WO2010068587A2

WO2010068587A2 - Method of packaging and package for sensors

Info

Publication number: WO2010068587A2
Application number: PCT/US2009/066968
Authority: WO
Inventors: Kenneth Curry; Todd Fjield; Michael J. Higgins; Patrick Carlin; Gregory J. Carlin
Original assignee: Edwards Lifesciences Corporation
Priority date: 2008-12-12
Filing date: 2009-12-07
Publication date: 2010-06-17
Also published as: US20100293892A1; WO2010068587A3; EP2375983A2; EP2375983A4; JP2012511485A; CN102271580A

Abstract

There are provided methods of packaging and packages that prevent damage of the package contents while maintaining sterility and that limit the negative effects of sterilization on sensors such as enzyme sensors. A method of packaging an enzyme sensor includes providing an enzyme sensor such as a glucose oxidase sensor in a gas impermeable package comprising one or more of oxygen and water, removing a significant portion of the oxygen and water present in the package, and sealing the package. The resulting package comprises the enzyme sensor in an atmosphere that is substantially free of oxygen and water. The package can also include a pressure indicator that indicates when the package has exceeded a predetermined pressure.

Description

METHOD OF PACKAGING AND PACKAGE FOR SENSORS

CLAIM OF PRIORITY UNDER 35 U. S. C. § 119 [0001] The application claims the benefit of U.S. Provisional

Application No. 61/122,246 filed December 12, 2008, entitled "Method of Packaging and Package for Sensors" and assigned to the assignee hereof and hereby incorporated by reference in its entirety.

FIELD AND BACKGROUND

[0002] The present invention relates to methods of packaging and packages for sensors such as enzyme sensors that prevent damage to the sensor and that maintain sterility of the sensor. [0003] Sensors are known in the medical industry for use in analyzing fluids such as blood. These sensors generally have to be sterilized for use in the medical environment; however, known sterilization methods can result in degradation of sensor performance and a reduction in the sensor's shelf life. In addition, packaging delicate medical devices such as sensors requires that particular care be taken such that damage to either the sensor or the package itself does not occur. In particular, damage to the sensor can compromise performance of the device and damage to the package can compromise sterilization of the sensor. [0004] One type of sensor used in the medical industry is an enzyme sensor. Glucose oxidase (GOx)-based enzyme sensors, for example, are used to measure blood glucose concentration. An enzyme sensor includes an enzyme that is immobilized using a membrane at the surface of an electrode. The membrane limits diffusion to the enzyme layer. Typically, these sensors are sterilized using radiation. However, radiation has been shown to denature the enzymes used in the sensor and to modify the polymer structure of the membranes thereby increasing the permeability of the membranes. Therefore, the amount of radiation used to sterilize enzyme sensors is preferably limited. Alternatively, steps must be taken to limit the effect sterilization has on the enzyme sensors. [0005] The maintenance of low bioburden levels is necessary during manufacturing to minimize the radiation dose required to ensure the sterilization of enzyme sensors. Typically, lower bioburden levels are accomplished by limiting human contact with the sensor during production. However, maintaining low bioburden levels has the negative effect of increasing production time by requiring additional cleaning steps, increasing production cost by requiring replacement of gowns, gloves and other equipment used to maintain a sterile environment, and reduced yield resulting from the rejection of products not having the desired bioburden levels. This becomes particularly problematic for more complex devices where the bioburden levels are generally higher or at least much more difficult to minimize.

[0006] Furthermore, if the enzyme sensor is exposed to moisture and oxygen during sterilization, it can further reduce the shelf life of the enzyme sensor. In particular, the formation of ozone by subjecting oxygen and water to sterilization can result in denaturing enzymes. A reduction of ozone formation is typically accomplished by using lower radiation doses by controlling bioburden levels thereby limiting the amount of ozone formed by radiation. However, maintaining low bioburden levels has its own issues as discussed above.

BRIEF SUMMARY

[0007] There are provided methods of packaging and packages that prevent damage of the sensors while maintaining sterility and that limit the negative effects of sterilization on sensors. A method of packaging a sensor such as an enzyme sensor includes providing an enzyme sensor such as a glucose oxidase sensor in a gas impermeable package comprising one or more of oxygen and water, removing a significant portion of the oxygen and water present in the package, and sealing the package. The resulting package comprises the enzyme sensor in an atmosphere that is substantially free of oxygen and water, e.g., having an oxygen content of no more than 1 mm Hg.

