Vises 8.1. SIP process Biopharmaceutical sterilisation or steam in-place (SIP) systems are used to sterlise process equipment after a batch of product is completed. Such systems are necessery because equipment such as bioreactors, fermentors, and the accompanying tubing ‘must be cleaned and/or sterilised before a new production cycle begins. These systems are constructed from high grade, stainless steel materials, as well as flexible ‘materials (eg. teflon-lined piping) approved by the FDA or the USP. ‘Steam pressures for these systems are typically 1 to 2 bar g (15 to 30 psi g) with corresponding temperatures ranging from 121°C to 195°C. The relationship between pressure and temperature ie predictable; however, sterilisation times will depend fon the temperature and nature of the item being sterilised. In general, the lower the temperature, the longer it takes to sterilse. The sterilisation time / temperature relationship ina typical SIP process will occur at about 121°C for 30 - 40 minutes. For systems with hard-to-reach components, time may be longer. ‘Steam quality is very important. Typically, a dedicated steam generator provides the necessary volume; tomperature and pressure of steam needed to steriise each system, To ensure that each component and all piping are completely sterilised, ‘temperature sensors are placed in critical and hard to reach areas to gauge whether ti components and piping reach the sterilisation temperature for the required time. During this entire process, modulating valves are used to maintain the required clean steam pressure, temperature and flowrate. During the SIP process, condensate generated from the steam must be quickly removed from the system. This is done through proper placement of clean steam trans hich also maintain the high temperatures needed for the sterilisation cycle. key considerations for designing an SIP system: = Process vessels and piping to be sterilised must be fully capable of withstanding th temperature and pressures associated with the steam. = Provision must be made for adequate condensate removal. The process system should be suitably trapped, and designed to promote drainage of condensate, ‘An adequate cooling leg should be provided to allow condensate to not back-up into the vessel, resulting in potential cold spots. In SIP applications, itis ikely that process fluid and debris will enter steam traps along with condensate, especially during start-up. In order to reduce the risk of trer blockage, the trap should have a smooth surface finish typically 0.4 micron Ra to 0.8 micron Ra and have a large valve orifice, which allows fluids to pass freely prior to normal steam operation.Sufficient air venting should be provided on the process system to prevent the ‘formulation of air pockets, which can lead to cold spots. Inverted thermostatic ‘steam traps or a specifically designed, clean air vent, are the most sultable products {or this application. Process systems, which incorporate SIP, should be designed to ensure that steam will pass through the entire system, for example narrow restrictions should be avoided. Furthermore, all potential cold spots should be identified and if necessary, the temperature of these areas should be monitored throughout the SIP process. Stee! structures connected to the process vessel, such as supporting structures, will act as heat sinks and will often be cold spots. Compensating steam may be required to heat these areas to overcome the effects. Most vesse!s will have dead legs, for example, for piping to a pressure gauge or toa valve. Steam will not readily flow into these dead spaces and there may be insufficient heat transfer to eterlise them. The length of dead legs should therefore be minimised. In the pharmaceutical industry, dead legs are typically limited to three pipe diameters in length.Sterile barriers, or block and bleed systems, are used extensively in the biopharmaceutical industry to prevent contaminating organisms from entering the rocess and, for some applications, to prevent possible contamination of the ‘outside ‘ovironment’. & simple example is shown in Figure 17. ‘Due to piping arrangements, process fluids will often be flushed through the trap. This can often result in plugging if standard industrial designs of traps are used. Therefore ‘raps with large self-draining design should be selected. Quick release sanitary clamps ‘are also preferable to facilitate periodic cleaning