The sterility of a lot purported to be sterile is therefore defined in probabilistic terms, where the likelihood of a contaminated unit or article is acceptably remote.
Such a state of sterility assurance can be established only through the use of adequate sterilization cycles and subsequent aseptic processing, if any, under appropriate current good manufacturing practice, and not by reliance solely on sterility testing.
However, this absolute definition cannot currently be applied to an entire lot of finished compendial articles because of limitations in testing.
Absolute sterility cannot be practically demonstrated without complete destruction of every finished article.
It is then appropriate to make a worst-case assumption and treat the microbial burden as though its heat resistance were equivalent to that of the BI, although it is not likely that the most resistant of a typical microbial burden isolates will demonstrate a heat resistance of the magnitude shown by this species, frequently employed as a BI for steam sterilization.
In the above example, a 12-minute cycle is considered adequate for sterilization if the product had a microbial burden of 10 probability of survival could be expected; i.e., 1 in 100 BIs may yield positive results.
This determination requires the employment of temperature-sensing devices inserted into samples of the articles, as well as separate BIs in operationally fully loaded autoclave configurations.