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A General Discussion of the Steam Sterilization of Freeze-Dryers
Ana Bacaoanu, Ph.D.
Department of Chemical Engineering, “Gh. Asachi” Technical University of Iasi, Romania
Abstract
An analysis of the heat transfer in the stationary large-scale dryers, during saturated steam sterilization, is realized. The inside surfaces temperature of dryers can be significantly different and time dependent. To ensure that all surface temperatures are equal or greater than 121 C, the steam temperature must be higher.
Introduction
The principal problem in the freeze-drying of pharmaceutical solution is to operate in sterile conditions. In the modern plants, the internal sterilization of equipment is usually made with pressured steam at 121 C.
Sterilization is the process of the elimination (by removal or killing) of all microorganisms and the inactivation of viruses present in or on a product. It is an absolute condition and, in practice it is an ideal, which is approached in terms of achieving an acceptable probability of the absence of viable organisms. The practice has shown, however, that this theoretical goal cannot always be achieved, depending of the respective conditions. Consequently, one accepts today, above all for calculation of the required lethality of sterilization process, a contamination probability of 10-6 [1]. In other processes, such as disinfecting or preservation to prevent microbial spoilage, one is prepared to accept lower killing and inactivation rates.
For sterilization process used in pharmaceutical and food industries we distinguish between processes employing:
moist heat (steam)
dry heat
microbicidal gases (ethylene oxide, formaldehyde)
ionizing radiation
germ removal by filtration [2].
Processes employing saturated steam is the most reliable sterilization process, but their results are decisively affected by following factors:
the type of microorganisms present and their functional state (vegetative forms or spores);
the initial germ count and acceptable final concentration (probability of contamination of 10-6, i.e., sterility by definition, or a reduction in the germ count with a few isolated germs being tolerated in the end of product);
the temperature at the coldest point and the treatment time at the lethal temperature.
In the following discussion some aspects regarding the sterilization of dryers in the lyophilization process are addressed. Primarily the types of microorganisms found in the equipment govern the choice of the treatment temperatures. The vegetative forms are killed or inactivated in few minutes at 65-100 C; the fungal spores (conidiospores) are killed at 100-105 C; the Clostridium and Bacillus spores cause more severe difficulties and make it necessary to use higher treatment temperatures (121 C) [ 2].
As a rule sterilization of stationary of large-scale dryers, the sterilization is realized with the saturated steam at 121 C.
The general procedure for thermal deactivation using condensing steam is:
open steam points
vent air
build up pressure
hold
collapse steam in a controlled manner [3].
The temperature-time profile employed depends on the selected organism and its susceptibility to infection. Generally, thermal deactivation is designed for the inactivation of Bacillus Stearothermophilus.
The entire system has to be brought to the sterilization temperature with special attention given to potential cold spots. The calculated sterilization time leads to desired effect, however, only if the lethal temperature (i.e., 121C) can be achieved at every point in the equipment being treated.
Analysis of the heat transfer processes during sterilization
In the pharmaceutical industry one consider the start of sterilization process when a sensor in the drain line reaches 121 C. Is this always true? We are trying to find an answer to this question. To this end, the variations in the local heat transfer during sterilization process have been studied.
The analysis of the heat transfer shows that the local conditions in the dryers are different and variable with time. In this situation, we are expecting that the surface temperature is not the same in every point, that is, the temperature in certain regions is lower than desired value (121 C), and the sterilization cannot be completed.
The build up pressure and collapse steam takes place in an unsteady state. All local parameters vary with time. The hold stage can be considered as a quasi steady state.
Inside of dryer, the heat transfer process during sterilization takes place by condensation of the steam. The condensation is an isothermal process, which supposes that a temperature difference between the wall temperature and steam temperature exists.
