Patent Publication Number: US-11040139-B2

Title: Drug delivery systems with sealed and sterile fluid paths and methods of providing the same

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 16/279,996, entitled “DRUG DELIVERY SYSTEMS WITH SEALED AND STERILE FLUID PATHS AND METHODS OF PROVIDING THE SAME”, filed Feb. 19, 2019, which is a continuation of U.S. Pat. No. 10,245,377, filed Nov. 10, 2017, which claims the benefit of U.S. Provisional Application No. 62/420,736, filed Nov. 11, 2016, U.S. Provisional Application No. 62/421,648, filed Nov. 14, 2016 and U.S. Provisional Application No. 62/422,291, filed Nov. 15, 2016, the disclosures of which are incorporated herein by reference in their entirety. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates generally to the field of drug delivery. In particular, the present disclosure relates to drug delivery systems that include a sealed and sterile fluid path attached to a drug-loaded container. The disclosure further relates to methods for sterilizing the drug delivery systems without exposing the drug-loaded container to harmful sterilization parameters. 
     BACKGROUND 
     Conventional drug delivery systems are not optimized for post-assembly sterilization protocols because the sterilization modality (e.g., heat, pressure, radiation, etc.) can tend to degrade or destroy the drug(s) contained within such systems. The inability to provide a sealed and sterile fluid path attached to a drug-loaded container requires that conventional drug delivery systems provide the fluid path and drug-loaded container as separate components. A user is thus required to assemble these components into a combined device prior to drug administration. In addition to the increased costs associated with individually packaging and shipping these components, the time required to assemble the drug delivery system may result in significant inconvenience to the user. For example, the time required for an individual experiencing a severe allergic reaction to assemble a drug delivery system (e.g., epinephrine pens, etc.) may be the difference between life and death. Similarly, the time required for medical personnel to load an empty syringe with the proper type and dosage of drug may unnecessarily prolong the administration of the drug during an emergency situation. 
     A variety of advantageous medical outcomes may be realized by the systems and/or methods of the present disclosure, which provide a drug delivery system that includes a sealed and sterile fluid path attached to a drug-loaded container. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Non-limiting embodiments of the present disclosure are described by way of example with reference to the accompanying figures, which are schematic and not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment shown where illustration is not necessary to allow those of ordinary skill in the art to understand the disclosure. In the figures: 
         FIG. 1  provides a schematic view of a single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 2  provides a schematic view of an alternative single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 3  provides a schematic view of an alternative single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 4A  provides a first schematic view of an alternative single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 4B  provides a second schematic view of an alternative single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 4C  provides a third schematic view of an alternative single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 5  provides a schematic view of an alternative single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 6  provides a schematic view of a double-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 7  provides a schematic view of an alternative double-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 8  provides a schematic view of an alternative double-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 9  provides a schematic view of a sterilization system using a single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 10  provides a schematic view of an activated single-barrier drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 11  provides a schematic view of a plunger drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 12  provides a schematic view of an alternative plunger drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 13  provides a first schematic view of an activated plunger drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 14  provides a second schematic view of an activated plunger drug delivery system, according to one embodiment of the present disclosure 
         FIG. 15A  provides a first schematic view of a pre-loaded syringe drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 15B  provides a second schematic view of a pre-loaded syringe drug delivery system, according to one embodiment of the present disclosure. 
         FIG. 16A  provides a first schematic view of a double-barrier drug delivery system disposed within a shield assembly, according to one embodiment of the present disclosure. 
         FIG. 16B  provides a second schematic view of a double-barrier drug delivery system disposed within a shield assembly, according to one embodiment of the present disclosure. 
         FIG. 17  provides a third schematic view of a double-barrier drug delivery system disposed within a shield assembly, according to one embodiment of the present disclosure. 
         FIG. 18  provides a fourth schematic view of a double-barrier drug delivery system disposed within a shield assembly, according to one embodiment of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     This disclosure presents various systems, components, and methods related to a drug delivery system and/or the sterilization of the drug delivery system. Each of the systems, components, and methods disclosed herein provides one or more advantages over conventional systems, components, and methods. 
     The present disclosure is not limited to the particular embodiments described. The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting beyond the scope of the appended claims. Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosure belongs. 
     Although embodiments of the present disclosure are described with specific reference to drug delivery, the systems and methods disclosed herein may be used to provide a sterile fluid path for a variety of sterile solutions, agents, materials, biological and/or pharmaceutical compositions from a variety of containers, cartridges, syringes, pens, needles and the like. 
     As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” or “includes” and/or “including” when used herein, specify the presence of stated features, regions, steps elements and/or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components and/or groups thereof. 
     As used herein, the terms “proximal” and “distal” refer to opposite portions of the devices or systems described herein, with “proximal” generally referring to the portion closest to the user of the devices or systems. 
     The present disclosure provides various drug delivery systems that include a drug-loaded container attached to a fluid path (e.g., transfer tube, needle, syringe, etc.) by a cap (e.g., plug, stopper, septum, etc.). As used herein, “drug” refers to any therapeutic agent administered to a user, as described herein. As used herein, “container” refers to any suitable space for containing a fluid drug. The cap may be configured to seal an opening of the container and establish sufficient separation between the fluid path and drug such that sterilization energy applied to a distal portion of the fluid path does not contact or otherwise act upon any portion of the drug. 
     Various embodiments provide drug delivery systems that can provide a fluid path and a drug container holding a liquid drug. The fluid path can be sterilized by an energy source without disturbing the liquid drug, which can be sterilized prior to sterilizing the fluid path. The fluid path can be coupled to the container such that after sterilization, the drug delivery system is immediately ready for use. Upon activation, for example based on a user input, the fluid path can be coupled to the stored liquid drug, thereby providing a route for delivery of the liquid drug to the user. The systems and methods described herein obviates the need for a user to transfer a liquid drug to a drug delivery system prior to use and also obviates the need for a user to assemble a drug delivery device prior to use—accordingly, embodiments provided herein provide fully assembled ready to use drug delivery systems through the arrangements and sterilizations techniques described herein. 
     Single-Barrier Systems 
     Referring to  FIG. 1 , in one embodiment, a drug delivery system  100  of the present disclosure may include, in combination, a container  112 , a cap  120  and a fluid path  140 . The container  112  may include a body  114  and a neck  116  defining an interior region  118 . The cap  120  may be disposed about at least a portion of the neck  116  to contain a fluid drug  150  within the interior region  118 . The fluid path  140  (e.g., transfer tube, needle, syringe, etc.) may define a lumen  146  and further include a first portion  142  with a sharpened first end  141 , and a second portion  144  with a sharpened second end  143 . 
     The cap  120  may include a “top hat” configuration secured to the neck  116  by a first crimp  126 . For example, the cap  120  may include a first portion  122  configured to extend at least partially into the neck  116 , a second portion  123  configured to overlap an end of the neck  116  and a third portion  124  configured to extend distally beyond (e.g., away from) the second portion  123 . The neck  116  may include a flared portion  117  to provide a surface against which the first crimp  126  may be compressed to secure the second portion  123  of the cap  120  against the end of the neck  116 . The first crimp  126  may include any suitably deformable and/or compressible material (e.g., metals, alloys, plastics, rubbers, and the like), as are known in the art. In various embodiments, the cap  120  may be secured to the neck  116  by a variety of additional and/or alternative attachment mechanisms, including, by way of non-limiting example, corresponding threaded or luer-lock surfaces, adhesives, glues, solders, resins and the like. 
