System and method for aseptic packaging of a drug delivery device components

A method for sterilizing a drug delivery device may comprise disposing a liquid drug container, a needle conduit and a cap in a sterilization enclosure so that a mouth portion of the liquid drug container is registered with, and spaced apart from, a circumferential lip of the cap; disposing a cover over the liquid drug container, the needle conduit, and the cap, sealing the sterilization enclosure; subjecting the interior of the sterilization enclosure to a sterilization process in which the liquid drug container, the needle conduit, and the cap are exposed to the sterilization fluid and are sterilized; and applying a downward force to the liquid drug container to move the mouth portion into engagement with the circumferential lip of the cap and to snap the cap onto the liquid drug container to seal the cap and needle conduit to the liquid drug container in an assembled configuration.

TECHNICAL FIELD

The present application generally relates to medication delivery devices, and more particularly to systems and methods for sterilizing drug delivery devices.

BACKGROUND

Drug delivery devices can be provided to a user with a liquid drug pre-filled in a drug container of the device. As will be appreciated, portions of the devices that will be exposed to the liquid drug must be sterilized. When a device is sealed for intended use, (such as a sterile fluid path in a non-sterile device) the options for sterilization become limited. It may not be possible or practical to use gaseous methods such as Ethylene Oxide, steam, vaporized Hydrogen Peroxide, and the like due to the inability of such fluids to penetrate into the sealed environment. It may possible to use radiation or heat to sterilize internal volumes of the sealed device, but such options may not be technically feasible because radiation and heat can have deleterious effects on certain materials of the device. Alternatively, the device could be aseptically assembled, which would allow the individual components to be sterilized by any method and then assembled into a sealed system, however, such an approach may be cost prohibitive.

Thus, it would be desirable to have allow components of a drug delivery device to be sterilized using any of a variety of methods, while eliminating the need for costly aseptic assembly environments and equipment.

SUMMARY

The present disclosure in various embodiments includes systems and methods for aseptic packaging of drug delivery device components. In an embodiment, a method for sterilizing a drug delivery device may include disposing a liquid drug container, a needle conduit, and a cap in a sterilization enclosure so that a mouth portion of the liquid drug container may be registered with, and spaced apart from, a circumferential lip of the cap. A cover may be disposed over the liquid drug container, the needle conduit, and the cap, sealing the sterilization enclosure. An interior of the sterilization enclosure may be subjected to a sterilization process in which the liquid drug container, the needle conduit, and the cap may be exposed to a sterilization fluid and may be sterilized. The interior of the sterilization enclosure may be subjected to a sterilization process that may sterilize respective interior portions of the liquid drug container, the needle conduit, and the cap. A downward force may be applied to the liquid drug container to move the mouth portion into engagement with the circumferential lip of the cap and may snap the cap onto the liquid drug container to seal the cap and the needle conduit to the liquid drug container in an assembled configuration. The downward force may be applied to a cover disposed over the enclosure. The applied downward force may move the needle conduit through a cap seal disposed in the cap, but may not move the needle through a container seal disposed in the container. The sterilization enclosure may be unsealed. A fluid assembly comprising the liquid drug container, the needle conduit, and the cap may be removed. A liquid drug may be supplied to the liquid drug container. A plunger may be disposed into the liquid drug container, sealing the liquid drug within the liquid container. A first tray may be disposed into the enclosure below the cap and the liquid drug container. A second tray may be disposed into the enclosure and may be configured to hold the liquid drug container. The liquid drug container, the needle conduit, and the cap may be enclosed in a radiation shield. A seal may be disposed within the cap, extending out of the cap, and extending through the radiation shield. The needle may be pierced through the seal. The seal may be crimped to the liquid drug container such that they abut each other. The interior of the sterilization enclosure may be subjected to a sterilization process comprising radiation. The cap may be locked to the liquid drug container.

In an aspect, a system for sterilizing a drug delivery device may include an enclosure. A first tray may be disposed within the enclosure. A second tray may be disposed within the enclosure. A cap may be disposed on the second tray. A needle conduit may extend from the cap. A liquid drug container may be disposed on the second tray such that a mouth portion of the liquid drug container may be registered with, and spaced apart from, a circumferential lip of the cap. A flexible cover may be disposed on the enclosure having a protrusion configured to substantially align with the liquid drug container. A plunger may be disposed within the liquid drug container configured to seal a liquid drug within the container. A container seal may be disposed within the liquid drug container. A cap seal may be disposed within the cap. The liquid drug container and the cap may assume a locked configuration when the mouth portion of the container that may be pressed against the circumferential lip of the cap. The needle conduit may extend through a cap seal disposed within the cap at a first end and may extend into a cannula at a second end.

