Gas sterilization

Gas Sterilants, Brochure E-208P-A, Liude Division, Union Carbide Corp., Danbury, Conn., 1985. 

One can see by the complexity of these types of manufacturing procedures that much care and attention to detail must be maintained by the manufacturer. This sterile manufacturing procedure must then be validated to prove that no more than 3 containers in a lot of 3000 containers (0.1%) are nonsterile. Ultimately, it is the manufacturer s responsibility to ensure the safety and efficacy of the manufacturing process and the absence of any adverse effect on the product, such as the possible formation of substances toxic to the eye, an ever-present possibility with gas sterilization or when using ionizing radiation. For ophthalmic products sterilized by terminal sterilization (sterilization in the final sealed container, e.g., steam under pressure), the sterilization cycle must be validated to ensure sterility at a probability of 106 or greater. 

Ethylene oxide and hydrogen peroxide are the typical gases for gas sterilization. Their advantage is that they can be used at much lower temperatures than steam sterilization 27-60 °C for ethylene oxide and 25-40 °C for hydrogen peroxide. Another advantage is that they do not cause damage to the product or the packaging. 

Bekus, D. Validation of gas sterilization. In Agalloco, J., Carleton, F. (eds.). Validation of Aseptic Pharmaceutical Processes. 2nd ed. New York Marcel Dekker, 1998. 

Pharmaceutical products can be sterilized by steam sterilization, dry-heat sterilization, filtration sterilization, gas sterilization, and ionizing-radiation sterilization. The USP provides monographs and standards for biological indicators required to test the validity of the sterilization process. These products must also be tested for pyrogens—fever-producing substances that arise from microbial contamination most likely thought to be endotoxins or lipopolysaccharide in the bacterial outer cell membrane. 

Gas sterilize equipment that requires decontamination but cannot be subjected to liquids. 

All these recommendations are summarized in the Decision trees for the selection of sterilization methods, edited by the EMEA [23] (Fig. 1).Two cases are considered on one hand, the aqueous products and on the other hand, the non-aqueous liquid, semi-solid and dry powder products. Figure 1 shows the order of preference of the sterilization methods for the second group. The terminal ones are ranked in the first place. Among them, thermal sterilization is still referred as the best choice, radio-sterilization ranking right after. Since gas sterilization is excluded and non-terminal methods are listed as the last choice, radiosterilization now precedes all these methods. It is deemed as the recommended alternative method to thermal sterilization. 

The USP recognizes six methods of achieving a sterile product (i) steam sterilization, (if) dry-heat sterilization, (Hi) gas sterilization, (iv) sterihzation by ionizing radiation, (v) sterilization by filtration, and (vi) aseptic processing (67). For ophthalmic products packaged in plastic containers, t5rpical for ophthalmic products, a combination of two or more of these six methods is routinely used. For example, for a sterile ophthalmic suspension, bottles, dropper tips, and caps may be sterilized by ethylene oxide or y-radiation the suspended solid may be sterilized by dry heat, y-radiation, or ethylene oxide and the aqueous portion of the composition may be sterilized by filtration. The compounding is completed under aseptic conditions. 

This system has been tested under chemical decontamination succes-fully, or it can be aseptically assembled after steam sterilization of hardware and gas sterilization of filter packets. Neither of... 

Skocypec, R. (1984). Installation and equipment performance qualification of gas sterilizers. In Sterilization Validation of Medical Devices and Surgical Products. EUCOMED International Conference, May 16-17,1984. 

Direct contact between gas and microorganisms is essential, and for this reason, gas sterilization may not be used when the risk exists that microorganisms are present in the material or product. 

With the use of gas sterilization, care must be taken that the gas and any decomposition products thereof can be evacuated with adequate effectiveness. 

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