Fluid barrier with stripping mechanism for large volume drug delivery device

Abstract

Devices and methods for providing a fluid-path barrier in an injection device, such as a reservoir-type injection device, are provided. The fluid-path barrier may be used to preferentially connect the injection device at the time of use to support an appropriate fluid delivery environment.

Description

Fluid Barrier With Stripping Mechanism for Large Volume Drug Delivery Device

[0001] This application claims the benefit of priority to European Patent Application No. 24315206.3 filed April 22, 2024, and to U.S. Provisional Patent Application No. 63 / 604,529 filed on November 30, 2023, the entire content of each of which is incorporated herein by reference in its entirety.

[0002] The present disclosure relates generally to devices and methods for providing a barrier to a fluid path connection in an injection device, and more specifically for a large volume injection device.

[0003] Injection devices may be used to deliver a fluid containing a pharmaceutical drug or medicament to a patient. For example, the medicament may be delivered by the injection device to the patient via a needle, cannula, tube, microneedle array, or other route.

[0004] One type of injector used to provide such a medicament is a large volume device (LVD), which may also be known as a bolus injector or a reservoir-type injector. A large volume device may provide a relatively large volume of medicament, typically at least 1 ml or more. The large volume device is generally positioned against the skin or held to the skin at a suitable injection site, and upon activation of the device, medicament is injected through the patient’s skin.

[0005] The medicament must be provided to the injection device and made accessible so that the injection device can deliver the medicament to the patient. The medicament will be provided in a vial or container, and invariably, the medicament is sterilized in the vial or container. The vial or container is loaded into the large volume delivery device, and when the device is ready to be used, a connection must be formed between a delivery flow path and the medicament in thecontainer. However, assembling the device in a sufficiently clean (e.g., sterile) manner such that the final device including the medicament container is substantially free of microorganisms, can be complicated and expensive. Furthermore, the assembled device must have a mechanism to maintain sterility or prevent introduction of microorganisms, but also allow formation of a connection between the medicament container and fluid flow path. Accomplishing these goals is challenging, and current devices for large volume delivery have various drawbacks. Accordingly, there remains a need for devices and methods to establish a fluid connection to a reservoir of medicament in an injection device in a sterile or aseptic manner. The present disclosure provides devices, systems, and methods for providing sterile or aseptic connections for medicament delivery in a drug delivery device.SUMMARY

[0006] The present disclosure provides systems, devices, and methods for providing in an injection device, such as a large volume or reservoir-type injection device, a fluid path connection for delivery of a medicament using the injection device.

[0007] In an embodiment, the present disclosure is directed to a fluid path connection for a medicament delivery device. The fluid path connection may include a medicament container and a needle assembly. The medicament container may include an internal volume to hold medicament, a stopper, and a stopper cover. The stopper cover may maintain a first region between the stopper and the stopper cover. The needle assembly may include a needle and a needle assembly cover. The needle assembly cover may maintain a second region between the needle and the needle assembly cover. Upon disrupting or removing the stopper cover and the needle assembly cover, an unobstructed fluid path from the needle to the stoppermay be formed. Upon breaking or removing the needle assembly cover and the stopper cover, the needle may move relative to the medicament container to pierce the stopper of the medicament container.

[0008] The needle assembly cover and the stopper cover may extend in part beyond a housing of the injection device to permit access to the needle assembly cover and the stopper cover from outside of the housing. The needle assembly cover may include a first pull tab, and the stopper cover may include a second pull tab. Each of the first pull tab and the second pull tab may extend outside of the housing. A user of the injection device or a medical provider may use the first pull tab and / or the second pull tab to remove, at least in part, the needle assembly cover and stopper cover, respectively. The needle assembly cover and the stopper cover may each be connected to a single pull tab and the single pull tab may extend outside of the housing and allow access by the user or medical provider.

[0009] The fluid path connection may also include a fluid path interface component positioned between the stopper cover and the needle assembly cover. The fluid path interface component may include at least a first cutting section configured to disrupt the stopper cover and a second cutting section configured to disrupt the needle assembly cover. The needle and medicament container may be configured for relative motion such that the needle establishes a fluid connection to the internal volume medicament container through the medicament container and a remainder of the fluid path region.

[0010] The needle cover and the stopper cover may each be a thin, flexible material such as a metal foil or polymer sheet. The first cutting section and the second cutting section may each be independently selected from: a single barb, a plurality of barbs, a blade, and a plurality of blades.

[0011] Each of the first cutting section and the second cutting section may engage the stopper cover and the needle assembly cover, respectively, in an initial state. The cutting section interface may be configured to begin to disrupt the stopper cover and the needle assembly cover during a portion of a range of motion of the fluid path interface within an interface gap of the medicament container and the fluid path connection.