[0008] In some embodiments, a method of packaging an enzyme sensor includes providing an enzyme sensor in a gas impermeable package, wherein the package is inflatable and sealable, and comprises one or more of oxygen and water. The package can be a flexible material. A significant portion of the oxygen and water present in the package is removed by flushing the package with an inert gas such as nitrogen. The package is then inflated with excess pressure of the inert gas and sealed, such that the packaged material including the enzyme sensor cannot touch more than one non-adjacent surface of the package at a time. Typically, the packaged material includes a catheter onto which the enzyme sensor is situated and can further include a tray or sheet such as a cardboard sheet onto which the catheter can be mounted or fixed. The sealed package can be exposed to radiation such as e-beam or gamma radiation, or other known means for medical use.

[0009] In some embodiments, a method of packaging an enzyme sensor includes providing an enzyme sensor in a gas impermeable package, wherein at least a portion of the package is a rigid or semi-rigid material and the package comprises one or more of oxygen and water. A significant portion of the oxygen and water present in the package can be removed by drawing a vacuum on the package and sealing the package. For example, the package can be a thermoformed tray and the method can include heat sealing a film layer onto the thermoformed tray to seal the package. The sealed package can be exposed to radiation such as e-beam or gamma radiation, or other known means for medical use. [0010] The removal of a significant amount of the oxygen and water present in the package results in a sensor package that is substantially free of oxygen and water. Thus, when radiation such as e-beam or gamma radiation is used to sterilize the package contents, it can be used at higher doses than those presently used for sterilizing enzyme sensors. This is because the removal of oxygen results in a reduction in the production of free radicals and thus the production of ozone in the package in the sterilization process.

[0011 ] The packaging methods allow enzyme sensors to be produced more quickly and more cheaply than by prior art methods wherein the effects of sterilization are mitigated by controlling bioburden alone. Furthermore, as there are many attributes of sensors that are difficult to control individually at design time, it is possible to design a sensor for the best performance without the need to focus on the effects of sterilization and the methods that must be used to mitigate the effects of sterilization. In addition, the packaging methods allow for a simple but reliable way to package the sensor without increasing mass, which is costly to ship and which can create mask areas during sterilization. These mask areas can make sterilization less predictable and can require higher doses of radiation, thereby possibly further degrading sensor performance. [0012] In some embodiments, a sensor package comprises a pouch including a sensor and a pressure indicator that indicates when a particular pressure is reached adjacent the pressure indicator. The pouch can include the pressure indicator and/or the pressure indicator can be provided elsewhere in the package such as in one or more isolated chambers. In some embodiments, the pressure indicator can include a burst point that avulses when the pressure indicator reaches a predetermined pressure, a color indicator that becomes activated when the pressure indicator reaches a predetermined pressure, and/or an audible sound when the pressure indicator reaches a predetermined pressure. The pouch can, in some embodiments, include an inner pouch and the inner pouch can include a burst point as a pressure indicator when the inner pouch reaches a predetermined pressure. The inner pouch can further include an aqueous electrolytic solution and/or a sterilizing agent. [0013] These and other features and advantages will become more readily apparent to those skilled in the art upon consideration of the following detailed description and accompanying figures.

BRIEF DESCRIPTION OF THE FIGURES

[0014] Figure IA is a side view of a multilumen catheter assembly.

[0015] Figure IB is a magnified detail of the distal end of the multilumen catheter of Figure IA including an enzyme sensor. [0016] Figure 2 is a top view of a catheter including an enzyme sensor and a package prior to insertion of the catheter into the package. [0017] Figure 3 is a side view of a package including a catheter that includes an enzyme sensor.

[0018] Figure 4 is a perspective view of the sealed and inflated package comprising a catheter that includes an enzyme sensor. [0019] Figure 5 is a top view of a catheter that includes an enzyme sensor provided in tray.

[0020] Figure 6 is a top view of a pouch that includes a pressure indicator in the form of a burst point.

[0021] Figure 7 is a top view of a package that includes a pouch and one or more compartments that include pressure indicators. [0022] Figure 8 is a top view of a pouch that includes a inner compartment that can include a liquid that enters the pouch at a particular pressure.

