Sterilization batch heat

Aqueous suspensions are prepared in much the same manner, except that before bringing the batch to final volume with additional sterile water, the solid that is to be suspended is previously rendered sterile by heat, by exposure to ethylene oxide or ionizing radiation (gamma or electrons), or by dissolution in an appropriate solvent, sterile filtration, and aseptic crystallization. The sterile solid is then added to the batch, either directly or by first dispersing the solid in a small portion of the batch. After adequate dispersion, the batch is brought to final volume with sterile water. Because the eye is... 

S. cerevisiae is produced by fed-batch processes in which molasses supplemented with sources of nitrogen and phosphoms, such as ammonia, ammonium sulfate, ammonium phosphate, and phosphoric acid, are fed incrementally to meet nutritional requirements of the yeast during growth. Large (150 to 300 m ) total volume aerated fermentors provided with internal coils for cooling water are employed in these processes (5). Substrates and nutrients ate sterilized in a heat exchanger and then fed to a cleaned—sanitized fermentor to minimize contamination problems. 

The most widely used sterilization method ia the food industry is moist heat. The heat is usually suppHed by high pressure steam, but because most foods already contain moisture the role of steam is to heat the food to the required temperature. The cooking and sterilization processes can frequendy be combined into one. The food may be sealed into impervious containers of glass, metal, or plastic film and undergo terminal sterilization, or it may be presterilized in batches or in a continuous operation and then filled into a presterilized container. The latter process is called sterile filling. 

Often batch process equipment needs to be located inside buildings. This is usually the case when the process needs to be shielded from extreme heat/cold conditions, the elements, and/or needs to be kept sterile. This leads to the need to provide adequate building ventilation to avoid buildup of hazardous material due to leaks and other process emissions. When the operation of a process involves opening, cleaning, charging etc., point source ventilation may also need to be provided. 

The production of benzylpenicillin is very sensitive to temperature. A lot of metabolic heat is generated and the fermentation temperature has to be reduced by controlled cooling. This heat transfer is achieved by circulating chilled water through banks of pipes inside the vessel (which also serve as baffles) or through external limpet coils on the jacket of the vessel. These coils consist of continuous lengths of pipe welded in a shallow spiral round the vessel. This cooling water system is also used to cool batched medium sterilized in the vessel prior to its inoculation. 

In general, aqueous ophthalmic solutions are manufactured by methods that call for the dissolution of the active ingredient and all or a portion of the excipients into all or a portion of the water and the sterilization of this solution by heat or by sterilizing filtration through sterile depth or membrane filter media into a sterile receptacle. If incomplete at this point, this sterile solution is then mixed with the additional required sterile components, such as previously sterilized solutions of viscosity-imparting agents, preservatives, and so on, and the batch is brought to final volume with additional sterile water. 

Typically, the manufacture of a batch of biopharmaceutical product entails filling the production vessel with the appropriate quantity of purified water. Heat-stable nutrients required for producer cell growth are then added and the resultant medium is sterilized in situ. This can be achieved by heat, and many fermenters have inbuilt heating elements or, alternatively, outer jackets through which steam can be passed in order to heat the vessel contents. Heat-labile ingredients can be sterilized by filtration and added to the fermenter after the heat step. Media composition can vary... 

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.

Tunnel sterilizers must demonstrate mechanical repeatability in the same manner as batch ovens. Air velocity, air particulates, temperature consistency, and reliability of all the tunnel controls (heat zone temperatures, belt speed, and blower functions) must be proved during the physical validation studies. 

A suggested step-by-step sequence in the microbial validation of a dry-heat process for sterilizing and depyrogenating large-volume glass containers by a convection batch oven is presented. Procedures for the validation of a tunnel sterilization process have been reported by Wegel [25] and Akers et al. [26],... 

---