Proper cleanroom cleaning procedure and maintenance protocol is an immediate, low-cost measure to enhance overall cleanliness, consistency, and contamination control within cleanrooms. This guide provides a framework for cleanroom management, protocol standards, specifications, and processes for general manufacturing and biomedical applications. Because each cleanroom class can require slightly different supplies and protocol, this overview connects best practices with application specific techniques for gowning, wipedown, and particle control. This guide should serve as a resource for understanding broad-line cleanroom consumable needs, but not as a replacement for expertise tailored to your application.
Quick Access Guide for Cleanroom Gowning, Cleaning, Design & Maintenance
What is a Cleanroom?
A cleanroom is a controlled environment where products are packed, manufactured, and assembled. The room eliminates sub-micron airborne contamination generated from people, processes, facilities and equipment. The higher the level of cleanliness, the lower the likeliness of particles or microbes damaging or corrupting production processes by tainting sterile and non-sterile products.
Cleanroom design and construction requires tight controls over contamination, air flow rate, pressure, temperature, and humidity. As a manufacturing asset, the ability to produce, assemble, preserve and inspect a clean end product is paramount before delivery. While most cleanrooms function in similar fashion, the levels of control and particulate levels vary widely. The dirtiest cleanrooms may contain 1,000,000 micron sized particles per cubic meter, while one of the cleanest cleanrooms (ISO Class 3) may contain just 1000 particles or less. The ISO class system provides an industry-wide standard for cleanliness and particles counts, therefore helping facilities measure and test their contamination levels against established benchmarks.
What’s the Difference Between ISO 14644 Cleanroom Standards and US Fed Standard 209E Cleanroom Standards?
ISO 14644 replaced the previous cleanroom standard, Federal Standard 209E in 2001. The federal standard provides an imperial measure of units (particles per cubic ft.), while ISO standards use metric units (particles per square meter). ISO Class standards outline a higher degree of micron level particulates starting at 0.1 micron, while FS 209E references a standard particle diameter of 0.5 micron.
It should be noted that these standards are easily confused, sometimes even in manufacturer spec sheets — a “Class 1” (Fed. Standard) cleanroom has a particle threshold equivalent of an “ISO Class 3” (ISO Standard). Unless specifically noted as an “ISO” standard, one could assume that the US Fed. Standard 209E is being referenced, which was officially canceled by the General Services Administration of the US Dept. of Commerce November 29, 2001, but is still widely used.
The impact of particles on a production process is not always predicated by volume, but instead by specific sizes of problematic particles based on the application. The increased specificity of ISO class cleanroom standards provides a more accurate and translatable picture of cleanliness, because it defines allowable particle counts in stages of 0.1 micron – 5 microns. The 0.5 micron standard of the FS 209E systems is continually growing outdated; as the rush for smaller components and more sensitive devices grows and cleanrooms become cleaner, particle thresholds require increased sensitivity. Likewise, particle counting technology has improved the ability to detect and differentiate aerosol (airborne) particles with impressive accuracy. Learn more about cleanroom standards, and additional standards such as British standard or GMP EU (e.g. Class A) standards.
Related Reading: How Do Particle Counters Work?
(A) ISO Class 5 Cleanroom (formerly Class 100) is an atmospheric environment that contains less than 3,520 particles 0.5 microns in diameter per cubic meter of air (formerly stated as 100 particles 0.5 microns in diameter per cubic foot of air).
(B) ISO Class 7 Cleanroom (formerly Class 10,000) is an atmospheric environment that contains less than 352,000 particles 0.5 microns in diameter per cubic meter of air (formerly stated as 10,000 particles 0.5 microns in diameter per cubic foot of air).
(C) ISO Class 8 Cleanroom (formerly Class 100,000) is an atmospheric environment that contains less than 3,520,000 particles 0.5 microns in diameter per cubic meter of air (formerly stated as 100,000 particles 0.5 microns in diameter per cubic foot of air).
(D) Cleanroom Buffer Area, Buffer or Core Room, Buffer or Clean Room Areas, Buffer Room Area, Buffer or Clean Area, or Buffer Zone–An ISO Class 7 area where the primary engineering control area is physically located. Activities that occur in this area include the preparation and staging of components and supplies used when compounding sterile preparations.
(E) Cleanroom Anteroom–An ISO Class 8 or better area where personnel may perform hand hygiene and garbing procedures, staging of components, order entry, labeling, and other high particulate generating activities. It is also a transition area that reduces heat and ventilation needs while maintaining positive pressure flow from clean to dirty work areas.
