Pharmaceutical Manufacturing Handbook: Production and

110 STERILE PRODUCT MANUFACTURING
2.1.3.6 Capping and Crimp Sealing Areas
The application of aluminum seals over rubber stoppers is essential to secure them
properly. In many older facilities this was accomplished outside the aseptic processing
area in an unclassifi ed environment. Current practice requires that air supplied
to this activity meet ISO 5 under static conditions. The protection of crimping has
resulted in a variety of designs to meet the requirement: Sterile crimps can be
applied with the aseptic core on the fi lling line; sterile crimps can be applied in a
separate crimping room accessible from the fi lling room. If the crimpling operation
is located within the APA, it should be in a separate room maintained at a negative
pressure differential relative to the fi lling environment. Crimping may alternatively
be performed in a classifi ed room accessed from a controlled but unclassifi ed environment.
In this case it is imperative to verify that the environmental controls satisfy
regulatory expectations for all relevant markets.
2.1.3.7 Sterilizer Unload (Cooldown) Rooms
Sterilizers/ovens are unloaded and items staged prior to transfer to the individual
fi ll rooms. ISO 5 air is provided over the discharge area of ovens (and autoclaves if
items are sterilized unwrapped) to provide protection until the items are ready for
transfer. The heat loads in this room may be such that special high - temperature
sprinkler heads may be necessary to avoid unintentional discharge when unloading
hot materials. This room may not be separate from the corridor used to connect the
fi ll rooms. It is ordinarily adjacent to any aseptic storage area.
2.1.3.8 Corridors
Corridors serve to interconnect the various rooms that comprise the APA. Fill
rooms, air locks, and gowning rooms are accessed from the corridor. They can also
be utilized for modest storage as well.
2.1.3.9 Aseptic Storage Rooms
In general, extensive use of in - process storage areas should be avoided. It is best to
operate the aseptic facility in a just - in - time mode in which components and
equipment are sterilized shortly before they are required for use in the fi lling or
compounding areas. Some limited storage is necessary for nonproduct contact
materials such as sanitizing agents, environmental supplies and equipment, and
other items.
2.1.3.10
Lyophilizer Loading and Unloading Rooms
The loading of lyophilizers is accomplished under ISO 5 environmental conditions
within the aseptic processing area. Several possible locations are possible: within
the aseptic fi ll room itself, in a separate room adjacent to the fi ll room, or in a separate
room remote from the fi ll room. There are pros and cons with each of these
selections which should be carefully considered in the facility design. There is a