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Choosing Overkill Cycle Parameters
Conventionally, the term “overkill cycle" in validation of a steam-sterilization autoclave process is understood to mean that all items were steamed beyond all hope of anything surviving a grossly exaggerated load cycle. This cavalier approach to sterilization validation, however, is no longer enough to satisfy most regulatory inspectors, who have grown accustomed to control strategies based on risk assessment and scientific rational for the mitigation of the identified risks. A more robust, quality-by-design philosophy based in sound science and process understanding is more appropriate and defendable.
A key component when presenting any autoclave validation package is to be able to clearly defend how the requirement to correlate biologic and physical lethality data from the validation reports is satisfied (1). Fulfilling this requirement can provide sound justification for autoclave critical process parameters (CPPs) and how they were validated.
Development work to justify load parameters
It is necessary to compare theoretical F0s (i.e., lethality levels) with the actual F0s delivered in an actual cycle. This real development testing will give a good idea of performance and capability of the autoclave and allow for realistic program-parameter settings.
It may be appropriate to add some time or temperature as a safety factor to account for all of the variables inherent to autoclaving items needed in a manufacturing process. Unknown incoming bioburden load is a reasonable driver to choose an overkill sterilization cycle. However, gross overage indicates a lack of control of the process and a lack of understanding of the appropriate lethality being delivered to load items. Delivered lethality should be well understood from development runs and applied judiciously, even in overkill cycles, in order for validation to be a credible assurance of process functionality.
Fractional cycles as a method of validating overkill cycles
By defining a fractional (i.e., partial) cycle time and temperature for validation loads based on an understanding of the autoclave capabilities in conjunction with particular load limitations, an excellent rationale can be made, and manufacturing cycles can be programmed as overkill cycles. The overkill compensates for deviations in time or temperature caused by calibration faults in controlling thermocouples, chamber leaks, variability in packaging and assembling components, or other production events.
—John Anderson is a quality assurance and validation professional with years of inspection experience. He can be reached at firstname.lastname@example.org.
This article is excerpted from an article on defining and presenting overkill cycle validation, which will appear in the Troubleshooting column of the November 2013 issue of Pharmaceutical Technology.