Communications

Communications for SIP are quite simple, unless capacity constraints
force you to limit simultaneous steam draws by different systems. In the
simplest of designs, the steam system controls steam header pressure, and
the process system controls all other aspects of SIP.

Sequences

The SIP sequence usually involves the following steps:

• Path confirmation (may include air pressure hold)
• Purge of non-condensables
• Steaming
• Cool-down
• Hold in steamed state

To ensure personnel safety, a "path confirmation" or even an "air pressure
hold" may be included prior to the start of the steaming operation. This
helps to ensure that any manual connections have been properly secured.
Since many movable connections are located at eye-level, the risk of hazard
to an operator can be quite high.

Also during path confirmation, the jackets of jacket-cooled vessels should
be drained. This significantly reduces condensate load, and will speed up
the SIP cycle.

The purge of non-condensables ensures that live steam can reach each
part of the equipment being steamed. This can be accomplished by starting
the feed of steam to the system while holding a vent valve open.

After purging, the vent valve is closed to allow the system temperature to
climb to its target. Specific criteria for the completion of an SIP cycle must
be agreed upon with Quality, Regulatory, and Process personnel. Typical
criteria for SIP completion is that a temperature of at least 121°C has been
maintained for at least 20 minutes.

For sensitive process materials or live cells, there may be a specific cooldown
required before the start of a batch or processing step. To cool down
after an SIP cycle, it is recommended to blow out the system with
pharmaceutical-grade air. This prevents the creation of a vacuum as the
vessels cool and steam condenses. Do NOT try to cool the system quickly
by re-introducing cooling fluids to jacketed tanks, as this will heat-stress
the tank, and will create a sudden vacuum.

At the completion of SIP, the vessel may be held in its "SIP complete state"
for some period of time before it is used for processing. Typically, all
valves are closed to minimize the risk of contamination from other parts
of the process. It may be helpful to start a timer to track the amount of
time elapsed since the completion of SIP.

Control Loops

Simple, independent temperature and pressure control loops are most
often used for SIP. One variation is to control the minimum temperature
of the system being steamed, using a low-selector switch, as shown in
Figure 3-2.

Calculations
If your control system has ad-hoc calculation capability, it is helpful to
calculate F_o, which can be correlated to bio-burden reduction. F_o is calculated
as shown in the equation below.

Tuneables

During development of the cleaning and steaming operations, it is useful
to allow adjustment of some key SIP parameters, such as steam pressure,
temperature target, and duration of steaming. At the completion of cycle
development, these parameters may be locked down. Again, batch management
software may help to organize tuneables.