Design qualification (DQ) demonstrates that the design meets the requirements of the URS (user requirements, German “Lastenheft”) and complies with GMP. For equipment, this design is usually the supplier specification (German “Pflichtenheft”). For rooms, that counterpart is often missing, because no single supplier “delivers” a room. Here the room book takes on the role of the specification. The term does not appear in the regulations. For rooms, however, the room book fulfils the function of the specification described in Annex 15 and serves as the basis for testing in the IQ. It describes each room with its quality-relevant properties and forms the basis of the DQ. Together with the layout, it is also the document that explains a facility most quickly during an inspection.
Where the data in the room book comes from
A room book is not written at the architect’s desk alone. The values follow from how the room will be used:
- From the product: sensitivity to temperature, humidity and light, and toxicity. These determine the room climate, the lighting and whether the climate needs to be monitored.
- From the process: sterile, aseptic or non-sterile, open or closed handling, adjacent process steps. These determine the cleanroom grade, the surface finish of walls, ceilings and floors, the ventilation concept and the pressure level.
- From operations: number of people, working hours, material and personnel flows, and the utilities required, such as compressed air or pharmaceutical water.
The design documents provide the rest: floor plans, zoning plans, the ventilation schematic and, where available, the bill of quantities (BoQ). In practice, we record the source and the drawing revision for every value. Where the drawings of two trades contradict each other, this is flagged in the room book until it is resolved.
Typical content of a room data sheet
Each room gets its own sheet. These sections have proven useful:
| Section | Examples |
|---|---|
| General room data | Room number, name, floor area, height, number of occupants |
| Finishes | Floor, walls, ceiling, coving, doors, windows, light fittings |
| Room air | Cleanroom grade, pressure level, airflow direction to adjacent rooms, temperature and humidity with tolerance and alarm limit, air change rate |
| Utilities | Compressed air, technical gases, pharmaceutical water, waste water |
| Special requirements | Explosion protection, handling of toxic substances, airlock door interlock |
| Approval | Prepared, reviewed, approved |
It is important that every value has a tolerance and, for critical parameters, an alarm limit as well. “Positive pressure” without a number cannot be tested.
From the room book to the ventilation schematic
The room book sits at the start of a short chain. The room data are used to derive the air volume schedule: supply, extract and transfer air for each room, plus the air change rate. The air volume schedule in turn gives the ventilation schematic, with the pressure cascade and airflow directions. To check whether the ventilation schematic matches the room book, you work back along this chain.
Differential pressures deserve a second look. If all rooms are measured against a common reference point, the differential pressure between two adjacent rooms can be calculated. This requires the measuring points and the reference point to be clearly defined in the ventilation schematic. In Annex 1 areas, however, indicators of the differential pressure between rooms are expected. With a calculated differential pressure, the measurement uncertainties of two sensors also add up. As a guidance value, Annex 1 gives at least 10 Pa between adjacent rooms of different grades.
Room and HVAC system: where is the boundary?
The room and the HVAC system are separate qualification objects. Where one ends and the other begins is not given from the outset. The qualification interface is defined in the qualification plan. Do the terminal HEPA filters and the room pressure sensors belong to the HVAC system or to the room? Who tests the airlock control that runs via the building management system? The answers determine which protocol a test appears in. What matters is that every test appears exactly once and that the protocols refer to each other. It has proven useful to record interfaces with other systems, such as monitoring, logistics or gas detection, in an interface table in the relevant sub-plan.
A typical split might look like this:
| Stage | Room | HVAC system |
|---|---|---|
| DQ | Room book against user requirements and design | Design basis, air volume schedule and ventilation schematic against the requirements |
| IQ | Finishes: surfaces, joints, coving, penetrations, doors, light fittings, drains | Components, ductwork, filters, instrumentation points and their calibration, documentation |
| OQ | Room functions: airlock door interlocks, airlock and status indicators, alarms at the room | Air volumes, filter leak and integrity test, control, alarms, behaviour after power failure |
| OQ, joint | Differential pressures and airflow direction, airflow visualisation, particle classification at rest, microbial contamination at rest, recovery time, temperature and humidity in the room | tested together with the room |
| PQ | Particles and microbiology in operation, stability of room conditions over a representative period | tested together with the room |
The room and the HVAC system come together in the OQ. The pressure cascade, airflow direction, cleanliness grade and recovery time can only be demonstrated in the finished room with the system running. Whether these tests sit in the room protocol, the HVAC protocol or a joint protocol follows from the defined interface.
So a room can have its own OQ. Under Annex 1, the entry and exit doors of airlocks and pass-through hatches should not be opened at the same time. Airlocks leading to grade A and B areas should have an interlocking system; for airlocks leading to grade C and D areas, a visual and/or audible warning system is the minimum. Functions like these are tested in the same way as any other function: against a predefined acceptance criterion, with a documented result.
What Annex 1 lists for cleanrooms
Annex 1 treats the classification of a cleanroom as part of its qualification. Classification is carried out at rest and in (simulated) operation against the limits in Table 1 of Annex 1. The number and position of the sampling locations follow ISO 14644-1. Outside Annex 1, rooms are classified according to ISO 14644-1 classes. For qualification, Annex 1 lists the following tests, where relevant to the design and operation of the installation:
- leak and integrity test of the installed filters
- airflow volume and air velocity
- differential pressures
- airflow direction and airflow visualisation
- microbial air and surface contamination
- temperature and relative humidity
- recovery time
- containment leak test, where relevant
Which of these tests sit in which protocol again follows from the interface between the room and the HVAC system.
How the testing is carried out
The IQ of a room is mostly a visual inspection. The room book serves as the checklist: for every room and every line, you record whether the installation matches the specification. The evidence consists of acceptance records from the individual trades, test certificates, material certificates and delivery notes. These are assigned to the room book and filed with it.
Cleanroom testing is structured by defined states. ISO 14644-1 distinguishes the occupancy states “as-built”, “at-rest” and “operational”. Annex 1 requires cleanrooms to be classified “at rest” and “in operation” and defines both states. The IQ and OQ tests are assigned to these states. For “in operation”, the maximum number of people is defined for each room. Where a room contains storage areas, temperature and humidity mapping is carried out before approval, as described in Temperature mapping of storage areas and cold rooms. In practice, rooms are approved in stages, one room group at a time.
How deeply you test depends on the cleanroom grade and the impact on the product. Annex 1 applies to the manufacture of sterile medicinal products. Its principles can be used for other products; in that case, it should be documented which principles are applied. The specific decisions for a project belong in the risk assessment.
Annex 1 is not binding for medical devices. There, ISO 13485 applies, and for the US market the QMSR (21 CFR Part 820). Rooms are classified according to ISO 14644-1 classes, such as ISO 7 or ISO 8. In practice, companies add their own room categories, for example classified, controlled not classified (CNC) or monitored only.
Construction work next to operating cleanrooms
When construction work takes place next to cleanrooms that remain in operation, in practice we define a plan for disruptive events in advance. The status of the affected rooms is checked before and after each switchover step. Once the work is complete, the rooms are requalified.
Conclusion
A good room book avoids duplicated work. It is the design basis, the specification, the basis of the DQ and the checklist all in one, and it links construction, ventilation and qualification through a shared room number. This requires it to be written early, derived from the actual use of each room, and to give every value a testable tolerance. The interface between the room and the HVAC system should be settled just as early.
How the stages from DQ to PQ fit together is explained in the article DQ, IQ, OQ and PQ explained. For support with room books and room qualification, see Qualification.