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SIP Sterilize in Place
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Sterilization in place with steam is considered by many as the least risky method of sterilzing the interior of a freeze dryer. Of course if you are processing non sterile injectibles, chemical compounds, nutraceuticals, and products that incoporate preservatives or those that can be terminally sterilized, SIP with steam is not necessary. Most pharmaceutical GMP systems available today incorporate some form of sterilization using steam.  Food freeze dryers never incorporate SIP in any form.  Older systems have been supposedly designed to be steam sterilized, and it is important when considering an older freeze dryer to ensure the presence of adequate steam inlet size, penetrations without threads, penetrations that have a L/D of less than 6:1 [This being adequate for sterilization and the norm currently is 3:1].  Pipes that enter the chamber and condenser must be sloped inward, the condenser to chamber tubulation sloped towards either chamber or condenser.  The chamber and condenser should have a working pressure rating of at least 18 psig.  The system must also have a liquid ring vacuum pump installed to dry out the system after sterilization, perhaps have water cooled jackets on the chamber exterior and the chamber door[s], and most importantly an completely automated cycle.  There are many other requirements to match the methods normally required by cGMP.

As concerns pressure rating, many older systems are rated only to a MAWP of 15 psig.  This pressure is not adequate for sterilizing systems unless a very long cycle is utilized, and perhaps control using f0.  Even then, there is a danger that the relief valves on the chamber and condenser will release because it is almost impossible to obtain a relief valve that releases at exactly 15 psig.  It is quite normal to have them relieve at less than that, and consequently may not be vacuum tight afterwards.  Not a workable process, because of product risk.

Filtered inert gas for vacuum control and release is required, and this may be available on systems either in single or series redundant configurations, with our without integrity testing in place, and with and without sterilzation in place, and incorporated into the automatic control cycle of the freeze dryer.  Many systems have the filter in the sterile room, capable of being added to the system at the right time via an aseptic connection SOP.  Filter sterilzation in this arrangement is via autoclave.  SIP of the system takes place using a spool piece in place of the filter housing.  Normal modern systems have the filters placed in the mechanical space, with appropriate pipe arrangements, with drains and steam trap[s] temperature sensors at the "cold" spots.

There are alternative methods to sterilize systems including H2O2 which have now been validated, and claimed to be acceptable.  The cost of these systems is really not justified and the risk is that SIP through any standing water [plentiful in freeze drying systems] is not possible.   The cost of these systems is equivalent or greater than sterilization with steam, and the cycle can be longer.  Using H2O2 therefore is cumbersome and risky. Remember that drying out a freeze dryer after cleaning in place with water for injection is not easy.  The water that forms in drains, chamber bottom, drains, on condenser surfaces must be completely removed before H2O2 is employed. I have great hope that the industry will be drawn to chlorine dioxide as an alternative sterilizing gas.  This gas is very effective, has very high penetration, does not require the presence of humidity to function, however it can sterilize through standing water.  All in all, this gas is much more acceptable too from the standpoint of workability and reduced risk, that it can be the gas of choice.  Will the industry follow this and be in agreement?  Chlorine dioxide is the gas of choice to sterilize contaminated buildings, clean rooms, and therefore can be highly regarded for SIP of freeze dryers.

Applewood Scientific is available to assist you in making important sterilization decisions, help you evaluate and remediate used freeze dryers you are planning to purchase, and assist you in SIP process development dealing with this important process.  We can help you rescue your existing freeze  drying infrastructure saving you time, money and manpower.