Heat sterilization processes

In the case of heat sterilization processes, the supporting data required include heat distribution and heat penetration studies (usually at least three runs at the minimum process parameters), with calculation of... 

The D value is the determining factor if the death rate is, indeed, exponential, an assumption which is not necessarily always valid. Although only conditions which supply a single D value would be sufficient to completely sterilize a solution containing, say, one organism per unit volume, most heat sterilization processes are designed to administer 12D. This is an example of overkill and becomes more evident the fewer organisms there are in the untreated product in the first place. 

There is another, nonkinetic parameter widely used when evaluating a heat sterilization process. This is the F0 value, defined as the number of minutes required to kill all endospores present in a system held at a temperature of 250°F or 121°C. It should be noted that, in principle, the kinetic approach implies that sterilization cannot be achieved (because there is no zero on a logarithmic plot) so the nonkinetic offers more hope. The F0 can be measured and there is an interconnection between F0 and D if F0 is slightly redefined as the number, n, of D values required to sterilize a system, i.e., F0 = nD. 

HSP Dry heat sterilization process TSP Fractional (tyndallization) sterilization process... 

SpeciLc problems exist with parenteral manufacture the most obvious being the need to ensure sterility. It is necessary to assess the effect that a heat sterilization process will have on a drug (e.g., pKg shift on heating) and on the formulation. Certain solubilization systems such as emulsions may not be suitable for autoclaving. 

Their use as an injectable warrants assurance of product sterility. Whereas the FDA-preferred heat-sterilization process is acceptable for total parenteral nutritional (TPN) emulsions, it could affect chemical as well as physical stability of emulsions containing therapeutic agents. Recently, data supporting the Liter sterilization of emulsions have been published. 

These terms heretofore have been applied exclusively in the validation of heat-sterilization processes. The Z value is the reciprocal of the slope resulting from the plot of the logarithm of the D value versus the temperature at which the D value was obtained. The Z value may be simplified as the temperature required for a one-log reduction in the D value ... 

Dry-heat sterilization is generally a less complicated process than steam sterilization it is, however, relatively slow and requires higher temperatures and/or longer exposure times. This is because of the fact that microbial lethality is lower with dry heat than that for steam at the same temperature. There are various temperatures and periods of treatment for dry heat depending on the pharmacopeia. The U.S. Pharmacopeia (USP) states that the dry-heat sterilization process for containers for sterile pharmaceutical products should be at a temperature of 160-170°C for a period of 2-4 hr. The British Pharmacopeia states that items sterilized by dry heat should be kept at a temperature not less than 160°C for at least 1 hr. For the Pharmacopeia Nordica, the recommendation is 30 min at 180°C. Different materials and sterilization equipment used account for the discrepancies between these pharmacopeias, but there is also a lack of sufficient information concerning dry-heat sterilization. ... 

The kinetics of dry-heat treatments is comparable to that of moist heat sterilization. The organisms that are considered to be representatives for dry-heat sterilization processes are spores of Bacillus subtilis var. nigerP ... 

Current pharmaceutical production practice uses substantially three moist-heat sterilization processes 1) pressurized saturated steam 2) superheated water and 3) steam-air mixture. Process 1 is the traditional multipurpose process, which obviously uses pure pressurized saturated steam as sterilizing medium. Processes 2 and 3 are so-called counterpressure processes they were introduced in pharmaceutical production practice approximately 20 years ago and, respectively, use a spray superheated water and a homogeneous... 

Sterilization processes are discussed in detail in Chapter 20. However, it is axiomatic that whatever method is chosen, the process should not cause damage to the product. By reference mostly to moist heat sterilization processes (the reader should remember that there are parallel approaches to other methods of sterilization) this section illustrates the factors that must be considered in the design of a sterilization process. 

For heat treatment, a D-value only refers to the resistance of a microorganism at a particular temperature. In order to assess the influence of temperature changes on thermal resistance a relationship between temperature and log D-value can be developed, leading to the expression of a z-value, which represents the increase in temperature needed to reduce the D-value of an organism by 90% (i.e. 1 log cycle reduction Fig. 20.2B). For bacterial spores used as biological indicators for moist heat (B. stearotbermopbilus) and dry heat (B. subtilis) sterilization processes, mean z-values are given as 10°C and 22°C, respectively. The z-value is not truly independent of temperature but may be considered essentially constant over the temperature ranges used in heat sterilization processes. 

Fig. 20.4 Typical temperature profile of a heat sterilization process.

In heat sterilization processes, a temperature record chart is made of each sterilization cycle with both dry and moist heat (i.e. autoclave) sterilizers this chart forms part of the batch documentation and is compared against a master temperature record (MTR). It is recommended that the temperature be taken at the coolest part of the loaded sterilizer. Further information on heat distribution and penetra-... 

As with sterilization by saturated steam, thermal damage to biological systems as a result of dry heat sterilization processes is a function of absorbtion of heat energy. Inactivation of microorganisms is by oxidation. The kinetics of oxidation and population death approximate to first-order reactions, but they are significantly different from the processes of coagulation of cellular proteins found with moist heat sterilization in that they require far higher temperatures and proceed more slowly. 

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