ASEPTIC PROCESSING: ONE - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 224

barrier system (RABS) came somewhat later in an effort to eliminate some of the
more difficult technical challenges with isolators, while endeavoring to maintain
the operational excellence attained by keeping the operator access to the critical
environment to a minimum.
PDA and ISO independently developed guidance documents that endeavored
to define the spectrum of aseptic processing systems [17,18]. Each of these docu-
ments included a continuum that strove to visually clarify the various technologies
and methodologies. A more contemporary continuum that essentially converts
the ISO 14644-7 continuum into recognizable pharmaceutical technologies is
presented in Figure 9.1.
The primary source of microbial contamination in aseptic processing is
universally acknowledged to be personnel [19]. The improvements in aseptic
performance have been driven by designs that endeavor to move personnel away
from sterile articles during the processing. Ascending the continuum, the various
systems provide for increasingly robust separation of personnel from the critical
processing area. The systems near the center incorporate physical barriers that
further increase the separation, partially in RABS systems and more fully in
isolator designs. There are no currently available means to measure the sterility
assurance in any of these systems; thus, there is likely considerable overlap in
their performance capabilities. The uncertainties of environmental monitoring,
infrequent and equally uncertain media fill, and the almost useless sterility
test cannot adequately differentiate the performance capabilities of the various
aseptic processing technologies. Microbiological monitoring methods have not
kept pace with the advances in aseptic process technology; their sensitivity is
too limited and sample sizes are too small to provide meaningful assessments,
especially in the most advanced technologies. Perceived improvements such as
Gloveless isolator
Closed gloved isolator
Open gloved isolator
Closed RABS
Open RABS
Barrier system
Conventional aseptic fill
Manual aseptic fill
Increased confidence in sterility assurance
Figure 9.1 Aseptic processing continuum. ( See insert for color representation of the
figure .)