DEFINITION OF STERILIZING VALUE
The Sterilizing Value F0 is expressed in units of time, it allows the effect of a sterilizing treatment to be quantified. In other words, this thermo-biological Function, expressed in minutes, quantifying the lethal effect of moist heat on viable organisms.
The estimate corresponds to the approximation necessary for configuring an automation that must achieve a final minimum sterilizing value.
This calculation method makes it possible to measure the sterilizing effect at a reference temperature, proportionally linking the reduction in biological contamination to the time it is exposed to thermal energy.
Practically, the interest also consists in allowing the comparison of different moist heat treatments (saturated steam and air – steam or superheated water). For example, a parallel can be drawn between the effectiveness of sterilization cycles compared with a regulatory objective or between them to determine the most effective or the most economical or the least traumatic for a heat-sensitive load.
CALCULATION OF THE STERILIZING VALUE
The sterilizing value F0 is defined as the sum of the sterilizing effects per unit of time over the entire duration of the phase declared as sterilizing in a sterilization cycle.
In practice, it is the surface defined between the baseline, i.e. the threshold temperature from which we agree to quantify the sterilizing effect (often 100°C) and the profile of the curve drawn during the load processing. This can easily be calculated mathematically by integration of the temperature/time couple and graphically by the trapezoid method.
The sterilizing value F0 therefore makes it possible to compare the thermal efficiency of different treatments by relating everything to reference conditions. (Z = 10°C et T = 121,1 °C).
F0 = ∫ 10((T-Tref)/Z) .Δt
LAW OF DECREASING THE NUMBER OF MICROORGANISMS AS A FUNCTION OF TIME AT CONSTANT TEMPERATURE
Sterilization being a bi-molecular chemical reaction between the microbial structure and the sterilizing agent (e.g. water vapor), the experiment demonstrated the validity of the first-order kinetic law model reflecting, at constant temperature, the decay logarithmic number of microorganisms as a function of time.
A true dose effect relationship links the biological effect to the absorption of moist (or dry) heat.
Initial and final concentration
Sterilization being an operation which gradually reduces the initial concentration of micro-organisms until a predetermined or regulatory objective is reached (the final concentration), it is appropriate to first know the initial concentration or bioburden (bioburden) and to define it. the unit.
- The initial concentration (N0) is either measured significantly, in the statistical sense of the term, or more commonly estimated and overestimated using the so-called overkill method if the product is not heat labile.
- The final concentration (N), obviously much lower than N0, is expressed as the Probability of Survival of a Micro-Organism (PSMO) on or in the treated unit; this can never be greater than 10-6: i.e. 1 “bad luck” in a million to retain a viable germ in this unit if it must meet European regulations for sterile human injectables.
If statistically we can extrapolate and express this PSMO linked to the unit as also one possibly contaminated unit out of a million units treated, in practice it will be necessary to integrate in addition the probability of homogeneity of the treatment applied to the load, the reproducibility all throughout the year, as well as the many variable parameters that can influence the bioload (raw materials, washing, disinfection, air conditioning, personnel, etc.).
Decimal reduction time: DT
At a given temperature, the decimal reduction time DT corresponds to the time necessary to reduce the population of microorganisms by a factor of 10, i.e. 90% or 1 log.
To define the time-temperature couple of a sterilization cycle of an injectable solution, the significant comparison of the D values of the local flora and at least that of the reference strain is essential because it must be kept in mind that this same D value can vary from 100% to 500% depending on the strain, the dilution medium and in particular the saline concentration or the presence of Ca2+, Mn2+, Mg2+ and KCl ions. Depending on the elastomer formulations, D also varies from 1 to 3.
After having determined the sterilizing value F0, we know the reference temperature, the necessary exposure time, and therefore the famous time/temperature couple. Example recommended by the European Pharmacopoeia: 15min at 121.1°C.
SECOND LOGARITHMIC LAW GOVERNING THE EQUIVALENCES OF A LETHAL BIOLOGICAL EFFECT FOR VARIABLE TEMPERATURES
The Z coefficient, expressed in degrees Celsius, characterizes the temperature variation modifying the resistance of a microorganism (D value) by a factor of 10 or 1 log. The reference Z value retained for moist heat is that of Geobacillus stearothermophilus which is worth Z = 10 °C for moist heat.
In order to be able to compare different heat treatments, the general function F(Z) (of which the values F0 and FH are special cases) makes it possible to compare efficiencies according to the time/temperature cuts. This function can be extended to other treatments but only thermal: we mention the values of pasteurizer P0, cooker C0, depyrogenizer FT, disinfection A0.
> See Sterilization Lethality Table
When Z = 10°C and T= 121.1°C; we note FZ = F0 in the context of sterilization by moist heat.
Please note, the scientific community agrees to recognize a good representativeness of the F0 model in temperatures around Tref +/- 2 Z.
EXAMPLE
How to compare the effectiveness of 2 moist heat treatments, one at 121°C for 20min and the other at 118°C for 30min
Thanks to the value of Z, we can determine for 1 minute of treatment at a temperature X what is its sterilizing effect equivalent to the reference temperature.
For example, 1min at 113.6°C in moist heat guarantees, according to this model, the same sterilizing effect as 0.1774min at 121.1°C. Equivalence calculations are available in the table above.
If, in our example, we have to reduce by 15 logs or 15min at 121.1°C with a value of D = 1 then the duration of the sterilizing phase at 113.6°C will be 15/0.1774, or approximately 1h25min .
Another example: 2 min at 118.1°C or 0.5min at 124.1°C are equivalent to 1min at 121.1°C.
So in the example 30 min at 118.1 °C (equivalent to 15 min at 121.1 °C) is a treatment of approximately 25% less than that of 20 min at 121.1 °C.
