Patent Application
20080141715
None
This invention relates to the production of sterile cryogen such as sterile nitrogen, and more particularly, to a method and system for sterilizing a cryogen that demonstrates improved thermodynamic efficiency and improved recovery of the cryogen.
During pharmaceutical manufacturing operations, temperature control of various reactions and process steps is often essential. Such temperature control is often achieved through cryogenic cooling of selected process reactions or freezing of pharmaceutical or bio-pharmaceutical materials. In some applications, the cryogenic cooling or freezing may be carried out by an indirect heat exchange process using a liquid or vapor cryogen, such as nitrogen. However, a direct heat exchange process involving direct contact of the liquid or vapor cryogen with the material to be cooled is preferred due to the more efficient transfer of refrigeration from the cryogen to the material.
Any material that comes into direct contact with various pharmaceutical or bio-pharmaceutical products is often required to be sterile. Liquid or vapor nitrogen, for example, may be used to cool various process reactions or freeze various pharmaceutical or bio-pharmaceutical materials using a direct heat exchange process provided the liquid nitrogen is sterile. Although bacteria and other microorganisms which may have been introduced during storage and distribution of the liquid nitrogen are generally inactive at the cryogenic temperatures of liquid nitrogen, such bacteria and other microorganisms can then return to activity when exposed to normal conditions. Cryogenic temperatures alone, therefore, are not enough to bring about sterility.
Previous cryogen sterilization processes, such as those disclosed in U.S. Pat. No. 5,737,926 has a relatively low recovery (e.g. the ratio of sterile liquid nitrogen produced to nitrogen used) and less than optimum thermal efficiency. What is needed is an improved cryogen sterilization system and process that demonstrates higher cryogen recovery and greater thermal efficiency.
In one aspect, the present invention may be characterized as a method of sterilizing a cryogen comprising the steps of: (a) vaporizing a liquid cryogen; (b) compressing the cold cryogen vapor; (c) sterilizing the compressed cryogen vapor; (d) pre-cooling the compressed, sterile cryogen vapor to produce a partially condensed, cool, sterile cryogen stream; and (e) further condensing the partially condensed, cool, sterile cryogen stream to produce a sterilized cryogen.
The invention may also be characterized as a cryogen sterilization system comprising: a source of cryogen vapor; a compressor adapted for compressing the cryogen vapor to a prescribed pressure; a biological filter adapted for sterilizing the compressed cryogen vapor; a pre-cooler adapted to receive the compressed, sterile cryogen vapor and produce a partially condensed, cool, sterile cryogen stream; and a secondary condenser adapted for further condensing the partially condensed, cool, sterile cryogen stream to produce a sterilized cryogen.
In another aspect, the invention may broadly be characterized as a method of sterilizing a cryogen comprising the steps of: (a) compressing a cryogen vapor; (b) sterilizing the compressed cryogen vapor; (c) pre-cooling the compressed, sterile cryogen vapor to produce a partially condensed, cool sterile cryogen stream; and (d) further condensing the partially condensed cool sterile cryogen stream to produce a sterilized cryogen.
The above and other aspects, features and advantages of the present invention will be more apparent from the following more detailed description taken in conjunction with the drawing.
The most commonly used sterile cryogen from a commercial standpoint is sterile nitrogen. Accordingly, the invention will be described in detail with reference to
Preferably, the first and second heat exchangers are plate-fin configuration heat exchangers and may be separate units or may be integrated as a single heat exchange system, which avoids unneeded interconnecting conduits and generally reduces the volume of the cold box 16 and associated insulation requirement.
Within evaporator 14, the liquid nitrogen 10 is vaporized to produce cold nitrogen vapor 20 having a temperature generally within the range of from about −30 degrees Centigrade to about −80 degrees Centigrade at or near the originating pressure. This cold nitrogen vapor 20 is passed to compressor 25 wherein it is compressed to a pressure of about 70 to 360 psia and the heat of compression raises the temperature within the range of from about −20 degrees Centigrade to about 30 degrees Centigrade to produce warm, compressed nitrogen vapor 30 suitable for use with biological filters. Preferably the warm, compressed nitrogen vapor 30 is at ambient temperature or at least a temperature that exceeds the embrittlement temperature and glass transition temperature of the biological filter materials.
