Biomedical Engineering Reference
In-Depth Information
hazard is subject to the same forces and vectors acting upon inanimate parti-
cles; concomitantly, the physical disposition and movement must be predictable.
Quite simply, under defined environmental conditions (including consideration
of air flow dynamics, temperatures, humidity), the probability of a microorgan-
ism accessing a product, resulting in nonsterility, is dependent upon the number
of microbial hazards and the time duration the product is vulnerable to ingress.
The subsequent algorithm or transfer coefficient permits the determination of a
statistically sound evaluation of product contamination; knowing the amount of a
microbial hazard within an environment and the duration for which a product is
vulnerable may thus be converted into a likelihood of contamination. Determina-
tion of such a transfer coefficient is highly dependent upon a well-defined testing
environment with proven air flow dynamics and microbial distributions. Tidswell
and McGarvey [19] achieved this relying on a quantification of microorgan-
ism using growth-based recovery and quantification, qualifying the methodology
by direct comparison to process simulation data [27]. Within the risk assess-
ment, transfer coefficients may also be assigned probabilistic distributions to build
into the quantification an appreciation for uncertainty and variability. Augmenta-
tion with the application of real-time rapid microbial monitoring by the likes of
cytometry [67,68] facilitates the real-time quantification of risk and a statistical
determination of product sterility far beyond that feasible by the combination of
current aseptic technologies, testing product disposition, and processes. Integra-
tion of real-time microbial monitoring data with an automated software platform
is as yet unrealized but would provide a continuous automated risk calculation
(ARC) for real-time deterministic assessment of product sterility, imparting a far
superior assurance of sterility than that achievable by sterility testing.
10.9 FUTURE TRENDS AND THEMES
Healthcare will continue to experience a growing population of more aged
patients and the continued burden of microbial infections linked to clinical
administration of a diversifying range of therapies. It is foreseeable that where
feasible healthcare practices, procedures, and treatments will be devolved
out into community, clinical, and outpatient settings, diminishing the risk of
hospital-associated infections and complications. This will further accentuate
our need to understand and design out risk to product sterility in the context
of out-of-hospital environments and settings. Economic and regulatory pressure
will additionally encourage the automation and refinement of risk assessment
processes and techniques that are not so heavily reliant on human input and
where the uncertainty and subjectivity of content is designed out. Adequate
assurance of the absence of microorganisms (sterility) from a product will likely
never be achievable by end product testing. Universal acknowledgement of
this fact will necessitate alternative strategies assuring sterility; automated risk
calculation (ARC) for real-time, as described earlier, is one strategy likely to
succeed. It is clear that risk analysis and risk evaluation of aseptic manufacture
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