DETAILED DESCRIPTION

[0023] As used in the specification, and in the appended claims, the singular forms "a", "an", "the", include plural referents unless the context clearly dictates otherwise. The term "comprising" and variations thereof as used herein is used synonymously with the term "including" and variations thereof and are open, non-limiting terms.

[0024] Methods of limiting possible damage to the sensor or the packaging material during shipping comprise providing an enzyme sensor such as a glucose oxidase sensor in a gas impermeable package. The methods can also limit the negative effects of sterilization on enzyme sensors.

[0025] In the normal process for producing a package and providing the sensor within the package, the package can include one or more of oxygen and water. Furthermore, regardless of the process used to produce the package and the desire to minimize the bioburden, microorganisms will generally exist in the package. In the packaging methods, a significant portion of the oxygen and water present in the package is removed using an inert process, i.e., a process that does not have an appreciable effect on the microorganisms present in the package. For example, the inert process would kill less than 50%, generally less than 25% and typically less than 10% of the microorganisms present in the package. The removal of a significant amount of the oxygen and water present in the package results in a sensor package that is substantially free of oxygen and water, e.g., having less than 1 mm Hg of oxygen prior to sterilization. [0026] In some embodiments, the sensor can be provided on a catheter. For example, Figure 1 A illustrates a multilumen catheter assembly 10 in which a sensor 20 is integrated into the catheter. The catheter assembly 10 can include multiple infusion ports 32a, 32b, and 32c (collectively referred to as reference number 32) and one or more electrical connectors 34 disposed adjacent to a proximal end 36 of the catheter assembly 10. One or more lumens 38a, 38b, and 38c (collectively referred to as reference number 38) can connect each infusion port 32a, 32b, and 32c, respectively, to a junction 40. Similarly, a conduit 42 can connect an electrical connector 34 to the junction 40, and can terminate at junction 40, or at one of the lumens 38a - 38c (as shown). Although the particular embodiment shown in FIG. IA is a multilumen catheter having three fluid lumens and one electrical lumen, other embodiments having other combinations of lumens and connectors can be used, including a single lumen catheter, a catheter having multiple electrical connectors, etc. In some embodiments, one of the lumens and the electrical connector can be reserved for a probe or other sensing element mounting device, or one of the lumens can be open at its proximal end and designated for insertion of the probe or biosensor mounting device.

[0027] The junction 40 connects the lumens 38a - 38c and the conduit 42 to a narrow elongated tube 44 that forms an insertion portion of the catheter assembly 10. The tube 44 is typically cylindrical, having a circular or somewhat oval cross section defining a longitudinal axis extending therethrough. The tube 44 can be formed from any material, including synthetic materials such as silicone, polyurethane, polyethylene, and the like. Through the junction 40, each of the lumens 38a - 38c extend in separate parallel paths for some distance into the distal end of tube 44. One or more support structures 46 within the tube 44 can be disposed along the length of the catheter to provide rigidity.

