Biomedical Engineering Reference
In-Depth Information
risk analysis to aid assessment of batch quality; assisting batch disposition
in a manner more methodical and data driven than is currently the norm.
Consistent and routine application of risk assessment of every batch can
be used to assist in a deterministic estimation of batch quality, instilling
a higher degree of product quality assurance. Furthermore, it warrants the
question as to whether such an application should be implemented to contin-
uously maintain the validation status of an aseptic manufacturing process and
associated controls in a state of currency. Agalloco and Akers rightly point
out that process simulations cannot directly validate an aseptic process [26];
however, a systematic quantification of risk, furnished with batch-associated
data performed in a structured manner on every single batch, represents a
means of establishing the highest level of sterility assurance [27].
In this context, it is essential to recognize the attendant, significant complexity
inherent in virtually all aseptic and clinical processes, circumstances, and sce-
narios vulnerable to the omnipresent microbial challenge. The interdependencies
of factors contributing to risk of microbial contamination during manufacture
are not always straightforward. Any application of routine risk formulaic and
systematic risk assessment to facilitate batch disposition must recognize and
account for such interdependencies. This cannot be adequately described or
computed (to an exacting quantitative level) using single-dimensional (e.g.,
traditional FMEA) risk assessment. This can be illustrated in the simplest terms
by simultaneously considering the combination of participating aseptic operators
and interventions for two parenteral batches manufactured in an identical
process within identical aseptic cleanroom filling processes (Fig. 10.2). In the
manufacture of each batch, the same aseptic operators participate, and each
executes an identical number of aseptic interventions. Each batch incorporates
the same number and type of aseptic intervention. Although, there is a high
degree of commonality, the risk of bioburden ingress into each product batch is
not identical. Here, the unique combination of intervention duration, proximity
to product, and the aseptic operator-associated bioburden levels combine to quite
Batch #1
Batch #2
Interventions
Interventions
A
B
C
A
B
C
1
2
1
1
1
2
3
2
2
1
3
5
3
2
1
2
Figure 10.2
Combination of aseptic operators and aseptic interventions associated with
two aseptically manufactured parenteral batches [27].
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