[0012] In an embodiment, the present disclosure is directed to a device to deliver a medicament. The device may include a housing, a medicament container, and a needle assembly. The medicament container may include an internal volume to hold medicament, a stopper, and a stopper cover. The stopper cover may maintain a first region between the stopper and the stopper cover. The needle assembly may include a needle and a needle assembly cover. The needle assembly cover may maintain a second region between the needle and the needle assembly cover. Upon disrupting or removing the stopper cover and the needle assembly cover, an unobstructed fluid path from the needle to the stopper may be formed.

[0013] The device may also include an adhesive on a side of the housing and a removable covering removably attached to the adhesive. Each of the needle assembly cover and the stopper cover may be connected to the removable covering, such that removing the removable covering also removes, at least in part, the needle assembly cover and the stopper cover. The needle assembly cover, the stopper cover, and the removable covering may be separate elements or one or more may be of a single, integral construction. The fluid path interface is moveable and clears at least a portion of the stopper cover and the needle assembly cover during its movement.

[0014] In an embodiment, the present disclosure is directed to a method for establishing a fluid path in a drug delivery device. The drug delivery device may include a stopper cover configured to maintain a first region between a stopper and the stopper cover and a needle assembly cover configured to maintain a second region between the needle assembly cover and the needle. The method may include removing, at least in part, the stopper cover. The method may include removing, at least in part, the needle assembly cover.

[0015] Removing, at least in part, the stopper cover and the needle assembly cover may create an unobstructed fluid path from the needle to the stopper. Removing, at least in part, the stopper cover may include pulling an interface component such that a first cutting section of the interface component engages with and removes, at least in part, the stopper cover. Removing, at least in part, the needle assembly cover may include pulling the interface component such that a second cutting section of the interface component engages with and removes, at least in part, the needle assembly cover.BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the present disclosure and together with the description, serve to explain the principles of the disclosure.

[0017] Fig. 1 is cut-away view of a large volume injection device.

[0018] Fig. 2 is a side cut-away view illustrating a fluid path connection in accordance with some embodiments.

[0019] Fig. 3 is a side cut-away view illustrating a large volume device with a fluid path connection in accordance with some embodiments.

[0020] Fig. 4A is a side cut-away view illustrating a fluid path connection in accordance with some embodiments.

[0021] Fig. 4B is a perspective view illustrating an isolated interface in accordance with some embodiments.

[0022] Fig. 4C is a side cut-away view illustrating a fluid path connection and interface component in accordance with some embodiments.

[0023] Fig. 4D is a side cut-away view illustrating a fluid path connection and unobstructed fluid interface in accordance with some embodiments.DETAILED DESCRIPTION OF CERTAIN EXEMPLARY EMBODIMENTS

[0024] Reference will now be made in detail to certain exemplary embodiments according to the present disclosure, certain examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.

[0025] In this application, the use of the singular includes the plural unless specifically stated otherwise. In this application, the use of “or” means “and / or” unless stated otherwise. Furthermore, the use of the term “including”, as well as other forms, such as “includes” and “included”, is not limiting. Any range described herein will be understood to include the endpoints and all values between the endpoints.

[0026] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including but not limited to patents, patent applications, articles, books, and treatises, are hereby expressly incorporated by reference in their entirety for any purposes.

[0027] The presently discussed devices, methods, and systems can be used to load a medicament container into a large volume delivery device in a convenient and cost-effective manner while maintaining a high degree of sanitation for critical components.

[0028] The present disclosure is described as providing “aseptic” connections for drug delivery devices. As used herein, “aseptic” will be understood to refer to a condition wherein a device is free of substantially all, but not necessarily all microorganisms such as bacteria, viruses or fungi. As used herein, an “aseptic connection” refers to components that can allow connection of a fluid flow path with a medicament container of a device while preventing introduction of microorganisms. The “connection” need not be already connected but can be capable of forming the connection when ready for use. The terms “aseptic” or “aseptic connection” may not necessarily require that the device be sterile or free of all microorganisms (as sterile may be defined by regulatory requirements), but “aseptic” and “aseptic connection” will be understood to encompass devices that are sterile or maintain sterility.

[0029] Typical injection volumes can range from about 1 mL to over 10 mL. The devices may produce a wide range of injection rates from 0.2 ml / min up to 204.0 ml / min. Such injection profiles may be generally constant in flow rate, generally continuous in duration, or both generally constant and generally continuous. These injections can also occur in a single step of administration. Such injection profiles may be referred to as bolus injections.

[0030] Delivery devices functioning with such medicaments may utilize a needle, cannula, or other injection element configured to deliver a medicament to the patient. Such an injection element may, for example, have an external size or diameter of 27G or less. Further, the injection element could be rigid, flexible, and formed usinga range of one or more materials. And in some embodiments, the injection element may include two or more components. For example, a rigid trocar may operate in conjunction with a flexible cannula. Initially, both the trocar and cannula may move together to pierce the skin. The trocar may then retract while the cannula remains at least partially within the target tissue. Later, the cannula may separately retract into the delivery device.