[0028] The distal end 48 of the catheter assembly 10 is shown in greater detail in FIG. IB. At one or more intermediate locations along the distal end, the tube 44 can include one or more recesses formed in an outer wall of the tube. In some embodiments, the recess can define an opening in the outer wall of the tube through which a body fluid can flow into a lumen that is in communication with the opening. In some embodiments, the recess can define a port formed in the outer wall of the tube that defines an opening through which a bodily fluid can flow through the port and into the lumen, and vice versa. In the illustrated embodiment, the ports include the intermediate ports 50a and 50b, and an end port 50c (collectively referred to as reference number 50) that can be formed towards the distal tip of tube 44. Each port 50a — 50c can correspond respectively to one of the lumens 38a - 38c or conduit 42. That is, each lumen can define an independent channel extending from one of the infusion ports 32a - 32c and conduit 42 to one of the ports 50a - 50c located towards the distal end of the tube 44. [0029] As shown in Figures IA and IB, the catheter 10 can include the sensor 20 proximate to the distal end 48 of the catheter for monitoring one or more analytes. The enzyme sensor can include one or more electrodes 62, 64, 66 created on a surface of a flexible substrate and associated with the catheter 10. The sensor 20 can communicate with the lumen 38 in the catheter 10 such that an active portion, e.g., a portion containing an electrode, can be exposed to space outside the tube 44. Electrical wires 68 coupled to electrodes 64 and 66 can extend from the sensor 20 through the lumen 38 to provide a conductive path through the lumen 38 and the conduit 42 that can terminate at the electrical connector 34. The electrical wires 68 can be attached to the sensor elements with a weld, solder, conductive adhesive, such as a conductive epoxy, and the like. In some embodiments, the electrical wires 68 can be bonded to the sensor 20. Although the electrical wires 68 are drawn such that they terminate within the tube 44, the electrical wires will typically extend and communicate with an electrical connector, e.g., electrical connector 34. [0030] The sensor provided on a catheter can be mounted or affixed to an insert tray or sheet 70. For example, in Figure 2, the sensor 20 is provided on catheter 10 and the catheter 10 is mounted onto the tray or sheet 70. The tray or sheet 70 can be made of a suitable material such as a cardboard. The catheter 10 can be further affixed to the cardboard sheet using plastic clips, plastic ties or plastic coated metal ties 72. As shown in the side view of the catheter 10 and the tray or sheet 70 illustrated in Figure 3, portions of the catheter 74 and the ties 72 can provide high points or rough points in the material to be packaged 76.

[0031] As shown in Figure 3, the material to be packaged 76 can be inserted into a gas impermeable package 80 that can be sealed and inflated. For example, a heat-sealable foil pouch made from a polyester outer layer, a polyethylene inner layer, and an aluminum lining layer can be used as the package 80. The material to be packaged 76 can be inserted through an open end 82 of a package 80 including two separate faces 84 and 86, and a closed end 88.

[0032] Once the material to be packaged 76 is placed in the package

80, oxygen and water from the package can be removed by flushing the package with an inert gas. For example, nitrogen, a noble gas, or a combination thereof can be used to flush the package contents. These gases are provided in dry form, with a moisture content of less than 1 %, more preferably less than 0.1%. This can be accomplished prior to sealing the package by using an opening in the package (such as open end 82) for entry of the inert gas and driving out any gases present in the package such as oxygen and water using the inert gas. The package can then be inflated with excess pressure of the inert gas and sealed, such that the packaged material including the enzyme sensor cannot touch more than one non- adjacent surface of the package at a time, e.g., cannot touch both interior faces 84 and 86 of a metal foil-lined pouch. The open end of the package 82 can then be sealed via known means such as heat sealing resulting in a sealed package such as the package 80 shown in Figure 4. [0033] By having the package 80 is at least partially inflated with an inert gas, the interior components of the package (the packaged material 76) are protected from damage upon external pressure. In particular, as pressure is applied, the trapped gases push back on the pouch increasing resistance. This pressure will match the external pressure and negate it, thus preventing damage to the contained sensors. For example, when the inflated packaged is further packaged (e.g. in a box), the movement from shipping will not cause adjacent packages in the box to damage each other and will not cause friction to wear a hole in the package. In addition, when the packaged material cannot simultaneously touch both horizontal faces of the pouch, the packaged material will not puncture the pouch during vibration of transportation, which will ensure sterility of the sensor until time of use.

[0034] In some embodiments, the sensor can be provided in a rigid or semi-rigid package that has enough rigidity that it does not significantly collapse when the vacuum is drawn on the package. For example, the sensor can be provided in a thermoformed tray. In some embodiments, the sensor can be provided on a catheter and the catheter provided in a tray. For example, as shown in Figure 5, a sensor 20 can be provided on a catheter 10 in a thermoformed tray 90. The thermoformed tray can include inset portions that prevent the catheter 10 from extending above the upper surface 92 of the tray. The thermoformed tray 90 can include protrusions 94 and/or plastic clips 98 that hold the catheter 10 in place within the tray. [0035] The sensor 20 and/or catheter 10 provided in the insert tray

90 can be placed in a vacuum chamber wherein the removal of oxygen and water can be accomplished by drawing a vacuum on the package. This can be accomplished by removing any gases from the package using a vacuum process and then sealing the package. For example, a film (not shown) can be heat sealed along an outer edge 96 of the package. The package can also be flushed with an inert gas prior to drawing a vacuum on the package and sealing the package.