     The first portion  142  of the fluid path  140  may be disposed (e.g., embedded, housed, etc.) within the third portion  124  of the cap  120  such that the sharpened first end  141  is maintained a pre-determined distance away from the interface between the fluid drug  150  and the first portion  122  of the cap  120 . For example, the sharpened first end  141  of the fluid path  140  may be separated from the fluid drug  150  by a distance of 10 cm or more, more preferably 20 cm or more, and even more preferably 30 cm or more. The third portion  124  of the cap  120  may also provide structural support to the first portion  142  of the fluid path  140 , thereby preventing bending and/or moving of the fluid path during shipping, storage and/or use, which might comprise the integrity of the fluid-tight seal. In one embodiment, the first portion  142  of the fluid path  140  may be disposed within a channel  125  formed within the third portion  124  of the cap  120  to reduce or eliminate the potential for the lumen  146  to become plugged with a “core” of the cap  120  as the fluid path  140  is advanced into the interior region  118 . Although the channel  125  is depicted as extending through the length of the third portion  124 , in various embodiments the channel  125  may extend through a portion of the third portion  124 . In addition, or alternatively, the channel  125  may extend through the third portion  124  into the first or second portions  122 ,  123  of the cap  120 . 
     The second portion  144  of the fluid path  140  may be disposed (e.g., embedded, housed, etc.) within a cover  148  such that the sharpened second end  143  is shielded prior to use. In one embodiment, a length of the second portion  144  may be sufficient to penetrate the dermal layer of a patient. For example, the second portion  144  of the fluid path  140  may have a length of 0.5 cm or more, more preferably 1.0 cm or more, and even more preferably 2.0 cm or more. 
     Referring to  FIG. 2 , in one embodiment, a drug delivery system  100  of the present disclosure may further include a cap  220  with a “top hat” configuration like that of  FIG. 1 , with a first portion  222  configured to extend at least half-way (e.g., approximately 50%) into the neck  116  to provide additional separation between the first portion  142  (and sharpened first end  141 ) of the fluid path  140  and the fluid drug  150  within the interior region  118  of the container  112 . In various embodiments, the first portion  222  may extend more than half-way into the neck  116 , including, for example, extending completely (e.g. 100%) into the neck. 
     Referring to  FIG. 3 , in one embodiment, a drug delivery system  100  of the present disclosure may further include a cap  320  which includes a first portion  322  configured to extend at least half-way (e.g., approximately 50%) into the neck  116 , and a second portion  323  configured to overlap an end of the neck  116 , without a corresponding third portion extending distally beyond the second portion  323 . The neck  116  may include a flared portion  117  to provide a surface against which the first crimp  126  may be compressed to secure the second portion  323  of the cap  320  against the end of the neck  116 . 
     Referring to  FIGS. 4A-4C , in one embodiment, a drug delivery system  100  of the present disclosure may further include a cap  420  with a “top hat” configuration like that of  FIG. 1 , with a third portion  424  configured to extend distally beyond (e.g., away from) a second portion  423 , and a first portion  422  configured to extend at least partially into the neck  116 . The third portion  424  may include a chamber  429  which defines an open area or space configured to house the first portion  142  of the fluid path  140  ( FIG. 4A ). The open area or space defined by the chamber  429  may provide various benefits as compared to a completely solid cap. For example, the chamber  429  may reduce the amount of resistance required to advance the first portion  142  of the fluid path  140  into the interior region  118  of the container  112  ( FIG. 4B ). In addition, the chamber  429  may extend proximally beyond the sharpened first end  141  of the fluid path  140  to further reduce or eliminate the potential for the lumen  146  to become plugged with a “core” of the cap  420  as the fluid path  140  is advanced in the direction of the arrow  105  into the interior region  118 . In addition, or alternatively, the chamber  429  may reduce the amount of resistance required to advance the first portion  142  of the fluid path  140  in the direction of the arrow  105  into the interior region by moving to a collapsed configuration ( FIG. 4C ). Although the chamber  429  is depicted entirely within the third portion  424  of the cap  420 , in various embodiments, the chamber  429  may extend into the second portion  423  or first portion  422  of the cap  420 . 
     Referring to  FIG. 5 , in one embodiment, a drug delivery system  100  of the present disclosure may further include a cap  520  with a “top hat” configuration, which includes a first portion  522  configured to overlap an end of the neck  116 , and a second portion  523  configured to extend distally beyond (e.g., away from) the neck  116 , without any portion of the cap extending into the neck  116 . The neck  116  may include a flared portion  117  to provide a surface against which the first crimp  126  may be compressed to secure the first portion  522  of the cap  520  against the end of the neck  116 . 
     In any of the embodiments of  FIGS. 1-4C , the first portion  122 ,  222 ,  322 ,  422  of the respective cap  120 ,  220 ,  320 ,  420 , which extends into the neck  116  may include one or more compliant or semi-compliant materials, as are known in the art (e.g., polymers, rubbers, silicones, etc.), which are sufficiently compressible to establish a friction or interference fit with an inner wall of the neck  116  with sufficient force to resist movement (e.g., creeping) of the cap, and provide a fluid-tight seal. In addition, at least the interface surface of the first portion  122 ,  222 ,  322 ,  422 ,  522  of the cap  120 ,  220 ,  320 ,  420 ,  520 , which contacts the fluid drug  150  may preferably include a material which is compatible with (e.g., does not react with or otherwise alter) the fluid drug  150 . 
     As illustrated in  FIG. 1 , in any of the embodiments of  FIGS. 1-5 , a length L 1  of the first portion  142  of the fluid path  140  disposed within the cap  120  may be greater than a distance L 2  between the sharpened first end  141  and an interface of the fluid drug  150  and the first portion  122  of the cap  120 . As will be understood by those of skill in the art, the length L 1  may be sufficient to allow only the first portion  142  of the fluid path  140  embedded within the cap  120  to be placed in contact with the fluid drug  150  when the fluid path  140  is advanced, thereby preventing a potentially non-sterile portion of the fluid path  140  extending distally beyond the cap  120  from contacting the fluid drug  150 . As will be understood by one of skill in the art, single-barrier system embodiments of  FIGS. 1-5  may include a cap to maintain separation between the portion of the fluid path disposed within the cap (including the first sharpened end) and the fluid drug inside the container. 
     Double-Barrier Systems 
     Referring to  FIG. 6 , in one embodiment, a drug delivery system  200  of the present disclosure may include, in combination, a container  212 , a septum  630 , a cap  620  and a fluid path  240 . The container  212  may include a body  214  and a neck  216  defining an interior region  218 . The septum  630  may be disposed about at least a portion of the neck  216  to retain a fluid drug  250  (e.g., drug, biological composition, pharmaceutical composition, etc.) within the interior region  218 . The cap  620  may be disposed against at least a portion of the septum  630 . The fluid path  240  (e.g., transfer tube, needle, syringe, etc.) may define a lumen  246  and further include a first portion  242  with a sharpened first end  241 , and a second portion  244  with a sharpened second end  243 . 
