Special conditions.

Certain product types including pathogens or

genetically modified microorganisms (e.g., some vaccines), and potent
compounds (e.g., cytotoxics and steroids) and sensitizing compounds (e.g.,
-lactam antibiotics) present particular issues and special conditions that
further impact facility design. Each of these product types requires special
accommodation for the containment of the product and protection of the
operators working directly with the product.
Special desing conditions include:

Isolators should be considered for all open processes and filling.

Process areas where open operations occur should be segregated
from adjoining areas with a barrier zone (bubble or sink airlocks)
Segregation must be provided for facilities processing potent and
sensitizing compounds and for pathogens and genetically modified
microorganisms. However, the facility is not required to be
constructed as a separate building.
For potent and sensitizing compounds and for pathogens and
genetically modified microorganisms, decontamination is required for
all product contact equipment.
For processes involving the potential generation of aerosols of live
cells, special provisions must be made for the decontamination of
operator gowns.
If personnel protective equipment (PPE) is required, the gown and
degown airlocks should be configured to accommodate shared
equipment (e.g., pass-through cabinets).
For potent compound products, a misting shower should be included
in the degown airlock for use in the event of a mishap.
Depending on the type of product and the
requirements/recommendations of applicable building and fire codes,
and regulators (e.g., NIH or CDC), containment of firewater may be
necessary (20).

Facility Finish Materials

Interior finishes and materials of construction should be appropriate for the
type of activity occurring in the area and the recommended level of CGMP
compliance - ease of cleaning is always of utmost importance.
Finish materials basic criteria. All exposed surfaces and finish materials
in classified areas should be smooth, nonporous, and:

Free from cracks and open joints

Resistant to shedding of particles
Resistant to sustaining microbial growth
Resistant to damage from normal mechanical abrasions and impacts
Resistant to damage from repeated application of cleaning agents,
disinfectants, sterilants, and sanitizers; note: it is important to identify
the cleaning agents and sanitizers used as well as the cleaning
protocol. Prior to specifying materials and finishes, confirmation

should be obtained from the manufacturer that the materials can

withstand exposure to the agents used.
Configuration of the surfaces and their method of interface are also
important. Horizontal ledges should be avoided as these are areas where
particles and microorganisms could accumulate. Materials should align in
the vertical plane, and joints between dissimilar materials should be caulked
with sanitary silicone sealant. Coved transitions should be provided between
walls and floors and between walls and ceilings.
The selection criteria for appropriate materials should include:

Constructability and maintainability (local labor capability, difficulty of

repair, ease of cleaning)
Desired appearance (patterns, solid colors)
Cost (both first cost and lifecycle costs)

Floor systems. Floor systems for critical and primary support areas of
aseptic manufacturing facilities can be divided into two categories: sheet
systems (PVC, rubber) and resin-based multi-layer systems. The appropriate
selection of either system is dependent on the following criteria among
others:

Substrate conditions (new or existing concrete slabs)

Expected frequency of traffic (material loads)
Expected loading of traffic (heavy rolling loads such as tanks, carts,
forklifts, etc.)

In controlled, non-classified CGMP areas, floor systems such as pigmented

concrete sealer, sheet vinyl and thinner resin-based systems may be
considered for both cost and functional reasons.
Wall systems. Wall systems for critical and primary support areas of fill
finish facilities can be composed of site fabricated assemblies (concrete
block or metal stud/gypsum board walls with applied coatings), premanufactured assemblies (modular clean room partition systems), or a
hybrid of the two.
Wall systems should also be evaluated on the basis of the following
additional criteria:

Expected frequency of reconfiguration/relocation

Ease of modification (future installation/removal of panels, doors,
windows, etc.)
Design and construction schedule
Regulations set by building code authorities and recommendations by
insurance underwriters (e.g., FM Global)

Coatings, on site-fabricated walls in classified areas, can range from high

performance epoxy paint systems to multilayer resin-based systems
depending on budget, schedule, and availability of skilled labor.
In controlled, non-classified CGMP areas, concrete masonry units or metal

stud/gypsum board walls are typically specified and finished with highquality epoxy paint unless there are other factors present that would require
more robust systems.
Ceiling systems. Ceiling systems are similar to wall systems in that they
may be site-fabricated assemblies (suspended or wall-supported gypsum
board with applied finish coating or material), pre-manufactured assemblies
(clean room ceiling system), or a hybrid of the two. In addition to the criteria
used for wall systems, the selection of the ceiling system is influenced by

Requirement for walk-able ceiling surface

Accessibility needs (to controls and devices located above the
ceiling); note: care should be taken to locating access points outside
of critical areas

The appropriate ceiling finish material is dependent on the system chosen

and includes epoxy paint, PVC rigid seamless sheet, high-build surfacing, or
PVC-coated composite panel.
Ceilings in controlled non-classified areas may be suspended clean room
type with gypsum or composite panels, hold-down clips, and gaskets or
sealant at panel perimeter.
Doors. Doors should be seamless, sealed, flush, and box-type without
recesses.

Doors in ISO 5, ISO 7, and ISO 8 areas: frames should be installed

flush with adjacent wall surfaces; vision panels should be double
glazed and flush with door face.
Fully glazed doors may be used as an alternative in all areas.
Door hardware shall be heavy duty commercial grade, and hinges
shall be sealed, non-particle generating.
Swinging doors should typically swing closed in the direction of
airflow to maintain sealing at the jamb and minimize air leakage.
Sliding doors are not recommended in ISO 5 and ISO 7 areas.
Doors at material airlocks and otherwise accessed for moving
equipment and materials are recommended to have automatic
operators.
Powered (electrical or pneumatic) doors shall be appropriate for the
level of classification, taking into account cleanability, exposure to
sterilizing agents (incluiding fumigants, if applicable), and electrical
classification of the room.

Windows

Windows in classified areas shall be of double pane glazing and flush

with the wall finish on both sides.
Windows between classified and controlled non-classified areas shall
have single pane glazing, be flush with the wall finish on the classified
side and may have a sloped sill on the unclassified side.

Windows in controlled non-classified areas shall have a single glazing

pane; the frame shall be epoxy-painted galvanized steel.
Exterior window are not recommended in classified areas.

Room fixtures

All fixtures installed in classified areas must be constructed of

materials meeting the same basic criteria for all finish materials.
All fixtures in classified areas should be designed and fabricated in a
manner to minimize joints, ledges, and seams.
All panels (utility, access) in classified areas shall be installed flush
with the wall or ceiling surface.
Recessed sprinkler heads are to be provided where permitted by
building code and underwriters (factory mutual) requirements.
All penetrations in the wall or ceiling surface in classified spaces must
be sealed and gasketed, as required, to prevent air leakage; sealants
and gasket materials must meet the same basic criteria for all finish
materials.