Sterilization specification, temperature

SIP systems range from very small systems (say, a mixing tank) where all parts may reach temperature within 2 or 3 min, to absolutely massive arrangements of vessels, valves, and pipework in which the expulsion of air, the drainage of condensate, and the attainment of the sterilization specification temperature at the slowest point can take 20 or 30 min. 

Steam (qv) sterilization specifically means sterilization by moist heat. The process cannot be considered adequate without assurance that complete penetration of saturated steam takes place to all parts and surfaces of the load to be sterilized (Fig. 1). Steam sterilization at 100°C and atmospheric pressure is not considered effective. The process is invariably carried out under higher pressure in autoclaves using saturated steam. The temperature can be as low as 115°C, but is usually 121°C or higher. 

Some indicators can determine whether a specific temperature has been achieved. Because the entrapment of large amounts of air can result in the lowering of steam temperatures, these indicators react to some critical defect in sterilization conditions. Eor each different temperature, a different indicator must be used. 

F Value The equivalent time, in minutes, at a specific temperature delivered to a product to produce a given sterilization effect at a reference temperature and specific Z value... 

A review of all sterilization specifications assigned to the sterilizer under consideration shall be made, with the specifications cycle requiring the maximum peak dwell temperature and heating rate to be selected for the empty sterilizer heat distribution runs. During the empty sterilizer heat distribution runs, sterilizer parameters and equipment component status shall be visually monitored to confirm applicable control operations. 

Sterilizer engineering drawings Sterilizer operation procedure Sterilizer sanitization procedure Sterilizer maintenance procedures Sterilizer specification utilization list Distribution thermocouple location diagrams Temperature sensing unit location diagram (continuous sterilizers) Sterilizer process log sheets... 

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. 

For pharmaceutical products and materials used in connection with aseptic manufacture, sterilization specifications apply to conditions of temperature and time, or Fq, or combinations of Fq, temperature and time to which the contaminating micro-organisms themselves must be exposed over the hold period of the sterilization process. In practice, this means actually within aqueous products, on the surfaces of rubber stoppers or metal machine parts, or within the folds of cartridge filters, etc. 

The sterilizer parameters are the practical criteria that must be specified to ensure that the sterilization specification is delivered to all parts of the load. They always include specifications for temperature and time, but it is important to recognize the distinction between sterilizer parameters applying to the machine settings on the autoclave console, and sterilization specifications applying to actual conditions within the load. Essential sterilizer parameters also include other specifications, e.g., for load configuration, number and depth of prevacuums, cooling characteristics, etc. 

Some products may be heat sensitive only above a threshold temperature for those that can withstand temperatures in the range of 110-118°C but cannot withstand 121°C it is possible to apply the Fq concept to the principles above and derive equivalent sterilization specifications to those given in Table 2. These specifications are summarized for 116°C in Table 3. As can be seen, if there is a requirement to sterilize at (say) 116°C, there are considerable time savings to... 

Sterilizer parameters are specific to combinations of product, presentation, and autoclave. They must be established empirically. Heat penetration studies done prior to the performance qualification phase of validation serve the purpose of determining the loading patterns, prevacuums, and temperature and pressure settings, etc.which ensure that the sterilization specification is delivered to the product and that it is delivered uniformly throughout the load. 

Systems that are sterilized in-place are often immensely complex. The initial challenges to their sterilization are the removal of air and the elevation of the temperature of the pipework to prevent heat losses and condensation. As such, most work in the development of sterilization specifications for SIP systems is concerned with the heat-up phase. Appropriate questions are Is the sterilization temperature achieved throughout the system Where is the slowest location to achieve... 

The time for which the system must be held at temperature (the sterilization specification) is often relegated to a minor consideration compared with this earlier development work. Typically, it is decided arbitrarily to use, 121°C for 15, 20, or 30min, with no real scientific basis. 

Sterilization specifications in the hold period are presented in terms of temperature and time with upper and lower tolerances set around them. The lower specification limits are critical to sterilization. 