     The septum  630  may be secured to the neck  216  by a first crimp  626 . For example, the septum  630  may include a first portion  632  configured to extend at least partially into the neck  216 , and a second portion  633  configured to overlap an end of the neck  216 . The neck  216  may include a flared portion  217  to provide a surface against which the first crimp  626  may be compressed to secure the second portion  633  of the septum  630  against the end of the neck  216 . The first crimp  626  may include any suitably deformable and/or compressible material (e.g., metals, alloys, plastics, rubbers, and the like), as are known in the art. Although the first portion  632  of the septum  630  is depicted as extending into a portion of the neck  216 , in various embodiments, the first portion  632  may extend into the entire portion (e.g., 100%) of the neck, less than the entire portion of the neck (e.g., approximately 50%), no portion (e.g., 0%) of the neck, or any variation thereof. The septum  630  may include one or more compliant or semi-compliant materials, as are known in the art (e.g., polymers, rubbers, silicones, etc.), which are sufficiently compressible (e.g., crimpable) to establish a fluid-tight seal between an inner surface of the first crimp  626  and the end of the neck  216 . In addition, at least the portion (e.g., interface surface) of the septum  630 , which contacts a fluid drug  250  may preferably include a material which is compatible with (e.g., does not react with or otherwise alter) the fluid drug  250 . 
     The cap  620  may be secured to the neck  216  by a second crimp  627  disposed around a portion of the first crimp  626 . For example, the cap  620  may include a “top hat” configuration which includes a first portion  622  configured to overlap at least a portion of the septum  630  and the first crimp  626 , and a second portion  623  configured to extend distally beyond (e.g., away from) the first portion  622 . The second crimp  627  may include any suitably deformable and/or compressible material (e.g., metals, alloys, plastics, rubbers, and the like), as are known in the art. In various embodiments, the cap  620  may be secured to the septum  630  by a variety of additional and/or alternative attachment mechanisms, including, by way of non-limiting example, corresponding threaded or luer-lock surfaces, adhesives, glues, solders, resins and the like. 
     The first portion  242  of the fluid path  240  may be disposed (e.g., embedded, housed, etc.) within the second portion  623  of the cap  620  such that the sharpened first end  241  is maintained a pre-determined distance away from the interface between the fluid drug  250  and the first portion  632  of the septum  630 . For example, the sharpened first end  241  of the fluid path  240  may be separated from the fluid drug  250  by any distance, including but not limited to, 10 cm or more, more preferably 20 cm or more, and even more preferably 30 cm or more. The second portion  623  of the cap  620  may also provide structural support to the first portion  242  of the fluid path  240 , thereby preventing bending and/or moving of the fluid path during shipping, storage and/or use, which might comprise the integrity to the fluid-tight seal. 
     The second portion  244  of the fluid path  240  may be disposed (e.g., embedded, housed, etc.) within a cover  248  such that the sharpened second end  243  is shielded prior to use. In one embodiment, a length of the second portion  244  may be sufficient to penetrate the dermal layer of a patient. For example, the second portion  244  of the fluid path  240  may have a length of 0.5 cm or more, more preferably 1.0 cm or more, and even more preferably 2.0 cm or more. 
     Referring to  FIG. 7 , in one embodiment, a drug delivery system  200  of the present disclosure may further include a cap  720  with a “top hat” configuration like that of  FIG. 6 , which includes a first portion  722  configured to overlap at least a portion of the septum  730  and the first crimp  726 , and a second portion  723  configured to extend distally beyond (e.g., away from) the first portion  722 . The first and second portions  722 ,  723  may include a chamber  729  which defines an open area or space configured to house the first portion  242  of the fluid path  240 . The open area or space defined by the chamber  729  may provide various benefits as compared to a completely solid cap. For example, the chamber  729  may reduce the amount of resistance required to advance the first portion  242  of the fluid path  240  into the interior region  218  of the container  212 . In addition, as compared to embodiments in which the first portion of the fluid path is embedded within the cap, the chamber  729  may reduce or eliminate the potential for the lumen  246  to become plugged with a “core” of the cap  720  as the fluid path  240  is advanced into the interior region  218 . In addition, or alternatively, the chamber  729  may reduce the amount of resistance required to advance the first portion  242  of the fluid path  240  into the interior region  218  by moving to a collapsed configuration (not shown). Although the chamber  729  is depicted as extending between the first and second portions  722 ,  723 , in various embodiments, the chamber may be formed entirely within the second portion  723  of the cap  720 . Referring to  FIG. 8 , in one embodiment, a drug delivery system  200  of the present disclosure may further include one or more O-rings  828  disposed between the septum  830  and first portion  822  of a cap  820  to maintain a fluid-tight seal about the neck  216 . 
     In any of the embodiments of  FIGS. 1-8 , the cap  120 ,  220 ,  320 ,  420 ,  520 ,  620 ,  720 ,  820 , may include a dual-durometer material. For example, a portion of the cap may include a high durometer material, e.g., to provide additional support to the fluid path and/or provide a firm surface against which the first or second crimps may press for improved sealing. Another portion of the cap may include a low durometer material, e.g., to reduce or eliminate coring and/or provide improved sealing as the fluid path is advanced into the interior region of the container. In addition, at least a portion of the cap may include a material that is compatible with the specific sterilization modality employed (e.g., does not degrade or otherwise break down), as discussed below. 
     As illustrated in  FIG. 6 , in any of the embodiments of  FIGS. 6-8 , a length L 1  of the first portion  242  of the fluid path  240  disposed within the cap  220  may be greater than a distance L 2  between the sharpened first end  241  and an interface of the fluid drug  250  and the first portion  632  of the septum  630 . As will be understood by those of skill in the art, the length L 1  may be sufficient to allow only the first portion  242  of the fluid path  240  embedded within the cap  220  to be placed in contact with the fluid drug  250  when the fluid path  240  is advanced, thereby preventing a potentially non-sterile portion of the fluid path  240  extending distally beyond the cap  220  from contacting the fluid drug  250 . As will be understood by one of skill in the art, double-barrier system embodiments of  FIGS. 6-8  may include a cap and/or septum to maintain separation between the portion of the fluid path disposed within the cap (including the first sharpened end) and the fluid drug inside the container. 
     Although the drug delivery systems disclosed herein generally include a cap ( FIGS. 1-5 ) or cap and septum ( FIGS. 6-8 ) attached to the neck of a container, in various embodiments the container may include a variety of shapes and or configurations (e.g., cartridges, vials, pens, etc.) that do not necessarily include a neck. 
     Sterilization Protocols 
     In one embodiment, any of the drug delivery systems disclosed herein may undergo a sterilization protocol to provide a sealed and sterile fluid path. Referring to  FIG. 9 , a drug delivery system  100 ,  200  may be placed within a sterilization system  900 , which includes an energy source  910  and a shield  920 . In various embodiments, the energy source  910  may emit x-ray, γ-ray or electrical-beam (e.g., e-beam) energy. The shield  920  may include a material with a suitable composition and/or thickness to prevent (e.g., block) energy emitted  930  from the energy source  910  from passing (e.g., penetrating) therethrough. In various embodiments, the shield may comprise a material which does not emit or generate energy (e.g. x-rays, etc.) when acted upon by an energy source (or limits such emissions). For example, the shield may be formed partially or entirely of aluminum having a thickness of approximately 30 mm or more. 
