Sterilization method, choice

Thermostability. The choice of sterilization method depends on the thermostability of the achve ingredient, autoclaving being applied only to dmgs that are heat stable in aqueous solution. 

The choice of the primary packaging should be justified. This should include consideration of the safety of the packaging for the patient and user. Account should be taken of the optimal sterilization method for the finished product. 

For sterile products, particular attention should be paid to the choice of an appropriate method of sterilization. Wherever possible a terminal sterilization process should be applied to the product in its final container-closure system, as suggested in the Ph Eur. The preferred options include steam sterilization, dry heat sterilization, and irradiation using the Ph Eur listed conditions (saturated steam at 121°C for 15 minutes dry heat at 160°C for 120 minutes irradiation with an absorbed dose of not less than 25 kGy). Where these cannot be used, the application must include justification for the alternative procedure adopted on the understanding that the highest achievable sterility assurance level should be achieved in conjunction with the lowest practicable level of presterilization bioburden. There is guidance in the form of decision trees as to the preferred options for sterilization method to be applied ... 

All these recommendations are summarized in the Decision trees for the selection of sterilization methods, edited by the EMEA [23] (Fig. 1).Two cases are considered on one hand, the aqueous products and on the other hand, the non-aqueous liquid, semi-solid and dry powder products. Figure 1 shows the order of preference of the sterilization methods for the second group. The terminal ones are ranked in the first place. Among them, thermal sterilization is still referred as the best choice, radio-sterilization ranking right after. Since gas sterilization is excluded and non-terminal methods are listed as the last choice, radiosterilization now precedes all these methods. It is deemed as the recommended alternative method to thermal sterilization. 

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] ... 

Sterile aqueous D-sorbitol solutions are fermented with y cetobacter subo >gichns in the presence of large amounts of air to complete the microbiological oxidation. The L-sorbose is isolated by crystallisation, filtration, and drying. Various methods for the fermentation of D-sorbitol have been reviewed (60). A.cetobacter suboyydans is the organism of choice as it gives L-sorbose in >90% yield (61). Large-scale fermentations can be carried out in either batch or continuous modes. In either case, stefihty is important to prevent contamination, with subsequent loss of product. 

The choice of a particular mining method depends on a number of parameters, typically the physical properties of the host matrix, the fiber content of the ore, the amount of sterile materials, the presence of contaminants, and the extent of potential fiber degradation during the various mining operations (33). However, most of the asbestos mining operations are of the open pit type, using bench drilling techniques. 

Principles of the methods employed to sterilize pharmaceutical products are described in Chapter 20. The British Pharmacopoeia (1993) recommends autoclaving and filtration as suitable methods applicable to aqueous liquids, and dry heat for non-aqueous and dry sohd preparatiorrs. The choice is determined largely by the ability of the formulation and container to withstand the physical stresses apphed by moist heat... 

Justifications for the use of nonstandard (i.e., nonpreferred or nonpharmacopeial) methods of sterilization may include the heat instability of the active ingredient or an essential excipient. The choice of a method based on filtration through a microbial retentive filter and/or aseptic assembly should be justified, and the appropriate in process controls (including bioburden controls on active ingredients, excipients, bulk solutions, process time constraints etc) discussed in detail in the application. Commercial considerations should not form part of the argument for the application of a nonstandard sterilization process. The highest possible sterility assurance level should be achieved. 

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. 

The influence of environmental factors has been established, but remains controversial. The strategy of strict avoidance of exposure to bacteria, viruses, and allergens until sensitization diminishes belongs to the canons of prophylaxis and treatment of choice of atopic diseases. For years, elimination of allergens from the environment of potentially-affected patients was not undermined as the method for preventing allergy. According to medical instructions, children with an atopy in their case history should have stayed in virtually sterile conditions. 

Validation of the lyophilizer cleaning and sterilization processes should be accomplished. Particular care should be taken to verify that there is no back-migration of contaminants, whether from adjuvant fluids integral to the equipment of by cross-contamination from previous product. Typically, an overkill approach using a sufficient number of thermocouples and biological indicators is the method of choice. Finally, fill testing to verify the adequacy of the sterilization procedure and the aseptic manipulations involved with product filling, transfers, and lyophilization needs to be performed. 

Terminal sterilization is a process by which product is sterilized in its final container. Terminal sterilization is the method of choice for products that are sufficiently stabile when subjected to a compatible lethal treatment. Because the process utilized is expected to be lethal to the microorganisms present, is highly reproducible, and generally readily validated, there is a clear preference for its use [1,40,41],... 

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