NAME: IBANGA EMMANUELLA MFONIDO
MARTIC NUMBER: 18/MHS07/022
COURSE CODE: PHA 206
ASSIGNMENT:Sterilization is an essential stage in the processing of any product destined for parenteral administration or for contact with broken skin.  Discuss?
Discuss the importance of sterilization in the production of Pharmaceutical products.
Explain Gaseous Sterilization, its Sterilizer design, and operation.
What is Radiation Sterilization?

1) Sterilization processes involve the application of a biocidal agent or physical microbial removal process to a product or preparation with the object of killing or removing all microorganisms. These processes may involve elevated temperature,reactive gas, irradiation or filtration through a microorganism-proof filter. The success of the process depends on a suitable choice of treatment conditions, e.g. temperature and duration of exposure.It must be remembered, however, that with all articles to be sterilized there is a potential risk of product damage, which for a pharmaceutical preparation may result in reduced therapeutic efficacy, stability or patient acceptability. Thus, there is a need to achieve a balance between the maximum acceptable risk of failing to achieve sterility and the maximum level of product damage that is acceptable. This is best determined from a knowledge of the properties of the sterilizing agent, the properties of the product to be sterilized and the nature of the likely contaminants. A suitable sterilization process may then be selected to ensure maximum microbial kill/removal with minimum product deterioration.
2) Terminal sterilization is the process of sterilizing a product in its final container. It is an important process as it ensures the product remains sterile.All medical, ophthalmic and parenteral equipment are sterilized in batches, and usually sterilized using heat. The products themselves however are not thermally sterilized as the heat may damage it. Alternative methods are therefore used, such as filtration which also reduces the risk of a product becoming contaminated.Before the sterilization process is started, the holding period must be established, which is the time the products must be held at the required temperature or exposed to other sterilization methods to ensure the microbial growth is killed effectively. Any microbial growth that occurs while the products are in storage can affect the quality of the product and must therefore be prevented. 
Methods of Terminal Sterilization:
Ethylene Oxide: for prefilled syringes and medical devices unable to tolerate high temperatures
Irradiation: also for prefilled syringes and medical devices unable to tolerate high temperatures
Moist Heat Sterilization: for large and small parenteral devices and ophthalmic products.
3)Gaseous Sterilization: Sterilizing gases are typically used when exposure to other methods (heat or radiation) could damage the materials or equipment. The most common gases used for sterilization include ethylene oxide (EO), ozone, mixed oxides of nitrogen, and chlorine dioxide). Its sterilizer desidn and operation: An ethylene oxide sterilizer consist of a leak proof and explosion proof steal chamber normally of 100-300 capacity. This can be surrounded by a hot water jacket to provide uniform chamber temperature. successful operation of the sterilizer require removal of air from the chamber by evaporation, humidification and conditioning of the load by passage of sub atmospheric pressure steam. Forced gas circulation is often employed to minimize variations in conditions through out the streilizer chamber, absorption of ethylene oxide by the load is enhanced by the introduction of excess gas at the beginning or by the addition of more gas as the pressure drops during the sterilization process, after treatment the gases are evacuated either directly to the outside atmosphere or through the special exhaust system, filtere sterile air is then admitted either for a repeat of the vacuum or for air purging until the chamber is opened, in this way safe removal of the ethylene is achieved reducing the toxic hazards to the operator.
4)Radiation sterilization has existed since the late 1950s and has grown tremendously in popularity over the last 60 years.  Radiation sterilization relies on ionizing radiation, primarily gamma, X-ray or electron radiation, to deactivate microorganisms such as bacteria, fungi, viruses and spores. Due to numerous advantages over heat or chemical based sterilization techniques, this method is particularly attractive in medicine and healthcare-related fields. For example, radiation sterilization is readily applied during tissue allograft preparation, pharmaceutical packaging and medical device manufacturing. Radiation can be lethal to biological organisms by inducing genetic damage and chemical changes in key biological macromolecules.  During sterilization treatment, the sample of interest is bombarded with high energy electrons or high energy electromagnetic radiation, which leads to the formation of extremely unstable free radicals, molecular ions and secondary electrons. These radiation products then react with nearby molecules to fracture and alter chemical bonds. DNA in particular is highly sensitive to the damaging effects of radiation and will break, depolymerize, mutate and alter structure upon exposure to ionizing radiation. Incomplete repair of DNA damage ultimately leads to loss of genetic information and cell death. Thus, radiation can kill harmful microorganisms and be used as a sterilization technique.Three forms of radiation commonly used for commercial radiation sterilization include gamma radiation, electron beam (e-beam) radiation and X-ray radiation.
Advantages and Disadvantages
Radiation based sterilization methods offer numerous advantages over traditional chemical or heat-based sterilization: 
1)Terminal Processing: Due to the penetration depth of ionizing radiation, products can be processed in their fully sealed, final packaging. This limits risk of contamination following sterilization.
2)Cold Method/Temperature Independence: Temperature increases during treatment are minimal. Furthermore, radiation sterilization has no heat dependence and is efficient at both ambient temperature and sub-zero temperatures. It is compatible with temperature sensitive materials, such as pharmaceuticals and biological samples.
3)Chemical Independence: No volatile or toxic chemicals are needed. In the case of X-ray or e-beam irradiation, no end products requiring disposal are generated during the procedure.
4)No residue: Radiation leaves no residue on the sterilized product.
5)Flexibility: Radiation can sterilize products of any phase (gaseous, liquid or solid materials), products with variable density, size or thickness, and homogeneous or heterogeneous systems. Furthermore, sterilization can be conducted at any temperature and any pressure.
6)Time efficiency: E-beam sterilization can be completed within seconds to minutes.
7)Sterility assurance level (SAL): Radiation treatment can yield a high SAL of 10-6 or better, ensuring that less than one out of a million microorganisms survive the sterilization procedure.
8)Ease: Only a single variable, the exposure dose/time, must be monitored, making radiation sterilization simple and easy to control.
However, radiation sterilization techniques do have a number of drawbacks: 
1)Instrumentation: Capital costs are high and specialized facilities are often needed. Gamma radiation requires a nuclear reactor; E-beam/X-ray radiation are generated using electron beam accelerators.
2)Product Degradation: Radiation based methods are not compatible with all materials and can cause breakdown of the packaging material and/or product. Common plastics such as polyvinyl chloride (PVC), acetal and polytetrafluoroethylene (PTFE) are sensitive to gamma radiation. The high energies involved in e-beam radiation can also lead to main chain scission (breaking of the long chain backbone) and chemical crosslinking of packaging polymers.
3)Radioactive material: When gamma radiation is used as an ionization source, radiation sterilization requires handling and disposal of radioactive material. Note that, at commonly used radiation levels, irradiation with gamma rays does not induce radioactivity in the treated sample itself.