Clean Room Classes for Cannabis Processing: ISO 14644-1 Classes and EU GMP Grades A to D Explained

💊 Medical Cannabis 💡GACP – GMP – EU-GMP – Export
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Clean room classification ranks a controlled room by how many airborne particles each cubic metre of its air may contain. A cleanroom has filtered supply air and is kept at a different air pressure from the rooms around it. People and materials can enter only in controlled ways. The room earns its rank when its air particles are counted. The design drawings alone do not give it a rank.

Medicine manufacturers use two ranking systems side by side. The first is the set of ISO 14644-1 classes, an international standard that many industries use. The second is grades A to D. These come from Annex 1 of the EU GMP guide, which covers sterile medicines.

This article is for you if you run or plan a licensed flower packing room or extraction room, and a buyer or inspector asks which grade it meets. Home growers do not need a classified room. The section on dust and cross-contamination still applies to any trimming or packing space.

Two ranking systems: ISO classes and GMP grades

The US Food and Drug Administration (FDA) publishes guidance on aseptic processing. Aseptic processing means filling a sterile medicine into containers inside a sterile environment, because the sealed product cannot be sterilised afterwards. That guidance says ISO 14644-1 gives uniform particle limits for cleanrooms across many industries.

EudraLex Volume 4 is the European Union’s collection of good manufacturing practice (GMP) rules for medicines. Annex 1 is the part of it that covers sterile products. It was revised in 2022 and has been fully applicable since 25 August 2024.

To qualify a cleanroom, you prove by testing that it performs as designed. For this, Annex 1 refers to the ISO 14644 series of standards. It uses ISO 14644-1 to set the minimum number of air sampling points and where they go.

Annex 1 still defines its grades in its own terms. Each grade has one set of limits for the room at rest and another for the room in operation. Each grade also has microbial limits as well as particle limits. If a contractor or buyer gives you only an ISO class, ask which GMP grade and which room state they mean. That way both sides are talking about the same requirement.

What the four grades are used for

Annex 1 describes four grades of cleanroom or clean zone for sterile manufacturing:

  • Grade A: the critical zone for high-risk steps. Examples:

    • the filling zone, where product goes into its final containers
    • open primary packaging, meaning containers that touch the product while they are still open
    • making aseptic connections, meaning joining sterile tubes or parts without contaminating them

    Grade A air normally comes from unidirectional airflow. This is filtered air that moves in one direction at a steady speed and sweeps particles away from the work. The airflow usually sits inside a barrier system or an isolator. A barrier system is a physical screen between the operator and the critical zone. An isolator is a sealed box that the operator works in through glove ports.

  • Grade B: the room surrounding grade A during aseptic preparation and filling, when grade A is not inside an isolator.

  • Grades C and D: rooms for less critical stages of making aseptically filled sterile products, or the room surrounding an isolator. They can also be used to prepare and fill terminally sterilised products. These products are sterilised after filling, inside their sealed final container, for example by heat.

List the steps in your own process where the product is exposed to room air. If you ever work to a grade, those are the steps that would need the cleanest zone.

Particle limits used to classify a room

Particle sizes are given in micrometres (µm), or thousandths of a millimetre. To classify a room, Annex 1 requires counting all particles of 0.5 µm and larger, and all particles of 5 µm and larger. Both counts are taken at rest and during simulated operations. The results are compared with Table 1 of Annex 1, which gives particles per cubic metre:

Grade ≥0.5 µm at rest ≥0.5 µm in operation ≥5 µm at rest ≥5 µm in operation
A 3,520 3,520 Not specified Not specified
B 3,520 352,000 Not specified 2,930
C 352,000 3,520,000 2,930 29,300
D 3,520,000 Not predetermined 29,300 Not predetermined

For grade D, the manufacturer sets its own in-operation limits. It bases them on a risk assessment and on its routine data.

