Sterilisation processes autoclaving

Manufacturing process Aseptic manufacture/sterile filtration (terminal sterilisation by autoclaving not possible ... 

Packaging for sterile products must be effectively contained and sealed to prevent microbial contamination, and must be robust enough to withstand any sterilisation process required. The sterilisation process can affect the leaching of components from the container into the product or affect the physical properties of the container. For example, autoclaving can soften plastic containers, and gamma irradiation can cause certain polymers to cross link. 

Check if washing and sterilisation process (i.e. autoclaving of stoppers) generates any particulate matter. 

There should be a clear means of differentiating products which have not been sterilised from those which have. Each basket, tray or other carrier of products or components should be clearly labelled with the material name, its batch number and an indication of whether or not it has been sterilised. Indicators such as autoclave tape may be used, where appropriate, to indicate whether or not a batch (or sub-batch) has passed through a sterilisation process, but they do not give a reliable indication that the batch is, in fact, sterile. 

Thermally stable material such as glassware or metal instruments may be sterilised by heating them in an oven at 185°C for two hours. The material is wrapped in autoclave paper prior to heating, and after removal remains sterile until the wrapping paper is removed. Steam treatment in an autoclave is normally used for the sterilisation of aqueous material. The autoclave uses steam at a pressure greater than atmospheric and laboratory systems normally operate at 15 lbs in which corresponds to a temperature of 121 °C. This makes the assumption that the atmosphere inside the autoclave is composed only of steam and therefore it is necessary to expel all the air before the sterilisation process commences. 

Current sterilisation processes are generally not well adapted to polymers, except in the cases of water-soluble polymers and colloids, which can be sterilised by filtration in solution. The simplest process is autoclaving with steam at 120 °C for 20 min. This process can be detrimental to devices that include polymers with thermomechanical properties not compatible with the temperature used in the sterilisation process. 

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. 

In a steam autoclave air is more effectively removed by downward displacement which makes loading with more and differently shaped objects possible as well. After removal of the air, the valve is closed and the steam pressure gradually increases. A pressure control valve is used to set the desired pressure, and thereby the desired temperature, since these parameters have a fixed relation in the absence of air (see Table 30.2). For control of the temperature and duration of the sterilisation process a timer or Programmable Logic Controller (PLC) can be used. A PLC is part of the computer of the autoclave. In a PLC the routine programs are factory set and fixed, so for the process operator it is not... 

Fig. 30.3 Temperature-time course (temperature profile) during a sterilisation process in an autoclave (Reprinted with permission of the publisher [9])...

Hot water sterilisers are also called hot water (immersion) autoclaves. In these sterilisers, hot distilled water, freshly filled in the stainless steel steriliser bath and heated in a sanitary heat exchanger is pumped around inside the autoclave and is continuously and with high flow sprayed top down over the load to be sterilised. The hot water autoclave contains a mixture of water and air before and during the sterilisation process no vacuum phase is used (see Fig. 30.5). 

To ensure an effective and reproducible sterilisation process, the steriliser should be qualified (see Sect. 34.15) and all sterilisation processes and the empty steriliser have to be validated before first use (see Sect. 34.14). Subsequently all sterilisation processes are revalidated periodically, mostly each year. During process validation, the performance of the combination of steriliser, specific load, and process is assessed. Different kinds of loads all require their own validation protocol. For example, validation of the sterilisation process of aqueous liquids often consists of an empty autoclave, an ampoule program and one or more programs for liquids for infusion in bottles, vials or bags. For medical devices, the load is never homogeneous multiple types of loads are sterilised at once. Therefore, validation of this process is done by a worst-case approach. 

Cyanoacrylates are quite widely used for the bonding of medical devices (especially small component parts, see Figure 9.5) as these adhesives show excellent adhesion to many of the plastics used in this industry. In this industry component parts are sterilised and, whilst cyanoacrylates will withstand gamma sterilisation and ethylene oxide (EtO) sterilisation processes, they would not generally be recommended for applications where the component assembly will be steam autoclaved. 

For small volumes, 13 or 25 mm diameter, filtration membranes may be fitted into plastic or stainless steel holders (e.g. the Swinnex filter holder made by the Millipore Corp. Appendix 3) which, after autoclaving, are fitted onto a syringe containing the liquid to be sterilised. Care must be taken in the assembling of the membrane in the holder as incorrect assembly leads to the escape of the membrane from its retaining gaskets with subsequent failure of the filtration process. The plastic holders have a limited life time as they distort on autoclaving. 

Ampoules may be sterilised by dry heat or steam autoclaved after filling provided the product will withstand this process. On-line sterilisation often uses dry heat at over 300°C for a controlled period. 

Steam autoclaving may be used for both filled (water-based) and empty packs and components which are subsequently assembled by aseptic processing. The plastics which can be steam sterilised include HDPE, PP, PC, PA and, under selected conditions, plasticised PVC. 

Retortable pouches can be made from combinations of foil, polyester, nylon, polypropylene, HD polythene, provided the laminant (or the process of lamination) employed will withstand the autoclaving conditions of temperature and moisture. Due to the flat shape of the pouch and high surface area, sterilisation times can usually be reduced compared with cans. 

Fig. 117. During its aseptic production the hyaluronic acid solution can be sterilised through a filter (0.22 pm) before the first step of the production process or at the last step (filling). In terminal sterilisation the already filled product is sterilised (e.g., autoclavation)...

The steam steriliser is commonly referred to as an autoclave. The simplest steam steriliser, however, is a pressure cooker. In a pressure cooker, the added distilled or deionised water is heated and eventually begins to boil. The steam that is formed pushes the air out through the vent valve in the lid. This is not a very effective process because the vent valve is in the upper part of the steriliser and it takes time to remove the air just by continuous boiling. Air is heavier than steam, so these gases are slowly removed by upwards displacement to the upper part of the pressure cooker. 

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