Method and system for sterilization of a cryogen

Abstract

A system and method for sterilizing a cryogen is provided. In the disclosed embodiment a liquid cryogen is first vaporized and subsequently compressed prior to undergoing sterilization using biological filters. The compressed, sterilized cryogen vapor is then pre-cooled, preferably with the cryogen being vaporized, to produce a partially condensed, cool, sterile cryogen stream and then further condensed using the liquid cryogen to produce a sterilized liquid cryogen.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

None

TECHNICAL FIELD

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.

BACKGROUND

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.

SUMMARY OF THE INVENTION

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.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a schematic representation of one preferred embodiment of the invention for producing cryogenic sterile cryogen.

DETAILED DESCRIPTION

The most commonly used sterile cryogen from a commercial standpoint is sterile nitrogen. Accordingly, the invention will be described in detail with reference to FIG. 1 and in conjunction with the production of sterile nitrogen. However, it should be understood that the described embodiments are equally applicable to sterilization of other cryogens such as argon, helium, hydrogen, carbon dioxide, oxygen, etc. Referring now to FIG. 1, liquid nitrogen 10 is passed from a source of liquid nitrogen such as a storage tank 12, through conduit means into first heat exchanger or evaporator 14 which is located within cold box 16. Liquid nitrogen 10 has a nitrogen concentration of at least 60 mole percent, preferably at least 95 mole percent, and is at a pressure generally within the range of from 15 to 250 pounds per square inch absolute (psia) and at a temperature of −160 degrees Centigrade or less. Preferably, the temperature of the liquid nitrogen is the saturation temperature of the liquid nitrogen at the corresponding pressure. Cold box 16 is an insulated container which preferably also houses a second heat exchanger or condenser/liquifier 18.

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 FIG. 1, the compressed nitrogen fluid is passed to filter module 32 containing a plurality of biological filters 34 and emerges as sterile, warm, compressed nitrogen vapor 40. Steam 50 may also be used for sterilization purposes in conjunction with the biological filters.

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. FIG. 1 also shows a diverted stream of liquid nitrogen 80 that is reduced in pressure by passage through valve 82 and subsequently passed into the secondary condenser/liquifier 18 as the low pressure, nitrogen cooling stream 90 wherein it is vaporized to effect the aforesaid further condensation of the cool, partially condensed, sterile nitrogen vapor 60. Resulting gaseous nitrogen 99 is then withdrawn from secondary condenser/liquifier 18 and vented as appropriate.

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 FIG. 1 and the stream numbers shown in Table 1 correspond to the reference numerals shown in FIG. 1. The example is presented for illustrative purposes and is not intended to be limiting.

TABLE 1
Example of Nitrogen Sterilization System
Operation
		Temperature		Flowrate
Present N2	Pressure	(degrees	Vapor	(CFH-
Sterilization System	(psia)	C.)	Fraction	NTP)
Liquid Nitrogen (10)	90	−176.4	0.0281	11,902
Cold Nitrogen Vapor	87	−52.3	1.0000	11,902
(20)
Compressed Nitrogen	200	26.8	1.0000	11,902
Vapor (30)
Sterile Nitrogen	190	26.7	1.0000	11,902
Vapor (40)
Partially Condensed,	187	−165.4	0.4300	11,902
Cool, Sterile
Nitrogen Stream (60)
Sterile Liquid	184	−165.7	0.0000	11,902
Nitrogen (70)
Low Pressure Cooling	100	−175.0	0.0094	4,457
Stream (90)
Gaseous Nitrogen (99)	97	−175.4	1.0000	4,457

TABLE 2
Nitrogen Sterilization System Comparative
Results
		Prior Art N2
		Sterilization
		(U.S. Pat. No.	Present N2
	Parameter	5,737,926)	Sterilization
	Sterile Liquid	5,500 Liters/min	5,500 Liters/min
	Nitrogen Output
	Supply Nitrogen Input	12,500 Liters/min	7,559 Liters/min
	Power Input	Heater: 21 kW	Compressor: 9 kW
	UA - Refrigeration	336 W/C	957 W/C
	Recovery
	(Evaporator)
	UA - Refrigeration	3130 W/C	688 W/C
	Recovery
	(Condenser/Liquefier)

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.

