A Theoretical Analysis for Assessing the Variability of Secondary Model Thermal Inactivation Kinetic Parameters

Traditionally, for the determination of the kinetic parameters of thermal inactivation of a heat labile substance, an appropriate index is selected and its change is measured over time at a series of constant temperatures. The rate of this change is described through an appropriate primary model and a secondary model is applied to assess the impact of temperature. By this approach, the confidence intervals of the estimates of the rate constants are not taken into account. Consequently, the calculated variability of the secondary model parameters can be significantly lower than the actual variability. The aim of this study was to demonstrate the influence of the variability of the primary model parameters in establishing the confidence intervals of the secondary model parameters. Using a Monte Carlo technique and assuming normally distributed D(T) values (parameter associated with a primary inactivation model), the error propagating on the D(Tref) and z-values (secondary model parameters) was assessed. When D(T) confidence intervals were broad, the secondary model’s parameter variability was appreciably high and could not be adequately estimated through the traditional deterministic approach that does not take into account the variation on the D(T) values. In such cases, the proposed methodology was essential for realistic estimations.