Fluid Barrier With Breaking Ram for Large Volume Drug Delivery Device
[0001] This application claims the benefit of priority to European Patent Application No. 24315119.8 filed April 4, 2024, and to U.S. Provisional Patent Application No. 63/604,471 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 the container. 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 large volume device.
[0007] In an embodiment, the present disclosure is directed to a fluid path connection for a large volume delivery device. The fluid path connection may include a medicament container including a cap with a first raised section, a stopper, and an internal volume to hold medicament. The cap may form a first region between the cap and the stopper. The fluid path connection may include a needle assembly operable to form a connection with the medicament container. The needle assembly may include a needle and a needle assembly cover with a second raised section. The needle assembly cover may form a second region between the needle assembly cover and the needle. [0008] The fluid path connection may include a moveable ram. The movable ram may disrupt the first raised section and the second raised section. The movable ram may provide an unobstructed path between the needle and the stopper.
[0009] Relative positions of the needle and the medicament container may be moveable between a first position and a second position. The needle in the second position may pass through the stopper and form a fluid connection with a fluid path configured to deliver fluid to a patient. In the second position, the needle may extend through the unobstructed path. In the first position, the needle assembly cover may cover the needle. The first raised section and the second raised section may project toward each other.
[0010] The moveable ram may be configured to move between a first ram position, a second ram position, and a third ram position. In the first ram position, the moveable ram may not be in contact with the first raised section or the second raised section. In other embodiments, the moveable ram may be in contact with the first raised section, the second raised section, or both, without shifting the first raised section, the second raised section, or both. In the second ram position, the moveable ram may be in contact with the first raised section and the second raised section and may begin to shift the first raised section, the second raised section, or both. In the third ram position, the moveable ram may shift or move at least in part the first raised section and the second raised section.
[0011] Movement of the moveable ram from the first position to the second position and to the third position may be perpendicular to a longitudinal axis of the path. The moveable ram may include a concave end section and an aperture. In the second position, the aperture of the moveable ram may lie along the path. [0012] In the second ram position, the moveable ram may engage a first side wall of the first raised section and a second side wall of the second raised section. Each of the first side wall and the second side wall may include a convex section. The moveable ram may include a concave end section configured to mate with the convex sections of the first side wall and the second side wall.
[0013] The movable ram may include a cutting arm having one or more blades configured to at least partially remove the first raised section and the second raised section. Action of the cutting arm may remove at least in part the first raised section and the second raised section. Action of the cutting arm may provide an unobstructed path between the needle and the stopper.
[0014] In an embodiment, the present disclosure is directed to a device to deliver a medicament. The device may include a housing, a medicament container, a needle assembly, and a moveable ram. The medicament container may include a cap with a first raised section, a stopper, and an internal volume to hold medicament. The cap may form a first region between the cap and the stopper. The needle assembly may be operable to form a connection with the medicament container. The needle assembly may include a needle and a needle assembly cover. The needle assembly cover may include a second raised section. The needle assembly cover may form a second region between the needle assembly cover and the needle. The moveable ram may disrupt the first raised section and the second raised section. The moveable ram may provide an unobstructed path between the needle and the stopper.
[0015] In an embodiment, the present disclosure is directed to a method for establishing an fluid path connection in a drug delivery device. The drug delivery device may include a medicament container with a cap and a needle assembly with a needle assembly cover. The method may include initiating operation of the drug delivery device. The method may include deploying a moveable ram to disrupt a first raised section of the cap of the medicament container and a second raised section of the needle assembly cover. The method may include changing the relative location of a needle of the needle assembly and the medicament container such that the needle accesses the medicament container. The moveable ram may be deployed by applying force along a primary axis or plane of the moveable ram to shift the moveable ram. The primary axis may be perpendicular to an path axis. The first raised section may include a first substantially planar outer surface. The second raised section may include a second substantially planar outer surface. The first substantially planar outer surface and the second substantially planar outer surface may be substantially parallel. The path axis may be normal to both the first substantially planar outer surface and the second substantially planar outer surface. The moveable ram may extend over each of the first substantially planar outer surface and the second substantially planar outer surface. Changing the relative location of a needle of the needle assembly and the medicament container may include moving the needle, moving the medicament container, or both.
