Medical Device Cleanroom Classification: ISO Classes Explained

If you read about contract manufacturing of medical devices, you will soon meet phrases like "ISO Class 7 cleanroom" or "Class 8 assembly area". They sound precise, and they are, but only about one thing: how many airborne particles are in the air. They say nothing on their own about whether a device is sterile, whether a process is validated or whether a supplier is a good one.

This guide explains what a cleanroom classification is, how the common ISO classes compare, how a classification is checked in outline, and why medical device makers treat the class number as one control among several. It is general information and does not replace the standards or a qualified engineer's advice for a specific facility.

What a cleanroom class actually measures

The international standard that defines cleanroom classes is ISO 14644-1. In its 2015 edition it specifies the classification of air cleanliness in terms of the concentration of airborne particles in cleanrooms and clean zones (and separative devices). Only particle populations with threshold sizes from 0.1 micrometres to 5 micrometres are considered for classification.

A few limits of the standard are worth knowing:

• It does not cover particles smaller than 0.1 micrometres. The standard notes that ultrafine particles will be dealt with separately, and that larger macroparticles can be described using a separate "M descriptor".
• It cannot be used to characterize the physical, chemical, radiological, viable or other nature of airborne particles. In other words, it counts particles. It does not tell you whether those particles carry microorganisms.

That second point matters for medical devices and is discussed again below.

How the ISO classes compare

Classes are numbered, and a lower number means cleaner air. One published description explains that the class number is the base-10 logarithm of the maximum permitted number of particles of 0.1 micrometres and larger per cubic metre of air. So each step down in class number is ten times fewer permitted particles.

For particles of 0.5 micrometres and larger, one commonly cited summary of the standard gives these maximum concentrations per cubic metre:

These figures are cumulative, meaning the count includes particles at and above the stated size. The standard itself contains the full table for other particle sizes and other classes, so use the standard when writing a specification.

Which class do medical devices use?

There is no single answer. The class a manufacturer chooses depends on the product, the process step and the risk of contamination, and it is a decision that has to be justified and documented.

Different products and process steps can call for different classes, and the standard's scope covers clean zones and separative devices as well as whole cleanrooms. Check the requirements for your own product type and market rather than copying another company's class.

Does the quality standard require a cleanroom?

The answer depends on the product and on the exact wording of the standard and your regulator, which this article does not reproduce. Published guidance on the medical device quality management standard ISO 13485:2016 (its requirement 6.4, contamination control) explains that manufacturers must establish and maintain processes for identifying potential sources of contamination, implement controls and monitor them. That guidance lists the use of cleanrooms as one example of a work environment practice, alongside measures such as gowning procedures and equipment maintenance.

In practice, the question to answer is: what contamination could affect this product, and what controls keep it at an acceptable level? The class of the room may be part of the answer for some products and not for others.

How a classification is verified

A class is demonstrated by testing, not just stated.

• Particle counting. ISO 14644-1 bases the determination of particle concentration on light-scattering discrete airborne particle counters.
• Routine monitoring. A companion standard, ISO 14644-2:2015, specifies minimum requirements for a monitoring plan for cleanroom or clean zone performance. Check that standard for the details of what a plan must contain.

Because those measurements support a quality decision, the particle counters themselves should be within calibration. For more on that, see the general guide on medical equipment calibration.

Why the class number is not enough

Two limits of a particle-based class explain why medical device manufacturers add other controls.

First, as noted, ISO 14644-1 does not characterize the viable nature of particles. Meeting a particle class therefore says nothing by itself about microbial contamination. Manufacturers whose products must be sterile or kept low in microbial contamination need additional controls; the ISO 13485 guidance cited above notes, for example, that companies must document requirements for control of contamination with microorganisms and particulate substances in the work environment, including during assembly and packaging after sterilization, and it lists gowning procedures among contamination controls.

Second, a room is only one part of the system. The same ISO 13485 guidance lists gowning procedures, equipment maintenance and personnel training alongside cleanroom requirements, which reflects the point that a well-classified room used with poor procedures may not protect the product.

So a contamination control approach can include:

1. A risk assessment identifying contamination sources and their effect on the product.
2. A defined classification for each area, with justification.
3. Gowning, hygiene and entry procedures.
4. Cleaning and disinfection procedures and records.
5. Environmental monitoring, covering particles and, where relevant, microorganisms.
6. Qualified equipment and validated processes inside the room.
7. Trend review and a response plan for excursions.

Questions to ask a contract manufacturer

If you are an original equipment manufacturer choosing a partner, the class number is a good starting question but not the last one. Useful follow-ups include:

• Which areas are classified, to which class, and when were they last qualified?
• What does routine particle and microbial monitoring look like, and can you see the trend data?
• How does the supplier decide which class a product needs?
• How are excursions handled and how is affected product assessed?
• Are the processes performed in the room validated?

The short version

A cleanroom class, such as ISO Class 7, is a statement about the number of airborne particles allowed per cubic metre. It is useful, standardized and testable. It is not a statement about sterility, process control or product quality. Medical device makers choose a class based on risk, prove it by testing, and surround it with the other controls that actually protect the product.

This article is general information for readers interested in medical technology manufacturing. It is not engineering, regulatory, legal or medical advice.

Sources

• ISO 14644-1:2015, Cleanrooms and associated controlled environments, Part 1: Classification of air cleanliness by particle concentration (scope summary, Estonian Centre for Standardisation and Accreditation): https://www.evs.ee/en/iso-14644-1-2015
• Cleanroom (ISO class definition and particle limits at 0.5 micrometres), Wikipedia: https://en.wikipedia.org/wiki/Cleanroom
• ISO 14644-2:2015, Cleanrooms and associated controlled environments, Part 2: Monitoring (scope summary, Estonian Centre for Standardisation and Accreditation): https://www.evs.ee/en/iso-14644-2-2015
• Advisera, Managing cleanliness of a product and contamination control according to ISO 13485:2016: https://advisera.com/13485academy/blog/2017/07/04/managing-cleanliness-of-a-product-and-contamination-control-according-to-iso-134852016/