Sterilizers dry heat

Dry-heat sterilization is generally conducted at 160—170°C for >2 h. Specific exposures are dictated by the bioburden concentration and the temperature tolerance of the products under sterilization. At considerably higher temperatures, the required exposure times are much shorter. The effectiveness of any cycle type must be tested. For dry-heat sterilization, forced-air-type ovens are usually specified for better temperature distribution. Temperature-recording devices are recommended. 

Superheated steam results when steam is heated to a temperature higher than that which would produce saturated steam. The equiUbrium between hquid and vapor is destroyed, and the steam behaves as a gas. It loses its abiUty to condense into moisture when in contact with the cooler surface of the article to be sterilized. This process resembles dry-heat sterilization more than steam sterilization and, under ordinary time—temperature conditions for steam sterilization, does not produce stetihty. 

Application of the F- value concept has been largely lestrieted to steam sterilization processes although there is a less frequently employed, but direet parallel in dry heat sterilization (see section 4.3). 

The lethal effects of dry heat on microorganisms are due largely to oxidative processes which are less effective than the hydrolytic damage which results firm exposure to steam. Thus, dry heat sterilization usually employs higher temperatures in the range 160-180°C and requires exposure times of up to 2 horns depending upon the temperatrrre employed (section 10). 

The F-value concept which was developed for steam sterilization processes has an equivalent in dry heat sterilization although its application has been limited. The Fh designation describes the lethality of a dry heat process in terms of the equivalent number of minutes exposure at 170°C, and in this case a z value of 20°C has been found empirically to be appropriate for calculation purposes this contrast with the value of 10°C which is typically employed to describe moist heat resistance. 

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. 

Recent sterilizer developments have led to the use of dry-heat sterilizing tunnels where heat transfer is achieved by infra-red irradiation or by forced convection in filtered laminar airflow tunnels. Items to be sterilized are placed on a conveyer belt and pass through a high-temperature zone (250 - 300 + °C) over a period of several minutes. 

Metal instruments (including scalpels) Autoclave Dry heat Sterilization Dry heat Cutting edges should be protected from mechanical damage during the process... 

Various drugs are known to exist in different polymorphic forms (e.g., cortisone and prednisolone). The rate of conversion from a metastable into the stable form is an important criteria to be considered with respect to the shelf life of a pharmaceutical product. Polymorphic changes have also been observed during the manufacture of steroid suspensions. When steroid powders are subjected to dry heat sterilization, subsequent rehydration of anhydrous steroid in the presence of an aqueous vehicle results in the formation of large, needle-like crystals. A similar effect may be... 

The two principal methods of dry-heat sterilization are infrared and convection hot air. Infrared rays will sterilize only surfaces. Sterilization of interior portions must rely on conduction. Convection hot-air sterilizers are normally heated electrically and are of two types gravity or mechanical. In gravity convection units, a fan is used to promote uniformity of heat distribution throughout the chamber. 

Dry-heat processes kill microorganisms primarily through oxidation. The amount of moisture available to assist sterilization in dry-heat units varies considerably at different locations within the chamber and at different time intervals within the cycle. Also, the amount of heat available, its diffusion, and the environment at the spore/air interface all influence the microorganism kill rate. Consequently, cycles tend to be longer and hotter than would be expected from calculations to ensure that varying conditions do not invalidate a run. In general, convection dry-heat sterilization cycles are run above 160°C [37],... 

USP Type III has been found acceptable in packaging some dry powders that are subsequently dissolved to make a buffered solution and for liquid formulations that prove to be insensitive to alkali. Type III glasses are usually not used for those products that are sterilized in their final container. Type II glass containers can be dry heat sterilized and filled under aseptic conditions. 

For sterile products, particular attention should be paid to the choice of an appropriate method of sterilization. Wherever possible a terminal sterilization process should be applied to the product in its final container-closure system, as suggested in the Ph Eur. The preferred options include steam sterilization, dry heat sterilization, and irradiation using the Ph Eur listed conditions (saturated steam at 121°C for 15 minutes dry heat at 160°C for 120 minutes irradiation with an absorbed dose of not less than 25 kGy). Where these cannot be used, the application must include justification for the alternative procedure adopted on the understanding that the highest achievable sterility assurance level should be achieved in conjunction with the lowest practicable level of presterilization bioburden. There is guidance in the form of decision trees as to the preferred options for sterilization method to be applied ... 

