EU GMP grades A to D compared with ISO classes

By ZY Cleanroom · Updated 2026-11-01 · Sources at the end of the page

Grades against ISO classes

Annex 1 states limits in particles per cubic metre and names no ISO class in its text. The ISO class below is the class whose 0.5 µm limit in ISO 14644-1:2015 has the same number.

Sources: EU GMP Annex 1, Table 1, published 25 August 2022 and applied from 25 August 2023; ISO 14644-1:2015, Table 1. FDA's 2004 aseptic guidance says ISO 5 approximately equals EU Grade A.

At rest and in operation

Annex 1 defines both states. At rest means utilities complete and HVAC working, main equipment installed but not operating, and no people. In operation means HVAC fully working, equipment running in the manufacturer's defined mode, and the maximum number of people doing or simulating routine work.

Classification is done in both states, and initial classification should take place in simulated operations. After operations end, the at-rest limits should be met after a clean-up period. The guidance value is under 20 minutes.

ISO 14644-1 defines at rest as equipment installed and running as agreed between customer and supplier, with no people. A test with equipment running may therefore not match the Annex 1 at-rest state, where main equipment is not operating. Name the state you mean.

Where the mapping differs

One grade, two classes. Grades B, C and D change class between states. A room that meets ISO 7 in operation is not Grade B on that basis alone.

Grade D in operation. Annex 1 sets no limit. The manufacturer sets one from risk assessment and routine data.

Particles of 5 µm and larger. Annex 1 Table 1 gives no classification limit for Grade A, or for Grade B at rest. Its monitoring table (Table 5) gives 29 per cubic metre for both. ISO 14644-1:2015 handles larger particles through an M descriptor, which cannot define an ISO class.

Microbial limits. Annex 1 Table 2 sets limits for qualification. Grade A allows no growth. Air samples allow 10 CFU per cubic metre in Grade B, 100 in Grade C and 200 in Grade D. ISO 14644-1 cannot characterise viable particles.

Other duties. Annex 1 gives a guidance pressure difference of at least 10 Pa between adjacent rooms of different grades. It sets maximum requalification intervals of 6 months for Grades A and B and 12 months for Grades C and D. These duties sit outside ISO 14644-1, which covers classification only.

Who confirms the grade

Annex 1 applies to the manufacturer of sterile medicines, who qualifies cleanrooms using Annex 15 methods. In the EU, the national competent authority inspects the manufacturer and can issue it a GMP certificate. A contractor can supply classification results. A contractor cannot grant a grade.

To have a room list reviewed, send it to ZY Cleanroom, a cleanroom design-and-build contractor with its own panel and door factory in Tianjin, China.

Related guides

• HEPA and ULPA filters: EN 1822, ISO 29463 and integrity testing
• Aseptic filling suite layout: grade A and B rooms and flows
• Cleanroom failed particle count: causes and fixes
• USP <797> compounding cleanroom for hospital pharmacy
• Turnkey cleanroom contractor
• Room list builder

Sources

• EudraLex Volume 4, Annex 1: Manufacture of Sterile Medicinal Products (published 25 August 2022, applied from 25 August 2023; checked 31 October 2026)
• ISO 14644-1:2015, Cleanrooms and associated controlled environments, Part 1: Classification of air cleanliness by particle concentration (published 9 December 2015; Table 1 checked 31 October 2026)
• FDA, Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing, Current Good Manufacturing Practice (September 2004, nonbinding; checked 31 October 2026)
• EudraLex Volume 4, Annex 15: Qualification and Validation (European Commission, 30 March 2015; in operation from 1 October 2015; checked 31 October 2026)
• EMA, EudraGMDP public database: GMP certificates are issued by the national competent authority that carried out the inspection (checked 31 October 2026)