Environmental technology risk
Once the risk contributions from the components of an overall aseptic process have been determined, the authors recommend
an overall adjustment according to the environmental technology providing the aseptic conditions. If aseptic compounding is
a substantial part of the process, and is not performed using the same technology, the environmental factor should be applied
separately and then added. The authors have placed an arbitrary weighting on the various technologies throughout this article
(see Table VII). As stated earlier, consistency in the evaluation of an aseptic process will be manifest in the overall risk
assessment, regardless of the specific values chosen.
Table VII: Environmental technology.
In the application of the present method, a glaring difference in risk analysis "score" is apparent between conventional staffed
aseptic processing and advanced technologies. Manual processes fare even more poorly. The authors believe that the distinctions
this method reveals among different aseptic technologies are real and accurately represent the risk of contamination. The
reader may disagree with the numerical weighting factors selected, but the rationale for them is sound. It is possible to
debate the present recommendations in a strictly numerical sense, but such a debate would result only in subtle changes and
would not materially affect the objective assessment of the differences among the various practices evaluated. This method
should not be used to determine what is acceptable or unacceptable in absolute terms, but should serve as a means of identifying
opportunities for process improvement, regardless of the practices and technologies used. There may come a time when a system
similar to this one can be used to define the acceptability of practices for products, but that time has not yet arrived.
The authors also see potential for the application of this method in the selection of technologies to be used.
Perhaps even more important, the authors believe that the present risk analysis model can facilitate the determination of
an appropriate level of validation and revalidation suitable to the technology used. Aseptic technologies that either mitigate
the risk of human intervention or eliminate such activities entirely through automation or separative technologies are inherently
safer than technologies that allow direct human intervention. It follows that the more reliant a technology is on human intervention,
the more risky it must be. Logically then, such traditional tests as the media fill are far less likely to provide value in
assessing the performance of advanced technologies. Thus, media-fill test frequency could be reduced, as could sample size,
particularly in systems that allow direct real time control and evaluation of the environment and the process.
In fact, the authors propose that it is possible to draw a clear line of demarcation between "advanced" aseptic technologies
and more conventional systems using risk analysis. For a technology to be considered advanced, there must be no direct human
intervention at any time. For example, a RABS system would be considered advanced only if there were never direct human interventions
through temporarily opened barriers. Similarly, a blow–fill–seal system would be considered advanced only if no containers
were put at risk after an intervention and the fluid path were subjected to sterilization-in-place before the resumption of
manufacturing. In the authors' view, firms that invest in technologies that have been demonstrated objectively to mitigate
risk and in which key control parameters can be measured and controlled in real time should benefit from reduced validation,
revalidation, and traditional microbiological-monitoring requirements. Imposing the same validation requirements for advanced
technologies as for more risk-intensive alternatives not only provides no safety benefit, it does actual harm through implementation
delays caused by excessive requirements.
This article may be considered a positive step in an effort to assess risk in aseptic processing. The authors believe that
a broadened perspective of risk relative to aseptic processing increases awareness that risk can vary substantially in what
are perceived by many to be equivalent—and thus equally acceptable—practices and technologies. The authors welcome constructive
criticism of this effort in the hope that it will lead to a clearer definition of risk issues and evaluation approaches as
they relate to aseptic processing.