[0031] An example drug delivery device may involve a needle-based injection system as described in ISO 11608-1 :2022. Needle-based injection systems may be broadly distinguished into multi-dose container systems and single-dose (with partial or full evacuation) container systems. The container may be a replaceable container or an integrated non-replaceable container.

[0032] A multi-dose container system may involve a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user). Another multi-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In such a system, each container holds multiple doses, the size of which may be fixed or variable (pre-set by the user).

[0033] As further described in ISO 11608-1 :2022, a single-dose container system may involve a needle-based injection device with a replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume is expelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation). A single-dose container system may involve a needle-based injection device with an integrated non-replaceable container. In one example for such a system, each container holds a single dose, whereby the entire deliverable volume isexpelled (full evacuation). In a further example, each container holds a single dose, whereby a portion of the deliverable volume is expelled (partial evacuation).

[0034] An insertion mechanism for inserting the needle may take any suitable form. It may be a mechanical spring-based mechanism. Alternatively, the insertion element mechanism may for instance include an electric motor and a gear mechanism that causes insertion of the insertion element into the user. Needle insertion may also be part of a manual action by a user achieved before medicament delivery starts. Alternatively, the insertion mechanism may be a gas or fluid pressure operated mechanism, in which case the needle driving energy source is either a reservoir of pressurized gas or a chemical system in which two or more chemicals are mixed together to produce gas or fluid pressure.

[0035] One type of delivery device includes a Large Volume Device (LVD). An LVD delivery device is configured to dispense a relatively large dose of medicament, in particular at least 1 ml and typically up to 2.5 ml, but possibly up to 10 ml. LVDs can also be configured for bolus or basal delivery.

[0036] A bolus LVD injector device is configured to deliver a bolus of the respective medicament to bring a volume of the medicament into a patient's body within a predetermined time. The injection rate, however, may not be critical, i.e. , tight control may not be necessary. However, there may be an upper (physiological) limit to the delivery rate in order to avoid damage to the tissue surrounding the delivery site. The time taken to deliver a bolus dose of medicament may be between a few minutes and many hours depending on a number of factors including the quantity (volume) of medicament, the viscosity of the medicament and the nature of the injection site at which the injection device is intended to be used.

[0037] From a user or health care professional perspective, it is desirable for an injection device to be configured to minimally impact the patient's lifestyle and schedule, providing the patient with minimal reminder of his or her disease between the injections. The treatment schedule for therapies is usually intermittent, i.e. may be one injection per week, one injection every other week, or one per month. Therefore, the patient usually has no routine in dealing with his or her disease, and hence has minimal routine / experience in performing the required injections. Thus, configuration of the injection device to simplify its operation by patients is highly desirable.

[0038] If an LVD is intended for bolus operation, the configuration of the LVD injection device is quite different compared to an LVD injection device that is intended to be used for basal operation. Also, its use is quite different. For instance, a basal-type insulin pump generally is relatively expensive as it includes many sophisticated diabetes specific features like programmable delivery rate profiles, bolus calculators etc. Further, the connection to the body via an infusion set allows the patient to handle and manipulate the pump in his / her field of view while the therapy is ongoing. Further, diabetes patients usually have a routine in setting-up the infusion set, connecting and operating the pump, and disconnecting the pump temporarily for events like taking a shower so not to expose the pump to water. In contrast, the bolus injector devices described above can be relatively simple and inexpensive devices. They may be provided as single-use devices, which cannot be recharged with medicament, which further reduces complexity and cost.

[0039] To use an LVD injection device, it is first located on a suitable injection site on a patient's skin. The device is typically adhered to the patient’s skin throughout the medicament delivery process. Injection is usually initiated by the patient oranother person (user). Typically, the initiation is started by a user operation, such as depressing a switch (mechanical or electrical) or by placing the LVD on the patient’s body and depressing a lever on the device’s underside. If the LVD includes electronics, a controller can operate the device. Operation includes firstly injecting a needle into the user and then causing the injection of medicament into the user's tissue. The delivery process can take several minutes up to several hours. Following, the LVD can be removed from the injection site and disposed of.

[0040] Biological medicaments are being increasingly developed which comprise higher viscosity injectable liquids and which are to be administered in larger volumes than long-known liquid medicaments. LVDs for administering such biological medicaments may comprise a pre-filled disposable drug delivery device or, alternatively, a disposable drug delivery device into which a patient or medical personnel must insert a drug cartridge prior to use.

[0041] In some embodiments, medicaments of various viscosities can be injected. For example, viscosity could range from about 3 to about 50 cP. In other embodiments, viscosity could be less than about 3 cP or greater than about 50 cP. Injection can further include delivering a medicament to a sub-cutaneous, an intramuscular, or a transdermal location within a patient’s body. The medicament can be in the form of a liquid, gel, slurry, suspension, particle, powder, or other type.