     The energy source  910  and shield  920  may be positioned relative to each other such that a portion of the energy emitted  930  from energy source  910  contacts and is blocked by the shield  920 , and another portion of the energy emitted  930  is direct beyond an end of the shield  920  and remains unblocked. Alternatively, the shield  920  may include an opening (not shown) such that the energy emitted  930  from the energy source  910  contacts and is blocked by the shield  920  on either side of the opening. By way of example, the drug delivery system  100  may be positioned within the sterilization system  900  such that the entire portion of the container  112  which contains the fluid drug  150 , and at least part of the first portion  122  of the cap  120 , is aligned with (e.g., underneath) the shield  920  and protected from the energy emitted  930  from the energy source  910 . 
     The remaining portion of the drug delivery system  100 , including the cover  148 , entire fluid path  140 , and at least the portion of the cap  120  disposed around the first portion of the  142  of the fluid path  140 , is not aligned with (e.g., extends beyond) the shield  920 . Upon activation of the energy source  910 , the emitted energy  930  passes through and sterilizes the entire unshielded portion of the drug delivery system  100 , including the first portion  142  of the fluid path  140  embedded within the cap  120 , the second portion  144  of the fluid path  140  embedded within the cover  148  and the lumen  146  extending therebetween, thereby providing a sterile and sealed fluid path. Since the energy source  910  does not generate heat, the drug delivery system  100  may remain within the sterilization system  900  as long as required for sterilization of the entire fluid path  140  without the need for any form of refrigeration, light and/or humidity control systems. As explained above, various cap (and septum) configurations may be used to increase or decrease the distance between the portion of the fluid path embedded within the cap and the fluid drug within the container depending, e.g., on the preferred target surface area for the energy source, the duration of the sterilization protocol and/or the stability requirements of the specific fluid. Although  FIG. 9  depicts a drug delivery system  100  of the present disclosure undergoing a sterilization protocol, in various embodiments, any of the drug delivery systems disclosed herein  200 ,  300 ,  400  may undergo a sterilization protocol in a sterilization system of  FIG. 9  or  FIGS. 16-18  (discussed below). 
     In various embodiments herein, the drug stored in the container can be exposed to limited amounts of the emitted energy (e.g., radiation or electron beam). The amount of exposure can be less than a critical level and/or less than a level that can cause substantial degradation of the drug stored in the container. 
     As will be understood by one of skill in the art, the drug delivery systems, sterilization systems and protocols described herein may provide a number of advantages over conventional drug delivery systems, sterilization systems and modalities. By way of a non-liming example, the disclosed sterilization systems and protocols may be temperature independent, thereby allowing sterilization to be performed in a cold (e.g., refrigerated) environment to prevent degradation or inactivation of temperature sensitive drugs, biological and/or pharmaceutical compositions. In addition, the ability of the disclosed sterilization systems and protocols to be performed at the ideal temperature for a specific drug, biological and/or pharmaceutical composition, may eliminate the need for special formulations to be compatible. The disclosed drug delivery devices, sterilization systems and protocols may also eliminate the need for specialized environmental conditions (e.g., vacuum sealed containers, etc.). The disclosed drug delivery devices, sterilization systems and protocols may also prevent exposure of the biological and/or pharmaceutical composition, as well as certain material components of the drug-delivery system, to the specific sterilization modality (x-ray, γ-ray or electrical-beam (e.g., e-beam) energy). The disclosed sterilization systems and protocols may also be compatible with conventional containers, thereby eliminating the need to exchange containers during the filling or finishing process. 
     Referring to  FIG. 10 , in use and by way of example, a user may “activate” a drug delivery system by proximally advancing the fluid path  140  in the direction of the arrow  105  towards the container  112  such that the sterile first portion  142  of the fluid path  140  housed within the cap  120  enters the interior region  118 . With the lumen  146  of the fluid path  140  in contact with the fluid drug  150 , the sterile second portion  144  of the fluid path  140  may be advanced through the cover  148  and dermal layer of the patient. Since only the first and second portions  142 ,  144  of the fluid path  140  penetrate the interior region  118  of the container  112  and the dermal layer, respectively, any non-sterile portion of the fluid path  140  (e.g., between the cap  120  and cover  148 ) is prevented from penetrating either the patient or the container. In one embodiment, the steps of advancing the first portion  142  of the fluid path  140  into the interior region  118  of the container  112 , and advancing the second portion  144  of the fluid path  140  through the dermal layer, may occur almost simultaneously. For example, a user may employ a “jabbing” or “stabbing” motion to advance the sterile second portion  144  of the fluid path  140  into the dermal layer. The force exerted on the fluid path  140  by this “jabbing” or “stabling” motion may simultaneously drive the sterile first portion  142  of the fluid path  140  into the interior region  118  of the container  112 . In one embodiment, the container  112  may be pressurized such that the proper dosage of fluid drug  150  is automatically delivered through the lumen  146  of the fluid path  140  and into the patient. Alternatively, the container  112  may include a delivery mechanism, e.g., plunger, etc. (not shown) which the user may actuate as necessary to deliver the fluid drug  150  through the lumen  146  of the fluid path  140  and into the patient. Alternatively, the drug delivery system may include an inertia driven system that includes, e.g., a safety and trigger mechanism configured to automatically drive the first portion  142  of the fluid path  140  into the interior region  118  of the container and/or drive the second portion  144  of the fluid path  140  through the dermal layer. In various embodiments, the drive/delivery mechanism which conveys movement of the fluid path in either (or both) directions may include an electromechanical or mechanical system. 
     Assembly Protocols 
     Prior to implementing the sterilization protocol, the drug delivery systems of the present disclosure may undergo various assembly protocols using aseptic techniques, as are known in the art. For example, a drug delivery system  100  that includes a single-barrier may be assembled by sterilizing the container  112  with ethylene oxide, and sterilizing the cap  120  with steam or γ-irradiation. In some embodiments, the cap may comprise a gas-permeable material compatible with nitrous oxide (NO 2 ) sterilization, which may be beneficial for sterilizing a cap that includes an inner chamber. The sterilized container  112  may then be filled with a sterile fluid drug  150  under aseptic conditions. The sterilized cap  120  may then be positioned on the neck  116  of the fluid-filled container  112  and secured using the first crimp  126 . Alternatively, the sterilized cap  120  may be attached to an empty sterilized container  112 , as outlined above, and the container  112  filled with sterile fluid drug  150  through the cap  120  using a sterile syringe. The first portion  142  of the fluid path  140  may then be positioned (e.g., inserted) a predetermined distance within the cap  120 , and the second portion  144  of the fluid path  140  may be positioned a predetermined distance within a cover  148 . 
     A drug delivery system  200  that includes a double-barrier system may be assembled by sterilizing the container  212  with ethylene oxide, and sterilizing the cap  620 ,  720 ,  820  and septum  630 ,  730 ,  830  with steam or γ-irradiation. The container  212  may then be filled with sterile fluid drug  250  under aseptic conditions. The sterilized septum  630 ,  730 ,  830  may then be positioned on the neck  216  of the fluid-filled container  212  and secured using the first crimp  626 . Alternatively, the sterilized septum  630 ,  730 ,  830  may be attached to an empty sterilized container  212 , as outlined above, and the container  212  filled with the fluid drug  250  through the septum  630 ,  730 ,  830  using a sterile syringe. The sterilized cap  620 ,  720 ,  820  may then be positioned on or above the septum  630 ,  730 ,  830  and secured using the second crimp  627 . The first portion  242  of the fluid path  240  may then be positioned (e.g., inserted) a predetermined distance within the cap  620 ,  720 ,  820  and the second portion  244  of the fluid path  240  may be positioned a predetermined distance within the cover  248 . The fully assembled drug delivery system  100 ,  200  may then undergo a sterilization protocol to provide a sealed and sterile fluid path, as discussed above. 
