Steam-in-place systems

Process related utilities such as purified water, water-for-injection, pharmaceutical compressed air (and/or other gases), clean or water-for-injection steam, and dean-in-place/steam-in-place systems shall be validated. 

The following measures should be addressed for steam-in-place systems ... 

The removal of air from a steam-in-place system may be accomplished by one of two methods ... 

Standard components for a bioreactor comprise the vessel, the agitator and impeller, heat exchangers, seals, and valves. Other components include utilities such as clean-in-place (CIP), and steam-in-place (SIP) systems, auxiliary tanks, pH and foam control, inlet tubes,... 

Aseptic BPS machines are subject to steam-in-place sterilization following standard CIP cycles. The SIP cycles are routinely measured by thermocouples located in fixed positions along the product pathway. Validation of SIP cycles should be carried out to demonstrate that consistent sterilization temperatures are achieved throughout the equipment to prove that the system can be effectively sterilized. Validation should also identify suitable positions for routine use, or justify the fixed probe positions already in place. The SIP validation is generally carried out with the help of additional thermocouples and should include the use of biological indicators (appropriate for moist heat sterilization). Test locations should include areas which may be prone to air or condensate entrapment. An accurate engineering line drawing of the system to aid identification of suitable test locations and document test locations selected should be available. 

Pipework systems, valves and vent filters should be properly designed to facilitate cleaning and sterilization. The use of clean in place and sterilize in place systems should be encouraged. Valves on fermentation vessels should be completely steam sterilizable. Air vent filters should be hydrophobic and validated for their scheduled lifespan. 

Figure 34 Freeze-drying plant condenser and shelves cooled with LN2. Clean-in-place system in chamber and condenser. 1, LN2 inlet to condenser and heat exchanger 2, N2 outlet from the condenser and heat exchanger 3, heat exchanger for the brine in shelves 4, brine to and from shelves 5, pressure plate for stoppering of vials 6, piston rod with bellows 7, hydraulic piston for 5 and 6 8, hydraulically operated valve 9, hydraulic system 10 and 13, water and steam inlet 11, pumping system 12, water outlet. (AMSCO Finn-Aqua GmbH, D-50354 Hiirth, Germany.)...

The science that underpins steam sterilization is well known and has been long established. It is the preferred method of sterilization in the pharmaceutical industry it is used for sterilization of aqueous products in a wide variety of presentations, for sterilization of equipment and porous materials required in aseptic manufacture, in microbiology laboratories for sterilizing media and other materials, and for sterilization of massive systems of vessels and pipework [steam-in-place (SIP) systems]. Numerous rules and guidelines have been published on the topic, yet steam sterilization and particularly bio-validation of steam sterilization is still a subject for controversy and debate. 

Qualification activities are normally associated with buildings, facilities, utility systems (e.g., water, air handling, Clean-in-place/Steam-in-place (CIP/SIP), and compressed gases) major equipment (including laboratory instrumentation), whereas validation likely is in reference to those confirmatory tasks related to processes and analytical methods. In simplistic terms, validation (and qualification) can be defined as documented evidence that a process, activity, or piece of equipment can consistently meet its predetermined acceptance criteria and quality attributes. This section will be dedicated towards outlining the requirements for validation of manufacturing processes, as... 

Steam-in-Place Steam-in-place allows the entire healthcare product processing system to be steam sterilised as a single entity, eliminating or reducing the need for aseptic connections. Examples include tanks, filling lines, transfer lines, filtration systems and water for injection systems. 

The concentrations of water and nitrogen were established by use of a stream-nitrogen mixing manifold. If applied to large systems, some economy can result from producing the steam in place. Specifically, a high-temperature gas blower could be employed to recycle the inert gas in the system to be recleaned. 

A. Dispiro[5.1.5.1]telradecane-7,14-dione. Cyclohexanecarbon-yl chloride (Note 1) (30.0 g., 0.205 mole) and 250 ml. of dry benzene are placed in a three-necked, round-bottomed flask equipped with a stirrer, condenser, and dropping funnel. A nitrogen atmosphere is maintained in the system. Dry triethylamine (35.0 g., 0.35 mole) is slowly added, and the mixture is heated under reflux overnight. The amine hydrochloride is then filtered, and the filtrate is washed with dilute hydrochloric acid and with water. Solvent is removed on a steam bath, and the residue is recrystallized from ligroin-ethanol yield 11-13 g. (49-58%), m.p. 161-162°. 

The scheme of commercial methane synthesis includes a multistage reaction system and recycle of product gas. Adiabatic reactors connected with waste heat boilers are used to remove the heat in the form of high pressure steam. In designing the pilot plants, major emphasis was placed on the design of the catalytic reactor system. Thermodynamic parameters (composition of feed gas, temperature, temperature rise, pressure, etc.) as well as hydrodynamic parameters (bed depth, linear velocity, catalyst pellet size, etc.) are identical to those in a commercial methana-tion plant. This permits direct upscaling of test results to commercial size reactors because radial gradients are not present in an adiabatic shift reactor. 

Ferrous bicarbonate may be transported to a point where little or no amine is available, which then provides the source for various secondary corrosion reactions. Corrosion mechanisms and deposition formation often take place at points in the system well downstream of the original points of steam condensation and initiation of corrosion. 

In liquefaction systems wood and wood wastes are the most common fuelstocks. They are reacted with steam or hydrogen and carbon monoxide to produce liquids and chemicals. The chemical reactions that take place are similar to gasification but lower temperatures and higher pressure are used. Liquefaction processes can be direct or indirect. The product from liquefaction is pyrolytic oil which has a high oxygen content. It can be converted to diesel fuel, gasoline or methanol. 

Chamber clean-in-place (CIP) system Steam sterilization... 

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