Pharmaceutical Manufacturing Handbook: Production and

104 STERILE PRODUCT MANUFACTURING
The FFS utilizes in - line sterilization/drying of the fi lm prior to shaping of the
containers.
2.1.2.3 Process Objectives
The production of parenteral products requires near absolute control over microorganisms.
Endotoxin contamination is a serious health concern, particularly among
neonates and infants and also requires a high level of control and validation. Additionally,
the control of foreign matter, including particles and fi bers of various types,
is also vitally important to end - user safety. Assuring appropriate control over these
potential contaminants requires careful attention to several factors: facility design,
equipment selection, sterilization procedures, cleaning regimens, management of
personnel, and the process details associated with compounding, fi lling, and sealing
of product containers. Each of these will be discussed in detail.
2.1.3
FACILITY DESIGN
To provide control of microbial, pyrogen, and particles controls over the production
environment are essential. The facility concerns encompass the entire building, but
the most relevant components are those in which production materials are exposed
to the environment.
2.1.3.1 Warehousing
Environmental protection of materials commences upon receipt where samples for
release are taken from the bulk containers. Protection of the bulk materials is
accomplished by the use of ISO 7 classifi ed environments for sampling. All samples
should be taken aseptically, which mandates unidirectional airfl ow and full operator
gowning. This practice is mandated by current good manufacturing practice (CGMP)
and assures that sampling does not introduce contaminants to the materials that
will be used in the production. Where central weighing/subdivision of active ingredients
and excipients are performed, similar protection is provided for identical
reasons. The expectation is that these measures reduce the potential for contamination
ingress into materials that have yet to receive any processing at the site. Materials
and components that are supplied sterile are received in this area, but samples
are often packaged separately by the supplier to eliminate the need for potentially
invasive sampling of the bulk containers. Where so - called delivery samples are used,
it is critical that these samples are known to be fully representative of the production
process. Additionally, where sterility or bioburden control of sampled materials
is critical, thought must be given to the methods used to reseal the containers to
ensure that moisture levels, bioburden levels, or in the case of sterile products sterility
assurance are not compromised.
2.1.3.2
Preparation Area
The materials utilized for production of sterile processes move toward the fi lling
area through a series of progressively cleaner environments. Typically, the fi rst step