[0042] In some embodiments, the large volume devices may include a housing configured to be held against the user’s body when the device is in use, a medicament cartridge, a fluid pathway connected to the medicament cartridge and extending to an insertion mechanism, such as a needle insertion mechanism or a trocar and cannula insertion mechanism. The medicament may be drawn or forced from the medicament cartridge by any method, such as by a plunger mechanism orby a pump, and injected into the user by the same force, or by a separate plunger or pump. In some embodiments, the plunger may be driven by one or more springs, drive screws, motors, or any other suitable drive mechanism.

[0043] The terms “drug”, “medicament”, or “pharmaceutical”, which are used interchangeably herein, mean a pharmaceutical formulation that includes at least one pharmaceutically active compound, which may be, for example, a small molecule or biologic active pharmaceutical ingredient. Further descriptions of contemplated drugs, medicaments or pharmaceuticals are provided below.

[0044] Standards or best practices for the design of drug delivery devices may require or recommend providing a fluid path unobstructed from barriers that function during storage of the device. The path can maintain an aseptic or sterile path during storage or use. Additionally, standards or best practices for manufacturing and assembling a drug-delivery device, such as a large volume or reservoir-type injection device, may require that certain steps in the assembly occur in a clean room or aseptic facility or may require sanitizing certain components. Embodiments may provide an aseptic sterile path from a drug container to the needle or cannula, according to the present disclosure, without requiring that all aspects of the assembly be performed in clean room or highly sterilized environments.Embodiments may provide flexibility and cost-savings in manufacturing by allowing aseptic conditions to be maintained in the device without requiring the use of a clean room or other highly sanitized environment during all steps of the manufacturing process. For example, the medicament container may be inserted into the injection device outside of a clean room or highly sanitized environment while still providing an aseptic connection. Another advantage is that the manufacture of the injection device and the loading of the injection device with a medicament container may beperformed independently and the reservoir may be added in a wider range of facilities. For example, the reservoir may be supplied in a separate manufacturing process or may be supplied by a medical technician, compounding pharmacy, or a user without requiring a clean room or highly sterilized environment.

[0045] FIG. 1 illustrates an exemplary large volume device 100 with a housing 110, a needle insertion mechanism 120, a release mechanism 130, a drive mechanism 135, a cartridge holder 140, a needle 145, and a fluid path 147. The release mechanism 130 includes a button 131 , a button biasing member or other power source (not shown), and a release member 133. The drive mechanism 135 includes a drive mechanism biasing member or other power source (not shown), and a piston 137.

[0046] A medicament container 200 is included within the large volume device 100. The medicament container 200 includes a plunger 210, a stopper 215 (which may alternatively be referred to as a septum), and a cap 217 (e.g., a crimp cap) and has an internal volume 220 at least partially filled with a medicament 221 . The container 200 may be, for example, a glass vial with a polymer plunger and septum. Generally, the container will include a standard medicament container such that the disclosed devices and fluid path connections can be used with existing, standard containers without the need for development of a specialized container or medicament cartridge. The plunger 210 may be driven by the piston 137.

[0047] Fig. 1 should be understood to be an exemplary device. The drive mechanism 135 can include one or more springs, but other drive mechanisms or power sources may be possible. Other drive mechanisms may include other biasing elements, screw drives, gear drives, gas or chemical sources, or electric motors.The medicament container 200 should be understood as exemplary only. Forexample, different types of containers or vials may be used, including containers with different stopper or piston arrangements, or without a stopper or piston.

[0048] The large volume device 100 is prepared for use by loading the medicament container 200 and setting the drive mechanism 135 in the energized state (as shown in Fig. 1 ). The drive mechanism biasing member 136 is held in an energized state by engagement of the release member 133 with a detent 138 of the piston 137. To operate the large volume device 100, the large volume device 100 is positioned with the needle insertion mechanism 120 against skin of a user. The large volume device 100 may be attached to skin of the user by removing a removable covering mounted on the housing 145 to expose an adhesive on the housing 110. The user, or someone assisting the user, presses the button 131 of the release mechanism 130 to shift the release member 133 out of the detent 138 and release the drive mechanism biasing member 136, whereupon the drive mechanism biasing member 136 drives the piston 137 against the plunger 210 of the medicament container 200, forcing the plunger 210 into the medicament container 200 and pressurizing the internal volume 220 with medicament 221 . An action of the large volume device 100 causes the needle 145 to pierce the stopper 215 and access the medicament 221 within the medicament container 200. The pressurized medicament flows from the medicament container 200 into the needle 145 and then along the fluid path 147 to the needle insertion mechanism 120. An action of the large volume device 100 causes the needle insertion mechanism 120 to insert a needle and / or cannula into the user. The medicament 221 is delivered through the needle or cannula to the patient.

[0049] The large volume device 100 also includes a fluid path connection 300. The fluid path connection 300 is positioned near the stopper 215 and needle 145 andpermits the needle 145 to travel through an unobstructed path to the stopper 215 to establish a fluid path connection with the medicament container 200. In some embodiments, the fluid path connection 300 is connection is configured to isolate the fluid path during storage and / or use and to maintain an aseptic or sterile fluid path.