     Plunger Systems 
     In various embodiments, a drug delivery system of the present disclosure may include a needle path that does not extend through the cap and/or septum positioned at the neck of the container, but instead extends through a cap and plunger located at the opposite end of the container. The container may be filled under aseptic conditions by introducing the needle of a separate syringe (not shown) through the septum into the interior region  118 . 
     Referring to  FIG. 11 , in one embodiment, a drug delivery system  300  of the present disclosure may include, in combination, a container  312 , a cap  1120 , a plunger  1160  and a fluid path  340 . The container  312  may include a body  314  defining an interior region  318 . The cap  1120  may be disposed within an end portion of the container  312 . The fluid path  340  (e.g., transfer tube, needle, syringe, etc.) may define a lumen  346  and further include a first portion  342  with a sharpened first end  341 , and a second portion  344  with a sharpened second end  343 . The cap  1120  may include one or more semi-compliant materials, as are known in the art (e.g., polymers, rubbers, silicones, etc.), which are sufficiently compressible to establish a friction or interference fit with an inner wall of the container  312  with sufficient force to resist movement of the cap, and provide a fluid-tight seal. The cap  1120  may further include one or more O-rings  1128  disposed between the cap  1120  and inner wall of the container  312  to maintain the fluid-tight seal. A septum  1130  may be disposed within, and extend through, a central portion of the cap  1120 . The septum  1130  may be permanently affixed within the cap  1120  using suitable adhesives, glues and/or resins, as are known in the art. 
     Alternatively, in place of a septum, the cap  1120  may include a dual-durometer material such that, e.g., an outer portion of the cap  1120  is formed of a high-durometer material for improved compression against the inner wall of the container  312 , and an inner portion of the cap  1120  is formed of a low-durometer material to reduce or eliminate coring and/or provide improved sealing around the fluid path  340 . The cap  1120  and/or septum  1130  may also provide structural support to the first portion  342  of the fluid path  340 , thereby preventing bending and/or moving of the fluid path during shipping, storage and/or use, which might comprise the integrity of the fluid-tight seal. In addition, at least a portion of the plunger  1160 , cap  1120  and/or septum  1130  may include a material that is compatible with the specific sterilization modality employed (e.g., does not degrade or otherwise break down), as discussed above. 
     The plunger  1160  may be slidably disposed within the container  312  proximal to the septum to retain a fluid drug  350  (e.g., drug, biological composition, pharmaceutical composition, etc.) within the interior region  318 . The first portion  342  of the fluid path  340  may be disposed within an open space  362  between the cap  1120  and plunger  1160  such that the sharpened first end  341  is maintained a predetermined distance away from the interface between the fluid drug  350  and the plunger  1160 . For example, the sharpened first end  341  of the fluid path  340  may be separated from the fluid drug  350  by a distance of 10 cm or more, more preferably 20 cm or more, and even more preferably 30 cm or more. The second portion  344  of the fluid path  340  may be disposed (e.g., embedded, housed, etc.) within a cover  348  such that the sharpened second end  343  is shielded prior to use. In one embodiment, a length of the second portion  344  may be sufficient to penetrate the dermal layer of a patient. For example, the second portion  344  of the fluid path  340  may have a length of 0.5 cm or more, more preferably 1.0 cm or more, and even more preferably 2.0 cm or more. 
     Referring to  FIG. 12 , in one embodiment, the first portion  342  of the fluid path  340  may extend through the open space  362  into a portion of the plunger  1160  to provide additional support and/or protection to the fluid path. 
     In various embodiments, the drug delivery system  300  may be positioned within a sterilization system, as discussed above, such that the entire portion of the container  312  which contains the fluid drug is aligned with (e.g., underneath) a shield and protected from energy emitted from an energy source. The remaining portion of the drug delivery system  300 , including the first portion  342  of the fluid path  340  and at least a portion of the plunger  1160 , is not aligned with (e.g., extends beyond) the shield. Upon activation of the energy source, the emitted energy passes through and sterilizes the entire unshielded portion of the drug delivery system  300  (e.g., the first portion  342  of the fluid path  340  and a portion of the plunger  1160 ), thereby providing a sterile and sealed fluid path. In various embodiments, the first portion  342  of the fluid path  340  can be positioned within a portion of the plunger  1160 . In such embodiments, the first portion  342  of the fluid path  340  can be partially embedded in the plunger  1160 . The first portion  342  of the fluid path  340  can be exposed to emitted energy from the energy source for sterilization. After sterilization, upon activation, the first portion  342  of the fluid path  340  can pierce through the remaining portion of the plunger  1160 . 
     The individual components (e.g., container  312 , cap  1120 , septum  1130  and plunger  1160 ) of the drug delivery system  300  of  FIG. 11 or 12  may be individually sterilized, assembled and filled with fluid drug  350  using aseptic techniques, as described above. Similarly, the drug delivery systems  300  of  FIG. 11 or 12  may undergo a sterilization protocol which shields the portion of the container  312  filled with the fluid drug  350  and exposes the full length of the fluid path  340  to sterilization energy to provide a sealed and sterile fluid path  340 , as described above. 
     Referring to  FIG. 13 , in use and by way of example, a user may “activate” a drug delivery system  300  by proximally advancing the fluid path  340  in the direction of the arrow  105  towards the container  312  such that the sterile first portion  342  of the fluid path  340  housed within the open space  362  ( FIG. 11 ) or plunger  1160  ( FIG. 12 ) enters the interior region  318 . Referring to  FIG. 14 , with the lumen  346  the fluid path  340  in contact with the fluid drug  350 , the sterile second portion  344  of the fluid path  340  may be advanced in the direction of the arrow  105  through the cover  348  to penetrate the dermal layer of the patient, and the plunger  1160  and fluid path  340  advanced proximally to force the fluid drug  350  through the lumen  346  of the fluid path  340  into the patient. Since only the first and second portions  342 ,  344  of the fluid path  340  penetrate the interior region  318  of the container  312  and dermal layer, respectively, any non-sterile portion of the fluid path  340  (e.g., between the cap  320  and cover  348 ) is prevented from penetrating either the patient or the container. 
     In any of the embodiments of  FIGS. 11 and 12 , a length L 1  of the first portion  342  of the fluid path  340  disposed within the open space  362  ( FIG. 11 ) or plunger  1160  ( FIG. 12 ) may be greater than a distance L 2  between the sharpened first end  341  and an interface of the fluid drug  350  and the plunger  1160 . As will be understood by those of skill in the art, the length L 1  may be sufficient to allow only the first portion  342  of the fluid path  340  embedded within the open space  362 , or plunger  1160 , to be placed in contact with the fluid drug  350  when the fluid path  340  is advanced proximally, thereby preventing a potentially non-sterile portion of the fluid path  340  extending distally beyond the open space  362  or plunger  1160  from contacting the fluid drug  350 . 
