Room for regulations: the basics of ISO cleanrooms for medical manufacturing

Tom Hoover, business development manager, medical, Emerson Automation Solutions discusses the basics of ISO Cleanrooms for medical manufacturing.

Generally, cleanroom performance specifications or contamination limits are based upon the products being developed or manufactured. For example, cleanroom specifications for manufacturing semiconductors differ in being several orders of magnitude “cleaner” than, for example, a cleanroom used to manufacture disposable surgical instruments such as scalpels or hemostat clamps.

Cleanrooms typically are rated by cleanliness levels, which establish quantitative limits on the number of particles and their size per cubic metre volume of air. The International Standards Organization (ISO) has developed standards dedicated to cleanrooms, outlining the practices and procedures required to manage the risk of contamination.

Levels of permissible particulate concentrations for manufacturing in cleanrooms have been established by the International Standards Organization in the ISO 14644-1 standard. This standard defines nine levels, or classes, of cleanrooms — ISO Class 1 through Class 9 — based on permissible particulate contaminant levels, with ISO Class 1 being the “cleanest” and Class 9 being essentially equal to ambient room air. The most used ISO cleanroom classifications for medical device or consumer electronics manufacturing are ISO 7 and ISO 8. Generally, each class has 10x fewer permissible particles than the class above it. So, for example, while a Class 8 cleanroom can have 100,000 particles per cubic metre volume of air, Class 7 cleanrooms only allow 10,000 particles per cubic metre.

Cleanrooms at ISO Class 7 or cleaner require double pass-through entrances. These special entrances provide a controlled environment — essentially an airlock — that is positively pressurised to help prevent particle transmission into the cleanroom. The outermost pass-through door leads into a gowning room where workers don smocks, booties, headwear, masks and gloves usually made of non-shedding, nonwoven fabrics, as well as specialised gloves. Gowning rooms often feature special gowning procedures, “air showers” to remove passive particulates on clothing or personal protective equipment (PPE), and “sticky” floor mats to help remove and capture particles carried in on the soles of shoes. After proper gowning, personnel may pass through the inner door to the cleanroom space. 

Managing cleanroom airflows

Laminar airflow analysis is used to visualise the flow of air in a cleanroom and how that flow is affected by people, objects or process equipment. Ideal laminar airflow is uniform in direction and velocity, like a smooth-flowing river that consistently sweeps particles down toward the floor before flowing them horizontally to low-wall air returns.

Disruptions in laminar airflow cause turbulence — a rapid or uncontrolled movement of contaminating particles — while inadequate laminar airflow can result in “dead zones” where no air is moving at all. Both of these are problems: Turbulent airflows can suspend particles in the air, while dead zones can allow for particles to settle on exposed surfaces. In either case, particulate contamination tends to build up over time and circulate within the cleanroom, rather than being swept down to the air returns and filtered away.

Airflow problems can also result from surface irregularities, such as cracks or joints, because they can trap particles. Sharp edges can also be troublesome, since they can snag and retain fine strands of PPE garments or the cleaning cloths used during periodic wipe-down procedures. Even sharply angled surfaces, such as the 90-degree corner on a table, can create turbulent airflows that hold particulates in suspension and prevent their efficient movement toward the air returns. 

As the cleanroom class, or cleanliness level, increases so does the level of required filtration and air turnover. The air supply for a cleanroom is typically filtered through HEPA (high-efficiency particulate air) or ULPA (ultra-low particulate air) filters. These filter requirements, as well as the air volumes cycled through them, are calculated to enable the cleanroom to manage and overcome the particulate loads generated by human activity, process equipment and manufacturing operations.  

HEPA filters are often constructed with corrugated internal structure and aluminium support, using dense nonwoven fibre material designed for the appropriate filtration levels. HEPA filters also have an ISO rating corresponding to a specific level of filtration and particulate removal or reduction, defined by the requirements of the ISO 29463 standard.

Cleanroom cost factors

Manufacturing in cleanroom environments adds significant operational costs to the manufacturing process. The ISO operating class is a primary driver of the clean space operational costs because each class mandates specific levels of filtration and room-air cycling. However, particulates generated by processing equipment, which can represent as much as 35% of all particulates generated during production operations, also contribute significantly to cleanroom operational costs. Careful selection and specification of processing equipment, specific to the process requirements, should consider the known levels of potential shedding of particulate, and be quantified to effectively manage and minimise clean space operational costs.

Managing active and passive particulate generation 

Particulates and contaminants can be generated actively or passively. Two significant sources of active particulate contamination are human activity and process equipment. Therefore, it is essential that process equipment be specified and selected based not only on production needs but also on the level of particulate generated when in use. For example, process equipment or positioning stages that have moving or sliding surfaces, such as linear bearings or ball screws, can generate airborne particulates. Some lubricants used on these moving surfaces can also contribute particulates. As a best practice, manufacturing process equipment should be designed to reduce both active and passive particulate generation, so that the cleanroom environment can operate within ISO specifications while minimising operational costs.  

Best practices to reduce active particulate generation include:

• Use synthetic lubricants and greases instead of hydrocarbon-based products.
• Use sealed bearings whenever possible.
• Use laminar flow analysis to analyse design of process equipment surfaces and maximise smooth airflow across those surfaces.
• Ensure air-filtration and room-air turnover capacity is sufficient to overcome particulate generation from people, process and equipment. 

Best practices for reducing passive particulate generation include: 

• Use stainless steel or anodised aluminium for all exposed surfaces and fasteners. 
• Design and construct cleanroom equipment with smooth surfaces that minimise or eliminate joints or cracks. 
• Use low-VOC (volatile organic compound) paints to minimise outgassing from any painted surfaces. 

Successful design and operation of a cleanroom for manufacturing medical devices or components begin with attention to the basics. Consult with your cleanroom supplier, as well as your assembly equipment supplier, for the information you will need to make wise decisions that ensure the most productive and cost-efficient operation possible.