(F) Cleanroom Contamination— A process, act, or energy that causes materials to be soiled or coated with substances is called contamination. Contamination is distinguished within two categories: film layers and particulates. Electrostatic discharge (ESD) could also be considered as a contaminant, although ESD prevention differs incomparably in regards to cleanroom protocol and practices discussed here. Get more info on ESD cleanrooms here.
(G) Controlled environments— Feature a building, cell, or room in which the supply, exhaust, and filtration of room air and surface cleanliness are tightly controlled.
Cleanroom Contamination Control Processes
Common Cleanroom Contaminants
Some of the most common cleanroom contamination include solid dust, liquid, bacteria, fungus, human skin cells and hair, trace moisture, spills and leaks, cosmetics, perfumes, lint, fibers, and more. The vast majority of cleanroom contamination comes from those that work within it.
Cleanroom design and construction address contamination in a few ways:
- Preventing particle entry from air filtration systems or air gaps
- Purging and filtering room air throughout the production process
- Providing parallel stages and adjacent rooms of differing cleanliness eg; gowning or garbing room for dressing and donning, cascaded anter and buffer rooms for preparation and storage
- Isolated clean spaces and air pressure within laminar flow hoods for isolated procedures such as sterile compounding or hazardous chemicals
Best Practices for Entrance Rooms, Garment Rooms, Ante-rooms
- The section leading into a cleanroom should be at least as clean as the room itself
- All personal items such as keys, watches, rings, matches, lighters and cigarettes should be stored in the personal locker outside the
- Place a sticky mat at the entrance of a gowning room with a waste receptacle nearby for discarding saturated sticky tack layers
- Watches, jewelry, and any clothing should be stored on the “dirty” side of the gowning room.
- Don’t smoke 30 minutes before entering.
Hand Washing Best Practices for Cleanrooms
While wearing gloves in a cleanroom is standard practice, those who wear gloves are less likely to wash or clean their hands prior to donning gloves. Poor hand hygiene increase the vulnerability of cleanrooms to bacteria and potential transfer or introduction of microbes such as viruses and fungus.
How to Wash Hands with Soap & Water in a Cleanroom
- Wet hands first with water, then apply soap
- Apply the manufacturer recommended amount of soap
- Use of paper towels is prohibited. Use HEPA equipped hand dryers
- Scrub hands for at least 15 seconds, and cover all hand surfaces
- Avoid using hot water, which may increase the risk of dermatitis
- Do not add soap to a partially empty soap dispenser
- Get input from employees about any fragrance or irritation issues
- Never touch a clean garment of clean material before thorough hand washing
- For EPA (electrostatic protected areas) cleanrooms, apply an ESD lotion, as standard lotions may compromise the effectiveness of ESD wristbands and monitoring stations
- Keep natural fingernails less than 1/4″ long
- Monitor the volume of use for alcohol based hand rubs
Sterile Gloving Technique for Cleanrooms
Cleanroom gloves are worn for one of two reasons: to protect the wearer from exposure to dangerous or irritative substances, and to protect cleanroom products from contaminants introduced through operators, equipment, or airborne particles. Pharmaceutical manufacturers will generally require sterile gloves with cleanroom designated packaging. Standard surgical glove packaging generally uses a polycellulose spunwoven fabric which generates a high count of particles when opened and handled. Cleanroom glove packaging features a polyethylene, easy open packaging which is washed with deionized water, assembled in an ISO Class 4 cleanroom, and then packaged for delivery in an ISO Class 5 Cleanroom.
Best Practices for Donning Cleanrooms Gloves
You Should Not:
- Wear jewelry, fingernail polish, or cosmetics.
- Do not wave gloved hands to speed drying after applying alcohol solution.
- Never touch exposed skin with a gloved hand.
Cleanroom Gowning Procedure and Protocol
Cleanroom gowning protocol differs depending on cleanroom class and application. In ISO Class 7 or ISO Class 8 cleanrooms, frocks are often acceptable. A cleanroom classified as ISO Class 5 or ISO Class 6 (or cleaner) requires cleanroom coveralls, along with hoods, gloves, and booties (shoe covers). For sterile processing, additional precaution is needed to assure that no sterile surfaces contact non-sterile surfaces during gowning, processing, or cleaning.
Cleanroom Gowning Procedure Checklist
- Before entering gowning room taking at least three small steps with each foot; remove dirty sticky mat layer if needed.
