Gas sterilisation

Pharmaceuticals for injection must be presented in a sterile form. Sterility may be achieved by filtration through 0.22 pm filters under aseptic conditions, or by steam, dry heat, radiation or gas sterilisation methods, which may be applied to packaged products. Irrespective of the method, the process must be validated and monitored to assure its effectiveness. As discussed in Chapter 2, this is an example of a process that cannot be assured by verification testing because of its destructive nature. 

Autoclaves, gas sterilisers, sterilising ovens and lyophilisers should be equipped with automatic recorders which monitor the time and temperatures and, where necessary, other parameters of the sterilising cycle. This equipment should be qualified upon commission and should be calibrated periodically. Records should permit verification of achievement of these parameters with an appropriate degree of accuracy. 

Every gas sterilisation cycle should be monitored with microbiological indicators. 

Validation studies for gas sterilisation should be conducted following the guidelines of Appendix E (see also Contract Manufacture) and should include ... 

Gas sterilisation (ethylene oxide) Low temperature range Lengthy process owing to degassing, residues are toxic... 

Classical sterilisation techniques using an autoclave and saturated steam under pressure, hot water or dry heat are practical and reliable. Other reliable sterilisation methods include membrane filtration, ionising radiatirm sterilisation (gamma and electron-beam radiation) and gas sterilisation (ethylene oxide, formaldehyde). Sterilisation equipment (autoclaves, membrane filters, and other sterilisers) is often used in industrial manufacturing, in preparation in pharmacies, and in other healthcare establishments. Standard sterilisation processes are described in the Ph. Eur., in other current Pharmacopoeias, in ISO standards and National guidelines. 

Sterilisation Autoclave Sterile products Saturated steam Hot air Dry heat Radiation Ethylene oxide Hydrogen peroxide Plasma Membrane filtration Gas sterilisation... 

Gas sterilisation including gas plasma sterilisation Gas, penetrated with moisture, enters the material to be sterilised, which is followed by the elimination of the gas. The gas (ethylene oxide or hydrogen peroxide) alkylates the purine and pyrimidine bases in the RNA and DNA of micro-organisms. 

Gas sterilisation is performed with ethylene oxide or hydrogen peroxide gas. Sometimes peracetic acid is used, but this method is too specialised to mention here in detail. In the past (fi-om 1940) formaldehyde was used as well, but this method is rarely used anymore. Gas sterilisation is used for sterilisation of medical devices and of surfaces of pharmaceutical containers where the contents are too sensitive to the high temperature of steam sterilisation and/or cannot withstand radiation sterilisation. 

Regarding in-process controls, the Ph. Eur. states Whenever possible, the gas cmicentration, relative humidity, temperature and duration of the process are measured and recorded [1]. The validation of a gas sterilisation process consists of a physical and microbiological validation [8]. 

For non-aqueous liquids, semisolids and dry powders 2 h sterilisation at 160 °C in dry heat is preferred. Where it is not possible to carry out terminal sterilisation by heat due to formulation instability, a decision should be taken to utilise an alternative method of terminal sterilisation, filtration and/or aseptic processing. It is recognised that new terminal sterilisation processes other than those described in the pharmacopoeia may be developed to provide sterility assurance levels equivalent to present official methods and such processes, when properly validated, may offer alternative approaches. If necessary, a different time-temperature combination may be applied to obtain an SAL of 10 . If too much degradation occurs in dry heat, ionising radiation or gas sterilisation can be applied. If these methods are not suitable either, sterilising membrane filtration and validated aseptic processing, sometimes robotised or with barrier system technology are considered as a last resort. 

Liquid chlorine dioxide, ClOj, boils at 284 K to give an orange-yellow gas. A very reactive compound, it decomposes readily and violently into its constituents. It is a powerful oxidising agent which has recently found favour as a commercial oxidising agent and as a bleach for wood pulp and flour. In addition, it is used in water sterilisation where, unlike chlorine, it does not produce an unpleasant taste. It is produced when potassium chlorate(V) is treated with concentrated sulphuric acid, the reaction being essentially a disproportionation of chloric(V) acid ... 

Phthalocyanines are excellent lubricants at temperatures of 149—343°C (191). Combinations with other lubricants, like grease, molybdenum, or tungsten sulfides, have found appHcations in the automotive industry or professional drilling equipment (192—195). Further uses include indicators for iron(Il), molybdenum(V), and uranium(IV) (196) or redox reactions (197), medical appHcations like hemoglobin replacements (198) or sterilisation indicators (199), or uses like in gas filters for the removal of nitrogen oxides from cigarette smoke (200). 

Low humidity ethylene oxide gas sterilisa tion procedures and moisture-proof packaging for polyglycoHc acid products are necessary because of the susceptibihty to degradation resulting from exposure to moisture and gamma sterilisation. 

Humidity can be a problem. Whereas it was shown (284) that 33% RH was best for spore inactivation, and that at least 30% RH was needed for effective sterilisation (285), dried spores are difficult to kill, and the spore substrate material and wrappings compete with the spore for the available moisture (286). Therefore, the relative humidity is adjusted to 50—70% to provide sufficient moisture for the spores to equiUbrate. The exposure time depends upon the gas mixture, the concentration of ethylene oxide, the load to be sterilised, the level of contamination, and the spore reduction assurance requited. It may be anywhere from 4—24 hours. In a mn, cycles of pre-conditioning and humidification, gassing, exposure, evacuation, and air washing (Fig. 9) are automatically controlled. 

It is worthwhile drawing attention to health hazards associated with film infected water systems which also cause corrosion. Two of the most common are Legionnaires disease and so called humidifier fever . Because of strong adhesion of biofilms and diffusion rates through the film treatment based on cleaners and chemical sterilisers such as chlorine often fail similar considerations apply to other systems in industry, e.g. food, paint, oil and gas are examples where biofilm activities have given massive problems. 

Hazards attendant on use of ethylene oxide in steriliser chambers arise from difficulties in its subsequent removal by evacuation procedures, owing to its ready absorption or adsorption by the treated material. Even after 2 evacuation cycles the oxide may still be present. Safety is ensured by using the oxide diluted with up to 90% of Freon or carbon dioxide. If high concentrations of oxide are used, an inert gas purge between cycles is essential [7], The main factors in safe handling... 

The direct sterilisation of particulafe solid foods in a gas-solid fluidized bed was proposed as long ago as 1968 by Lawrence et al. (1968) who sterilised wheat flour in steam-air mixtures at the pilot scale. However, Jowitt (1977) described an atmospheric pressure process for fhe sferilisation of canned foods in which the cans are immersed in a fluidized bed of inert particles. This has a number of advantages compared to the conventional retorting process using pressurised steam or hot water ... 

Finally, a little chlorine gas is added, which sterilises the water and kills any remaining bacteria. Excess chlorine can be removed by the addition of sulfur dioxide gas. The addition of chlorine gas makes the water more acidic and so appropriate amounts of sodium hydroxide solution are added. Fluoride is sometimes added to water if there is insufficient occurring naturally, as it helps to prevent tooth decay. 

---