A pharmaceutical cleanroom is a controlled environment designed to EU GMP Annex 1, where beyond particle concentration you also control microbiological cleanliness, the pressure cascade and air recovery time. GMP classification divides zones into grades A, B, C and D, mapped onto ISO 14644-1 classes in the at-rest and in-operation states. Clima Line designs and builds such environments turnkey: from URS, through HVAC with HEPA H14 filtration, to IQ/OQ/PQ validation and the qualification documentation package.
GMP grades A, B, C and D versus ISO classes
The pharmaceutical industry runs two classification systems in parallel. ISO 14644-1 describes particle concentration only. GMP adds microbiological limits and, critically for HVAC design, the distinction between at rest (installation complete, equipment running, no personnel) and in operation (full production with staff present).
| GMP grade | At rest | In operation | Airflow | Typical use |
|---|---|---|---|---|
| A | ISO 5 | ISO 5 | Unidirectional (laminar), 0.36–0.54 m/s at the working position | Critical zone: aseptic filling, open ampoules, transfer of sterile components |
| B | ISO 5 | ISO 7 | Turbulent, high air change rate | Direct background for grade A in aseptic processes |
| C | ISO 7 | ISO 8 | Turbulent, 30–60 ACH | Less critical stages of sterile production, solution preparation |
| D | ISO 8 | not defined | Turbulent, 10–25 ACH | Component preparation, washing, buffer zones |
The practical consequence of this table: the same installation can meet ISO 7 at rest and only ISO 8 in operation. A room designed tightly for the at-rest state falls out of class the moment operators enter, so design must target the in-operation state. If a request for quotation does not state in which state the class must be achieved, comparing offers makes no sense: the difference in HVAC cost between the two variants reaches 40%.
What EU GMP Annex 1 (2022 revision) changed
The revised EU GMP Annex 1 (published on 22 August 2022, in force since 25 August 2023) changed the way pharmaceutical cleanrooms are designed. The most important consequences for a construction project:
- Contamination Control Strategy (CCS): a documented, holistic contamination control strategy covering room design, personnel and material flows, utilities and monitoring. The CCS is not an appendix to the design; it is the superior document the design should follow from.
- Emphasis on airflow visualisation: smoke studies in grade A have become a standard element of qualification rather than an option. Plan and budget for them at design stage.
- Periodic requalification: grades A and B every 6 months, grades C and D every 12 months. This is a real, recurring operating cost that belongs in the investment TCO.
- Barriers and isolators: Annex 1 clearly favours RABS and isolator technology where feasible, which changes the demands on the supporting HVAC.
HVAC requirements for pharmaceutical cleanrooms
In a pharmaceutical investment, HVAC accounts for 50–60% of the budget and effectively determines the qualification outcome. Key design parameters:
- Pressure cascade: typically 10–15 Pa between adjacent cleanliness grades, with continuous measurement and alarms. The cascade has to be designed together with the airlocks, not adjusted after the fact.
- Air change rate (ACH): usually 30–60 air changes per hour for grade C; grade A zones are solved with unidirectional airflow, not with air change rate.
- Terminal HEPA H14 filtration: filters installed in the ceiling supply diffusers, not in the air handling unit, so that DOP/PAO integrity testing is possible in place.
- Recovery time: after a disturbance the room must return to its class within a time confirmed by measurement to EN ISO 14644-3; in practice the design target is some fifteen minutes.
- Temperature and humidity stability: typically 20–22 °C (±0.5 °C) and 45–55% RH (±5%), which calls for two-stage cooling with dehumidification and controlled humidification.
- Redundancy: for critical zones, standby air handling units and power supply, so that the failure of a single unit does not mean losing a production batch.
Qualification and documentation
A pharmaceutical cleanroom is accepted on the basis of documents, not declarations. We run the full qualification path:
- DQ, design qualification: confirmation that the design meets the URS and the requirements of Annex 1.
- IQ, installation qualification: the installation matches the documentation, with a complete set of certificates and material approvals.
- OQ, operational qualification: measurement of airflows, pressure differences, temperature and humidity, DOP/PAO integrity testing of HEPA filters, recovery time test.
- PQ, performance qualification: particle counts at rest and in operation, confirmation of the class to EN ISO 14644-1.
The documentation is handed over ready to present during an inspection by the Polish Chief Pharmaceutical Inspectorate (GIF) or a client audit, and it can be prepared in English for international audits.
The most common causes of failed qualification
From the projects and modernisations delivered by our team: the problems that stop pharmaceutical investments at PQ rarely concern the quality of the room build itself.
- class selected for the at-rest state while the process requires it to be held in operation,
- pressure cascade designed without allowing for airlocks opening at the same time during material transfer,
- HEPA filters in the air handling unit instead of terminal filters, with no possibility of integrity testing at the supply point,
- no cooling capacity reserve, so temperature tolerance is lost in summer,
- monitoring without continuous recording, so there is no evidence of class compliance between periodic qualifications.
Clima Line experience in controlled environments
Clima Line has been delivering cleanrooms since 2016, and the core engineering team has worked together in Silesia since 2013. We have completed five cleanrooms above 1 000 m² and hundreds of modernisations and service jobs in operating facilities. In the medical sector we delivered the HVAC system for a Regional Blood Donation and Haemotherapy Centre.
The technology side is led by Marcin Sompoliński, PhD Eng., co-owner of Clima Line. We cooperate with academic staff of the Wrocław University of Science and Technology and hold full licences to design, build and operate the installations.
See also: turnkey cleanroom construction, the complete ISO 7 cleanroom guide and our projects.
Frequently asked questions
Which GMP grade corresponds to ISO 7?
GMP grade C corresponds to ISO 7 at rest and ISO 8 in operation. Grade B corresponds to ISO 5 at rest and ISO 7 in operation.
How much does a pharmaceutical cleanroom cost?
Indicatively 6 000–20 000 PLN/m², depending on grade and scope: grade C (ISO 7) sits in the lower part of the range, from 6 000 PLN/m², and grade A and B zones with unidirectional airflow in the upper part, up to 20 000 PLN/m². Qualification and periodic requalification come on top, every 6 months for grades A and B.
Can the class of an existing room be raised?
Usually yes, but the deciding factor is the reserve in the HVAC system, not the room build. We start with measurements and an air balance on site: only these show whether new filtration and a rebuilt supply are enough or a new air handling unit is needed.
Do you work in operating plants?
Yes. We carry out modernisations in stages and during shutdown windows, keeping production running in adjacent zones and protecting the clean zones for the duration of the works.
What is a Contamination Control Strategy?
The CCS is the document required by Annex 1 that describes the plant's overall contamination control strategy: from room design and flows, through utilities and procedures, to monitoring. The cleanroom design should follow from it rather than being developed independently.
Planning a pharmaceutical investment?
Send us your process description and the facility layout. We will prepare a concept with GMP grade selection, pressure cascade, air balance and a quotation that includes the cost of qualification. Contact us or call +48 32 450 56 66.