In an aspect, a system for sterilizing a drug delivery device via radiation may include a liquid drug container. A liquid drug may be disposed within the container. A radiation shield may be disposed about the liquid drug container. A cap may be about an end of the liquid drug container. A seal may be disposed within the cap, may be coupled to the liquid drug container, and may extend out of the cap and through the radiation shield. A needle conduit may be registered with, and spaced apart from, a portion of the seal extending through the radiation shield. The needle conduit may be configured to extend through the seal and into the liquid drug container upon application of a force onto the needle conduit. The seal may comprise rubber. The liquid drug container may comprise glass. The seal may be coupled against the liquid drug container. A sterilization enclosure and a cover may be disposed about the radiation shielding and needle conduit. The cover may comprise a flexible cover having a protrusion configured to substantially align with the needle conduit and the liquid drug container.

DETAILED DESCRIPTION

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. 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.

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. 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 conjunction “and” includes each of the structures, components, features, or the like, which are so conjoined, unless the context clearly indicates otherwise, and the conjunction “or” includes one or the others of the structures, components, features, or the like, which are so conjoined, singly and in any combination and number, unless the context clearly indicates otherwise.

All numeric values are herein assumed to be modified by the term “about,” whether or not explicitly indicated. The term “about”, in the context of numeric values, generally refers to a range of numbers that one of skill in the art would consider equivalent to the recited value (i.e., having the same function or result). In many instances, the term “about” may include numbers that are rounded to the nearest significant figure. Other uses of the term “about” (i.e., in a context other than numeric values) may be assumed to have their ordinary and customary definition(s), as understood from and consistent with the context of the specification, unless otherwise specified.

The recitation of numerical ranges by endpoints includes all numbers within that range, including the endpoints (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

This disclosure presents various systems, components, and methods related to drug delivery devices. Each of the systems, components, and methods disclosed herein provides one or more advantages over conventional systems, components, and methods.

The disclosure contemplates performing a final assembly of a device inside a sterilization container such as, e.g., a tub, bag, custom fixture, etc. The final assembly step will provide the means to convert the device from “open”, e.g., with internal portions of the device exposed to the external atmosphere, to “closed”, e.g., with internal portions of the device not exposed to the external atmosphere. Converting a device from an “open” configuration to a “closed” configuration may be accomplished by snapping together shells, plugging a hole, capping a hole, closing a flap or door, or the like. In all cases the device will be “open” prior to and during sterilization, and then “closed” while still inside a sterile packaging. The closing step can be performed in any of a variety of ways, including through the use of mechanical manipulation of the packaging, magnetics to manipulate the device or packaging, and/or electromechanical activation (e.g., applying power through wireless charging, solar power, or activating electrical components). This disclosure provides disposable or reusable aseptic environments in which to perform the final assembly of sterilized device components without the added risks associated with breaching an aseptic environment to introduce parts.

In various embodiments, described here or otherwise, within the scope of the present disclosure, the device arrangements and methods may be applied to sub-assemblies as well as complete drug delivery devices. In the case of a pre-filled drug delivery device, the drug may not be compatible with a preferred or any sterilization method. In such a case a sealed fluid path may be attached to a drug container and sterilized prior to filling. The fluid path may remain open during sterilization and may be sealed prior to or after filling the drug container with a liquid drug and assembled into a final device, thereby maintaining the sterility and integrity of the fluid path while allowing for the use of more sterilization modalities than a filled and/or sealed device. The sealed and sterile fluid path may be filled and assembled into a final device providing a pre-filled device with a sterile fluid path, and without risk of damaging the drug that could be caused by sterilizing the fluid path after filling.

The disclosed systems and methods address issues relating to device sterilization and providing a device that is pre-filled with a liquid drug. The disclosed systems and methods facilitate aseptic filling of a terminally sterilized drug delivery device, resulting in a terminally sterilized pre-filled device. As mentioned, one problem with providing a pre-filled drug delivery device may be that it can be difficult or impossible to sterilize the pre-filled device without damaging the liquid drug, because conventional sterilization processes may require heat, radiation, or chemicals, all of which may be capable of damaging the drug.

