ASEPTIC PROCESSING: ONE - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 228

• likelihood of the contamination's survival, proliferation, and retention (if
introduced);
• level of personnel activity and/or equipment traffic; and
• probability of detecting the hazard due to testing or other method of
detection.

These factors are ranked to provide a risk score for each operation of a given
manufacturing process. This risk score is then compared to a pre-established
threshold, beyond which a process step is considered unacceptably risky
and subject to improvement via the implementation of additional protective
measures [28].
The authors of this chapter initially developed an aseptic processing risk
method in 2005, and modified it substantially a year later [29,30]. The
Agalloco-Akers (A-A) method endeavored to evaluate aseptic risk using only
quantifiable metrics, a significant departure from Whyte, but one that eliminated
the uncertainties associated with estimate of proportions of microorganisms
transferred. The central premise focus of the A-A method is that contamination
in aseptic processing is almost exclusively associated with human activity.
The metrics in the A-A method focuses on the operator's activities, their
complexity, duration, and proximity to sterile surfaces being primary drivers
in the estimation of risk. Other involved factors are weighted by the extent
to which they entail human intervention. The original method had some
inherent redundancies and lacked flexibility for varying environments across
the aseptic processes, which are corrected in the second version of

the

method. ∗∗
Unlike the other risk assessment methods, which rely on subjective determina-
tions, the A-A method uses only easily identifiable and/or quantifiable metrics;
thus, it affords a truly objective assessment of risk. In addition, the A-A method
is actually three separate methods in one. The intervention risk, which estimates
the number of operator touches per container, is an integral part of the method
that can be utilized independent of the rest. †† The remaining elements address
processing technology and system design and can be used without determina-
tion of the intervention risk, allowing for technology and procedural assessment
independent of the operator's impact. This is useful in a design context when

Multiple post-conference communications with Berrios have revealed that the Lilly method has
continued to evolve. The risk factor ranking “Personnel Activity/Equipment Traffic” was replaced
in 2010 by a risk factor that rates the impact of “Personnel Interventions/Manipulations” at each
process step. This change was prompted by the perceived need to evaluate the role of personnel in
the manufacturing process more objectively.
∗∗ The publications are not identical and in order to understand and apply the A-A method both
should be considered.
†† Intervention risk (IR) is a measure of the need for operator intervention. Manual procedures and
extensive intervention during machine-based filling result in higher numbers of operator contact per
container and are thus considered higher risk.