Claims

1. A method of sterilizing a cryogen comprising the steps of:

vaporizing a liquid cryogen to produce a cold cryogen vapor;

compressing the cold cryogen vapor to produce a compressed cryogen vapor;

sterilizing the compressed cryogen vapor to produce a compressed, sterile cryogen vapor;

pre-cooling the compressed, sterile cryogen vapor to produce a partially condensed, cool, sterile cryogen stream; and

further condensing the partially condensed, cool, sterile cryogen stream to produce a sterilized cryogen.

2. The method of claim 1 wherein the step of compressing the cold cryogen vapor further comprises compressing the cold cryogen vapor to a pressure greater than the saturation pressure of the liquid cryogen that is vaporized.

3. The method of claim 2 wherein the step of compressing the cold cryogen vapor further comprises compressing the cold cryogen vapor to a pressure of between about 70 psi and about 360 psi.

4. The method of claim 1 wherein the cold cryogen vapor is further warmed to a temperature of between about −20 degrees Centigrade to about 30 degrees Centigrade during the compressing step.

5. The method of claim 1 wherein the step of further condensing comprises passing the partially condensed, cool, sterile cryogen stream through an indirect heat exchanger together with a portion of the liquid cryogen.

6. The method of claim 1 wherein the cryogen is selected from the group consisting of nitrogen, hydrogen, helium, oxygen, and argon.

7. The method of claim 1 wherein the step of sterilizing the compressed cryogen vapor further comprises passing the compressed cryogen vapor through a biological filter.

8. A cryogen sterilization system comprising:

a source of cryogen vapor;

a compressor fluidically coupled to the source of cryogen vapor and adapted for compressing the cryogen vapor to a prescribed pressure;

a biological filter fluidically coupled to the compressor and adapted for sterilizing the compressed cryogen vapor;

a pre-cooler fluidically coupled to the biological filter and adapted to receive the compressed, sterile cryogen vapor and produce a partially condensed, cool, sterile cryogen stream; and

a secondary condenser fluidically coupled to the pre-cooler and adapted for further condensing the partially condensed, cool, sterile cryogen stream to produce a sterilized cryogen.

9. The system of claim 8 wherein the source of cryogen vapor further comprises:

a source of liquid cryogen; and

an evaporator fluidically coupled to the source of liquid cryogen and adapted to vaporize the liquid cryogen.

10. The system of claim 9 wherein the pressure of the compressed, cryogen vapor is greater than the saturation pressure of the liquid cryogen that is vaporized.

11. The system of claim 8 wherein the pressure of the compressed, cryogen vapor is between about 70 psi and 360 psi.

12. The system of claim 8 wherein the cryogen vapor is at a temperature of between about −20 degrees Centigrade to about 30 degrees Centigrade prior to entering the biological filter.

13. The system of claim 8 wherein the cryogen is selected from the group consisting of nitrogen, hydrogen, helium, oxygen, and argon.

14. The system of claim 8 further comprising a storage tank fluidically coupled to the secondary condenser and adapted for storing the sterile cryogen.

15. A method of sterilizing a cryogen comprising the steps of:

compressing a cryogen vapor;

sterilizing the compressed cryogen vapor to produce a compressed, sterile cryogen vapor;

pre-cooling the compressed, sterile cryogen vapor to produce a partially condensed, cool sterile cryogen stream; and

further condensing the cool sterile cryogen stream to produce a sterilized cryogen.

16. The method of claim 15 wherein the step of compressing the cryogen vapor further comprises compressing the cryogen vapor to a pressure of between about 70 psi and about 360 psi.

17. The method of claim 15 wherein the cold cryogen vapor is further warmed to a temperature of between about −20 degrees Centigrade to about 30 degrees Centigrade during the compressing step.

18. The method of claim 15 wherein the cryogen is selected from the group consisting of nitrogen, hydrogen, helium, oxygen, and argon.