Warm, compressed nitrogen vapor 30 is passed to a biological filter module 32 wherein it is sterilized to produce sterile, warm, compressed nitrogen vapor 40. In the embodiment of the invention illustrated in
Sterile, warm, compressed nitrogen vapor 40 is passed by conduit from the biological filters 34 of filter module 32 to evaporator 14 wherein the heat within the sterile, warm, compressed nitrogen vapor 40 is used to vaporize the liquid nitrogen 10 through an indirect heat exchange. In the course of this heat exchange the sterile, warm, compressed nitrogen vapor 40 is cooled to produce a partially condensed, cool, sterile nitrogen stream 60 having a temperature generally within the range of from about −157 degrees Centigrade to about −193 degrees Centigrade. Because of the higher pressure of the sterile nitrogen stream, the vapor is partially condensed which results in improved thermal efficiency of the system as well as improved nitrogen recovery rates.
The partially condensed, cool, sterile nitrogen stream 60 is then passed from the evaporator 14 to the secondary condenser/liquifier 18. Within the secondary condenser/liquifier 18, the cool, partially condensed sterile nitrogen stream 60 is further condensed by indirect heat exchange to produce cryogenic sterile liquid nitrogen 70. The cryogenic sterile liquid nitrogen 70 may be used directly, in whole or in part, for cooling and/or freezing purposes, or may be passed, in whole or in part, to storage tank 72 prior to use.
Using the present embodiment, the re-liquification or condensation of the sterile nitrogen is accomplished in two steps. Through use of the vapor compressor, the sterile, warm, compressed nitrogen vapor partially condenses during the pre-cooling step provided the pressure of the sterilized vapor is greater than the saturation pressure of the liquid nitrogen that is being vaporized. Using the two-step condensation process, the thermal efficiency of the sterilization system is improved by extracting more refrigeration from the vaporizing nitrogen stream which in turn improves the overall recovery.
The following tables summarize an example of the present invention wherein sterile liquid nitrogen is produced at the rate of 850 lb/hr (11,902 cf/hr at NTP). The example is of an embodiment of the invention similar to that illustrated in
As seen in Table 1, in order to produce about 5500 liters/min of sterile liquid nitrogen the prior art system used approximately 12500 liters/min of supply liquid nitrogen resulting in a nitrogen recovery of about 44%. The balance of about 7000 liters/min of nitrogen is vented. The power consumption used by the heater in the prior art nitrogen sterilization system is about 21 kW. Conversely, the presently disclosed embodiment of the liquid nitrogen sterilization system uses about 7559 liters/min of supply liquid nitrogen to produce about 5500 liters/min of sterile liquid nitrogen. This results in a nitrogen recovery of about 73%. Also, the power input to the compressor is only about 9 kW resulting in significant power savings and the associated cost savings compared to the prior art nitrogen sterilization systems.
Although the invention has been described in detail with reference to a certain preferred embodiment, those skilled in the art will recognize that there are other embodiments of the invention within the spirit and the scope of the claims. For example, as discussed above, other sterile cryogens may be produced with the practice of this invention. It is recognized that the sterile cryogen produced, e.g. sterile nitrogen, may be pure, e.g. 100 percent nitrogen, or may be a mixture containing less than 100 percent of the cryogen species.
From the foregoing, it should be appreciated that the present invention thus provides a method and system for the sterilization of a cryogen. While the invention herein disclosed has been described by means of specific embodiments and processes associated therewith, numerous modifications and variations can be made thereto by those skilled in the art without departing from the scope of the invention as set forth in the claims or sacrificing all its material advantages.
