Steam Sterilization of the Stationary Large-Scale Freeze-Dryers (Lyophilizers)

Steam Sterilization of the Stationary Large-Scale Freeze-Dryers (Lyophilizers)
May/June 2004
Ana Bacaoanu, Ph.D.
Department of Chemical Engineering, Technical University of Iasi, Romania
APR
Abstract
Lyophilization, or more generally freeze-drying, has quite peculiar characteristics. As a consequence of its high capital and process costs, its use has been mainly limited to the treatment of very valuable raw materials.
The principal problem in the freeze-drying of pharmaceutical solutions is operating in sterile conditions. 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. In the modern plants, the internal sterilization of equipment is usually made with pressured steam at 121?C. The practice has shown, however, that this theoretical goal cannot always be achieved, depending on the respective conditions.
In the following, a theoretical analysis of the heat transfer in the stationary large-scale dryers, during saturated steam sterilization, is realized.
1. Introduction
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.
There is a scientific convention to describe the effectiveness of sterilization processes. The effectiveness of the sterilization process has been expressed as a Probability of a Non-Sterile Unit (PNSU) [1,2,3]. This probability value is typically expressed as a negative exponent of ten. The 10-6 value is merely the most common PNSU utilized by practitioners in the physical sterilization, but the methods used to demonstrate the capability and reliability of the sterilization processes in the health care industry argues against placing too much significance on the 10-6 criterion.
There is nothing immutable about a PNSU of 10-6 value for terminal sterilization or other physical sterilization processes, and it in no way represents the process capability of terminal sterilization.
Processes employing saturated steam are the most reliable, but their results are decisively affected by the following factors:
- the type of microorganisms present and their functional state (vegetative forms or spores);
- the initial germ count and acceptable final concentration;
- the temperature at the coldest point and the treatment time at the lethal temperature.
In the following discussion, some aspects regarding the steam sterilization of the large scale dryers are addressed.
Primarily, the types of microorganisms found in the equipment govern the choice of the treatment temperatures. The Clostridium and Bacillus spores cause more severe difficulties and make it necessary to use high treatment temperatures (121?C).
A generally recognized acceptable method of sterilizing the lyophilizer is through the use of moist steam under pressure. As a rule, sterilization of stationary large-scale dryers 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 [4].
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 the desired effect, however, only if the lethal temperature (i.e., 121?C) can be achieved at every point in the equipment being treated.
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