With reference toFIGS. 1 and 2, an embodiment of a drug delivery device1may be an OmniPod® (Insulet Corporation, Billerica, Mass.) insulin delivery device in some embodiments. The drug delivery device1may include a fluid assembly3(seeFIG. 2), which includes a liquid drug container2, a cap10sealing the container2at a first end, a needle conduit4coupled to the cap10, and also sealed by a plunger6at an opposite, second, end of the container2. The fluid assembly3ofFIG. 2is illustrated in a closed, assembled configuration. A quantity of liquid drug8may be disposed within the liquid drug container2. A cap10may be coupled to the first end of the liquid drug container2and the needle conduit4may pass through the cap10. The needle conduit4extending through the cap10may provide a fluid path for the drug8out of the container2. The plunger6may move as fluid is supplied to or egressed from the container2. The plunger6may vary its position to control a volume of the fluid drug8within the container2. It will be appreciated that the position will be variable based on a desired fill volume of fluid drug8in the container2. Any of the fluid arrangements, including any of the drug delivery systems disclosed herein, can be part of a wearable or on-body drug delivery device or pump, such as an OmniPod® (Insulet Corporation, Billerica, Mass., USA) device and/or any of the drug delivery devices described in U.S. Pat. Nos. 7,303,549; 7,144,384; 7,137,964; 6,960,192; 6,740,059; 6,699,218; 9,402,950; 7,771,412; 7,029,455; 6,740,05; and 6,656,159, each of which is incorporated herein by reference in its entirety and for all purposes.

With reference toFIGS. 3 and 4, a fluid assembly may be in a partially disassembled configuration. In this configuration, a liquid drug container2is not coupled to a cap10nor a plunger. A cap seal14is disposed within the cap10, sealing an end of the cap10while the opposing end of the cap10is open. The needle conduit4is coupled at a first end to the cap10through the cap seal14, and is also coupled to a cannula12at an opposite, second end. In this configuration the container is sealed by a container seal9disposed in a neck portion of the container2at one end, but the container2is open and is not sealed by a plunger at an opposing end.

In various embodiments, the cap10may have an inwardly protruding circumferential lip16that is configured to engage a corresponding circumferential shoulder18disposed on a mouth portion20of the liquid drug container2. When the cap10is aligned with, and pressed against the mouth portion20of the container2, the circumferential lip16flexes outwardly to pass over the shoulder18, and then flexes inwardly once the lip16passes the shoulder18such that the fluid assembly assumes an assembled, locked configuration (e.g.,FIG. 2). In the assembled configuration, the cap seal14disposed in the cap10seals against the mouth portion20of the liquid drug container2.

With reference toFIGS. 5 and 6, a liquid drug container2, a needle conduit4, and a cap10may be positioned within an exemplary sterilization enclosure22(e.g., a tub).FIG. 5illustrates an arrangement in which multiple sets of fluid assemblies (i.e., liquid drug containers2, needle conduits4, and caps10) can be sterilized together. A first tray28is disposed in a bottom portion of the enclosure22and a second tray26is disposed in a top portion of the enclosure22. The cap10and needle conduit4are disposed on the second tray26, however, the cap10, needle conduit4, and container2may be snap fit into the first24or second26tray. The liquid drug container2is disposed on the second tray26such that a mouth portion of the liquid drug container2is registered with, and spaced apart from, a circumferential lip of the cap10. A cover28is disposed on the enclosure22having protrusions29, and each protrusion29may be configured to substantially align with a liquid drug container2. As illustrated inFIG. 6, the interiors of the liquid drug container2, needle conduit4, cap10, and cannula12are exposed to the atmosphere of the sterilization enclosure22. After the components within the enclosure22have undergone a sterilization process, a forced may be exerted on the cover28such that one or more protrusions exert a force onto a respective container2. The force on the container2may move the mouth portion of the container2into engagement with the circumferential lip of the respective cap10, snapping the cap10onto the liquid drug container2to seal the cap10and the needle conduit4to the liquid drug container2in an assembled configuration. The first tray24and/or second tray26may hold the cap and/or needle conduit4in place for the top tray26to force and snap the container2into the cap10. The first tray24and/or the bottom of the enclosure22may act as a backstop for the container2to be forced and snapped into the cap10. The first tray28or the bottom of the enclosure22may hold and align the cap10and/or needle assembly with the second tray26and/or the contents held in the second tray. Various alignment geometries may be incorporated into the trays24and26, the cover28, and/or the enclosure22.

With reference toFIG. 7, a cover28for a sterilization enclosure22may include a plurality of protrusions28for aligning with individual liquid drug containers2within the sterilization enclosure22. The protrusions29may be staggered in rows and/or columns such that they may align with respective containers2of fluid assemblies disposed within the enclosure22. The cover28and/or the protrusions29may be flexible. In various embodiments, the cover28may seal the sterilization enclosure22. Alternatively, an additional sealing element (such as a Tyvek® seal, which is not shown) may seal the sterilization enclosure22. The cover28may be bonded to the tub and may allow a sterilizing agent, e.g., gas and/or vapor) through the cover28, but not other materials, e.g., microbes, molds, spores, or the like, so the tub may remain sterile until28is removed.

