Design of the steam circuit

During sterilization, a large number of valves have to be opened and closed in complex specific sequences. To ensure that this is performed reproducibly, automation should (as for CIP), be an essential part of a modern SIP system.

For the sterilization of vessels, the steam inlet should be located at the top of the bioreactor, whereas condensates should be eliminated from the bottom through a drain valve and diverted to a stream trap, or flow orifice, to regulate the flow (Oakley 1994). To ensure proper sterilization of all process inlets and outlets, such as sparger, inoculation dip tubes, side inlets, spray balls and secondary outlets, it is recommended that steam be supplied through all of them during the SIP cycle; this requires some additional valve configurations. Mechanical seals of the agitator must also be sterilized by direct injection of steam into the seal chamber. With respect to sterility maintenance, magnetically coupled stirrers are actually preferable.

SIP of hydrophobic filters must be performed so that they do not become wet, otherwise steam cannot cross the membrane, resulting in improper sterilization. Such filters are thus often the most difficult part of the system to sterilize (Agalloco 1990). The filter housing and the associated pipework should be installed so as to guarantee a supply of dry steam and a proper draining of the condensate via separate steam traps, on both sides of the filter membrane (Oakley, 1994). Care should be taken to minimize hydraulic stress on the membrane; this is best achieved by using two steam inlets, upstream and downstream of the filter, with a small and carefully controlled pressure difference (Rowe et al. 1996). Gas filters are typically sterilized during the same cycle as the corresponding tank. However for long-lasting cultures, during which the filter may have to be replaced, separate sterilization steps of the tank and of the filter housing(s) should be made possible; this requires a more complex valve configuration.

SIP of hydrophilic filters is less problematic since wetting does not block the passage of steam through the membrane. Each housing point should nonetheless have a drain valve to remove condensate efficiently. At the beginning of the sterilization cycle, the vent valve of the housing should be opened for a few minutes to purge air thoroughly. Regarding the sequence of sterilization, it is generally best to sterilize the vessel first and then the transfer line and filter together; in this way, at the end of the filter sterilization, the system steam pressure can be released into an already sterile vessel. Figure 14.7 shows an example of valve and piping configuration for the sterilization in place of a complete vessel.

In piping, the condensate produced must be removed promptly at all low points (Agalloco 1990). In practice, this is done either via steam traps, which are able to remove condensate from steam lines automatically, or via diaphragm valves that are controlled by the plant automation system to open for short periods at regular intervals. This second system tends to be preferred, being more reliable and better able to stabilize temperature at the sterile boundary (Wilde 1998). Steam should circulate in only one direction, in order to avoid the accumulation of a cool condensate at a point of conflicting streams. As previously discussed (Section 14.3.2.6), transfer lines should be designed to be sterilizable independently of adjacent vessels. Figure 14.10 shows one example of a piping configuration that provides this flexibility.

The only two parameters to be monitored during a SIP cycle are temperature and pressure. In vessels and pipes, temperature should be measured at various critical points, including near steam traps or near large heat sinks, in order to measure the lowest values during a SIP cycle. Typical probes for these measurements are discussed in Chapter 13. Temperature sensors (Pt-100) can be installed either inside the equipment or mounted on the external surface of pipes, in 'collars' (Wilde 1998).

For mobile tanks, an alternative to building a complete steam distribution network is to use stand-alone SIP stations, by analogy with CIP stations (see Section 14.3.3.2). In this case, the tank

Figure 14.10 Example of a valve and piping configuration for the SIP of a transfer line between two vessels. This configuration enables the sterilization of the transfer line independently of the two vessels; vessel 2 is normally sterilized first, with valves E and F open and valve D closed. For the sterilization of the transfer line, the steam inlet valve is opened as well as valves C, B and D, while valves A and F are kept closed. At the end of the sterilization cycle, valves E and C are closed and valve F is opened to release the steam pressure and to avoid the risk of vacuum formation; vessel 2 and the transfer line are now ready to use (reproduced with permission from Oakley 1994).

Figure 14.10 Example of a valve and piping configuration for the SIP of a transfer line between two vessels. This configuration enables the sterilization of the transfer line independently of the two vessels; vessel 2 is normally sterilized first, with valves E and F open and valve D closed. For the sterilization of the transfer line, the steam inlet valve is opened as well as valves C, B and D, while valves A and F are kept closed. At the end of the sterilization cycle, valves E and C are closed and valve F is opened to release the steam pressure and to avoid the risk of vacuum formation; vessel 2 and the transfer line are now ready to use (reproduced with permission from Oakley 1994).

is moved to the station and connected to it only for the duration of the sterilization cycle. As with CIP, our recommendation is to use SIP stations even for bioreactors as small as 25-30 litres.

Was this article helpful?

0 0
Healthy Chemistry For Optimal Health

Healthy Chemistry For Optimal Health

Thousands Have Used Chemicals To Improve Their Medical Condition. This Book Is one Of The Most Valuable Resources In The World When It Comes To Chemicals. Not All Chemicals Are Harmful For Your Body – Find Out Those That Helps To Maintain Your Health.

Get My Free Ebook


Responses

  • Karis
    Is a steam trap normally part of sterile boundary?
    3 years ago

Post a comment