[0036] The interior of the package produced by the above methods can be substantially free of oxygen and water. The environment in the package typically has an oxygen content of less than 1 mm Hg. By using appropriate techniques of vacuum cycling with inert gas, then sealing in vacuo, the partial pressure of oxygen can be a small fraction of the total pressure in the sealed package, which can be 1 to 10 mm Hg. Likewise, the partial pressure of water in the sealed package will be a small fraction of the total pressure as stated previously. Thus, the amount of oxygen can be less than 0.5 mm Hg or even less than 0.1 mm Hg in the sealed package. Furthermore, the amount of water can be less than 1 mm Hg, less than 0.5 mm Hg, or even less than 0.1 mm Hg in the sealed package. [0037] The sealed package produced by any of the above methods can be exposed to radiation or any other known means to sterilize the contents therein. Preferably, e-beam or gamma radiation is used to sterilize the package contents although other forms of radiation can alternatively be used. The radiation can be used at higher doses and/or the sensor package can be at higher bioburden levels than those presently used for sterilizing enzyme sensors because of the reduction in the production of free radicals and thus the production of ozone in the package resulting from the sterilization process. In particular, in present systems, the required e-beam dose is in the order of about 19 kGy and requires a bioburden level to be below about 19.7 CFU's. Using the method of the present invention, the bioburden level can be greater than 25 CFU's, greater than 50 CFU's, greater than 75 CFU's, greater than 100 CFU's, greater than 125 CFU's and even greater than 150 CFU's and still provide a sufficiently sterilized enzyme sensor. Alternatively, much higher does of radiation at these bioburden values can be used in the order of 25 kGy or greater, 30 kGy or greater, 35 kGy or greater, or even 40 kGy or greater, for e-beam radiation levels.

[0038] A system for producing a package for a sensor can include means for inserting a sensor (or packaged material including a sensor) into the package; means for one of flushing the sensor with an inert gas or drawing a vacuum on the package; optionally means for inflating the package, and means for sealing the package. The system can also include means for forming the package includes therraoforming or trimming a sheet of plastic, or by other means known in the art. The sensor is typically inserted into the open package by a conveyor, by hand or by other means known in the art. The open sensor package can be flushed with an inert gas by inserting a nozzle into the open end of the pouch and by closing the bars on an impulse sealer at such a time as to leave the pouch partially inflated. The resulting package can be sterilized by subjecting the package to radiation using e-beam or gamma radiation or another process known in the art.

[0039] As an alternative to or in addition to including means for flushing with an inert gas, the package can include means of drawing a vacuum and sealing the package while it is subjected to the vacuum and suitable means are known in the art. For example, a vacuum can be drawn on a rigid package by using a pump to pull air and other gases from the open package by placing the package in a vacuum chamber and then sealing said package, or by other means known in the art. The open package can be sealed using a heat sealing process or another process known in the art.

[0040] The sensors packaged according to the invention are particularly useful in systems where enzyme sensors are typically used. For example, the sensors can be used for real-time measurement of redox active chemical species in a bodily fluid by taking in vivo measurements; however, the membranes and electrodes are also useful otherwise. For example, the sensors can be used for continuous measurement in a laboratory setting. In certain embodiments, the sensors can be used with automated testing equipment.