     Pre-Loaded Syringe Systems 
     Referring to  FIG. 15A , in one embodiment, a drug delivery system  400  of the present disclosure may include, in combination, a container  1512 , a cap  1520  and a fluid path  440 . The container  1512  may include, e.g., a standard syringe comprising a needle  1516  in fluid communication with an interior region  1518  of the container and a plunger  1560  slidably disposed within the interior region  1518 . The needle  1516  may define a lumen  1546  and further include a distal portion  1542  with a sharped end  1541 . The distal portion  1542  of the needle  1516  may be embedded within a first portion  1522  of the cap  1520 . The fluid path  440  (e.g., transfer tube, needle, syringe, etc.) may define a lumen  446  and further include a first portion  442  with a sharpened first end  441 , and a second portion  444  with a sharpened second end  443 . The first portion  442  of the fluid path  440  may extend through a second portion  1523  of the cap  1520  and into a chamber  1529  within the cap  1520 . The second portion  444  of the fluid path  440  may be disposed (e.g., embedded, housed, etc.) within a cover  448  such that the sharpened second end  443  is shielded prior to use. 
     The container  1512  may be sterilized using ethylene oxide, steam or γ-irradiation and loaded with a sterile fluid drug  450  using aseptic techniques, as described above. The distal portion  1542  of the needle  1516  and first portion  442  of the fluid path  440  may then be positioned within the first portion  1522  and chamber  1529  of the cap  1520 , respectively. Once assembled, the drug delivery system  400  may undergo a sterilization protocol to provide a sealed and sterile fluid path  440  and/or sterile needle  1516 , as described above. 
     For example, the drug delivery system  400  may be placed within a sterilization system  900 , which includes an energy source  910  and a shield  920 . In various embodiments, the energy source  910  may emit x-ray, γ-ray or electrical-beam (e.g., e-beam) energy. The shield  920  may include a material with a suitable composition and/or thickness to prevent (e.g., block) energy emitted  930  from the energy source  910  from passing (e.g., penetrating) therethrough. In various embodiments, the shield  920  may comprise a material which does not emit or generate energy (e.g. x-rays, etc.) when acted upon by an energy source (or limits such emissions). For example, the shield  920  may be formed partially or entirely of aluminum having a desired thickness such as, for example, a thickness of approximately 30 mm or more. 
     The energy source  910  and shield  920  may be positioned relative to each other such that a portion of the energy emitted  930  from energy source  910  contacts and is blocked by the shield  920 , and another portion of the energy emitted  930  is directed beyond an end of the shield  920  and remains unblocked. By way of example, the drug delivery system  400  may be positioned within the sterilization system  900  such that the entire portion of the container  1512  which contains the fluid drug is aligned with (e.g., underneath) the shield  920  and protected from the energy emitted  930  from the energy source  910 . The remaining portion of the drug delivery system  400 , including the distal portion  1542  of the needle  1516 , the cap  1520 , the fluid path  440  and cover  448 , is not aligned with (e.g., extends beyond) the shield  920 . Upon activation of the energy source  910 , the emitted energy  930  passes through and sterilizes the entire unshielded portion of the drug delivery system  400 , thereby providing a sterile and sealed fluid path. Since the energy source  910  does not generate heat, the drug delivery system  400  may remain within the sterilization system  900  as long as required for sterilization of the entire fluid path  440  without the need for any form of refrigeration, light and/or humidity control systems. 
     Referring to  FIG. 15B , in use and by way of example, a user may “activate” a drug delivery system  400  by distally advancing the container  1512  in the direction of the arrow  105  towards the cap  1520  such that sterile distal portion  1542  of the needle  1516  housed within the first portion  1522  of the cap  1520  enters the and chamber  1529 , thereby placing the respective lumens  1546 ,  446  of the needle  1516  and fluid path  440  in fluid communication. The second portion  444  of the fluid path  440  may be inserted through the dermal layer, and the plunger  1560  depressed such that fluid drug  450  flows through the lumen  1546  of needle  1516  into the sterile chamber  1529  and through the sterile lumen  446  of the fluid path  440  into the patient. 
     In any of the embodiments of  FIGS. 1-8, 11, 12 and 15A-15B , the cover  148 ,  248 ,  348 ,  448  may be removed from the second portion  144 ,  244 ,  344 ,  444  of the fluid path  140 ,  240 ,  340 ,  440  prior to penetrating the dermal layer of a patient. Alternatively, the second portion  144 ,  244 ,  344 ,  444  of the fluid path  140 ,  240 ,  340 ,  440  may be advanced through the cover  148 ,  248 ,  348 ,  448  and through the dermal layer of a patient. The drug delivery systems  100 ,  200 ,  300 ,  400  may include a depth setting such that only the second portion  144 ,  244 ,  344 ,  444  of the fluid path  140 ,  240 ,  340 ,  440  penetrates the dermal layer, thereby preventing a potentially non-sterile portion of the fluid path  140 ,  240 ,  340 ,  440  extending proximally beyond the cover  148 ,  248 ,  348 ,  448  from penetrating the dermal layer of the patient. 
     Shield Assemblies 
     With reference to the sterilization system  900  schematically depicted in  FIG. 9  (above), in one embodiment, the shield  920  may be configured to block sterilization energy emitted from an energy source  910  along or above one side of the drug delivery system. Referring to  FIGS. 16A, 16B, and 17-18 , in one embodiment, the present disclosure may include a shield assembly  1600  configured to provide 360 degrees of shielding to a drug delivery system disposed therein. In various embodiments, the shield assembly  1600  may include, in combination, first and second interlocking components  1610 ,  1620  (interlocking component  1620  not shown in the overhead view of the assembly  1600  in  FIG. 16A  or the close-up view thereof in  FIG. 16B ). The first component  1610  may include a first window or opening  1615  extending through a width thereof, and the second component  1620  (e.g., positioned under the first component  1610 ) may include a corresponding second window or opening  1625  (see  FIG. 17 ) extending through a width thereof. 
     Each of the first and second windows  1615 ,  1625  may be configured to define a contiguous opening  1630  (see  FIG. 18 ) through the assembled shield assembly  1600 , e.g., when the first and second interlocking components  1610 ,  1620  are locked together. One or both of the first or second components  1610 ,  1620  may be dimensioned to securely receive the outer surface of a portion of a drug delivery system such that the portion of the drug delivery system to be sterilized (e.g., the entire length of the fluid path  240  and portion of the cap  620  and/or septum  630 ) extends into the contiguous opening  1630 , and the portion of the drug delivery system to be shielded from an energy source is covered, encased or otherwise blocked around an entire circumference thereof by the shield assembly  1600 . 
     As described above, the shield assembly  1600  may be formed partially or entirely of a material (e.g., aluminum) with a sufficient thickness (e.g., approximately 30 mm or more) to prevent (e.g., shield) energy emitted from the energy source from acting upon the fluid drug and/or material components of the drug delivery system which may degrade or otherwise become compromised by such energy, and without emitting x-ray&#39;s or other deleterious energy when acted upon by the energy source (or limiting such emissions). In various embodiments, with the drug delivery system previously loaded with a fluid drug under aseptic conditions (as discussed above) and secured within an assembled shield assembly  1600 , the entire shield assembly  1600  may be placed within a suitable chamber and exposed to an energy source to provide 360 degrees of sterilization of the portion of the drug delivery system extending through the contiguous opening  1630 , while providing complete shielding of the remaining portion of the drug delivery system housed within the interlocked first and second components  1610 ,  1620 . 
