Heat sterilization effectiveness

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. 

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. 

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). 

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... 

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. 

SpeciLc problems exist with parenteral manufacture the most obvious being the need to ensure sterility. It is necessary to assess the effect that a heat sterilization process will have on a drug (e.g., pKg shift on heating) and on the formulation. Certain solubilization systems such as emulsions may not be suitable for autoclaving. 

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. 

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. 

Huikari A. Effect of heat sterilization on the viscosity of methylcellulose solutions. Acta Pharm Penn 1986 95(1) 9—17. 

Ethylene Oxide. Ethylene oxide, C2H4O. is a colorless flammable gas that liquefies at I2°C. It has been used to sterilize temperature-sensitive medical equipment and certain pharmaceuticals that cannot be heat sterilized in an auuxrlavc. Ethylene oxide diffuses readily through porous materials and very effectively de.stroys all forms of microorganisms at ambient temperatures."... 

Gram-negative bacteria contain lipopolysaccha-rides (endotoxins) in their outer cell membranes (Chapter 19) these can remain in an active condition in products even after cell death and some can survive moist heat sterilization. Although inactive by the oral route, endotoxins can induce a number of physiological effects if they enter the bloodstream via contaminated infusion fluids, even in nanogram quantities, or via diffusion across membranes from contaminated haemodialysis solutions. Such effects may include fever, activation of the cytokine system, endothelial cell damage, all leading to septic and often fatal febrile shock. 

A 10% solution of povidone K 30 in water can be stabilized by the addition of 0.5% of cysteine or 0.02% of sodium sulfite against discolouration by heat sterilization. The Table 26 shows in a storage test of aqueous solution of povidone that the application of nitrogen is not effective because it contains always some residues of oxygen. The formation of peroxides, free vinylpyrrolidone or turbity is no problem and the influence of the pH is negligible. 

Hoxey EV, Soper CJ, Davies DJG. 1985. Biological indicators for low temperature steam formaldehyde sterilization Effect of defined media on sporulation, germination index and moist heat resistance at 110 degrees C of bacillus strains. J Appl Bacteriol 58 207-214. 

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