- Use a shoe brush cleaner
- Don shoe cover booties
- Don cleanroom bouffant
- Wash hands thoroughly (use waterless alcohol solution for USP 797)
- Put on cleanroom glove liners
- Apply alcohol solution to outside of liners
- Put on cleanroom gloves
- Wash or apply alcohol solution to cleanroom gloves
- Apply cleanroom bouffant (beard covers for those with facial hair)
- Apply a freshly laundered cleanroom hood
- Attach facemask
- Apply coveralls, only touch the floor on the clean side of a gowning bench
- Hoods are tucked inside of coveralls
- Put on cleanroom booties
- Put on cleanroom gloves
- Ensure that booties and gloves overlap the coveralls
- Wipedown the gowning bench with a clean, sterile wiper
- Use cleanroom mirror for self-check
USP 797 Protocol and Gowning Requirements
While USP 797 provides a dedicated order for personnel cleansing and garbing, these specifications may change according to state regulation. For help regarding localized requirements, contact an expert.
USP 797 Personnel Cleansing and Garbing Best Practices
- Do include employees in the quality assurance process and keep them informed of positive and negative hygiene or procedure evaluations.
- Careful and thorough hand cleansing is essential hygiene performed in the anteroom and prior to donning a non-shedding gown.
- Ensure that operators of all shapes and body sizes have access to properly fitting garments.
- Wash hands and forearms up to the elbows for at least 30 seconds with soap and water in the ante-area. (either non-antimicrobial or antimicrobial soap)
You Should Not
- Don’t use scrub brushes on the hands as any skin damage increases skin shedding.
- Don’t use any type of drying wipe except disposable wipes or an electronic hand dryer with HEPA filtration
- Don’t don a gown before completing proper hand hygiene, as splashes from the sink while wearing a non-shedding gown could be a source of microbial contamination.
Cleanroom Garments - Considerations for launderable and disposable cleanroom garments.
The requirements for disposal and use of gowns and garments differs upon cleanroom classification and application. The cleanest cleanrooms dispose of garments after each exit and entry, while cleanrooms with the highest particle thresholds may only change garments twice a week.
Compounding personnel generally prefer gowns that snap or button in the front for easy use, but USP Chapter 797 does not specify a requirement.
All garbs, except for the launderable cleanroom gowns must be disposed of after exiting the cleanroom compounding area.
- Avoid the introduction of non-cleanroom specified cleaning agents
- DI water (deionized water) is recommended for scrubbing of all surfaces, floors, walls, and benches.
- Never use scrubs, rags, or powders for cleanroom use. Cleanroom mops provide materials, such as woven polyester which limit shedding or tearing during cleaning.
- Use an autoclave ready multi-bucket mopping system with non-marring wheels, deep drawn seamless buckets, designated clean and dirty water control.
- Floors will be damp mopped daily before normal work shifts with distilled water and vacuumed dry.
- Floors will be damp mopped weekly with a cleanroom detergent, distilled water, and a HEPA filter vacuum.
- Vacuum walls daily
- Wipe walls with a damp cleanroom sponge and distilled water and vacuum dry once weekly.
- Windows and cleanroom pass-throughs are to be washed and wiped dry daily with lint-free 70% IPA wipes.
- Vacuum ceilings daily
- Wipe ceilings with a damp sponge and distilled water weekly, vacuum dry.
- Wash ceilings with detergent and distilled water whenever necessary to remove deposits, based on application.
- All daily cleaning maybe be performed during normal work shifts with the exception of floors.
- Overhand light lenses and troffers will be wiped with a damp sponge and distilled water weekly, vacuumed dry.
- Change cleanroom sticky mats as needed, and without hesitation.
Proper Cleanroom Working Procedure Protocol
- Walk and move slowly to prevent air turbulence.
- Anticipate and gather all materials and tool supplies to perform the task at hand before entering the cleanroom.
- Clean, inspect, and wipedown all materials and tools entering the cleanroom with a 70% IPA solution.
- Wipe down work areas at the end of each shift, or as designated by classification compliance, for pharmaceutical applications this may be as often as every 30 minutes.
- Understand your cleanrooms airflow patterns and organize accordingly with special attention as not to:
- Block HEPA filtered air from reaching the product with your body or equipment
- Pin or tape note or instruction sheets on a wall or laminar flow tables so as to not block HEPA filter air
- Keep tools, chemicals, and supplies in proper containers or storage cabinets; ensure that placement is downstream from the product as not to contaminate it.
- During lunch or long interruptions, and at the close of the work shift, ensure that all products, supplies, and materials are stored or covered as to protect them from contamination.
- Wipe up any spills or replace soiled garments immediately.
- Wipe down any object that is potentially contaminated with a 70% IPA or discard depending on the item and associated risk.