[0041] The sensor can be provided within a probe or catheter for intravenous insertion into a patient. When the sensors and methods of the invention find use for in vivo testing in a live subject, placement of the sensor can be by any useful method known in the art using known devices, such as catheters. In these settings, the sensor can function as an amperometric sensor while immersed in a patient's bloodstream. In certain embodiments, catheters such as a multilumen catheter, a central venous catheter (CVC), a pulmonary artery catheter (PAC), a peripherally inserted central catheter (PICC), or other commonly used peripheral intravenous (IV) lines can provide a suitable platform for effective intravenous positioning of the sensor. For example, the sensor can be positioned in the patient's bloodstream by inserting a probe including the sensor through a CVC or PAC or through a peripheral IV catheter or by using an introducer. One advantage of using a CVC or PAC for installing an intravenous sensor is its ability to reach the largest blood vessels of the body where a sensor can be exposed to an abundant flow of blood. Further, certain embodiments of the invention can be economically employed for use with multilumen catheters. Alternately, the sensor can be attached to a venous arterial blood management protection (VAMP) system by drawing a blood sample from the intravascular space and exposed to the sensor ex vivo. [0042] Specifically, in one embodiment, a sensor according to the invention can be described as being in association with a catheter. In such embodiments, "association" comprises any method of combining a sensor and a catheter allowing for in vivo sensing using the sensor. For example, association can refer to direct attachment of the sensor to a surface of the catheter subject to ambient conditions. Association can also refer to a combination of the sensor and a catheter such that the sensor is directly adjacent the catheter (i.e., in a working proximity thereto) but not attached thereto. Still further, association can encompass placement of the sensor within a lumen of the catheter. Thus, association means that the sensor and the catheter are sufficiently related such that placement of the catheter in vivo likewise results in placement of the sensor in vivo. [0043] In embodiments where a pouch or bag is used, the pouch or bag can include an indicator that shows when the pouch or bag has exceeded a maximum pressure. For example, as shown in Figure 6, a pouch 100 including the sensor (or a catheter including the sensor 104) can have a weakened location or burst point 102 that avulses when the pressure exceeds a maximum value. The burst point 102 can be provided by providing a portion of the pouch 100 with a thinner film layer or by roughening the surface of the pouch at the location of the burst point without creating a hole in the pouch. The burst point 102 can have a color indicator 106 (e.g. a bright red indicator) that is readily apparent on the pouch 100 and that can further include a warning not to use the sensor. The color indicator 106 can be provided on the interior side of the film forming the pouch 100 and can become colored, e.g., upon exposure to oxygen. The pouch 100 can be inflated to a predetermined pressure at a predetermined temperature (e.g. at room temperature) and a predetermined volume (e.g. the fully inflated volume of the pouch). Based on the ideal gas law (PV=nRT), a maximum pressure could be determined that would cause the burst point 102 to avulse. Accordingly, if the pouch 100 were to burst at the burst point 102, the end user would know that the pouch exceeded the maximum pressure.

[0044] In some embodiments, the burst point 102 could alternatively or additionally provide a sound such as a "pop" that would indicate to a person involved in the delivery or storage of the sensors provided in the pouches that the pouches need to be moved to a higher pressure and/or lower temperature environment to preserve the sterility of the other sensors provided in the pouches.

[0045] In some embodiments as shown in Figure 7, a package 110 can include a pouch 112 including the sensor and one or more isolated chambers (e.g. 114, 116 and 118) on the package of different sensitivities that burst progressively based on the pressures the package is subjected to. For example, the isolated chambers 114, 116 and 118 could have burst points that would burst at 90%, 95% and 100% of what would be the maximum pressure for the pouch 112. Alternatively, if the pouch 112 also includes a burst point provided at 100% of the maximum pressure, the isolated chambers 114, 116 and 1 18 could have burst points at 85%, 90% and 95% of the maximum pressure. The isolated chambers 114, 1 16 and 1 18 can help to preserve the sterility of the sensor for pressures below a maximum pressure.

[0046] In some embodiments as shown in Figure 8, a pouch 120 can include an inner compartment 122 that includes a burst point that is set to avulse at a particular pressure. The inner compartment 122 can include a liquid (e.g. an aqueous electrolytic solution) that can wet the sensor or a sterilizing agent that can provide sterility to the sensor and extend its life. In the event a liquid is used pre-wet the sensor, the liquid can be used to reduce run-in time for the sensor.

[0047] The method of the present invention allows enzyme sensors to be produced more quickly and more cheaply than by prior art methods wherein the effects of sterilization are mitigated by controlling bioburden alone. Furthermore, as there are many attributes of sensors that are difficult to control individually at design time, it is possible to design a sensor for the best performance without the need to focus on the effects of sterilization and the methods that must be used to mitigate the effects of sterilization.

Claims

THAT WHICH IS CLAIMED:

1. A method of packaging an enzyme sensor, comprising: providing an enzyme sensor in a gas impermeable package, said package being inflatable and sealable, and comprising one or more of oxygen and water; removing a significant portion of the oxygen and water present in the package by flushing the package with an inert gas; inflating the package with excess pressure of said inert gas, and sealing the package, wherein the package is inflated such that the packaged material including the enzyme sensor cannot touch more than one non-adjacent surface of the package at a time.