Lee [73] studied the stability of miconazole on dry heating in vegetable oils. Miconazole was stable when subjected to dry heat (160 °C for 90 min) in either peanut or castor oil as determined by high performance liquid chromatography analysis. Thus, ophthalmic preparations of miconazole can be prepared in peanut or castor oil with dry heat sterilization without the loss of the drug due to degradation. The procedure also facilitates quick and easy dissolution of the drug in the oil base. 

Dry heat is used to sterihze and depyrogenate components and drug products. The definition of dry heat sterilization is 170 °C for at least 2 hours and a depyrogenation cycle at 250 °C for more than 30 minutes. Typical equipment includes tunnel sterilizers (force convection, infrared, fiame) and microwave sterilizers. An important aspect is the need to ensure air supply is filtered through HEPA filters. Biological indicators such as Bacillus subtilis can be used to gauge the performance of sterilization. 

Contamination with endotoxin is an important and frustrating problem in LEH manufacturing for two reasons. Firstly, hemoglobin has a strong tendency to bind endotoxin, where one hemoglobin molecule binds to four endotoxin molecules (K 3.1 x lO M) (117). Secondly, endotoxin has amphiphilicity that enables its stable insertion into lipid bilayer. Such an interaction not only presents contamination and stability problems, but also hampers accurate quantitation of endotoxin. The best possible way to prevent endotoxin contamination is to use aseptic precautions with utmost care. All the machinery, filters, and water should be endotoxin-free. Glass and metallic components may be dry-heat sterilized at about 200° C for three... 

Compoimding pharmacists routinely use in-process sterilization, such as sterile filtration, or terminal sterilization, such as autoclaving or dry-heat sterilization. In some situations, combinations of these methods may be used along with chemical sterilization. 

To provide a written procedure to be used as a guideline for the certification and validation of a dry heat sterilizer... 

Dry heat sterilization validation. The tunnel operations conform to the master validation plan employed at ABC Pharmaceutical Industries. The sterilizing tunnel has undergone installation qualification, operational qualification, and performance qualification. The sterilizing tunnel is revalidated on an annual basis. The sterilization/depyrogenation cycle revalidation data for the tunnel are provided in validation archives. Sterilization validation reports are provided in validation archives. 

Laminar air flow Autoclave Water bath Incubator at 376°C Dry heat sterilizer Refrigerator Gas burner... 

Review and verify the washing parameters per the validated cycle dry heat sterilization/depyrogenation. 

Dry heat sterilization, carried out in an oven, is defined exposing the product to at least 150°C for 1 hour and is required for the sterilization of surfaces, such as metal... 

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

Figure 2 presents thermal resistance plot for a Z value of 10°C, the accepted standard for steam sterilization of B. stearothermophilus spores, and for a Z value of 20°C, the proposed standard [13] for dry-heat sterilization of B. subtilis spores. These plots are important because one can determine the I) value of the indicator micro-organism at any temperature of interest. In addition, the magnitude of the slope indicates the relative degree of lethality as temperature is increased or decreased. 

V. VALIDATION OF DRY-HEAT STERILIZATION CYCLES A. General Considerations... 

Two types of dry-heat sterilization systems are utilized in the pharmaceutical industry today. They are the conventional hot air oven and the tunnel system. The major difference between the two systems, as far as validation is concerned, is the belt or line speed variable with the tunnel system. 

The key to validating a dry-heat sterilizer is to prove its repeatability. This... 

As with any sterilization process, the first step in dry-heat sterilizer validation involves qualification of all the equipment and instrumentation used. This step includes examination and documentation of all utilities, ductwork, filters, and control valves or switches for the oven or tunnel unit, and the calibration of the instrumentation used in validating and monitoring the process. The instruments used are as follows ... 

Table 5 Key Process Features to Control Prior to Validating Dry-Heat Sterilizers ...

Validation studies conducted on dry-heat sterilizers can be divided into two basic components. One component envelops all the physical elements that must be qualified, such as temperature control, air particulate levels, and belt speeds. The other component is the biological constituent, which involves studies that prove that the process destroys both microbial and pyrogenic contaminants. 

D. Biological Process Validation of Dry-Heat Sterilization Cycles... 

---