     As will be understood by those of skill in the art, the entire shield assembly  1600  with a drug delivery system disposed therein may be exposed to a given sterilization modality for a variety of times as previously determined to provide complete sterilization of the exposed portions thereof (e.g., extending through the contiguous opening  1630 ). In one embodiment, the energy source may rotate around the shield assembly  1600  to provide optimal exposure to the sterilization energy. Alternatively, the energy source may remain in a fixed position, and the shield assembly rotated to provide optimal exposure to the sterilization assembly. In various embodiments, one or more energy sources may be used. Further, the assembly  1600  can exposed to a given sterilization modality in bulk—that is, multiple assemblies  1600  can be together grouped and sterilized at the same time. Any of the drug delivery devices described herein can be used with the assembly  1600 . 
     The following examples pertain to additional embodiments: 
     Example 1 is a method for providing a sealed and sterile fluid path, comprising exposing a drug delivery system to an energy source, the drug delivery system comprising a container comprising a fluid drug, a cap disposed about an opening of the container, and a fluid path defining a lumen, the fluid path comprising a first portion disposed within a portion of the cap, and a second portion disposed within a cover, wherein energy emitted from the energy source passes through and sterilizes the fluid path, and does not pass through any portion of the container comprising the fluid drug. 
     Example 2 is an extension of example 1 or any other example disclosed herein, wherein a length of the first portion of the fluid path disposed within the cap is greater than a distance between a sharpened first end of the fluid path and an interior region of the container. 
     Example 3 is an extension of example 1 or any other example disclosed herein, wherein the energy emitted from the energy source is selected from the group consisting of x-ray energy, γ-ray energy and electrical-beam energy. 
     Example 4 is an extension of example 1 or any other example disclosed herein, wherein the cap is configured to form a fluid-tight seal about the opening of the container. 
     Example 5 is an extension of example 1 or any other example disclosed herein, further comprising a septum disposed between the cap and the opening of the container. 
     Example 6 is a method for providing a sealed and sterile fluid path, comprising exposing a drug delivery system to an energy source, the drug delivery system comprising a container comprising a fluid drug, a cap disposed about an opening of the container, a plunger slidably disposed within the container and proximal to the cap, wherein the cap and plunger are separated by an open space, and a fluid path defining a lumen, the fluid path comprising a first portion extending through the cap and disposed within the open space, and a second portion disposed within a cover, wherein energy emitted from the energy source passes through and sterilizes the fluid path, and does not pass through any portion of the container comprising the fluid drug. 
     Example 7 is an extension of example 6 or any other example disclosed herein, wherein a length of the first portion disposed within the open space is greater than a distance between a sharpened first end of the fluid path and an interior region of the container. 
     Example 8 is an extension of example 6 or any other example disclosed herein, wherein the energy emitted from the energy source is selected from the group consisting of x-ray energy, γ-ray energy and electrical-beam energy. 
     Example 9 is an extension of example 6 or any other example disclosed herein, wherein the cap is configured to form a fluid-tight seal about the opening of the container. 
     Example 10 is an extension of example 6 or any other example disclosed herein, further comprising a septum disposed within a portion of the cap. 
     Example 11 is a method for providing a sealed and sterile fluid path, comprising exposing a drug delivery system to an energy source, the drug delivery system comprising a container comprising a fluid drug, a cap disposed about an opening of the container, a plunger slidably disposed within the container and proximal to the cap, wherein the cap and plunger are separated by an open space, and a fluid path defining a lumen, the fluid path comprising a first portion extending through the cap and the open space and disposed within a portion of the plunger, and a second portion disposed within a cover, wherein energy emitted from the energy source passes through and sterilizes the fluid path, and does not pass through any portion of the container comprising the fluid drug. 
     Example 12 is an extension of example 11 or any other example disclosed herein, wherein a length of the first portion disposed within the plunger is greater than a distance between a sharpened first end of the fluid path and an interior region of the container. 
     Example 13 is an extension of example 11 or any other example disclosed herein, wherein the energy emitted from the energy source is selected from the group consisting of x-ray energy, γ-ray energy and electrical-beam energy. 
     Example 14 is an extension of example 11 or any other example disclosed herein, wherein the cap is configured to form a fluid-tight seal about the opening of the container. 
     Example 15 is an extension of example 11 or any other example disclosed herein, further comprising a septum disposed within a portion of the cap. 
     Example 16 is a sterilization system an energy source, and a drug delivery device, the drug delivery device comprising a cap having a first portion, a second portion, and a chamber disposed between the first and second portions, a container storing a fluid drug and having a needle in fluid communication with an interior region of the container, wherein a distal portion of the needle is disposed within the first portion of the cap, and a fluid path defining a lumen, the fluid path having a first portion extending though the second portion of the cap and disposed within the chamber and a second portion disposed within a cover, wherein energy emitted from the energy source passes through and sterilizes the fluid path, and does not pass through any portion of the container storing the fluid drug. 
     Example 17 is an extension of example 1 or any other example disclosed herein, wherein the energy emitted from the energy source is selected from the group consisting of x-ray energy, γ-ray energy and electrical-beam energy. 
     Example 18 is a sterilization system, comprising an energy source, the drug delivery system of claim  1 , and a shield, wherein the shield is positioned between the energy source and the drug system such that energy emitted from the energy source passes through and sterilizes the fluid path, and does not pass through any portion of the container comprising the fluid drug. 
     Example 19 is a sterilization system, comprising an energy source, the drug delivery system of claim  6 , and a shield, wherein the shield is positioned between the energy source and the drug system such that energy emitted from the energy source passes through and sterilizes the fluid path, and does not pass through any portion of the container comprising the fluid drug. 
     Example 20 is a sterilization system, comprising an energy source, the drug delivery system of claim  11 , and a shield, wherein the shield is positioned between the energy source and the drug system such that energy emitted from the energy source passes through and sterilizes the fluid path, and does not pass through any portion of the container comprising the fluid drug. 
     Example 21 is a sterilization system, comprising an energy source, the drug delivery system of claim  18 , and a shield, wherein the shield is positioned between the energy source and the drug system such that energy emitted from the energy source passes through and sterilizes the fluid path, and does not pass through any portion of the container comprising the fluid drug. 
     Example 22 is a drug delivery system, comprising a container comprising a fluid drug, a cap disposed about an opening of the container, and a sealed and sterile fluid path comprising a first portion disposed within a portion of the cap and a second portion disposed within a cover. 
     Example 23 is an extension of example 22 or any other example disclosed herein, wherein the cap is configured to form a fluid-tight seal about the opening of the container. 
     Example 24 is an extension of example 2 or any other example disclosed herein, further comprising a septum disposed between the cap and the opening of the container. 
     Example 25 is an extension of example 22 or any other example disclosed herein, wherein a length of the first portion of the fluid path disposed within the cap is greater than a distance between a sharpened first end of the fluid path and an interior region of the container. 
     Example 26 is an extension of example 22 or any other example disclosed herein, wherein the cap includes a first portion, a second portion and a third portion. 
     Example 27 is an extension of example 26 or any other example disclosed herein, wherein the first portion of the cap extends at least partially into a neck of the container, the second portion overlaps the opening of the container, and the third portion extends distally beyond the second portion. 
     Example 28 is an extension of example 26 or any other example disclosed herein, wherein the first portion of the fluid path is disposed within the third portion of the cap. 
