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 help organizations interpret cleanroom expectations and support long-term control through best-in-class consumables and practical, field-tested 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 refers to the validated absence of viable microorganisms to a defined sterility assurance level, which generally requires 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)
| ISO Class | Typical Use | Operational Reality |
|---|---|---|
| ISO 8 | Controlled support, staging, packaging where risk is lower | Housekeeping + material controls drive outcomes |
| ISO 7 | Common controlled manufacturing rooms; many regulated support areas | People/material discipline matter as much as design |
| ISO 6 | Higher-control processes with elevated contamination risk | Tighter behavior, stronger controls, more monitoring/trending |
| ISO 5 | Critical zones for exposed product/process (often under unidirectional airflow) | Interventions are the risk; protect clean air paths (“first air”) |
Why standards matter: Standards make “clean” measurable and help global teams maintain consistent expectations for quality and control.
Cleanroom programs often reference multiple standards. The key is understanding what each one is designed to control. ISO tells you how clean the air measures; USP tells you how compounding is performed and controlled; and EU GMP Annex 1 tells you how sterile medicines are expected to be manufactured and controlled in the EU market.
| Framework | What it is primarily for | What it typically covers |
|---|---|---|
| ISO 14644 | Global cleanroom classification and testing framework | Air cleanliness classification by particle concentration; qualification and testing concepts used broadly in cleanroom design and verification |
| USP <795> | U.S. nonsterile compounding in healthcare settings | Standards for compounding quality nonsterile preparations to reduce contamination, dosing, and quality risks (revised chapter official date: Nov 1, 2023) |
| USP <797> | U.S. sterile compounding in healthcare settings | Sterile compounding requirements: personnel qualification, aseptic technique, facilities, cleaning/disinfection, and environmental controls (revised chapter official date: Nov 1, 2023) |
| USP <800> | U.S. hazardous drug handling safety | Requirements to minimize exposure to hazardous drugs for personnel, patients, and the environment (USP lists an official date of Dec 1, 2019; adoption/enforcement depends on state and site policy) |
| EU GMP Annex 1 | EU expectations for sterile medicinal manufacturing | CCS, Grades A–D, aseptic process controls, barrier emphasis, and monitoring/trending expectations (in operation: Aug 25, 2023; point 8.123: Aug 25, 2024) |
| If you make or do... | You most often live in... | Day-to-day risk focus |
|---|---|---|
| Compounded medications (nonsterile or sterile) | USP <795> / <797> (and <800> when hazardous drugs are involved) | Technique, cleaning/disinfection, documentation, and consistent execution across staff |
| Sterile medicinal products for the EU market | EU GMP Annex 1 (often referencing ISO concepts in qualification) | CCS, interventions, monitoring/trending, barrier strategy, and process control |
| Industrial manufacturing (devices, electronics, optics, aerospace, etc.) | ISO 14644 + customer/industry requirements | Particles, residues, material discipline, and repeatable cleaning methods |
A common misconception is that EU GMP Annex 1 Grades (A, B, C, D) are simply another way of saying ISO 5/7/8. In practice, they are not interchangeable labels and should not be treated as a one-to-one conversion.
| What ISO class describes | What Annex 1 Grade describes | Why it matters |
|---|---|---|
| A measured air cleanliness level based on particle limits and sampling conditions | A risk-based zone concept for sterile manufacturing, tied to criticality, interventions, CCS, and monitoring expectations | You can meet an ISO class and still fail a Grade expectation if interventions, monitoring, or CCS controls are weak |
| Usually focuses on non-viable particles (plus defined testing/verification practices) | Includes strong emphasis on process control, microbiological control (as applicable), and routine trend review | Sterile operations require evidence of sustained control, not just a passing classification test |
| Often applied across many industries (devices, electronics, pharma support areas) | Specifically written for sterile medicinal products under EU regulation | When Annex 1 applies, your program must be justified through CCS, barrier strategy (where appropriate), and monitoring/trending aligned to sterile risk |
Practical takeaway: Many sterile programs align Grade A to the highest-control environments and may reference ISO terms in qualification, but the correct approach is to start with the governing framework (Annex 1 / USP / ISO), define risk-based controls, and then demonstrate performance with documented evidence and trends.
| Term | What it means | Why it matters |
|---|---|---|
| ISO class | A numeric air cleanliness level based on particle limits measured in a defined volume of air | Turns “clean” into a measurable requirement and supports qualification |
| At rest / In operation | At rest: running/ready without people; In operation: actual work with people and interventions | Most real contamination problems show up in operation |
| First air | The clean, uninterrupted air path coming from a HEPA filter to the critical work area | Blocking first air is a common root cause of findings and contamination events |
| Viable vs non-viable | Viable: living microorganisms; Non-viable: particles (dust/fibers/skin) without life | Sterile programs must manage both; industrial programs often focus on particles + residues |
| CCS (Contamination Control Strategy) | A documented plan linking contamination risks to controls across people, materials, facility, equipment, cleaning, and monitoring | Annex 1 expects CCS as the backbone of sterile contamination control maturity |
In the United States, many sterile manufacturing expectations are driven by FDA current Good Manufacturing Practice (cGMP) regulations and guidance. Globally, another major benchmark is the European Union’s EU GMP Annex 1, titled “Manufacture of Sterile Medicinal Products.”
