Steam sterilizer operation

The relationship between temperature and pressure holds true only in the presence of pure steam adulteration with air contributes to a partial pressure but not to the temperature of the steam. Thus, in the presence of air the temperature achieved will reflect the contribution made by the steam and will be lower than that normally attributed to the total pressure recorded. Addition of further steam will raise the temperature but residual air surrounding articles may delay heat penetration or, if a large amount of air is present, it may collect at the bottom of the sterilizer, completely altering the temperature profile of the sterilizer chamber. It is for these reasons that efficient air removal is a major aim in the design and operation of a boiler-fed steam sterilizer. 

Rigorous cleaning operation allowable (steam sterilization, high backflush capability)... 

A temperature control system. Although operating under pressure, temperature is the controlling factor in steam sterilization. The modern temperature controller is made up of several key elements to sense, record, and react. These are discussed in a later section. 

The documentation (installation qualification, operational qualification, etc.) established prior to initiating validation studies provides the foundation for the subsequent validation. A comprehensive steam sterilization protocol should include the following items ... 

The lyophilizers are cleaned using a validated clean-in-place (CIP) cycle using hot WFI. After the cleaning process, a validated sterilization cycle is mn. The qualification of the steam sterilization cycle was performed during the operation qualification (OQ) of the lyophilizer. 

The first station is the filling station. This station has four nozzles. Each pump can be adjusted independently. The filling operation uses four rotary piston stainless steel pumps. The dosing system, consisting of buffer tank, filling nozzles, and dosing pumps, is easily disassembled for cleaning and is steam sterilized before use. 

Steam sterilization validation. All autoclave operations conform to the Master Validation Plan employed at ABC Pharmaceutical Industries. The autoclave has undergone installation qualification, operational qualification, and performance qualification. The autoclave is revalidated on an annual basis. The equipment steam sterilization cycle revalidation data for the autoclave are provided in validated archives. 

The qualification studies conducted indicated that the GMP steam sterilizer (autoclave) performance is satisfactory and in accordance with the operational parameters defined previously. 

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. 

When carrying out cell disruption operations it is often necessary to provide cooling of the cell concentrate due to the high pressures developed in the equipment. An additional consequence of high-pressure operation is that cell disruption equipment can generate aerosols which may be undesirable, particularly for biologically hazardous organisms. In these cases, the ability to steam sterilize the equipment is required, for decontamination, and some type of secondary containment may also be required, such as an isolator or a contained area within a facility to which access is controlled. 

Electronic records include data-storing memory cards used in embedded control systems such as steam sterilizers. These cards are used to transfer data (critical parameters, cycle times, etc.) from the control system to a main database application which is usually networked. A memory card is about the size of a credit card. Manual installation, removal, and transfer of the memory cards must be conducted in accordance with defined procedures. Reuse of cards must be carefully considered data must not be deleted until confirmation is received that it has been successfully downloaded to the database. The local operating enviromnent and the possibility of EMl/ESD damage to data integrity of the memory card must also be evaluated. 

For pushing the stoppers into the closed position in the vials, the shelves are pressed together by a plate. For this operation 1 kg per stopper can be expected. If there are more than 1000 vials per shelf substantial forces have to be applied. This can be done by motor-driven spindles or steel ropes or by a piston rod, as shown in Figure 26. The piston rod system can be steam-sterilized and excludes abrasion. The part of the piston rod that is moved into the chamber during compression is sterilized in a separate chamber. The only disadvantage is the additional space required below or above the drying chamber for the length of the rod. 

Steam sterilization can be avoided by using the Vaporized Hydrogen Peroxide (VHP) process. VHP operates at ambient pressure and temperature. Nakahari [35] describes the development of the necessary steps in this process, the changes... 

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. 

Blow-fill technology is an aseptic process whereby the container is formed from thermoplastic granules, filled with sterile solution and sealed, all within one automatic operation. The bulk solution should have a low bioburden and is delivered to the machine through a filling system that has been previously sanitized and steam sterilized in situ. Concern has been expressed that the machine itself may generate particles. The plastic granules are composed usually of polyethylene, polypropylene or one of their copolymers and are heat extruded at 200°C into a tube. The two halves of a mould close around this tube and seal the base. The required quantity of sterile fluid is filled into the container, which is then sealed. Products packed in this way include intravenous solutions, and small volume parenteral, ophthalmic and nebulizer solutions. The... 

Steam sterilizers, or autoclaves as they are also known, are stainless steel vessels designed to withstand the steam pressures employed in sterilization. They can be (i) portable sterilizers, where they generally have internal electric heaters to produce steam and are used for small pilot or laboratory-scale sterilization and for the treatment of instruments and utensils or (ii) large-scale sterilizers for routine hospital or industrial use, operating on dry saturated steam from a separate boiler (Fig. 20.6). Because of their widespread use within pharmacy this latter type will be considered in greatest detail. 

The hot water from Tank 5 also supplies Tank 4 and Pump 3 (or 4), This is necessary to start and finish a batch through the sterilizer. For example, to start, the sterilizer is first steam sterilized (no liquid). At the end of this cycle, hot water from Tank 5 is started through the sterilizer to set or balance the instrumentation. When this is achieved, media is fed to Pump 3 (or 4) by remote operating valves. Similarly, after all the media has been pumped, it is necessary to pump water through the sterilizer until the fermenter volume is correct. If another fermenter is to be filled immediately, the sterile water is diverted to the awaiting empty (and sterile) fermenter, and then the new media for the second fermenter is pumped into the sterilizer. The control room for the operation of a continuous sterilizer should be close to Tank 4, Pumps 3 and 4, the main steam valves and the valves of the sterilizer itself This location is essential to sterilize the empty sterilizer and control the pumping of water and/or media. 

Table 12 shows the typical LRV values obtained using a polymeric and ceramic microfilter. Sterile filtration requires 100% bacteria retention by the membrane, whereas in many industrial bacteria removal applications the presence of a small quantity of bacteria in the filtrate may be acceptable. For example, drinking water obtained by microfiltration may contain nominal counts of bacteria in the filtrate which is then treated with a disinfectant such as chlorine or ozone. The use of ceramic filters may allow the user to combine the sterile filtration with steam sterilization in a single operation. This process can be repeated many times without changing filters due to their long service life (5 years or longer). 

Air filtration with ceramic filter, spring loaded, steam sterilizable Peristaltic pumps for low delivery capacity and sterile operation O-ring packings for piping and reactor parts... 

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