[0050] Fig. 2 illustrates the fluid path connection 300 for a large volume medicament delivery device 100. The fluid path connection 300 includes the medicament container 200 with the internal volume 220 to hold medicament, the stopper 215, and a stopper cover 217 configured to maintain a first region 311 between the stopper 215 and the stopper cover 217. The fluid path connection 300 includes a needle assembly 320 including the needle 145 and a needle assembly cover 322. The needle assembly cover 322 is configured to maintain a second region 326 between the needle 145 and the needle assembly cover 322. Disrupting or removing the stopper cover 217 and the needle assembly cover 322 at least in part may form an unobstructed path 355 (see Fig. 4D) from the needle 145 to the stopper 217 so that the needle 145 may access the medicament container 200 on an aseptic manner.

[0051] The needle assembly cover 322 and stopper cover 217 cover the needle assembly 320 and the medicament container 200 forming covered regions 311 , 326. As such the covered regions are isolated from possible contaminants such that once the components of the large volume delivery device are assembled in a sterile or sufficient clean environment, or are sterilized after assembly, the needle 145 and stopper 215 of the container 200 cannot be inadvertently contaminated. Furthermore, the fluid path connection 300 includes component(s), which is configured to disrupt of remove a portion of the needle assembly cover 322 and stopper cover 217 to form an opening or passage that allows the needle 145 to beadvanced through the stopper 215, thereby forming a sterile or sufficiently clean fluid connection between the medicament container and a fluid path 147 to allow delivery of medication to a patient. In this way, the individual components of the large volume delivery device 100 can be assembled, and even if minor contaminants are introduced outside the needle assembly 320 and stopper cover 217, a sterile connection can be made between the medicament container and fluid path 147.

[0052] In the fluid path connection 300 shown in Fig. 2, the needle assembly cover 322 and the stopper cover 217 extend in part beyond the housing 110 to permit access to the needle assembly cover 322 and the stopper cover 217 by a user or medical provider. Where the needle assembly cover 322 and the stopper cover 217 extend beyond the housing 110, the user or a medical provider may pull directly on the needle assembly cover 322 and the stopper cover 217 to remove the needle assembly cover 322 and the stopper cover 217, at least in part, from the medicament container 200 and the needle assembly 320, respectively.

[0053] In some embodiments, the needle assembly cover 322 may include a first pull tab 327 and the stopper cover 217 may include a second pull tab 218, with each of the first pull tab 327 and the second pull tab 218 extending outside of the housing 110 to facilitate a user or medical provider pulling and moving the needle assembly cover 322 and the stopper cover 217. In order to remove the needle assembly cover 322 and the stopper cover 217, the user or medical technician may pull on the first pull tab 217 and the second pull tab 218 to remove the respective needle assembly cover 322 and stopper cover 217, sequentially in either order or together.

[0054] In other embodiments, the needle assembly cover 322 and the stopper cover 217 may be connected to a single pull tab extending outside of the housing 110 and accessible to be pulled by the user or medical provider.

[0055] In other embodiments, the needle assembly cover 322 and the stopper cover 217 may be connected directly, or via the first pull tab 327 and the second pull tab 218, to a covering over an adhesive layer on a portion of the exterior of the housing 110, such that when the user or medical provider removes the covering, the needle assembly cover 322 and the stopper cover 217 are also displaced from the respective needle assembly 320 and medicament container 200.

[0056] Furthermore, it is contemplated that the needle assembly cover 322 and / or stopper cover 217 may be removed via an internal power system. For example, the tabs 218 and 327 may be attached to a holder that can be moved via a spring or other force. Further, the tabs may be integrally connected with other components such as an activation mechanism 130, which, when activated, causes movement of the needle assembly cover 322 and / or stopper cover 217.

[0057] Upon breaking or removing the needle assembly cover 322, the needle 145 may move relative to the medicament container 200 to pierce the stopper 215 of the medicament container 220. Changing the relative location of the needle 145 of the needle assembly 320 and the medicament container 200 may include moving the needle 145, moving the medicament container 200, or both.

[0058] Fig. 3 shows the fluid path connection 300 in the large volume device 100’. The large volume device 100’ includes the needle assembly 320, the medicament container 200, and the housing 110. The needle assembly 320 includes the needle 145. The medicament container 200 includes the stopper 215 and the internal volume 220 of medicament. The fluid path connection 300 includes the needle cover 322 positioned over the needle assembly 320 to form the second region 326. The needle cover 322 includes the first pull tab 327 extending beyond the housing 110.A user or medical provider pulls the first pull tab 327 to displace or remove theneedle cover 322. After removal of the needle cover 322, the needle 145 may pass through the second region 326 to access the stopper 215 and the internal volume 220 via an unobstructed path. The large volume device 100’ is shown without a stopper cover 217, however in embodiments, the stopper cover 217 may be provided as described above in connection with Fig. 2.