Classification is separate from routine monitoring. Monitoring is the day-to-day checking of a room that is already qualified. It has its own maximum “action limits”. An action limit is the level at which you must investigate and correct the problem. Annex 1 gives these limits for total particles in Table 5. Table 6 covers viable particles, meaning living microorganisms such as bacteria and mould spores.

Whenever someone quotes a particle number, check that it includes three things: the particle size, the room state, and whether it is a classification limit or a monitoring limit. A number missing any of these cannot be compared with Table 1.

“At rest” and “in operation”

“At rest” means the room with no normal production going on. “In operation” means the room while the work, or a simulation of the work, is going on. People and moving materials release particles, so the in-operation limits are higher.

The table shows how large the gap is. Grade B allows 3,520 particles of 0.5 µm per cubic metre at rest, but 352,000 in operation. Grade C goes from 352,000 at rest to 3,520,000 in operation.

Annex 1 requires suitable cleanliness levels in both states. Grade A is the exception: its 0.5 µm limit is the same in both states.

When you order a test, ask for counts in both states. A report from an empty room does not tell you what the air is like on a packing day.

Approximate ISO equivalents

The FDA guidance lists these ISO limits for particles of 0.5 µm: ISO 5 = 3,520, ISO 7 = 352,000 and ISO 8 = 3,520,000 per cubic metre. Comparing only the 0.5 µm figures gives this approximate match:

EU GMP grade At rest (0.5 µm) In operation (0.5 µm)
A about ISO 5 about ISO 5
B about ISO 5 about ISO 7
C about ISO 7 about ISO 8
D about ISO 8 Set by the manufacturer

The FDA guidance itself says an ISO 5 concentration is approximately equal to EU grade A. The word “approximately” matters. A GMP grade also includes 5 µm limits, microbial limits and separate requirements for each room state. An ISO class number does not cover any of these.

In a specification, quotation or standard operating procedure (SOP), write the GMP grade and the room state, for example “grade C, at rest”. This stops a contractor from building to the ISO figure alone.

A grade is measured, and then measured again

Annex 1 treats classification as one part of qualifying a cleanroom. Classification is done by measuring the total concentration of particles in the air.

Annex 1 also requires requalification at regular intervals. The maximum interval is 6 months for grade A and B areas and 12 months for grade C and D areas. At minimum, requalification includes:

  • classification (a new particle count)
  • integrity testing of the final filters, which checks the last filters before air enters the room for leaks
  • measuring the volume of air supplied
  • checking the pressure differences between rooms
  • an air velocity test where there is unidirectional airflow; rooms without it get a recovery test instead, which measures how quickly the room clears particles

Adjacent rooms of different grades should differ in air pressure by at least 10 pascals. Annex 1 gives this as a guidance value. The pressure difference keeps air flowing from the cleaner room to the less clean one, including when a door opens.

Put the requalification dates into your maintenance calendar when the room is first qualified. A grade is valid only while the tests behind it are current.

What this means for medical cannabis processing

Annex 1 is written for sterile products. However, it says some of its principles, including cleanroom classification, may support the manufacture of non-sterile products. This applies where controlling contamination by microbes and particles is important. A manufacturer that does this should document which principles it applies. It must also accept that it has to show it complies with them.

For non-sterile manufacturing, the general part of the EU GMP guide asks for effectively ventilated production areas. Air control must suit the products and operations, including filtration where needed. The guide also names packaging of dry products as a step that creates dust. This step needs measures against cross-contamination, meaning one product or material getting into another.

Annex 7 of the EU GMP guide, which covers herbal medicinal products, adds more rules for dust. Sampling, weighing, mixing and processing herbal substances need specific provisions whenever they create dust. Examples are dust extraction, which sucks dust away where it forms, or premises used only for that work. For extraction, the equipment and filters must be compatible with the extraction solvent.

These texts do not, on their own, require any grade from A to D for a flower packing room or an extraction suite. If you choose to work to a grade, document the choice, its limits and your monitoring plan, and explain why. The room must also be classified by actual measurement. The inspecting authority decides whether your approach is acceptable. The facility designer does not.

