A cleanroom is a controlled environment designed to limit contamination—especially tiny airborne particles you may not be able to see, such as dust, fibers, skin flakes, and residue from everyday materials. In some industries (especially pharmaceutical and biotech environments), contamination can also include microorganisms like bacteria and fungi.
Cleanrooms exist because in modern manufacturing and science, contamination that looks “small” in everyday life can cause serious issues—product defects, equipment failures, safety risks, and regulatory non-compliance. At SOSCleanroom, we focus on helping organizations understand cleanroom expectations and support long-term control through best-in-class cleanroom consumables and practical guidance.
Many rooms can look clean. Fewer rooms are measurably clean.
When someone says a room is “clean”, that can be subjective. When a room is “ISO-classified”, it means the room’s air cleanliness has been measured and shown to meet a specific cleanliness level defined by an international standard.
In practical terms: ISO classification turns “clean” into a number—based on particle counts in a measured volume of air.
Not automatically.
A cleanroom typically refers to controlling airborne particles (and sometimes microorganisms, depending on the industry). Sterile means “free of viable microorganisms,” which generally requires additional validated sterilization methods, microbiological control programs, and stricter operational controls.
In other words: sterile areas are highly controlled, but not all cleanrooms are sterile.
ISO stands for the International Organization for Standardization. ISO publishes international standards so customers, suppliers, and auditors can align on consistent requirements globally.
ISO 14644 is the primary family of cleanroom standards used worldwide. Different parts of ISO 14644 address classification, testing, monitoring, and operations (day-to-day practices used to keep cleanroom performance in control).
What do ISO 5, ISO 7, and ISO 8 mean? These are air cleanliness classes based on particle limits in the air.
- Lower number = cleaner air (fewer particles allowed)
- Higher number = less strict (more particles allowed)
In the United States, many sterile manufacturing expectations are driven by FDA current Good Manufacturing Practice (cGMP) guidance and regulations. Globally, another major benchmark is the European Union’s EU GMP Annex 1, titled “Manufacture of Sterile Medicinal Products.”
Annex 1 was published in 2022 with a stated timeline for coming into operation of August 25, 2023 (and a later date for one specific clause). The core idea is straightforward: sterile operations must be controlled through a risk-based contamination control approach that is documented, measurable, and sustained over time.
Here are the Annex 1 concepts that most directly affect European cleanrooms (and influence global expectations):
- Grades A, B, C, and D for sterile operations: Annex 1 describes four cleanroom/zone grades used in sterile medicinal manufacturing. In plain terms, Grade A is the highest-control zone where the most critical, exposed sterile work occurs. Grades B–D support or surround critical activities with decreasing levels of control.
- “At rest” vs. “in operation” performance expectations: European sterile cleanrooms are commonly evaluated both when equipment is running without operators (at rest) and during actual work with operators and interventions (in operation). This reinforces the reality that people and activity change the contamination picture.
- CCS (Contamination Control Strategy) is central: Annex 1 expects a documented, facility-wide plan that connects contamination risks and controls across premises, equipment, utilities, personnel, materials, cleaning/disinfection, and monitoring. This is not just “a document for the binder.” It is intended to be a living framework that drives decisions, change control, and trending.
- Barrier technology emphasis (where appropriate): Annex 1 strongly encourages reducing direct human interventions in critical zones using technologies such as RABS (Restricted Access Barrier Systems) and isolators. These systems help separate people from the most sensitive product exposure points.
- More focus on monitoring and trends: Annex 1 places strong emphasis on environmental and process monitoring that is designed intelligently, reviewed routinely, and used to detect drift early—before it becomes a batch-impacting event.
- Validated cleaning and disinfection programs: In sterile environments, a risk-based approach often includes disinfectant effectiveness validation and practical rotation strategies (including sporicidal use where appropriate to the contamination risks). The key point is not “use more chemicals,” but “use the right chemistry with documented effectiveness and disciplined execution.”