[0059] Fig. 4A illustrates the fluid path connection 300 with an interface component 360 between the stopper cover 217 and the needle assembly cover 322 to receive an interface component 360. Fig. 4B illustrates the interface component 360. The interface component 360 includes a first cutting section 362 configured to disrupt the stopper cover 217 and a second cutting section 364 configured to disrupt the needle assembly cover 322. The second cutting section 364 includes a cutting surface 365 that extends outwardly and (when the interface component 360 is inserted in the fluid path connection 300) toward the needle assembly cover 322. As illustrated in Fig. 4B, the first cutting section 362 includes a cutting surface that extends into the plane of the page (not visible in Fig. 4B) to disrupt the stopper cover 217. The interface component 360 includes an interface pull tab 366 with a finger hold 367 to facilitate a user or medical provider grasping the interface component 360 via the pull tab 366 and / or finger hold 367 to pull downwardly on the interface connection 360. The finger hold 367 may be an indentation in the interface component 360 or an aperture in the interface component 360 to provide additional purchase for the user on the interface component 360.

[0060] Fig. 4C illustrates the interface component 360 included within the fluid path connection 300 between the needle cover 322 and the stopper cover 217. As illustrated in Fig. 4C, the interface component 360 has been partially pulled downwardly (as by a user or medical provider) to begin to disrupt the needle cover322 and the stopper cover 217. Specifically, Fig. 4C illustrates the needle cover 322 partially disrupted by the first cutting section 362 to begin to expose a portion of the second region 326.

[0061] Fig. 4D illustrates the fluid path connection 300 after disruption of the needle cover 322 and the stopper cover 217, at least in part, to form the path 355. After the needle cover 322 has been removed in the area near the needle 145 and the stopper cover 217 has been removed in at least a corresponding area to form the unobstructed path 355, the needle 145 may be moved through the first region 311 and the second region 326 through the unobstructed path 355 to access the stopper 215 and the internal volume 220 holding the medicament of the medicament container 200. Accordingly, the medicament may be supplied in an aseptic manner.

[0062] The needle cover 322 and the stopper cover 217 may each be independently formed from a thin, flexible material, such as a metal foil or a polymer sheet. For example, suitable materials can include biocompatible metals or polymers such as stainless steel, TYVEK, or other suitable materials that are of sufficient strength and flexibility while preventing passage of microbes.

[0063] The first cutting section 362 and the second cutting section 364 may each be independently selected from: a single barb, a plurality of barbs, a blade, and a plurality of blades.

[0064] The systems and devices described herein may be used in a method for establishing a fluid path aseptically in a drug delivery device, such as the exemplary large volume device 100 or another injection device. For example, with reference to fluid path connection 300, the method may include removing, at least in part, the stopper cover 217 and removing, at least in part, the needle assembly cover 322. Removing, at least in part, the stopper cover 217 and the needle assembly cover322 creates an unobstructed path 355 from the needle 145 to the stopper 217. Furthermore, removing, at least in part, the stopper cover 217 may include pulling the interface component 360 such that a first cutting section 362 of the interface component 360 engages with and removes, at least in part, the stopper cover 217. Additionally, removing, at least in part, the needle assembly cover 322 may include pulling the interface component 360 such that a second cutting section 364 of the interface component 360 engages with and removes, at least in part, the needle assembly cover 322.

[0065] The method may further include changing the relative location of the needle 145 of the needle assembly 320 and the medicament container 200 such that the needle 145 accesses the medicament container 200. This movement may be along the axis of the needle. The relative location of the needle 145 can be changed by either causing the needle to move towards the medicament container, or by causing the medicament container to more towards the needle, or both. In any case, “advancing the needle” into or through the stopper 215 will be understood to include any action that causes the needle to penetrate the stopper 215 to form a fluid connection with the medicament container.Exemplary Drugs or Medicaments

[0066] The terms “drug” or “medicament” are used synonymously herein and describe a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally a pharmaceutically acceptable carrier. An active pharmaceutical ingredient (“API”), in the broadest terms, is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or medicament is used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mentalwell-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.

[0067] As described below, a drug or medicament can include at least one API, or combinations thereof, in various types of formulations, for the treatment of one or more diseases. Examples of API may include small molecules having a molecular weight of 500 Da or less; polypeptides, peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double or single stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA (including RNAi & siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more drugs are also contemplated.

[0068] The drug or medicament may be contained in a primary package or “drug container” adapted for use with a drug delivery device. The drug container may be, e.g., a cartridge, syringe, reservoir, or other solid or flexible vessel configured to provide a suitable chamber for storage (e.g., short- or long-term storage) of one or more drugs. For example, in some instances, the chamber may be designed to store a drug for at least one day (e.g., 1 to at least 30 days). In other examples, the container may be made of a flexible elastomeric material and designed to be loaded by the health care provider or patient, then placed on the body for administration. In some instances, the chamber may be designed to store a drug for about 1 month to about 2 years. Storage may occur at room temperature (e.g., about 20°C), or refrigerated temperatures (e.g., from about - 4°C to about 4°C). In some instances, the drug container may be or may include a dual-chamber cartridge configured to store two or more components of the pharmaceutical formulation to-be-administered(e.g., an API and a diluent, or two different drugs) separately, one in each chamber. In such instances, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components prior to and / or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., by way of a conduit between the two chambers) and allow mixing of the two components when desired by a user prior to dispensing. Alternatively or in addition, the two chambers may be configured to allow mixing as the components are being dispensed into the human or animal body.

