer equipment.

Step 4: Remove Waste and Defined Gross Contamination

Remove waste and any defined gross contamination according to the SOP. Use approved containers and avoid spreading contamination to adjacent areas.

Step 5: Clean Surfaces According to the Approved Zone Sequence

Clean surfaces in the sequence defined by the SOP. The sequence should be determined through risk assessment, considering airflow, zoning, contamination sources, surface layout, personnel and material routes, and waste removal. No single universal sequence applies.

Step 6: Perform Disinfection Where Required

Apply the approved disinfectant using the specified method. Concentration, preparation, and contact time should follow the facility's approved procedure, with validation where required by the applicable regulatory or quality system. Manufacturer instructions should be followed. Universal contact times should not be assumed.

Step 7: Complete Floor Cleaning According to the SOP

Clean floors according to the approved method and sequence. Floor cleaning should avoid recontaminating cleaned surfaces or spreading contamination to other areas.

Step 8: Remove Used Supplies and Waste

Remove used wipes, mops, solutions, and waste according to the SOP. Do not leave used cleaning materials in the controlled area.

Step 9: Inspect and Verify the Area

Perform the required visual inspection and any specified verification activities. Verification methods should match the contamination of concern and the facility's approved procedures.

Step 10: Complete Cleaning Records and Release the Area

Record the cleaning activity, including date, area, method, materials, and personnel. Release the area according to the facility's quality system.

Cleanroom Cleaning Tools: What Should Be Selected?

Selecting Cleaning Agents and Disinfectants

Match the Agent to the Contamination

Select agents based on the contamination to be removed or controlled. Cleaning agents address soil and residue; disinfectants address specified microorganisms. The two functions are not interchangeable.

Verify Material Compatibility

Confirm compatibility with panels, sealants, flooring, coving, and equipment surfaces. Supplier guidance and facility testing can support this assessment.

Concentration, Preparation and Contact Time

Follow the facility's approved procedure and manufacturer instructions for preparation and use. Do not assume universal concentrations or contact times.

Cleaning-Agent Residues

Residues from cleaning agents may affect surfaces or processes. ISO 14644-13:2026 addresses surface cleanliness by chemical concentration, which is relevant to residue assessment.

Pharmaceutical cleanroom Cleaning and Disinfection

U.S. Pharmaceutical Facilities

FDA 21 CFR 211.56 requires written sanitation procedures covering buildings and facilities, cleaning schedules, methods, equipment, and materials. FDA 21 CFR 211.67 specifically addresses equipment and utensil cleaning and maintenance. FDA aseptic-processing guidance concerns sterile drug and biological products manufactured using aseptic processing in the U.S. and provides additional recommendations for those products.

EU GMP Annex 1 for Sterile Manufacturing

EU GMP Annex 1 is primarily intended for sterile medicinal-product manufacture, though selected principles may be applied to some non-sterile products where justified and documented. For EU sterile manufacturing environments, Annex 1 requires a written cleaning and disinfection programme. Cleaning before effective disinfection is explicitly required. Disinfectant residues should be removed. Disinfection should be validated for its specific use and surface material.

Sterile vs. Non-Sterile Areas

Sterile areas typically have more stringent contamination-control expectations. Non-sterile areas may have different requirements based on product and process risk. The SOP should reflect the applicable regulatory framework.

How Often Should a Modular Cleanroom Be Cleaned?

Factors That Determine Frequency

Frequency should be determined by:

• cleanroom classification and area function
• Product and process risk
• Contamination type and monitoring data
• Facility activity level and personnel traffic
• Regulatory and quality-system requirements
• Historical cleaning and monitoring trends

No universal frequency applies. IEST-RP-CC018.6:2026 provides guidance for establishing appropriate housekeeping frequency and monitoring effectiveness. The facility should document the rationale for its chosen frequency.

Cleaning High-Risk and Difficult-to-Reach Modular Cleanroom Areas

Panel Joints and Seams

Inspect and clean accessible joints and seams according to the SOP. Where access is limited, the procedure should define how cleaning is performed or why the area is excluded.

Floor-to-Wall Coving and Corners

Coving and corners can accumulate soil and residue. Cleaning should include these areas using compatible tools and agents.

Doors, Handles and Interlocks

High-touch surfaces such as handles and interlocks may require defined cleaning attention. Compatibility with electronic components should be verified.

Windows and Pass-Throughs

Clean window surfaces and pass-through interiors according to the SOP. Pass-throughs may require cleaning on both sides.

Supply and Return-Air Components

Air-supply and return components should be cleaned only according to an approved procedure. HVAC and filter components should not be cleaned without appropriate authorization and training.

Service Penetrations and Utility Interfaces

Penetrations and utility interfaces should be assessed for cleanability. Where required, seals and covers should be inspected and maintained.

Cleaning After Maintenance, Repair or Construction

Why Maintenance Changes Contamination Risk

Maintenance, repair, and construction can generate particles, introduce tools and materials, and disturb surfaces. The contamination risk may change during and after these activities.

