Sterilization batch

The values of Vheat and Vcool are determined by the methods used for the heating and cooling. The value of Vhold is determined by the length of the controlled holding period. The design procedure for the estimation of the holding time is as follows  

The direct injection of steam into the medium can be assumed to follow the hyperbolic temperature-time profile of Eq. (8.9), which can be used to calculate the time required to heat the medium from 25°C to 122°C. From the steam table (Felder and Rousseau, 1986), the enthalpy of saturated steam at 345 kPa and water at 25°C is 2,731 and 105 kj/kg, respectively. Therefore, the enthalpy of the saturated steam at 345 kPa relative to raw medium temperature (25°C) is 

The solution of the preceding equation for t when T = 395°K and T = 298°K by using a numerical technique or a trial and error approach yields that the time required to reach 122°C is 1.46 hrs. 

Numerical integration of the preceding equation by using Advanced Continuous Simulation Language (ACSL) or other method yields 

During the cooling process, the change of temperature can be approximated by Eq. (8.12) as 

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The temperature profile is obtained by placing at least 10 thermocouples distributed in the empty tunnel or batch sterilizer in such a way as to determine heat profiles. In the flames sterilizer the thermocouples should be placed at the level of the ampules. The thermocouple tips should be suspended to avoid contacting any solid surfaces (wall, ceiling, support rods, etc.). A good profile should demonstrate uniform temperatures across the sterilizer. 

Figure 10.1 Modes of heat transfer for batch sterilization (a) direct steam sparging,...

Table 10.1 Temperature versus time relations in batch sterilization by various heating methods.

It can be operated at a high temperature (140°C instead of 121 °C in batch sterilization) therefore, the sterilization time can be shortened (holding time of 1 to 2 minutes). 

H enthalpy of steam relative to raw medium temperature, J/kg n flux of microorganisms due to axial dispersion, m 2s 1 k Boltzmann s constant, 1.3805 x 10 23 J/K or 1.3805 x l-16 erg/K kd specific death rate, s or kg/m s L length of holding section, m M initial mass of medium in batch sterilizer, kg Mw molecular weight of gas molecules, kg/kmol ms steam mass flow rate, kg/s mc coolant mass flow rate, kg/s... 

In industry, the LFCB is used to conduct small batch sterile filling operations, in the general manipulation and isolation of non-hazardous materials, and in quality assurance/quality control (QA/QC) sterility testing. 

In industry, the BSC is used to conduct small batch sterile-fill operations, manipulation (weighing and pouring), isolation of hazardous materials, and in QA/QC testing applications. All classes of BSC are encountered in pharmaceutical manufacturing operations for a wide variety of processing applications. 

The two types of processes currently used in dry-heat sterilization include 1) dry-heat batch sterilization/ oven sterilization and 2) dry-heat tunnel sterilization. Process 1 is the type of dry heat unit widely used in the pharmaceutical industry it uses the principle of convective heat transfer to heat the load. Process 2 is only found in large-scale processes, and the main application of this process is in the sterilization and depyrogenation of glass.f ... 

Fig. 2 shows a schematic diagram of a modern forced-convection batch sterilizer. The unit is a two-door sterilizer where the unloading door leads to the sterile area. The pressure inside the chamber must continuously be controlled so that the inside is always slightly higher than the pressure in the non-sterile loading area and slightly lower than the pressure in the sterile unloading area. ... 

The size and niunber of batching tanks depend upon whether the plant uses continuous sterilizers or batch sterilization. The difference is that in the latter case, the tanks can be large (5 0 to 80% of the size of the fermenter), and usually all the materials are mixed together. For continuous sterilizers, there is usually a minimum of four smaller tanks so that proteins, carbohydrates and salts can be batched and sterilized separately. In this case, the tanks are considerably smaller than the fermenter. 

More Effective Sterilization. The internal parts of a fermenter are sterilized easier with no liquid inside. A lower percentage of media contamination can be achieved with a continuous sterilizer than by batch sterilization. 

Reduced Agitator Cost. It is not necessary to buy a two-speed motor where the slow speed (low horsepower) is used for mixing during batch sterilization and high speed only during aeration. 

When designing a fermenter, one primary consideration is the removal of heat. There is a practical limit to the square feet of cooling surface that can be achieved from a tank jacket and the amount of coils that can be placed inside the tank. The three sources of heat to be removed are from the cooling of media after batch sterilization, from the exothermic fermentation process, and the mechanical agitation. 

Structurally, internal coils present no problems with continuous sterilization. However, if batch sterilization is insisted upon, vertical coils are one solution to avoiding the stress between the coil supports and tank wall created when cooling water enters the coils while the broth and tank wall are at 120°C. Notice that the method of media sterilization, batch or continuous, is related to the fermenter design and the capital cost. 

Batch sterilizing in fermenters is frequently a problem because the slow agitation speed is not adequate to keep all the suspended material equally dispersed. Some may settle out in poor circulation areas of the vessel some materials may enter the air ring while filling the vessels. Solutions to these problems can be prehydrolyze the starch or protein with enzymes use a longer sterilizing time or higher temperatures use a continuous sterilizer (abandon batch sterilization). 

Figure 10.1 Modes of heat transfer for batch sterilization.

Records of sterilization in case of parenteral preparations which are heat sterilized including particulars of time, temperature and pressure employed. Such records should be marked to relate to the batch sterilized. 

Sterilization of solid substrates could be done in specialized vessels, in which case transfer into the bioreactor must be done aseptically. This is more problematic to achieve than with liquid media, and therefore it is preferable to sterilize in situ in the bioreactor, meaning that the bioreactor must be designed to enable this. In most processes batch sterilization will be used [80]. For processes operated in continuous mode a continuous steriUzer will be required at the inlet end of the bioreactor, with provision for sterile transfer into the inoculation chamber [81,82]. 

In types of thermal processing which are not necessarily involved with sterilization of foods, other types of design criteria are used. In foods the minimum heat process should reduce the number of spores by a factor of 10 i.e., N/Nq = 10 However, in other batch sterilization processes, such as in the sterilization of fermentation media, other criteria are often used. Often the equation for k, the reaction velocity constant for the specific organism to be used, is available. 

ILLUSTRATIVE EXAMPLE 19.11 Calculate the time for a batch sterilization unit contents to cool from 121°C to 35°C. Data is provided below. 

Design of a batch sterilization unit Design of a continuous sterilization unit Design of an air sterilizer Scale-up of a fermentation unit... 

The consequences of long heat-up and cool-down times in batch sterilization can be severe if the medium components are heat-sensitive. This arises because the destruction due to heat is dependent on the value of the thermal death constant. It can be shown that the spore B. stearothermophilus is only significantly inactivated above 110°C due to its high activation energy of 67.7 kcal/mol. On the other hand, many organic nutrients which also follow Arrhenius relationship for thermal degradation, have a much... 

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