     Example 29 is an extension of example 28 or any other example disclosed herein, wherein the third portion of the cap includes a chamber, and wherein the first portion of the fluid path is at least partially disposed within the chamber. 
     Example 30 is an extension of example 29 or any other example disclosed herein, wherein the chamber is configured to collapse as the first portion of the fluid path is proximally advanced an interior region of the container. 
     Example 31 is a drug delivery system, comprising a container comprising a fluid drug, a cap disposed within an end portion of the container, a plunger slidably disposed within the container and proximal to the cap, wherein the cap and plunger are separated by an open space, and a sealed and sterile fluid path, the sealed and sterile fluid path comprising a first portion extending through the cap and disposed within the open space, and a second portion disposed within a cover. 
     Example 32 is an extension of example 31 or any other example disclosed herein, wherein the cap is configured to form a fluid-tight seal about the opening of the container. 
     Example 33 is an extension of example 31 or any other example disclosed herein, wherein the plunger is configured to form a fluid-tight seal between the open space and the fluid within the container. 
     Example 34 is an extension of example 31 or any other example disclosed herein, wherein a length of the first portion of the fluid path disposed within the open space is greater than a distance between a sharpened first end of the fluid path and the fluid within the container. 
     Example 35 is a drug delivery system, comprising a container comprising a fluid drug, a cap disposed within an end portion of the container, a plunger slidably disposed within the container and proximal to the cap, wherein the cap and plunger are separated by an open space, and a sealed and sterile fluid path, the sealed and sterile fluid path comprising a first portion extending through the cap and open space and disposed within a portion of the plunger, and a second portion disposed within a cover. 
     Example 36 is an extension of example 35 or any other example disclosed herein, wherein the cap is configured to form a fluid-tight seal about the opening of the container. 
     Example 37 is an extension of example 6 or any other example disclosed herein 35, wherein the plunger is configured to form a fluid-tight seal between the open space and the fluid within the container. 
     Example 38 is an extension of example 35 or any other example disclosed herein, wherein a length of the first portion of the fluid path disposed within the plunger is greater than a distance between a sharpened first end of the fluid path and the fluid within the container. 
     Example 39 is a drug delivery system, comprising a cap, comprising a first portion, a second portion, and a chamber disposed between the first and second portions, a container comprising a fluid drug and a needle in fluid communication with an interior region of the container, wherein a distal portion of the needle is disposed within the first portion of the cap, and a sealed and sterile fluid path, the sealed and sterile fluid path comprising a first portion extending though the second portion of the cap and disposed within the chamber, and a second portion disposed within a cover. 
     The following examples pertain to additional further embodiments: 
     Example 1 is a system comprising a container having a main body and a neck, the container configured to hold a liquid drug, a cap coupled to the neck, the cap configured to seal an open end of the container, a fluid path having a first end disposed within the cap and a second end disposed within a cover, an energy source configured to emit energy, and a shield positioned adjacent to the container, the shield configured to expose the fluid path to the emitted energy while blocking exposure of the liquid drug to a substantial portion of the emitted energy. 
     Example 2 is an extension of example 1 or any other example disclosed herein, wherein the emitted energy is configured to sterilize the fluid path. 
     Example 3 is an extension of example 2 or any other example disclosed herein, wherein the emitted energy comprises an electron beam. 
     Example 4 is an extension of example 3 or any other example disclosed herein, wherein the shield comprises aluminum. 
     Example 5 is an extension of example 4 or any other example disclosed herein, wherein the aluminum shield has a thickness of at least 30 mm. 
     Example 6 is an extension of example 3 or any other example disclosed herein, wherein the fluid path comprises a lumen. 
     Example 7 is an extension of example 3 or any other example disclosed herein, wherein the liquid drug is sterilized prior to sterilizing the fluid path. 
     Example 8 is an extension of example 1 or any other example disclosed herein, wherein the first end of the fluid path comprises a first sharpened tip and the second end of the fluid path comprises a second sharpened tip. 
     Example 9 is an extension of example 8 or any other example disclosed herein, wherein the first sharpened tip is configured to pierce the cap and to extend through the cap to couple the first sharpened tip to the liquid drug based on an activation by a user. 
     Example 10 is an extension of example 9 or any other example disclosed herein, wherein the cap comprises a first portion configured to extend into a portion of the neck. 
     Example 11 is an extension of example 10 or any other example disclosed herein, wherein the cap comprises a second portion configured to overlap an end of the neck. 
     Example 12 is an extension of example 11 or any other example disclosed herein, wherein the cap comprises a third portion configured to extend away from the neck and the first portion of the cap. 
     Example 13 is an extension of example 12 or any other example disclosed herein, wherein the first sharpened tip is positioned within the first portion of the cap prior to the activation by the user. 
     Example 14 is an extension of example 12 or any other example disclosed herein, wherein the first sharpened tip is positioned within the third portion of the cap prior to the activation by the user. 
     Example 15 is an extension of example 14 or any other example disclosed herein, wherein the third portion comprises an open chamber. 
     Example 16 is an extension of example 15 or any other example disclosed herein, wherein the third portion is configured to collapse when the first sharpened tip pierces the cap upon activation by the user. 
     Example 17 is an extension of example 11 or any other example disclosed herein, wherein the cap is coupled to the neck by a crimp component overlapping the second portion of the cap. 
     Example 18 is an extension of example 9 or any other example disclosed herein, further comprising a septum positioned between the cap and the liquid drug. 
     Example 19 is a method comprising positioning a first end of a fluid path within a container configured to hold a liquid drug, positioning a second end of the fluid path within a cover, positioning a shield between an energy source and the container, and exposing the fluid path to energy emitted by the energy source to sterilize the fluid path while blocking exposure of the liquid drug to a substantial portion of the energy emitted by the energy source. 
     Example 20 is an extension of example 19 or any other example disclosed herein, wherein positioning the shield comprising positing an aluminum shield having a thickness of at least 30 mm between the container and the energy source. 
     Example 21 is an extension of example 19 or any other example disclosed herein, further comprising sterilizing the liquid drug prior to sterilizing the fluid path. 
     Example 22 is an extension of example 19 or any other example disclosed herein, further comprising piercing a cap sealing the container with the first end of the fluid path to couple the liquid drug to the fluid path upon activation by a user. 
     Example 22 is an extension of example 22 or any other example disclosed herein, further comprising piercing a septum sealing the container with the first end of the fluid path to couple the liquid drug to the fluid path upon activation by a user. 
     Example 23 is an extension of example 19 or any other example disclosed herein, further comprising piercing a plunger sealing the container with the first end of the fluid path to couple the liquid drug to the fluid path upon activation by a user. 
     Example 24 is an extension of example 19 or any other example disclosed herein, wherein positioning the shield between the energy source and the container comprises placing the fluid path and the container within a first shield component having an exposure window and coupling a second shield component to the first shield component. 
     Certain embodiments of the present invention were described above. It is, however, expressly noted that the present invention is not limited to those embodiments, but rather the intention is that additions and modifications to what was expressly described herein are also included within the scope of the invention. Moreover, it is to be understood that the features of the various embodiments described herein were not mutually exclusive and can exist in various combinations and permutations, even if such combinations or permutations were not made express herein, without departing from the spirit and scope of the invention. In fact, variations, modifications, and other implementations of what was described herein will occur to those of ordinary skill in the art without departing from the spirit and the scope of the invention. As such, the invention is not to be defined only by the preceding illustrative description.