The overkill method is perhaps the most common method used in the development and validation of sterilization processes. Overkill
sterilization primarily is applied to the moist-heat processing of materials, supplies, and other heat-stable goods. It generally
is considered to be the simplest and most straightforward method for the design and validation of moist-heat sterilization
processes. Although this is true, there is substantial confusion about how to use the overkill method and, in fact, regarding
what actually constitutes an overkill process. Confusion associated with the overkill approach exists in all of the widely
used sterilization technologies; that is, moist heat, dry heat, gas, and radiation. This article focuses on steam sterilization,
of which there is both a greater amount of published definitions and a more precise and generally accepted understanding of
the underlying science.
A contemporary definition of overkill moist-heat sterilization follows: "This is usually achieved by providing a minimum 12-log reduction of microorganisms having a D-value of at least one minute at 121 °C" (1). This is a simple-enough definition. Unfortunately, it cannot be demonstrated
in a straightforward manner with presently available technology. What this definition suggests is that overkill requires a
12-D process, which equates to lethality sufficient to deliver a 12 × D
121 lethality level. This is not a lethality standard at all, however, because it inappropriately links the process lethality
requirement to the characteristics of a specific biological indicator (BI). This article reviews present sterilization practices
and explores the difficulties inherent in this definition.
Sterilization basics
Sterilization as a process can be rather simply defined as:
a validated process used to render a product free of viable organisms. In a sterilization process, the nature of microbiological
death or reduction is described by an exponential function. Therefore, the number of microorganisms which survive a sterilization
process can be expressed in terms of probability. While the probability may be reduced to a very low number, it can never
be reduced to zero (2).
Figure 1
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The difficulty lies in demonstrating the effectiveness of that process. The death of microorganisms by any sterilization method
has been shown to generally follow a straight line termed the "death curve" (see Figure 1).
Figure 2
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This phenomenon occurs with all microorganisms and is not restricted to any particular species. The slope of this line represents
the resistance of the microorganism to the sterilization process. The death curve for organisms exhibiting substantial resistance
will have a shallow slope, and those with low resistance to the sterilization process will have a much steeper slope (see
Figure 2).
The difference in microbial resistance is critical to sterilization validation. The microbial genera Geobacilli, Bacilli, and Clostridia, having substantial resistance to the sterilization process, are commonly chosen as BIs to provide an appropriate evaluation
of the process. These BI organisms are stipulated to be spore populations that have much higher resistance to sterilization
processes than the vegetative cells that predominate in the normal microflora found in pharmaceutical production environments.
Using these spores as indicator organisms creates a process challenge that is inherently worst-case. In the case of moist
heat in which sterilization conditions are very well defined and understood, BIs are best used to establish that there is
sufficient correlation between physically measured lethality, generally in the form of thermometric data, and biological lethality
measured using calibrated BIs.