[0016] In an embodiment, a method of forming a connection in a large volume delivery device is provided. The method can include providing a medicament container having a sterile medicament therein and a first cover with a first raised section surrounding a stopper of the container; providing a needle assembly proximate, the needle assembly including a second cover with a second raised section surrounding a needle tip, and first and second raised sections aligned proximate one another; and disrupting the first and section raised sections to open a pathway between the needle assembly and medicament container. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] 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.
[0018] Fig. 1 is cross-sectional view of a large volume injection device.
[0019] Fig. 2A is a perspective cut-away view illustrating a fluid path connection in accordance with some embodiments.
[0020] Fig. 2B is a cross-sectional view illustrating a fluid path connection with a moveable ram in accordance with some embodiments.
[0021] Fig. 3 is a perspective cut-away view illustrating a moveable ram in accordance with some embodiments.
[0022] Fig. 4 is a perspective view illustrating a fluid path connection in accordance with some embodiments.
[0023] Fig. 5A is a cut-away view illustrating a fluid path connection with a moveable ram with a cutting arm in accordance with some embodiments.
[0024] Fig. 5B is a cross-sectional view illustrating a moveable ram with a cutting arm in accordance with some embodiments.
[0025] Fig. 5C is a cross-sectional view illustrating a moveable ram with a cutting arm in accordance with some embodiments.
[0026] Fig. 5D is a cut-away view illustrating a fluid path connection with a moveable ram with a cutting arm in accordance with some embodiments.
[0027] Fig. 6A is a perspective view illustrating an example moveable ram with a cutting arm in accordance with some embodiments.
[0028] Fig. 6B is a perspective view illustrating a disrupted raised section in accordance with some embodiments. [0029] Fig. 6C is a perspective view illustrating a moveable ram with a cutting arm in accordance with some embodiments.
[0030] Fig. 6D is a perspective view illustrating a disrupted raised section in accordance with some embodiments.
DETAILED DESCRIPTION OF CERTAIN EXEMPLARY EMBODIMENTS
[0031] 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.
[0032] 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.
[0033] 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.
[0034] 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. [0035] 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.
[0036] 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.
[0037] 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 using a 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.
[0038] 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.
[0039] 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).
[0040] 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 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).
[0041] 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.
[0042] 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.
[0043] 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.
[0044] 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.
[0045] 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.
[0046] 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 or another 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.
[0047] 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.
[0048] 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.
[0049] 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 or by 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.
[0050] 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.
[0051] Standards or best practices for the design of drug delivery devices may require or recommend providing an unobstructed path from the medicament container to a needle or cannula used to deliver the medicament to a user.
Additionally, standards or best practices for manufacturing and assembling a drugdelivery 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 be performed 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. [0052] 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.
[0053] 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 use 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.
[0054] 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. For example, different types of containers or vials may be used, including containers with different stopper or piston arrangements, or without a stopper or piston.
[0055] 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 133 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.
[0056] 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 and permits 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. [0057] Figs. 2A and 2B illustrate a fluid path connection 300 in accordance with some embodiments. The fluid path connection 300 may be used in a large volume device 100. The fluid path connection 300 includes the medicament container 200 including a cap 217 with a first raised section 310, a stopper 215, and an internal volume 220 to hold medicament. The cap 217 may form a first region 311 between the cap 217 and the stopper 215.
[0058] The fluid path connection 300 may include a needle assembly 320 operable to form a connection with the medicament container 200. The needle assembly 320 includes a needle 145 and a needle assembly cover 322 with a second raised section 324. The needle assembly cover 322 forms a second region 326 between the needle assembly cover 322 and the needle 145.
[0059] The needle assembly cover 322 and cap 217 cover the needle assembly 320 and the medicament container 200 forming regions 311 , 326. As such the 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) (i.e., the ram), which is configured to disrupt of remove a portion of the needle assembly cover 322 and cap 217 (the raise sections) to form an opening or passage that allows the needle 145 to be advanced 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 cap 217, a sterile or sufficiently clean connection can be made between the medicament container and fluid path
147.
