Biomedical Engineering Reference
In-Depth Information
TABLE 10.3 Calculation of the Risk Rating for the Air Originating Outside a
Cleanroom (from a Corridor), Potentially Contaminating the Cleanroom (Adapted
from [24])
Risk Factor
A
B
C
D
Risk Rating
Amount
Ease of
of Microbial
Dispersion or
Risk
Contamination
Transfer of
Proximity Effectiveness
Factor
on or in a Microorganisms of Source
of Control
Description
Source (Air)
Area
to critical
Measure
Risk score
1.5 (lower
classifica-
tion
area)
1
0.5
1 (positive air
outflow
from the
cleanroom)
0.75
including an evaluation of more accurate product risk. Transfer coefficients are
numerical values defining the relative transfer efficiency of a microbial hazard
into a vulnerable product, in other words, over time, considering the area of
an open product, the quantity of bioburden in the context of the manufacturing
environment, and the rate of ingress of microorganisms. This is a fundamentally
important development that permitted a link between the microbial hazard in the
manufacturing area to product risk; this incorporation of transfer coefficients has
permitted the innovation of truly quantitative risk assessment and risk modeling
(see Section 10.8.3). Systematic application of these forms of risk assessment
effectively distinguishes in arbitrary but relative terms the risk, and therefore
permits a rational decision regarding monitoring or bioburden management.
Determination of worst-case conditions . Throughout the aseptically man-
ufactured product or aseptic process, life cycle validation exercises have
traditionally incorporated worst-case conditions. Risk assessment permits
a data-driven, science- and engineering-based rationale for the expedient
identification and choice of those conditions that truly represent the great-
est challenge and jeopardy to a process. One area where this has been
effectively accomplished is in the validation of microbial control during
equipment cleaning and hold [25]. The rational choice of worst-case condi-
tions in the equipment cleaning and hold process in the aseptic manufactur-
ing arena can be complex. This is especially the case within multiproduct,
multiprocess facilities utilizing nondedicated equipment of varying design,
material of construction, fabrication, cleaned, and dispositioned by multiple
means, cycles, and processes. Identification of worst-case equipment, prod-
uct residues, cleaning cycles, and hold processes (pre- and postcleaning) can
be accomplished by assessment of the microbial hazard. In this application,
risk of microbial retention and proliferation, in addition to contamination
(of equipment), are essential considerations. For example, some equipment
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