Dry-heat sterilization is generally conducted at 160—170°C for >2 h. Specific exposures are dictated by the bioburden concentration and the temperature tolerance of the products under sterilization. At considerably higher temperatures, the required exposure times are much shorter. The effectiveness of any cycle type must be tested. For dry-heat sterilization, forced-air-type ovens are usually specified for better temperature distribution. Temperature-recording devices are recommended. 

Great care is needed in the design of autoclaves and sterilization cycles because of the requirement for the presence of moisture. The autoclave must be loaded to allow complete steam penetration to occur in all parts of the load before timing of the sterilization cycle commences. The time required for complete penetration, the so-called heat-up time, varies with different autoclave constmction and different types of loads and packaging materials. The time may not exceed specific limits in order to guarantee reproducibility and, for porous loads, saturated steam. The volume of each container has a considerable effect on the heatup time whenever fluids are sterilized. Thermocouples led into the chamber through a special connector are often employed to determine heatup times and peak temperatures. The pressure is refleved at the end of each sterilization cycle. Either vented containers must be used or... 

General recommendations for instmmentation include monitoring gas concentration, temperature, time, and the moisture content of the chamber. Hospital sterilizers are not usually equipped with instmmentation providing direct display of gas concentration and moisture content. These rely instead on a specific sequence of steps performed automatically and the recording of pressure which when 100% ethylene oxide is used is a perfect measure for the concentration of this gas. 

Both polyester- and polyether-based TPU could be used to blend with PVC, although the former constitutes the majority of the commercial products. All of the blends should meet the following requirements (I) they must have good or relatively good compatibility with PVC, (2) their processing temperature should be close to or lower than that of PVC, (3) they have to meet the specific requirements of the products, for example, TPUs used for medical purposes should be colorless (if possible), transparent, nontoxic, and able to be sterilized, and (4) they should not be expensive. 

The non-technical nature of the problem becomes apparent when we consider a specific example. For instance, plastic bottles, which are tighter and cheaper than those made from glass, have superseded the traditional material in all sectors of the modern drinks industry. In Britain five billion plastic bottles are used a year, which leads to serious environmental problems. They are difficult to recycle or reuse and expensive to dispose of. They cannot be reused because of the need for sterility. Sterilising is done using high temperatures, which would cause softening or even melting if applied to plastics. 

Conhrm that sterilizers are capable of processing at established time and temperature ranges that assure conformance with respective specification requirements... 

The sterilization/depyrogenation specifications developed are transferred to production personnel by appropriate SOP procedures as time and temperature specifications. 

A medium, which flows through an 80 mm i.d. stainless tube at a flow rate of 1.0 m h , is to be continuously sterilized by indirect heating with steam. The temperature ofthe holding section is maintained at 120 °C. The number of bacterial spores of 10 rn in the entering medium must be reduced to 0.01 m . The specific death rate of the bacterial spores in the medium, medium density, and medium viscosity at 120 °C are 180 h , 950 kgm , and 1.0kgm h , respectively. 

Container Capacities, Fill Point Variation, Sterile Filter Monitoring, Start-Up Checks. These all can be checked easily on a statistical basis. The frequency of each check should be specified so that these become routine functions of quality control. Filler-bowl wine temperature fluctuations are extremely important since they may be a major cause of fill-point fluctuation in bottles. This fluctuation cannot be overemphasized because of legal ramifications. Specific standards of fill and head-space maxima are listed by the Bureau of Alcohol, Tobacco and Firearms in 27 CFR, part 4. 

All modem fillers are designed for clean-in-place (CIP) to ensure the sterility of the system. The CIP process operates from a centrally located system that is piped to the filler. A return cycle to the CIP set from the filler is included, the temperature of the return liquor being sensed at the filler outlet. Specifically designed CIP cups are attached to each filling valve to allow the CIP process to take place entirely through the filler bowl and filling valves and all associated... 

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