[0069] The drugs or medicaments contained in the drug delivery devices as described herein can be used for the treatment and / or prophylaxis of many different types of medical disorders. Examples of disorders include, e.g., diabetes mellitus or complications associated with diabetes mellitus such as diabetic retinopathy, thromboembolism disorders such as deep vein or pulmonary thromboembolism.Further examples of disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0070] Examples of APIs for the treatment and / or prophylaxis of type 1 or type 2 diabetes mellitus or complications associated with type 1 or type 2 diabetes mellitus include an insulin, e.g., human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1 ), GLP-1 analogues or GLP-1 receptor agonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms “analogue” and “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturallyoccurring peptide, for example that of human insulin, by deleting and / or exchanging at least one amino acid residue occurring in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or exchanged amino acid residue can either be codable amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogues are also referred to as "insulin receptor ligands". In particular, the term “derivative” refers to a polypeptide which has a molecular structure which formally can be derived from the structure of a naturally occurring peptide, for example that of human insulin, in which one or more organic substituent (e.g. a fatty acid) is bound to one or more of the amino acids. Optionally, one or more amino acids occurring in the naturally occurring peptide may have been deleted and / or replaced by other amino acids, including non-codable amino acids, or amino acids, including non-codable, have been added to the naturally occurring peptide.

[0071] Examples of insulin analogues are Gly(A21 ), Arg(B31 ), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine);Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Vai or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0072] Examples of insulin derivatives are, for example, B29-N-myristoyl- des(B30) human insulin, Lys(B29) (N- tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B30) human insulin; B29-N- myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl- ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin, B29-N- omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30) human insulin (insulin degludec, Tresiba®); B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(co-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(co- carboxyheptadecanoyl) human insulin.

[0073] Examples of GLP-1 , GLP-1 analogues and GLP-1 receptor agonists are, for example, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide which is produced by the salivary glands of the Gila monster), Liraglutide (Victoza®), Semaglutide, Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211 , CM-3, GLP-1 Eligen, GRMD-0901 , NN- 9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1 , CVX-096, ZYOG-1 , ZYD-1 , GSK-2374697, DA-3091 , MAR-701 , MAR709, ZP-2929, ZP-3022, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651 , ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten.

[0074] An example of an oligonucleotide is, for example: mipomersen sodium (Kynamro®), a cholesterol-reducing antisense therapeutic for the treatment of familial hypercholesterolemia or RG012 for the treatment of Alport syndrome.

[0075] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0076] Examples of hormones include hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

[0077] Examples of polysaccharides include a glucosaminoglycane, a hyaluronic acid, a heparin, a low molecular weight heparin or an ultra-low molecular weight heparin or a derivative thereof, or a sulphated polysaccharide, e.g. a polysulphated form of the above-mentioned polysaccharides, and / or a pharmaceutically acceptable salt thereof. An example of a pharmaceutically acceptable salt of a polysulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate.

[0078] The term “antibody”, as used herein, refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigen. The antibody can be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human, (e.g., murine), or single chain antibody. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody has reduced or no ability to bind an Fc receptor. For example, the antibody can be an isotype or subtype, an antibody fragment or mutant, which does not support binding to an Fc receptor, e.g., it has a mutagenized or deleted Fc receptor binding region. The term antibody also includes an antigen-binding molecule based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or a dual variable region antibody-like binding protein having cross-over binding region orientation (CODV).

[0079] The terms “fragment” or “antibody fragment” refer to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not comprise a full-length antibody polypeptide, but that stillcomprises at least a portion of a full-length antibody polypeptide that is capable of binding to an antigen. Antibody fragments can comprise a cleaved portion of a full length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that are useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP), binding-domain immunoglobulin fusion proteins, camelized antibodies, and VHH containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0080] The terms “Complementarity-determining region” or “CDR” refer to short polypeptide sequences within the variable region of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term “framework region” refers to amino acid sequences within the variable region of both heavy and light chain polypeptides that are not CDR sequences, and are primarily responsible for maintaining correct positioning of the CDR sequences to permit antigen binding. Although the framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in CDRs to interact with antigen.

[0081] Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti-IL-6 mAb (e.g., Sarilumab), and anti-IL-4 mAb (e.g., Dupilumab).

[0082] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in a drug or medicament in a drug delivery device. Pharmaceutically acceptable salts are for example acid addition salts and basic salts.

[0083] Those of skill in the art will understand that modifications (additions and / or removals) of various components of the APIs, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompass such modifications and any and all equivalents thereof.

