Understanding Overkill Sterilization: An End to the Confusion - Pharmaceutical Technology

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Understanding Overkill Sterilization: An End to the Confusion
The author clarifies the definition and objectives of overkill sterilization for steam sterilization cycles. Current sterilization practices are reviewed and the validation difficulties associated with the various definitions of overkill sterilization are explored.

Pharmaceutical Technology

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
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
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.


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