Sterilization method changes

Changes in the sterilization method (e.g., gas, dry heat, irradiation). These include changes from sterile filtered or aseptic processing to terminal sterilization, or vice versa. 

For larger scales, shallow trays made of corrosion-resistant metal or plastic placed in portable trolleys may be used for efficient liquid-air contact. The trolleys are placed in a sterile room with frequent sterile air changes under closely controlled temperature and humidity conditions. Efficient air-liquid contact may also be obtained from a loosely packed, moist, solid medium permeated with air. For instance bran is used as the substrate for enzyme production by Aspergillus oryzal. Wine vinegar (acetic acid) is produced by trickling wine (basically ethanol in water) over a short tower of wood chips, which are used both as a support and to provide air to Acetobacter aceti [13] (Eq. 16.15). By law, the acetic acid (3-5% in water) in vinegar must be produced by fermentation, and not by petrochemical methods. 

Sterilized and -sterilized products and materials must be clearly distinguishable, preferably by making use of an indicator which changes color under the influence of the sterilization method employed. 

Not all materials respond alike when subjected to various means of sterilization. Some are heat sensitive, some will absorb sterilization fluids, some will be affected by molecular changes when subjected to radiation sterilization and others will absorb and hold irritating gases for extended periods of time. Table 4.13 gives sterilization methods that have been judged most appropriate for each elastomer. The consequences of using an inappropriate method can be loss in physical properties and an adverse biological response. 

An essential requirement for medical products is that the materials and components used must be sterilizable. Once the sterilization method has been established, the list of materials that are suitable for a medical product is already limited. For certain sterilization processes, plastics cannot be used because of their low heat distortion temperature, low hydrolysis resistance, or low resistance to color change and degradation of the molecular chains. 

The polymer stability was also tested in terms of a suitable sterilization method. It was reported that the molecular weight Mw is decreased by 5% or 17% after sterilization by ethylene oxide or gamma-irradiation. Significant changes in both the physicochemical and tensile properties were observed after gamma-irradiation [284]. 

Apart from biocompatibility, the possibility to sterilize the textile is also important. The standard DIN EN 556 describes the procedures and the respective tests in detail. Many sterilization processes cause changes in the polymeric materials that can even lead to the macromolecules decomposing. For each material and for every product geometry, an appropriate sterilization method must be found, as described in Wintermantel (2009). 

The production of elfamycins is described in the references cited in Table 1. Fermentation yield improvements with aurodox (1, R = CH ) proved difficult because of feedback inhibition (48). Aurodox-resistant strains (49), however, responded positively to conventional mutagenic methods leading to yield increases from 0.4 to 2.5 g/L (50). Scale-up of efrotomycin (7, R = CH ) fermentations were found to be particularly sensitive to small changes in sterilization conditions of the oil-containing medium used (51). 

Because membrane filtration is the only currently acceptable method of sterilizing protein pharmaceuticals, the adsorption and inactivation of proteins on membranes is of particular concern during formulation development. Pitt [56] examined nonspecific protein binding of polymeric microporous membranes typically used in sterilization by membrane filtration. Nitrocellulose and nylon membranes had extremely high protein adsorption, followed by polysulfone, cellulose diacetate, and hydrophilic polyvinylidene fluoride membranes. In a subsequent study by Truskey et al. [46], protein conformational changes after filtration were observed by CD spectroscopy, particularly with nylon and polysulfone membrane filters. The conformational changes were related to the tendency of the membrane to adsorb the protein, although the precise mechanism was unclear. 

Some injecting users may be willing, after counselling, to change to an oral method. If not, they need information about how they can inject safely. Access to sterile injecting equipment is necessary for safe injections. Where access is limited, some drug takers will attempt to sterilise their works . 

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