Sterilization monitors

Use in the production of vaccines As assay organisms to determine antibiotic, vitamin and amino acid concentrations Quality control of immunological products Assay methods Sterilization methods Sterilization monitoring and validation procedures Sterility testing Assessment and calculation of sterility assurance Aseptic manufacture... 

Monitoring by Electromechanical Instrumentation. According to basic engineering principles, no process can be conducted safely and effectively unless instantaneous information is available about its conditions. AH sterilizers are equipped with gauges, sensors (qv), and timers for the measurement of the various critical process parameters. More and more sterilizers are equipped with computerized control to eliminate the possibiUty of human error. However, electromechanical instmmentation is subject to random breakdowns or drifts from caUbrated settings and requires regular preventive maintenance procedures. 

An inherent problem is the location of the sensors. It is not possible to locate the sensors inside the packages which are to be sterilized. Electromechanical instmmentation is, therefore, capable of providing information only on the conditions to which the packages are exposed but cannot detect failures as the result of inadequate sterilization conditions inside the packages. Such instmmentation is considered a necessary, and for dry and moist heat sterilization, a sufficient, means of monitoring the sterilization process. 

Industrial sterilization cycles tend to vary considerably, not only from manufacturer to manufacturer, but often from product type to product type, depending on the bioburden present on a given load. Chemical indicators have historically been used only to differentiate between sterilized and nonsterilized packages. More recent developments have resulted in the availability of chemical dosimeters of sufficient accuracy to permit their appHcation either as total monitors or as critical detectors of specific parameters. 

Biological indicators for steam sterilization utilize bacillus stearothermophilus. In monitoring industrial cycles, a sufficient number of preparations each having a known degree of resistance are added to the load and retrieved after exposure, and cultured. 

General recommendations for instmmentation include monitoring gas concentration, temperature, time, and the moisture content of the chamber. Hospital sterilizers are not usually equipped with instmmentation providing direct display of gas concentration and moisture content. These rely instead on a specific sequence of steps performed automatically and the recording of pressure which when 100% ethylene oxide is used is a perfect measure for the concentration of this gas. 

Pharmaceuticals for injection must be presented in a sterile form. Sterility may be achieved by filtration through 0.22 pm filters under aseptic conditions, or by steam, dry heat, radiation or gas sterilisation methods, which may be applied to packaged products. Irrespective of the method, the process must be validated and monitored to assure its effectiveness. As discussed in Chapter 2, this is an example of a process that cannot be assured by verification testing because of its destructive nature. 

Filtered air may be used to purge a complete room, or it m be confined to a specific area and incorporate the principle of laminar flow, which permits operations to be carried out in a gentle current of sterile air. The direction of the airflow may be horizontal or vertical, depending upon the type of equipment being nsed, the type of operation and the material being handled. It is important that there is no obstruction between the air supply and the exposed product, since this may resnlt in the deflection of microorganisms or particulate matter fiom a non-sterile surface and canse contamination. Airflow gauges are essential to monitor that the correct flow rate is obtained in laminar flow units and in complete suites to ensure that a positive pressure fiom clean to less clean areas is always maintained. 

In the following sections, factors governing the successful use of these sterilizing methods will be covered and their application to pharmaceutical and medical products considered. Methods for monitoring the efficacy of these processes are discussed in Chapter 23. 

Dry heat sterilization is usually carried out in a hot air oven which comprises an insulated polished stainless steel chamber, with a usual capacity of up to 250 litres, surrounded by an outer case containing electric heaters located in positions to prevent cool spots developing inside the chamber. A fan is fitted to the rear of the oven to provide circulating air, thus ensuring more rapid equilibration of temperature. Shelves within the chamber are perforated to allow good air flow. Thermocouples can be used to monitor the temperature of both the oven air and articles contained within. A fixed temperature sensor connected to a chart recorder provides a permanent record of the sterilization cycle. Appropriate door-locking controls should be incorporated to prevent interruption of a sterilization cycle once begun. 

The operation of an ethylene oxide sterilizer should be monitored and controlled automatically. A typical operating cycle for pure ethylene oxide gas is given in Fig. 20.7, and general eonditions are summarized in section 10. 

Radiation monitors are continually employed to detect any radiation leakage during operation or source storage, and to confirm a return to satisfactory background levels within the sterilization chamber following operation. The dose delivered is dependent upon source strength and exposure period, with dwell times typically up to 20 hours duration. 

Under no circumstances should living cultures of microorganisms, whether they be for vaccine preparation (Chapter 16) or for use in monitoring sterilization processes (Chapter 23), be taken into aseptic areas. As already pointed out, separate premises are needed for the aseptic filling of live or of attenuated vaccines. 

This chapter will discuss briefly the principles and applications of the various methods of monitoring and validating sterilization processes. 

Monitoring of the sterilization process canbe achieved by the rrse of physical, chemical or biological indicators of sterilizer performance. Such indicators are frequently employed in combination. 

For gaseous sterilization procedures, elevated temperatures are monitored for each sterilization cycle by temperature probes, and routine leak tests are performed to ensure gas-tight seals. Pressure and humidity measurements are recorded. Gas concentration is measured independently of pressure rise, often by reference to weight of gas used. 

---