2. The method according to claim 1, wherein said inert gas is nitrogen.

3. The method according to claim 1, further comprising the step of exposing the sealed package to radiation.

4. The method according to claim 3, wherein the radiation is e- beam radiation.

5. The method according to claim 3, wherein the radiation is gamma radiation.

6. The method according to claim 1, wherein the package is a metal foil-lined pouch.

7. The method according to claim 1, wherein the enzyme sensor is a glucose oxidase sensor.

8. The method according to claim 1 , wherein the enzyme sensor is provided on a catheter.

9. The method according to claim 8, wherein the catheter is provided on a sheet or tray and affixed thereto.

10. The method according to claim 1, wherein the gas impermeable package is a flexible material.

11. A sensor package, comprising: an enzyme sensor stored in a sealed gas impermeable package, said package being inflated with an inert gas such that the packaged material including the enzyme sensor cannot touch more than one non-adjacent surface of the package at a time.

12. The package according to claim 1 1, wherein the package is substantially free of oxygen and water.

13. The package according to claim 11, wherein the package includes no more than 1 mm Hg oxygen.

14. The package according to claim 11, wherein the enzyme sensor is a glucose oxidase sensor.

15. The package according to claim 1 1 , wherein said inert gas is nitrogen.

16. The package according to claim 11, wherein the package is a metal foil-lined pouch.

17. The package according to claim 11, wherein the enzyme sensor is provided on a catheter.

18. The package according to claim 17, wherein the catheter is provided on a sheet or tray and affixed thereto.

19. The package according to claim 11, wherein the gas impermeable package is a flexible material.

20. A method of packaging an enzyme sensor, comprising: providing an enzyme sensor in a gas impermeable package, wherein at least a portion of the package is a rigid or semi-rigid material and the package comprises one or more of oxygen and water; removing a significant portion of the oxygen and water present in the package by drawing a vacuum on the package; and sealing the package.

21. The method according to claim 20, further comprising the step of exposing the sealed package to radiation.

22. The method according to claim 21, wherein the radiation is e-beam radiation.

23. The method according to claim 21, wherein the radiation is gamma radiation.

24. The method according to claim 21 , wherein the package comprises a tray.

25. The method according to claim 24, wherein the tray is thermoformed.

26. The method according to claim 25, wherein said sealing step comprises heat sealing a film layer onto said thermoformed tray.

27. The method according to claim 21, wherein the enzyme sensor is a glucose oxidase sensor.

28. The method according to claim 21, wherein the enzyme sensor is provided on a catheter.

29. A sensor package, comprising: an enzyme sensor stored in a sealed gas impermeable package, said package being vacuum sealed and being substantially free of oxygen and water.

30. The package according to claim 29, wherein the package includes no more than 1 mm Hg oxygen.

31. The package according to claim 29, wherein the enzyme sensor is a glucose oxidase sensor.

32. The package according to claim 29, wherein at least a portion of the package is a rigid or semi-rigid material.

33. The package according to claim 32, comprising a thermoformed tray.

34. The package according to claim 33, further comprising a film layer heat sealed to said thermoformed tray.

35. The package according to claim 29, wherein the enzyme sensor is provided on a catheter.

36. A sensor package comprising: a pouch including a sensor; and a pressure indicator that indicates when a particular pressure is reached adjacent the pressure indicator.

37. The package according to claim 36, wherein the pouch includes the pressure indicator.

38. The package according to claim 36, wherein the pressure indicator includes a burst point that avulses when the pressure indicator reaches a predetermined pressure.

39. The package according to claim 36, wherein the pressure indicator includes a color indicator that becomes activated when the pressure indicator reaches a predetermined pressure.

40. The package according to claim 36, wherein the pressure indicator provides an audible sound when the pressure indicator reaches a predetermined pressure.

41. The package according to claim 36, further comprising one or more isolated chambers wherein the isolated chambers include the pressure indicator.

42. The package according to claim 41, wherein the pouch also includes a pressure indicator.

43. The package according to claim 36, wherein the pouch includes an inner pouch and the inner pouch includes a burst point as a pressure indicator when the inner pouch reaches a predetermined pressure.

44. The package according to claim 43, wherein the inner pouch includes an aqueous electrolytic solution and/or a sterilizing agent.