Sterilization, heat

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. 

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. 

Biological wastes Sealed plastic bags 120 L Heat sterilization prior to bagging special heavy-duty bags... 

After the pH was adjusted, 5 g of calcium carbonate was added. This inoculum medium was then subjected to heat sterilization. The medium was then cooled and 2 ml of a spore sus-... 

Distilled water is often used in the formulahon of oral and topical pharmaceutical preparations and a low bacterial count is desirable. It is also used after distillation with a specially designed still, often made of glass, for the manufacture of parenteral preparations and a post-distillation heat sterilization stage is commonly included in the process. Water for such preparahons is often stored at 80°C in order to prevent bacterial growth and the production of pyrogenic substances which accompany such growth. 

Where floor drainage channels are necessary they should be open if possible, shallow and easy to clean. Connections to drains should be outside areas where sensitive products are being manufactured and, where possible, drains should be avoided in areas where aseptic operations are being carried out. If this cannot be avoided, they must be fitted with effective traps, preferably with electrically operated heat-sterilizing devices. 

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. 

Syringes (glass) Syringes (glass), dismantled Dry heat Moist heat Sterilization Sterilization Dry heat using assembled syringes Autoclave not recommended difficulty with steam penetration unless plungers and barrels sterilized separately... 

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... 

In the first example, procaine penicillin, an aqueous vehicle containing the soluble components (such as lecithin, sodium citrate, povidone, and polyoxyethylene sorbitan monooleate) is filtered through a 0.22 pm membrane filter, heat sterilized, and transferred into a presterilized mixing-filling tank. The sterile antibiotic powder, which has previously been produced by freeze-drying, sterile crystallization, or spray-drying, is aseptically added to the sterile solution while mixing. After all tests have been completed on the bulk formulation, it is aseptically filled. 

When drug solutions and containers can withstand autoclaving conditions, this method is preferred to other sterilization methods because moist heat sterilizes quickly and inexpensively. However, judgment must be exercised and experiments run to ensure that the solution and container are permeable to steam. Oils and tightly closed containers, for example, are not normally sterilizable by steam. 

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],... 

Most ophthalmic products, however, cannot be heat sterilized. In general, the active principle is not particularly stable to heat, either physically or chemically. Moreover, to impart viscosity, aqueous products are generally formulated with the inclusion of high molecular weight polymers, which may, similarly, be affected adversely by heat. 

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 ... 

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