Other methods of sterilization

Great strides have been made in developing and improving other methods of sterilization, but little has been accomplished where dry-heat sterilization is concerned. Sterilizers used today are still basically the same as they were a decade ago. ... 

Although much work has been performed to improve and develop other methods of sterilization, very little has been accomplished in the field of dry-heat sterilization. The process is time consuming and difficult to control because of the temperature stratification and slow heating rate. Dry heat is still the agent of choice for sterilizing items that might not be adequately penetrated by steam and that will tolerate high temperatures, such as oils, petrolatum, and closed containers. ... 

Sterilization processes are discussed in detail in Chapter 20. However, it is axiomatic that whatever method is chosen, the process should not cause damage to the product. By reference mostly to moist heat sterilization processes (the reader should remember that there are parallel approaches to other methods of sterilization) this section illustrates the factors that must be considered in the design of a sterilization process. 

Whilst the vast majority of parenteral products are rendered sterile either by moist heat sterilization or by filtration through sterilizing grade filters, other methods of sterilization should be considered, particularly in the development of non-aqueous formulations or novel drug delivery systems. For implants, for example, gamma irradiation is an option that should be explored early on in development. 

The efficacy of ethylene oxide as a sterilant depends upon its concentration, the temperatures and humidity (at low humidities or with free water in the chamber, efficacy declines rapidly), the time of exposure and the extent of microbial contamination. Where other methods of sterilization are possible they should be used in preference to ethylene oxide. 

The packaging material should normally be selected so as to allow the optimal sterilization process to be applied to the product as a whole. Lfowever, factors other than the method of sterilization have to be taken into account in selecting a container material, such as the route of administration and patient convenience and compliance. Where the choice of container-closure precludes the use of terminal processing in the final container, the application should include appropriate documentation to explain and scientifically justify such a choice. The guidelines indicate that in such cases it is still the manufacturer s duty to continue the search for alternative containers that would allow terminal processes while providing the necessary product characteristics. 

Currently the main application of interest for parametric release is to replace the sterility test as a control method in appropriate cases (given the limited value of that test to predict sterility assurance due to statistical considerations, although it is also pointed out that a sterility test provides a final opportunity to identify a major failure, although other means should provide a more reliable way of detecting such failures). The concept is applicable to well-founded methods of sterilization where the product stability is known and development data have identified the critical process parameters. The measured parameters should be such as to ensure that correct processing of the batch provides sufficient assurance that the sterility assurance level intended has been achieved. 

The science that underpins steam sterilization is well known and has been long established. It is the preferred method of sterilization in the pharmaceutical industry it is used for sterilization of aqueous products in a wide variety of presentations, for sterilization of equipment and porous materials required in aseptic manufacture, in microbiology laboratories for sterilizing media and other materials, and for sterilization of massive systems of vessels and pipework [steam-in-place (SIP) systems]. Numerous rules and guidelines have been published on the topic, yet steam sterilization and particularly bio-validation of steam sterilization is still a subject for controversy and debate. 

The principles behind the sterilization processes are described in Chapter 20. The choice of method is determined largely by the ability of the formulation and container to withstand the physical stresses applied during the sterilization process. All products intended for sterilization should be manufactured under clean conditions and therefore will be of low microbial content (bioburden) prior to sterilization. Under these conditions, the sterilization process will not be overtaxed and will generally be within the safety limits needed to provide the required level of sterility assurance (Chapter 20). The next section emphasizes parenteral products, but the practices described apply to many other types of sterile product. 

Other methods of controlling deionizing systems include establishment of water-quality specifications and corresponding action levels, remedial action when microbial levels are exceeded, documentation of regeneration, and a description of sanitization and sterilization procedures for piping, filters, and so forth. 

In addition to the physical parameters discussed above, a number of other factors related to the culture and to the medium should be considered for both transfer of a process from shake flasks to fermenters and for scale-up to larger vessels. These include the provision of a culture stock giving reproducible growth after regeneration, the method of inoculum build-up that may require a number of shake flask and fermenter seed stages, an assessment of the variability within the process, the cost and availability of the medium components, and the method of sterilization within the fermenter. 

Four other methods of preservation include the immersion of slants into liquid nitrogen (an expensive procedure) the inoculation of washed sterilized horse manure/straw compost that is then kept at 36-38 ° F. (See Chapter V on compost preparation) the inoculation of sawdust/bran media for wood decomposers (see section in Chapter III on alternative spawn media) or saving spores aceptically under refrigerated conditions—perhaps the simplest method for home cultivators. 

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