Perform an Impact Assessment

Assess the impact of the activity on the controlled area, including affected surfaces, air quality, and adjacent zones.

Recovery Cleaning

Perform recovery cleaning according to the SOP. IEST-RP-CC018.6:2026 includes a section on decontamination and recovery planning for planned or unplanned disruptions.

Verification or Requalification

Determine verification requirements through impact and change assessment and the applicable qualification programme. Not every repair requires full requalification.

How to Verify Cleaning Effectiveness

Visual Inspection

Visual inspection is a basic check but may not detect all contamination. It should be performed according to the SOP.

Airborne Particle Monitoring

Airborne particle monitoring provides information about air cleanliness. ISO 14644-2:2015 addresses monitoring to provide evidence of cleanroom performance related to airborne particle concentration. It does not verify surface cleanliness.

Surface Particle or Chemical Assessment

Surface particle or chemical assessment can evaluate surface cleanliness by particle or chemical concentration. ISO 14644-13:2026 provides guidance on surface cleanliness by particle concentration and chemical concentration, and excludes microbiological aspects.

Microbiological Monitoring

Microbiological monitoring addresses viable contamination. It is separate from airborne particle monitoring and surface particle assessment. The method should be appropriate for the contamination of concern.

Trend Review

Review monitoring and cleaning data over time to identify trends or recurring issues.

Deviations and CAPA

Investigate deviations according to the quality system and implement corrective and preventive actions as required.

Cleanroom Cleaning Checklist

Before Cleaning

During Cleaning

After Cleaning

Common Cleanroom Cleaning Mistakes

Modular cleanroom design Features That Support Cleanability

• Smooth, accessible surfaces
• Reduced recesses and difficult-to-clean features
• Appropriate junctions and coving
• Compatible panels, sealants, and flooring
• Accessible doors, windows, and pass-throughs
• Maintenance access that limits contamination risk

Industry-Specific Cleaning Considerations

Pharmaceutical and Biotechnology

Pharmaceutical and biotechnology facilities should follow applicable GMP requirements. FDA 21 CFR 211.56 and 211.67 are relevant for U.S. operations. For sterile products, FDA aseptic-processing guidance and EU GMP Annex 1 provide additional expectations.

Medical Device Manufacturing

Medical device manufacturing may have specific contamination-control requirements based on the device and its intended use. The SOP should reflect applicable regulatory and quality-system requirements.

Semiconductor and Electronics

Semiconductor and electronics manufacturing may have specific requirements for particle and chemical contamination control. ISO 14644-13:2026 addresses surface cleanliness by particle and chemical concentration.

Aerospace, Optics and Precision Manufacturing

These industries may have specific contamination-control needs. The cleaning procedure should be based on the contamination of concern and the facility's requirements.

Frequently Asked Questions

How do you clean a modular cleanroom?

Follow the facility's approved SOP. A typical framework includes preparation, cleaning, disinfection where required, waste removal, inspection, and documentation. The specific methods should be based on risk assessment.

What is the correct cleanroom cleaning sequence?

No single universal sequence applies. The sequence should be determined through risk assessment and the approved SOP, considering airflow, zoning, contamination sources, surface layout, personnel and material routes, and waste removal.

How often should a modular cleanroom be cleaned?

Frequency should be determined by risk assessment, monitoring data, process activity, and regulatory requirements. No universal frequency applies. IEST-RP-CC018.6:2026 provides guidance for establishing appropriate housekeeping frequency.

Which disinfectant should be used?

Disinfectant selection should be based on the contamination of concern, surface compatibility, and the facility's approved procedure. iso class does not dictate disinfectant choice.

How is cleaning effectiveness verified?

Verification may include visual inspection, surface particle or chemical assessment, and microbiological monitoring where applicable. Methods should match the contamination of concern and the facility's SOP. Airborne particle monitoring is not a substitute for surface verification.

Is modular cleanroom cleaning different from conventional cleanroom cleaning?

The principles are similar, but modular construction may require additional attention to seams, joints, penetrations, and interfaces. These features should be assessed for cleanability and included in the SOP where relevant.

Conclusion: Risk-Based Modular Cleanroom Cleaning Program

The modular cleanroom sanitation regimen must be developed according to the parameters set forth in the approved SOPs of the facility, the associated risks, the level of contamination, the compatibility of surfaces, the recorded monitoring information, and the regulatory requirements. The cleaning process’ goal is to eliminate contaminants and residues, but disinfection must be conducted as a separate step in the procedure. It is necessary to recognize that an assessment of the airborne concentration of particles does not indicate that a surface is sterile.

The cleaning process should take into consideration such parameters of modular construction as joints, seams, penetrations, and surface connections. The methods for confirming the success of the cleaning activities must correspond to the type of contamination identified.

Discuss Cleaning and Maintenance Requirements Before Specifying a Modular Cleanroom

Cleaning and maintenance requirements should be considered during the design and specification of a modular cleanroom. Surface materials, junctions, coving, access points, and utility interfaces can affect cleanability. Facility teams, quality, and suppliers should discuss these requirements before finalizing specifications.

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