Translator’s note: In Thailand, cannabis flower is a controlled herb under the Notification of the Ministry of Public Health Re: Controlled Herbs (Cannabis), B.E. 2568. The notification was issued under the Thai Traditional Medicine Protection Act B.E. 2542 and came into force on 26 June 2025. The Ministerial Regulation on Controlled Herbs (No. 2) B.E. 2569 came into force on 30 April 2026 and tightens licence criteria for flower. Extracts with more than 0.2% THC fall under the Ministerial Regulation on Cannabis or Hemp Extracts B.E. 2569, in force since 26 April 2026. Thailand’s two Ministerial Regulations of B.E. 2569 are explained in a separate topic.

Translator’s note: The articles above do not say which Thai authority inspects a cannabis packing or extraction room for each type of licence. They also do not say whether that authority expects any particular cleanroom standard. GACP certification for your farm covers growing and collection practice. It is not a cleanroom grade. The draft Cannabis Control Act is not law yet. The Cabinet approved the draft on 22 September 2026 and sent it to the House, so premises rules may still change. Before you spend money on filters or construction, ask your licensing authority in writing which standard it will inspect you against. The written answer tells you what to build and gives you a record if the rules change.

Applying this in Thai heat, humidity and power cuts

Translator’s note: Most cleanroom design assumptions come from cooler climates. With outdoor air at 30–35 °C, the HVAC (heating, ventilation and air-conditioning) system must cool and dry the air while pushing it through filters. In the rainy season, high outdoor humidity puts an extra load on cooling and drying. Mould spores count as viable particles, so humid air works against your microbial limits. Size your air-conditioning and dehumidifier capacity for the wettest months, not the average month.

Translator’s note: Outdoor dust and smoke, for example during the haze season in northern Thailand, fill pre-filters faster. Check the pressure drop across your filters or inspect them more often during those months. A clogged filter cuts the volume of air supplied, and that volume is one of the requalification tests.

Translator’s note: When the power fails, the fans stop and the pressure difference between rooms is lost. Unfiltered air from the corridor can then flow into the clean room. Write an outage procedure in advance:

  1. Stop any work where product is open to the air, and keep doors closed.
  2. When power returns, run the air system for a period you have tested and written down before reopening product.
  3. Check that the pressure gauge is back to its normal reading.
  4. Clean surfaces before restarting work.

The procedure stops contaminated air from reaching product that will be sold or tested. If outages are frequent, ask an electrician about backup power for the air-handling system: a generator, or a UPS (uninterruptible power supply, a battery unit that bridges short cuts).

Translator’s note: Local contractors may offer cleanroom particle counting. Before you hire one, ask for a sample report that names ISO 14644-1, gives the particle sizes and room state, and includes a current calibration certificate for the particle counter. To find one, ask other members about their experience in the B2B Services section of this forum.

A practical place to start:

  • Have your current packing room counted twice: once empty and once during a normal packing session. You will learn which ISO class the room actually meets in each state before you pay for upgrades.
  • Fit a differential pressure gauge between the packing room and the corridor, and record the reading at the start of each shift for 2 weeks. You will see whether pressure holds when doors open and after power cuts.

Common mistakes

  • Saying “ISO 7 equals grade C”. This is true only at rest. In operation, grade C allows the ISO 8 figure. Grade B in operation is the one that matches ISO 7.
  • Quoting a limit without its room state. A number without “at rest” or “in operation” is incomplete.
  • Assuming filters make a cleanroom. Classification tests and requalification show the grade. An equipment list does not.
  • Confusing classification with monitoring. Classification qualifies the room. Routine monitoring uses separate action limits.
  • Ignoring the 5 µm and microbial limits. They are part of a GMP grade even when the 0.5 µm count passes.

Before you design or buy equipment to meet a grade, read the current version of Annex 1. Then ask the authority that will inspect your site how it expects you to justify your choice. This way the room you build is the room that will pass inspection.

If you have counted particles in a Thai packing or extraction room, please share your results and room setup below this topic. You can also post questions about your own room there.

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