[0084] While principles of the present disclosure are described herein with reference to illustrative embodiments for particular applications, it should be understood that the disclosure is not limited thereto. Those having ordinary skill in the art and access to the teachings provided herein will recognize additional modifications, applications, embodiments, and substitution of equivalents all fall within the scope of the embodiments described herein. Accordingly, the invention is not to be considered as limited by the foregoing description.

Claims

WHAT IS CLAIMED IS1 . A fluid path connection for a large volume delivery device, the fluid path connection comprising: a medicament container comprising: an internal volume to hold medicament, a stopper, and a stopper cover configured to maintain a first region between the stopper and the stopper cover; a needle assembly comprising: a needle, and a needle assembly cover configured to maintain a second region between the needle and the needle assembly cover, wherein, upon disrupting or removing the stopper cover and the needle assembly cover an unobstructed path from the needle to the stopper is formed.

2. The fluid path connection of claim 1 , wherein, upon breaking or removing the needle assembly cover, the needle is configured for motion relative to the medicament container to pierce the stopper of the medicament container.

3. The fluid path connection of claim 1 , wherein the needle assembly cover and the stopper cover extend in part beyond a housing of the medicament delivery device to permit access to the needle assembly cover and the stopper cover.

4. The fluid path connection of claim 1 , wherein the needle assembly cover comprises a first pull tab and the stopper cover comprises a second pull tab, and each of the first pull tab and the second pull tab extend outside of the housing.

5. The fluid path connection of claim 1 , wherein the needle assembly cover and the stopper cover are each connected to a single pull tab and the single pull tab extends outside of the housing.

6. The fluid path connection of claim 1 , further comprising an interface component positioned between the stopper cover and the needle assembly cover and comprising at least a first cutting section configured to disrupt the stopper cover and a second cutting section configured to disrupt the needle assembly cover.

7. The fluid path connection of claim 1 , wherein the needle and medicament container are configured for relative motion such that the needle establishes a fluid connection to the medicament container through the first region and the second region.

8. The fluid path connection of claim 1 , wherein the needle cover and the stopper cover are each a thin, flexible material.

9. The fluid path connection of claim 6, wherein the first cutting section and the second cutting section are each independently selected from: a single barb, a plurality of barbs, a blade, and a plurality of blades.

10. The fluid path connection of claim 6, wherein each of the first cutting section and the second cutting section engage the stopper cover and the needle assembly cover, respectively, in an initial state.

11. A large volume device to deliver a medicament, the device comprising: a housing; a medicament container comprising: an internal volume to hold medicament, a stopper, and a stopper cover configured to maintain a first region between the stopper and the stopper cover; a needle assembly comprising: a needle, and a needle assembly cover configured to maintain an second region between the needle and the needle assembly cover, wherein, upon disrupting or removing the stopper cover and the needle assembly cover an unobstructed path from the needle to the stopper is formed; and a drive mechanism to drive a plunger in the medicament container.

12. The device of claim 11 , further comprising: an adhesive on a side of the housing and a removable covering removably attached to the adhesive, and wherein each of the needle assembly cover and the stopper cover are connected to the removable covering, such that removing the removable covering also removes, at least in part, the needle assembly cover and the stopper cover.

13. The device of claim 11 , wherein the interface component is moveable and clears at least a portion of the stopper cover and the needle assembly cover during its movement.

14. A method for establishing a fluid path in a large volume drug delivery device comprising a medicament container with a stopper cover configured to maintain a first region between a stopper of the container and the stopper cover and a needle assembly cover configured to maintain a second region between the needle assembly cover and a needle, the method comprising: removing, at least in part, the stopper cover, and removing, at least in part, the needle assembly cover, wherein removing, at least in part, the stopper cover and the needle assembly cover creates an unobstructed path from the needle to the stopper.

15. The method of claim 14, wherein removing, at least in part, the stopper cover comprises pulling an interface component such that a first cutting section of the interface component engages with and removes, at least in part, the stopper cover and wherein removing, at least in part, the needle assembly cover comprises pulling the interface component such that a second cutting section of the interface component engages with and removes, at least in part, the needle assembly cover.

16. The method of claim 14, further comprising advancing the needle through the stopper to produce a fluid connection between the needle and the container.

17. The method of claim 16, further comprising delivering medicament to a patient through a fluid flow path in fluid communication with the needle.

18. A method of forming a connection in a large volume delivery device, comprising: providing a medicament container having a sterile medicament therein and a first cover; providing a needle assembly proximate, the needle assembly including a second cover; and removing at least a portion of the first cover and second cover to create an opening between the needle assembly and medicament container.

19. The method of claim 18, wherein the medicament container and needle assembly are contained in a common housing.

20. The method of claim 18, further comprising advancing the needle through a stopper in the medicament container to establish a fluid pathway between the medicament container and needle assembly.21 . The method of claim 20, further comprising delivering the medicament to a patient by allowing the medicament to pass through the needle and into a fluid delivery pathway.

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