Heat Sterilization General

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. 

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. 

Transparent P.O.34 is somewhat sensitive to heat and generally only withstands temperatures up to 100 to 140°C. Higher sterilization or metal deco printing temperatures may produce a color shift towards a redder orange. 

Aseptic BPS machines are subject to steam-in-place sterilization following standard CIP cycles. The SIP cycles are routinely measured by thermocouples located in fixed positions along the product pathway. Validation of SIP cycles should be carried out to demonstrate that consistent sterilization temperatures are achieved throughout the equipment to prove that the system can be effectively sterilized. Validation should also identify suitable positions for routine use, or justify the fixed probe positions already in place. The SIP validation is generally carried out with the help of additional thermocouples and should include the use of biological indicators (appropriate for moist heat sterilization). Test locations should include areas which may be prone to air or condensate entrapment. An accurate engineering line drawing of the system to aid identification of suitable test locations and document test locations selected should be available. 

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

In step 5, the qualification stage, the critical issue is that the protocol for IQ/OQ of the equipment and the facility include the established method and acceptance criteria. The IQ/OQ report should include the maintenance program to keep the equipment in good condition for reproducibility of the product. For qualification of the equipment and process for terminal sterilization, the following standards should be referred to ISO 13408-1 [6] and 11138-1 [7] for general issues, ISO 11134 [8] and 11138-3 [9] for moist heat sterilization, ISO 11135 [10] and 11138-2 [11] for ethylene oxide sterilization, and ISO 11137 [12] for radiation sterilization. 

Common unit operations of food processing are reported to have only minor effects on the carotenoids (Borenstein and Bunnell 1967). The carotenoid-protein complexes are generally more stable than the free carotenoids. Because carotenoids are highly unsaturated, oxygen and light are major factors in their breakdown. Blanching destroys enzymes that cause carotenoid destruction. Carotenoids in frozen or heat-sterilized foods are quite stable. The stability of carotenoids in dehydrated foods is poor, unless the food is packaged in inert gas. A notable exception is dried apricots, which keep their color well. Dehydrated carrots fade rapidly. 

Dry-heat sterilization is generally a less complicated process than steam sterilization it is, however, relatively slow and requires higher temperatures and/or longer exposure times. This is because of the fact that microbial lethality is lower with dry heat than that for steam at the same temperature. There are various temperatures and periods of treatment for dry heat depending on the pharmacopeia. The U.S. Pharmacopeia (USP) states that the dry-heat sterilization process for containers for sterile pharmaceutical products should be at a temperature of 160-170°C for a period of 2-4 hr. The British Pharmacopeia states that items sterilized by dry heat should be kept at a temperature not less than 160°C for at least 1 hr. For the Pharmacopeia Nordica, the recommendation is 30 min at 180°C. Different materials and sterilization equipment used account for the discrepancies between these pharmacopeias, but there is also a lack of sufficient information concerning dry-heat sterilization. ... 

If an effective dry heat depyrogenation is performed, sterilization generally is achieved as well. Effective dry heat sterilization can be performed even without achieving depyrogenation. If moist heat sterilization is performed, in normal operating conditions depyrogenation is not achieved. 

Sterilization by moist heat usually involves the use of steam at temperatures in the range 121-134°C, and while alternative strategies are available for the processing of products unstable at these high temperatures, they rarely offer the same degree of sterility assurance and should be avoided if at all possible. The elevated temperatures generally associated with moist heat sterilization methods can only be achieved by the generation of steam under pressure. 

Dry heat application is generally restricted to glassware and metal surgical instruments (where its good penetrability and non-corrosive nature are of benefit), non-aqueous thermostable liquids and thermostable powders (see Chapter 19). In practice, the range of materials that are actually subjected to dry heat sterilization is quite limited, and... 

The use of dry heat as a method of disinfection has been largely confined to the sterilization of laboratory apparatus. It is used when steam heat would in some way damage the material being sterilized. Hot-air ovens are used in dry heat sterilization. The temperature most generally employed is 180° C. It is found that by slowly raising the temperature much glassware which would break if submitted to steam, can be satisfactorily sterilized. 

Generally, sterility is synonym with the absence of any viable microorganisms including their spores. Currently, the available sterilization methods include heat sterilization (steam and hot-air sterilization), cold sterilization (gas sterilization, sterilization by ionizing radiation), sterilization by aqueous solution (aldehydes, peracetic acid, hypochlorite, hydrogen peroxide), and sterilization by filtration methods. The choice of method is based on recommendations in medicinal literature, legal requirements, and the compatibility of a medical product with the method used. The decision for a particular method has to take the following factors into consideration [954] ... 

A wide variety of sterilization and disinfection methods are available, each generally suited for only certain kinds of situations. In general, sterilization and disinfection procedures can be divided into three categories heat, chemical, and radiation. Of these, the most important and most widely used is heat sterilization. 

Acid foods generally require the simplest equipment for heat preservation. The food can be heated to 100°C and filled hot into suitable containers. The containers are sealed, inverted to sterilize the closure, held at the filling temperature for a short time to ensure that the package is thoroughly heated, and then cooled. Tomato sauces, jellies, fmits, fmit juices (qv), and pickles are routinely preserved in this fashion. 

---