[0060] The cap 217 and the needle assembly cover 322 may be formed from an elastomeric material, such as natural rubbers, styrene-butadiene block copolymers, polyisoprene, polybutadiene, ethylene propylene rubber, ethylene propylene diene rubber, silicone elastomers, fluoroelastomers, polyurethane elastomers, and nitrile rubbers; or a metal material, such as a metal foil.
[0061] The fluid path connection 300 includes a moveable ram 330. The movable ram 330 is operable to disrupt the first raised section 310 and the second raised section 324. Operation of the movable ram provides an unobstructed path 350 (shown in Fig. 3) between the needle 145 and the stopper 215. In particular, the moveable ram 330, as described below, is operable to disrupt or shift parts of the cap 217 and needle assembly cover 322, thereby providing an open pathway for relative movement of the needle 145 and stopper 215 to cause the needle 145 to piece the stopper 215. The moveable ram 330 has a round shape to correspond to the shape of the first raised section 310 and the second raised section 324 so that the moveable ram 330 may engage the first raised section 310 and the second raised section 324. Although shown as a round shape, different embodiments may use different shapes, such as a flat shape, a full circle, a semi-circle, an ovoid, a portion or an ovoid, a square shape, or other geometric figure.. The moveable ram 330 is mounted on an arm 332 and driven by a spring 334 to cause rotation of the movable ram 330 when movement of the moveable ram 330 is activated. In some embodiments, other biasing means may be used to power the moveable ram 330. The moveable ram 330 may be driven by a main drive spring. Furthermore, although described specifically with a spring as a drive mechanism, other types of power sources besides a spring, are contemplated, including for example, electromechanical, chemical, or gas-based mechanisms.
[0062] Fig. 3 illustrates the fluid path connection 300 after the moveable ram 330 has driven through the first raised section 310 and the second raised section 324 and the needle 145 has extended through the stopper 215 to access the internal volume 220 of the medicament container 200. The first raised section 310 and the second raised section 324 are cleared by the moveable ram 330 to provide the unobstructed path 350 along which the needle 145 extends.
[0063] The fluid path connection 300 may be used to establish a unobstructed connection in a drug delivery device (e.g., the large volume device 100) that includes a medicament container 200 with a cap 217 and a needle assembly 320 with a needle assembly cover 322. The method may include initiating operation of the drug delivery device 100. The moveable ram 330 may be in a first position, as illustrated in Figs. 2A-2B. The method may include deploying the moveable ram 330 to disrupt the first raised section 310 of the cap 217 of the medicament container 200 and a second raised section 324 of the needle assembly cover 322 by moving through a second ram position The movable ram 330 may then be in the third ram position, as illustrated in Fig. 3.
[0064] 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 338. 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.
[0065] The method may include deploying the moveable ram 330 by applying force along a primary axis of the moveable ram 330 (e.g., along the direction of the arrow 337) to shift the moveable ram 330. The primary axis may be perpendicular to an axis 338 of the unobstructed path 350, where the first raised section 310 includes a first substantially planar outer surface 312 and the second raised section 324 includes a second substantially planar outer surface 325, the first substantially planar outer surface 312 and the second substantially planar outer 325 surface being substantially parallel, and the path axis 338 being normal to both the first substantially planar outer surface 312 and the second substantially planar outer surface 325, and wherein the moveable ram 330 extends over each of the first substantially planar outer surface and the second substantially planar outer surface. Although described as a substantially planar outer surface, the outer surface may have a round, convex, concave, or other shape. As illustrated in Figs. 2A-3, the motion of the moveable ram 330 may be axial. 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.
[0066] Fig. 4 illustrates a fluid path connection 300 in accordance with some embodiments including the moveable ram 330’ with a first cavity 335 and a second cavity 336, the first raised section 310 and the cap 217 of the needle assembly 320, and the second raised section 324 and the needle assembly cover 322 of the medicament container 200. The moveable ram 330’ features a first cavity 335 with a shape corresponding to the shape of the first raised section 310 and the second raised section 324. When the moveable ram 330’ moves in the direction indicated by an arrow 337, the first cavity 335 engages with and disrupts the first raised section 310 and the second raised section 324. As the moveable ram 330’ continues to move in the direction indicated by the arrow 337, the second cavity 336 moves into alignment with the centers of the cap 217 and the needle assemble cover 322 to provide an unobstructed path 350 for the needle 145 (not visible in Fig. 4) to access the medicament container 200.