In various embodiments, the liquid drug container2, needle conduit4, cap10, and cannula12may be held within the sterilization enclosure22within zero, one, or more trays (e.g.,24and26ofFIGS. 5 and 6) and subjected to one or more sterilization steps using any of a variety of sterilization techniques. For example, a sterilization technique may include evacuating the sealed sterilization enclosure22, and then introducing a sterilization gas. With reference toFIGS. 6 and 8, once the sterilization is complete, the cover28(or other element) may be pressed downward, which may cause the liquid drug container2to move downward (in the direction of arrow “A”) to engage the cap10and to snap the cap10into engagement with the mouth20of the liquid drug container2(seeFIG. 8). In this manner, the sterilized cap10and needle conduit4can be assembled to the liquid drug container2within the sterile environment of the sterilization enclosure22. The liquid drug container2may then be filled with liquid drug. In various embodiments, a fluid assembly in an assembled configuration may have the needle conduit4extending through the cap seal14and into the container2such that it is in fluid communication with the drug8. Alternatively, the needle conduit4may extend into the cap10such that it is not in fluid communication with the drug8in the assembled configuration. In this configuration, the needle conduit4would not extend through the container seal9that is disposed within the container2(e.g., within a neck of the container2). Once filled, the container seal9is between the end of the needle conduit4and the drug (e.g., the drug8inFIG. 2) in this assembled configuration. The needle conduit4may be driven into the container seal9by a motor of the device and/or by a user.

With reference toFIG. 9, an embodiment of a method according to the present disclosure will be described. At step100, a liquid drug container2, needle conduit4, and cap10are placed in a sterilization enclosure22such that a mouth portion20of the liquid drug container2is registered with (e.g., substantially aligned with, oriented towards, or the like), but spaced apart from, a circumferential lip16of the cap10. A first tray24may be disposed into the enclosure22below the cap10and the liquid drug container2. A second tray26may be disposed into the enclosure22configured to hold the liquid drug container2and/or the cap10. The liquid drug container2may have a container seal9disposed in a neck portion of the container2. At step110, the cover28is disposed over the liquid drug container2, needle conduit4, and cap10, and the sterilization enclosure22is sealed. At step120, the interior of the sterilization enclosure22is subjected to a sterilization process, which in one non-limiting exemplary embodiment, is an ethylene oxide (EO) sterilization process. During this sterilization process the interior portions of the liquid drug container2, needle conduit4, cap10, and cannula12are subjected to the sterilization fluid and are sterilized. At step130, downward force is applied to the liquid drug container2to move the mouth portion20into engagement with the circumferential lip16of the cap10. In some embodiments, the downward force is applied by a user, a robot, or other means to the cover28. At step140, the downward force snaps the cap10onto the liquid drug container2sealing the cap and needle conduit4to the liquid drug container2. The downward force may move the needle conduit4through a cap seal14disposed in the cap10, but not through the container seal9disposed in the container2. A space between the seal9, the cap10, the needle conduit4and the cannula12remains sterilized and sealed from the environment. At step150, the sterilization process is complete and the sterilization enclosure22is unsealed. A drug may be supplied to the liquid drug container2. A plunger6may be disposed into the liquid drug container2, sealing the liquid drug within the liquid container2. The assembled liquid drug container2, needle conduit4, and cap10may be removed from the enclosure22.

With reference toFIG. 10, an embodiment of a device according to the present disclosure may be configured for a radiation sterilization technique that may sterilize a portion of a drug delivery device while protecting a liquid drug8contained within the liquid drug container2. Radiation shielding28is disposed about the liquid drug container2(which contains liquid drug8). A cap10(e.g., a crimp cap) engages a seal30to couple the seal to the liquid drug container. A protruding portion32of the seal30may extend through an opening34in the shielding28such that only an end36of the protruding portion32is exposed to radiation during the sterilization procedure. The needle conduit4and associated components (e.g., a cannula) may be exposed to radiation and sterilized thereby in an open, unassembled configuration. The needle conduit4may then move into and through the seal30into a closed, assembled configuration, that may or may not extend into and through a container seal9. It will be appreciated that multiple assemblies could be loaded in a sterilization enclosure such that the protruding portions32of the multiple assemblies protrude through the shielding (seeFIG. 11), the group would be irradiated together

Certain embodiments of the present disclosure are described herein. It is, however, expressly noted that the present disclosure is not limited to these embodiments, but rather the intention is that additions and modifications to what is expressly described herein are also included within the scope of the disclosure. Moreover, it is to be understood that the features of the various embodiments described herein are not mutually exclusive and can exist in various combinations and permutations, even if such combinations or permutations are not made express herein, without departing from the spirit and scope of the disclosure. In fact, variations, modifications, and other implementations of what is described herein will occur to those of ordinary skill in the art without departing from the spirit and the scope of the disclosure. As such, the disclosure is not to be defined only by the illustrative description.