ASEPTIC PROCESSING: TWO - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 243

science- and engineering-based rationalization of environmental monitoring pro-
grams. Akers and Agalloco, [23] and Whyte and Eaton [24] choose the FMEAC
tool through which to apply the fundamental risk equation (risk = severity of
occurrence × frequency of occurrence). Risk factors representing the quantity
of microorganisms (criticality of occurrence), the probability of contamination
(frequency of occurrence), together with any applicable controls mitigating the
risk are individually identified by appropriately experienced and qualified subject
matter experts (SMEs). Each risk factor is assessed and a descriptor (risk score)
of its magnitude agreed on by the consensus of SMEs. Risk factors are assigned
individual risk scores by cross-reference to a predetermined table of surrogate
numerical values; Table 10.2 illustrates a predetermined table correlating surro-
gate value risk scores to perceived magnitudes for risk factors. In Table 10.2,
each risk factor is assessed in terms of arbitrary but relative terms; each risk
factor is assigned a risk score by comparison of term (e.g., nil, low, medium,
high, etc.) to the numerical surrogate descriptor, 0, 0.5, 1, 1.5, or 2 (adapted from
[24]).

• The risk factor scores are then multiplied, consistent with FMEA to generate
an overall risk rating; comparison of risk ratings permits the evaluation of
risk and appropriate decision. Table 10.3 illustrates the calculation of a risk
rating for an identified source of microbial hazard (air from a corridor)
using this methodology. The strength of this technique is that it is relatively
simple, easily trained, and a sufficient understanding of risk can be achieved
with a relatively small amount of information.

Within this technique, Whyte and Eaton [24] introduced the concept and
incorporation of “transfer coefficients” to aseptic manufacturing risk assess-
ments. This was an innovative development and provides a thorough means of

TABLE 10.2 Assignment of Risk Scores to Risk Factors

Risk Factor A B C D

Risk Factor
Description

Amount of
Microbial
Contamination on
or in a Source

Ease of Dispersion
or Transfer of
Microorganisms

Proximity of
Source to
Critical Area

Effectiveness of
Control
Measure

Risk score 0 (nil) 0 (nil) 0 (remote) 0 (full barrier

control)

0.5 (very low) 0.5 (very low) 0.5 (in outside

corridor)

0.5 (very good
control)

1 (low) 1 (low) 1 (periphery of

cleanroom)

1 (good control)

1.5 (medium) 1.5 (medium) 1.5 (general area

of cleanroom)

1.5 (some
control)

2 (high) 2 (high) 2 (critical area) 2 (no control)