[0067] The moveable ram is shown as moving by translation, but it is contemplated that the movement of the ram can be by translation, rotation, or some combination of the two, so long as the ram moves to cause disruption of the raised sections. Further, the ram may move in an abrupt, powerful and quick movement to break or cut the raiser sections, or the ram may move more slowly but with sufficient force to cut the raised section.
[0068] Although not illustrated, the movement of the ram can be activated in a number of ways. For example, the ram may be activated upon pushing a main release mechanism of the device, which may thereby activate the entire device. Alternatively, the ram may be operably connected to a separate activation mechanism (e.g., a separate button or pull-away safety tab). Further, the ram may be activated through a switch when the device 100 is placed in contact with a patient’s skin.
[0069] The raised sections 310 and 324 can be disrupted in a number of ways. For example, the raised sections can be formed of a variety of different materials and such materials can be configured to break or rupture by movement of the ram. The raised sections, for example, can include a metallic or polymeric material that is impervious to liquid or microbes. The material can be selected such that it can be cut or fractured by the ram and pushed out of the way. As such, the ram can include a blunt or sharp edge depending on the mechanism of removal of the raised sections.
[0070] Figs. 5A-5D illustrates a fluid path connection 300’ in accordance with some embodiments including a cutting arm 370. The cutting arm 370 has one or more blades 371 configured to at least partially remove the first raised section 310 and the second raised section 324 when the cutting arm 370 is driven across the first raised section 310 and the second raised section 324. The cutting arm 370 removes at least in part the first raised section 310 and the second raised section 324 to provide an unobstructed path 350 between the needle 145 and the stopper 215. Springs 373 bias the cutting arm 370 toward the extended position in order to provide force to drive the cutting arm 370 through the first raised section 310 and the second raised section 324.
[0071] Figs. 5A and 5B illustrate the fluid path connection 300 with the cutting arm 370 in an initial position, i.e. , before the cutting arm 370 is deployed to clear the first raised section 310 and the second raised section 324. In Figs. 5C and 5D, the cutting arm 370 has passed through the first raised section 310 and the second raised section 324, clearing both away and providing the unobstructed path 350. Figs. 5C and 5D shows a pair of biasing springs 373 used to bias the cutting arm 370 toward an extended position and to help drive the cutting arm 370 through the first raised section 310 and the second raised section 324.
[0072] Fig. 6A illustrates a first cutting arm 370’, which is a flat-ended blade. The first cutting arm 370’ was used to disrupt the first raised section 310’ of the cap 217’ as shown in Fig. 6B. The first raised section 310’ is made of a metal foil.
[0073] Fig. 6B illustrates a second cutting arm 370”, which is a curved knife blade. The second cutting arm 370” was used to disrupt the first raised section 310” of the cap 217” as shown in Fig. 6D. The first raised section 310” is made of a metal foil. The first cutting arm 370’ and the second cutting arm 370” demonstrate that the first raised section 310’, 310” made of a metal foil may be disrupted and cleared from the cap 217’, 217”, according to embodiments herein.
[0074] The first cutting arm 370’ and the second cutting arm 370” illustrate exemplary methods only. Other methods of cutting and other configurations of the first cutting arm 370’ and the second cutting arm 370” may be used including cutting arms with a different shape of blade, number of blades, or location of cutting surface. Exemplary Drugs or Medicaments
[0075] 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 mental well-being. A drug or medicament may be used for a limited duration, or on a regular basis for chronic disorders.
[0076] 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.
[0077] 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. [0078] 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.
[0079] 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 naturally occurring 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-codeable amino acids, or amino acids, including non-codeable, have been added to the naturally occurring peptide.
[0080] 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.
[0081] 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.
[0082] 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, ORMD-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.
[0083] 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.
[0084] Examples of DPP4 inhibitors are Linagliptin, Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.
[0085] 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.
[0086] 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 poly-sulphated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodium hyaluronate. [0087] 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).
[0088] 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 still comprises 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.
[0089] 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. [0090] 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).
[0091] 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.
[0092] 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. [0093] 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.