Grade C and D: These are cleanrooms used for carrying out less critical stages in the
manufacture of aseptically filled sterile
products or as a background for isolators. They can
also be used for the preparation/filling of terminally sterilised products. (See section 8 for the
specific details on terminal sterilisation activities).
4.5 In cleanrooms and critical zones, all exposed surfaces should be smooth, impervious and
unbroken in order
to minimize the shedding or accumulation of particles or micro-organisms.
4.6 To reduce accumulation of dust and to facilitate cleaning there should be no recesses that are
difficult to clean effectively, therefore projecting ledges, shelves, cupboards and equipment should
be kept to a minimum. Doors should be designed to avoid recesses that cannot be cleaned. Sliding
doors may be undesirable for this reason.
4.7 Materials used in cleanrooms, both in the construction of the room and for items used within the
room, should be selected to minimize generation of particles and to permit the repeated application
of cleaning, disinfectant and sporicidal agents where used.
4.8 Ceilings should be designed and sealed to prevent contamination from the space above them.
4.9 Sinks and drains should be prohibited in the grade A and grade B areas. In other cleanrooms, air
breaks should be fitted between the machine or sink and the drains. Floor drains in lower grade
cleanrooms should be fitted with traps or water seals designed to prevent back flow and should be
regularly cleaned, disinfected and maintained.
4.10 The transfer of equipment and materials into and out of the cleanrooms and critical zones is one
of the greatest potential sources of contamination. Any activities with the potential to compromise
the cleanliness of cleanrooms or the critical zone should be assessed and if they cannot be
eliminated, appropriate controls should be implemented.
4.11 The transfer of materials, equipment, and components into the grade A or B areas should be
carried out via a unidirectional process. Where possible, items should be sterilised and passed into
these areas through double-ended sterilisers (e.g. through a double-door autoclave or depyrogenation
oven/tunnel) sealed into the wall. Where sterilisation upon transfer of the items is not possible, a
procedure which achieves the same objective of not introducing contamination should be validated
and implemented, (e.g. using an effective transfer disinfection process, rapid transfer systems for
isolators or, for gaseous or liquid materials, a bacteria-retentive filter). The removal of items from
the grade A and B areas (e.g. materials, waste, environmental samples) should be carried out via a
separate unidirectional process. If this is not possible, time-based separation of movement
(incoming/exiting material) by procedure should be considered and controls applied to avoid
potential contamination of incoming items.
4.12 Airlocks should be designed and used to provide physical separation and to minimize microbial
and particle contamination of the different areas and should be present for material and personnel
moving between different grades. Wherever possible, airlocks used for personnel movement should
be separated from those used for material movement. Where this is not practical, time-based
separation of movement (personnel/material) by procedure should be considered. Airlocks should be
flushed effectively with filtered air to ensure that the grade of the cleanroom is maintained. The final
stage of the airlock should, in the “at rest” state, be of the same cleanliness grade (viable and total
particle) as the cleanroom into which it leads. The use of separate change rooms for entering and
leaving the grade B area is desirable. Where this is not practical, time-based separation of activities
(ingress/egress) by procedure should be considered. Where the CCS indicates that the risk of
contamination is high, separate change rooms for entering and leaving production areas should be
used. Airlocks should be designed as follows: