Steam sterilization processes

Application of the F- value concept has been largely lestrieted to steam sterilization processes although there is a less frequently employed, but direet parallel in dry heat sterilization (see section 4.3). 

The F-value concept which was developed for steam sterilization processes has an equivalent in dry heat sterilization although its application has been limited. The Fh designation describes the lethality of a dry heat process in terms of the equivalent number of minutes exposure at 170°C, and in this case a z value of 20°C has been found empirically to be appropriate for calculation purposes this contrast with the value of 10°C which is typically employed to describe moist heat resistance. 

The condenser housing is round and horizontal with vacuum- and pressure-resistant design for the freeze-drying and steam sterilization processes. The condenser is slanted toward the drain ports. 

Component sterilizers steam sterilization process. A steam autoclave is used at ABC Pharmaceutical Industries to sterilize equipment and components used in aseptic processing. The following system description... 

CSG Capsules, soft gelatin SSP Steam sterilization process... 

Each validation process should have a documented protocol of the steps to follow and the data to collect during the experimentation. As an example, App. I presents a protocol for the validation of a steam sterilization process. 

Table 2 Steam Sterilization Process Summary Sheet... 

With the main emphasis being the validation of a steam sterilization cycle based on the achievement of a certain reproducible value at the coolest part of the full batch load, procedures for validation of a steam sterilization process will now be discussed. 

If one knows the D value, the BI concentration or population A and the desired probability level of nonsterility B, the minimum F0 value that must be achieved by the sterilization cycle for the particular load can be calculated. For example, if A = 106 and II = 1 (f6 and laboratory studies determine the D value for B. stearothermophilus in the product to be sterilized to be 0.4 min (F0 = 0.4(12) = 4.8 min), a minimum F0 value of 4.8 min should be achieved at the worst case location during heat-penetration studies. The USP requires a steam sterilization process to deliver a lethality input of 12D for a typical overkill approach. 

The complexity of the sterile filtration operation and the CGMP regulations require the validation of sterilizing filter systems. The validation of a sterile filtration operation can be complex, with many operational parameters and their interactions needing to be identified, controlled, and predicted for each end product to demonstrate that sterility is adequately achieved by the filtration process. In the commonly used steam sterilization process, the heat parameters are identified and in-process controls specified such that a level of sterility assurance can be reproducibly obtained. In steam sterilization, the important parameter of heat, measured by temperature, can be accurately measured and continuously monitored to ensure the operational integrity of the autoclave however, unlike steam sterilization, filtration sterilization cannot be monitored on a continuous basis throughout the process. 

Use of a drying device for the filter housing - a water ring pump, for example - for optimum drying of the housing after a steam sterilization process. 

Table 2.4.2 Example of inactivation of bacterial populations during steam sterilization processes (logarithmic processes)...

Justification of the reliable achievement of SALs of 10 for particular pharmaceutical items treated according to particular specifications of temperature and time in particular sterilizers is predicated on the regularity and predictability of steam sterilization processes. The means of justification are through scientifically based development of sterilization specifications and sterilizer parameters, and through subsequent validation of the specified processes. 

Acceptance criteria for bio-validation of steam sterilization processes are usually (but not invariably) defined along the following lines ... 

Steam sterilization in autoclaves has a long and strong scientific basis (see above). The essence of validation of steam sterilization processes is to demonstrate that temperature and time conditions are being achieved uniformly through every item included the autoclave load and that the lethality being achieved in practical situations corresponds to that which would be expected from sterilization theory. 

Steam sterilization processes are monitored for compliance with strict specifications of temperature, pressure, and time. Routine monitoring with biological indicators is not necessary. Indeed, any item of steam sterilizingequipment that is operating so erratically as to merit routine monitoring with biological indicators should be replaced. 

There are several definitions of validation but, in simple terms, the word means demonstrating that a process will consistently produce the results that it is intended to. Thus, with respect to sterile products, validation would be necessary for each of the individual aspects of the manufacturing process, e.g. environmental monitoring, raw materials quality assessment, the sterilization process itself and the sterility testing procedure. Of these, it is the sterilization process that is likely to be subject to the most detailed and complex validation procedures, and these will be used to exemplify the factors to be considered. A typical validation procedure for a steam sterilization process is likely to incorporate most, or all, of the following features ... 

Validation of a steam sterilization process must cover the series of actions required to establish that the process is capable of doing what it is intended to do (i.e., supporting a claim of sterility) and must define a plan for maintaining the validated state of control. An overall scheme is described in Table 3. 

Academic texts on steam sterilization often state that routine control of steam sterilization processes should concentrate on the measurable detenninams of lethality, temperature and time. Temperature should be monitored at the coldest point, usually in the drain line, but if this is not the coldest spot there should be a floating probe at the coldest spot, or the relationship between the drain line and the coldest spot should have been well established and documented. A permanent record of the temperature throughout the sterilization cycle should be a compulsory feature of all production-scale autoclaves, and this should be inspected in detail for batch release. In practice this is not sufficient to confirm that sterilizing conditions have been attained. 

James, P. R. Tetrazolium salts as steam sterilization process indicators. PCT Int. Appl. WO 9837157, 1998 Chem. Abstr. 1998, 129, 218237. 

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