Bottom line: for European sterile cleanrooms, Annex 1 pushes teams toward stronger contamination control strategy (CCS), reduced human intervention where possible, and a higher expectation for monitoring, documentation, and continuous improvement. For U.S. teams, Annex 1 is often used as a useful secondary benchmark—especially for global supply chains or organizations aiming to strengthen contamination control maturity.
Cleanrooms stay within their target ISO class using a combination of engineering controls and operational discipline. The fundamentals are filtration, airflow, pressure control, and procedures.
What does HEPA mean? HEPA stands for High Efficiency Particulate Air. HEPA filters capture very small airborne particles and are a core component of cleanroom performance. You may also hear ULPA (Ultra Low Particulate Air) for even higher-efficiency filtration in some applications.
Why do cleanrooms have so much airflow? Airflow continuously delivers filtered air, dilutes particles generated by people and processes, and moves contamination toward return vents so it can be filtered out.
What is positive pressure—and why does it matter? Many cleanrooms operate at positive pressure relative to adjacent spaces. When doors open, air tends to flow outward, helping prevent less-clean air from entering. Some rooms use negative pressure for containment when the priority is keeping a hazard from escaping. The right approach depends on whether you are protecting the product or containing a process hazard.
What is the biggest contamination source in a cleanroom? In most cleanrooms, the answer is people. Humans naturally shed particles—skin flakes, hair, and fibers from clothing. Movement and unnecessary activity can also stir up particles and disrupt airflow.
Why do we wear cleanroom suits (“bunny suits”)? Cleanroom garments reduce the particles people release into the environment. The suit, hood, gloves, mask, and boot covers (as required by the cleanroom) are primarily there to protect the product and process from contamination.
How do we prove a cleanroom meets its ISO class? By measuring it. ISO-classified cleanrooms rely on objective data rather than assumptions.
- Airborne particle counting using calibrated particle counters
- Differential pressure checks between spaces
- Airflow verification (direction, volume, and consistency where required)
- Filter integrity checks (as applicable)
- Environmental trending to catch performance drift early
What are “as-built,” “at-rest,” and “operational” states? These describe what is happening in the cleanroom during testing. “As-built” is an empty finished room. “At-rest” has equipment installed and running but no people working. “Operational” means normal work is happening with people present. These states matter because people and activity generate particles.
How often do cleanrooms need to be tested or re-certified? It depends on the industry, risk level, customer requirements, and historical stability. Many programs use a combination of routine monitoring during operations, periodic certification (often annual or semi-annual), and re-testing after major changes.
Cleanrooms typically fail performance when contamination rises beyond allowable limits or when airflow/pressure control is disrupted. Common contributors include:
- Poor gowning discipline (increased shedding from people)
- Excess traffic and frequent door openings
- Construction or maintenance dust introduced into the controlled environment
- Damaged filters or seal leaks that reduce filtration performance
- Equipment layout changes that disrupt intended airflow patterns
- Improper cleaning methods (wrong wipes/chemicals, inconsistent technique)
| Acronym | Meaning |
|---|---|
| ISO | International Organization for Standardization |
| ISO 14644 | Cleanroom standards family (classification, testing, monitoring, operations) |
| HEPA | High Efficiency Particulate Air (high-efficiency air filter) |
| ULPA | Ultra Low Particulate Air (very high-efficiency air filter) |
| HVAC | Heating, Ventilation, and Air Conditioning (system that moves and conditions air) |
| Pa | Pascal (unit of pressure used for room-to-room pressure differences) |
| SOP | Standard Operating Procedure (written “how-to” instruction) |
| GMP | Good Manufacturing Practice (quality requirements used in regulated manufacturing) |
- ISO 14644-1 overview (ISO): https://www.iso.org/standard/53394.html
- EU GMP Annex 1 (European Commission PDF): https://health.ec.europa.eu/system/files/2022-08/20220825_gmp-an1_en_0.pdf
- FDA sterile drug products (aseptic processing) guidance portal: https://www.fda.gov/
- ASTM (test methods and standards): https://www.astm.org/
- IEST (contamination control recommended practices): https://www.iest.org/
SOSCleanroom supports critical environments with best-in-class cleanroom consumables and practical guidance that helps teams stay consistent, audit-ready, and in control.