Gases, filtration sterilization

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. 

Sterile Filtration of Gases. Primary appHcations for sterile gas filtration are the sterilization of fermentor inlet air, fermentor vent gas, vents on water for injection tanks, and vacuum break filters during lyophilization. Operational and process considerations apply. Typically, the membrane in gas... 

Filters for use in sterile gas filtration must conform to standards similar to those mandated for sterile hquid filtration. Nondestmctive integrity tests may be apphed. The tests are performed by wetting the filter with an appropriate solvent, commonly 60/40 isopropyl alcohol/water for hydrophobic membranes, and applying air or nitrogen gas at a preset pressure. 

Generally, sterility is synonym with the absence of any viable microorganisms including their spores. Currently, the available sterilization methods include heat sterilization (steam and hot-air sterilization), cold sterilization (gas sterilization, sterilization by ionizing radiation), sterilization by aqueous solution (aldehydes, peracetic acid, hypochlorite, hydrogen peroxide), and sterilization by filtration methods. The choice of method is based on recommendations in medicinal literature, legal requirements, and the compatibility of a medical product with the method used. The decision for a particular method has to take the following factors into consideration [954] ... 

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. 

Such sterilization procedures (see also Chapter 20) may include heat treatment, filtration, irradiation, recrystallization flxm a bactericidal solvent such as an aleohol, or for dry products where eompatible, ethylene oxide gas. If the raw material is only a minor constituent and the final product is adequately preserved either by lack of chemically... 

The British Pharmacopoeia (1993) recognizes five methods for the sterilization of pharmaceutical products. These are (i) dry heat (ii) heating in an autoclave (steam sterilization) (iii) filtration (iv) ethylene oxide gas and (v) gamma or electron radiation. In addition, other approaches involving steam and formaldehyde and ultraviolet (UV) light have evolved for use in certain situations. For each method, the possible permutations of exposure conditions are numerous, but experience and product stability... 

Five sterilization processes are described in the USP steam, dry-heat, filtration, gas, and ionizing radiation. All are commonly used for parenteral products, except gas and ionizing radiation, which are widely used for devices and surgical materials. To assist in the selection of the sterilization method, certain basic information and data must be gathered. This includes determining... 

Depending upon the intended application, the antibody may next be conjugated to specific molecular tags (e.g. a radionuclide or toxin). Finally, stabilizing agents (e.g. buffer components, glycine or sometimes human serum albumin) are added to the product. This is then aseptically filled into the final containers after sterile filtration. The product is then usually freeze-dried and sealed under an atmosphere of an inert gas. 

Chlorination is the most widely used disinfecting or sterilizing process. Where daily water requirements arc not large, it is common practice to use a hypochlorite, but for large plants liquefied chlorine gas is used. Chlorination may be practiced before filtration (prechlorination), after filtration (post-chlorination), or both before and after. 

Table 3 lists the sterilization methods used for sterile products. There are five basic methods—heat, gas, radiation, light, and filtration. The first four methods destroy microbial life, while filtration removes micro-organisms. Vali-... 

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