Important clarity for U.S. readers: EU GMP Annex 1 is a European requirement for EU-regulated sterile medicinal products. It is not a U.S. law. However, many global manufacturers use Annex 1 as a high bar for contamination control and as a practical reference when designing and operating sterile areas.
Timeline: Annex 1 came into operation on August 25, 2023, with a later deadline of August 25, 2024 for point 8.123.
Key Annex 1 concepts that influence sterile cleanroom programs:
- Grades A, B, C, and D: Grade A is the highest-control zone for critical exposed sterile work; Grades B–D support with decreasing levels of control.
- “At rest” vs. “in operation”: performance is evaluated both without operators and during real work with interventions.
- CCS (Contamination Control Strategy): a documented plan connecting risks and controls across facility, equipment, utilities, people, materials, cleaning/disinfection, and monitoring.
- Barrier emphasis where appropriate: RABS and isolators reduce direct human interventions in critical zones.
- Monitoring and trends: monitoring is designed to detect drift early and reviewed routinely.
- Validated cleaning/disinfection: risk-based validation and practical rotation strategies (including sporicidal use where appropriate).
Most cleanrooms win or lose on two fundamentals: filtration and airflow behavior. A cleanroom is not a sealed box; it is a controlled airflow system designed to dilute, capture, and remove contamination as it is generated.
- HEPA (and sometimes ULPA) filtration removes particles from supply air before it enters the controlled space.
- Unidirectional airflow is commonly used over critical work to help sweep particles away from product/process pathways.
- Mixed airflow rooms rely on dilution and returns; good behavior and material discipline become even more important.
- Practical rule: avoid blocking clean air paths with hands, boxes, carts, or poorly staged materials near critical work.
People are the largest routine generator of particles and viable contamination in controlled environments. Good gowning reduces shedding, but behavior is what keeps control stable from shift to shift.
| Common issue | What it causes | What to do |
|---|---|---|
| Blocking airflow with hands/materials | Particles settle in critical areas | Stage low and to the side; protect clean air paths |
| Fast motion / unnecessary traffic | Resuspension + higher counts | Slow movement; define roles; minimize entries/exits |
| Uncontrolled touch points (doors/carts/keyboards) | Transfer contamination | Define “dirty vs clean” surfaces; glove changes between tasks |
| Consumables not matched to the job | Residues, fibers, or chemistry mismatch | Use appropriate wipers/swabs/chemistry; document rationale |
Cleanroom performance is demonstrated with data. Strong programs do not wait for an audit to discover drift—they use monitoring to detect changes early and correct before product or compliance is at risk.
- Classification is periodic verification; monitoring is ongoing drift detection.
- Routine monitoring: trend review with defined response actions and documentation.
- Common elements: particles, pressure, temperature/humidity, alarms; viable monitoring in sterile programs as required.
- Operational truth: “in operation” drift is often a people/material control issue, not just HVAC.
Cleanrooms are maintained by design, but they are stabilized by what teams use every day. The right consumables reduce shedding, residues, and variability—and make procedures easier to execute consistently.
| Category | What to look for | Where it matters most | Common failure mode |
|---|---|---|---|
| Wipers | Low-lint, compatible material, consistent absorbency, sterile options where required | Surface cleaning, critical wipe-downs, residue control | Fiber shedding or incomplete removal leaves films/streaks that recur |
| Swabs | Head compatibility, strong bonding, low particles, precision shapes; ESD options when needed | Tight areas, equipment edges, seams, sensor cavities, connectors | Over-wetting spreads soils; weak heads shed |
| Solutions | Residue profile, contact time, validated use case; sterile grades where required | Cleaning/disinfection programs, wipe saturation control, rotation strategies | Chemistry mismatch causes residue films or ineffective disinfection |
| Gloves & apparel | Barrier + low shedding, fit/dexterity, sterile options, accelerator-free options when needed | People controls, touch-point control, aseptic technique support | No glove-change triggers = contamination transfer between tasks |
| Mops | Head material, coverage efficiency, solution compatibility, controlled wetness | Floors/walls, large-surface cleaning, routine sanitation, transitions | Too wet or wrong technique pushes soils; inconsistent coverage leaves “dirty lanes” |
Practical tip: The most stable programs define the consumables used for each task in the SOP (not just “wipe with IPA”) so results are repeatable across shifts and sites.
- Uncontrolled staging: reaching over critical work, blocking clean air paths, placing materials too high or too close to exposed product.
- Over-wetting: spreading soils into seams/edges and leaving residues that become recurring film issues.
- No glove-change triggers: the same gloves touch doors, carts, keyboards, and critical surfaces.
- Wrong wipe/swab choice: fibers or weak construction adds contamination while “cleaning.”
- Chemistry mismatch: residues, incomplete soil removal, or disinfectant use without a defensible rationale and records.
- Data without ownership: monitoring exists, but trend review and response actions are not clearly assigned or documented.
- ISO 14644-1 (ISO listing): https://www.iso.org/standard/53394.html
- EU GMP Annex 1 (European Commission PDF): Annex 1 PDF
- USP official notices portal: https://www.uspnf.com/notices
- FDA portal: https://www.fda.gov/
- ASTM: https://www.astm.org/
- IEST: https://www.iest.org/