Method and Fixture for Plunger Rod Removal Force

Abstract

A test system for a drug delivery device includes a frame member having a first end and a second end, a drive member disposed proximate the frame member, a substitute syringe barrel operably coupled to the frame member, a flange extension adapted to couple with a portion of the substitute syringe barrel, and a plunger rod coupled with the flange extension and disposed at least partially within the substitute syringe barrel while adapted to be movable within the substitute syringe barrel. The drive member is axially movable between the first end and the second end of the frame member. The plunger rod includes a first end, a second end, and a longitudinal length between the first end and the second end, the first end being disposed proximate a portion of the drive member. The drive member measures a maximum biasing force acting on the plunger rod as it moves axially toward the second end of the frame member.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Priority is claimed to U.S. Provisional Patent Application No. 63 / 283,798, filed November 29, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to drug delivery devices and, more particularly, to retention features for drug delivery devices. [Background technology]

[0003] Drug delivery devices, such as injectors, are used to deliver liquid medication to a patient. When actuated, the drug delivery device expels a drug stored in an internal reservoir, such as a prefilled syringe ("PFS"), through a needle, cannula, or other delivery member into the patient. Some drug delivery devices, such as pen autoinjectors or on-body injectors, can be placed adjacent to the patient's skin to deliver the drug over a period of time through an injection needle or some other means. The drug delivery device can be placed near tissue in the patient's abdomen, thigh, arm, or some other part of the patient's body.

[0004] To ensure patient and / or user safety, these devices undergo any number of sterilization steps to prevent undesirable contaminants from coming into contact with certain components of the device and / or the drug itself. One example of such a sterilization technique is commonly known as "external sterilization." External sterilization involves placing a partially or fully assembled drug delivery device into a sterilization chamber and exposing the device to a sterilizing gas or other sterilizing agent, such as nitrogen dioxide sterilization, ethylene oxide sterilization, light-based sterilization, and / or any other suitable technique. In many of these processes, a vacuum is applied to sterilize prior to the introduction of the sterilizing gas during the external sterilization process to maximize contact between the sterilizing gas and the exterior surfaces of the fully and / or partially assembled and filled device. When the vacuum is applied, the resulting pressure differential between the interior and exterior of the PFS causes air bubbles within the PFS to expand, which may further bias or displace additional components of the device (e.g., the plunger stopper) into an undesirable state.

[0005] Some drug delivery devices may include features that block and / or limit movement of the plunger stopper because such movement may result in previously sterilized components entering a non-sterile area. Furthermore, such movement may affect the performance of the device during administration of the drug. Existing test methods attempt to measure the force required to overcome such retention features, but often produce inaccurate results because they do not adequately replicate the forces encountered during the sterilization process. Summary of the Invention [Means for solving the problem]

[0006] The present disclosure describes fasteners and corresponding techniques for plunger rod removal force that embody advantageous alternatives to existing fasteners and techniques and that may address one or more of the problems or needs noted herein.

[0007] According to a first aspect, a test system for a drug delivery device includes a frame member having a first end and a second end, a drive member disposed proximate the frame member, a substitute syringe barrel operably coupled to the frame member, a flange extension adapted to couple with a portion of the substitute syringe barrel, and a plunger rod coupled with the flange extension and disposed at least partially within the substitute syringe barrel while adapted to be movable within the substitute syringe barrel. The drive member is axially movable between the first end and the second end of the frame member. The plunger rod includes a first end, a second end, and a longitudinal length between the first end and the second end, the first end being disposed proximate a portion of the drive member. The drive member measures a maximum biasing force acting on the plunger rod when moving axially toward the second end of the frame member.

[0008] In some examples, the plunger rod may include a protruding / projecting plunger rod interface feature disposed along its longitudinal length. The plunger rod interface may engage a floor area of ​​the flange extension to hold the plunger rod in the initial position. In some of these approaches, the plunger rod interface may include a ring having an outer dimension. Further, in these and other examples, the floor area of ​​the flange extension may include an opening having an inner dimension. The outer dimension of the ring of the plunger rod may be larger than the inner dimension of the opening of the flange extension. In these arrangements, axial movement of the plunger rod toward the second end of the frame member is prevented. In some examples, at least one of the plunger rod interface or the floor area of ​​the flange is constructed at least in part from a deformable material.

[0009] In some approaches, the substitute syringe barrel may include a syringe flange. The flange extension may include a flange adapted to rest on the syringe flange of the substitute syringe barrel.

[0010] In these and other examples, the frame member can include a lift platform disposed at a first end thereof. The lift platform can hold and suspend a substitute syringe barrel from the first end thereof. In these examples, when the drive member is moved toward the second end of the frame member, the plunger rod and flange extension are subjected to a gravitational force in the axial direction.

[0011] In some approaches, the drive member includes a push pin that is at least partially insertable and movable within the substitute syringe barrel. The push pin may include a recessed area that aligns with the first end of the plunger rod.

[0012] In some approaches, the drive member may be disposed above the first end of the frame member.

[0013] According to a second aspect, there is provided a method for measuring a maximum biasing force experienced by a portion of a drug delivery device, the method comprising disposing a drive member over a first end of a frame member. The drive member is axially movable between the first end of the frame member and a second end of the frame member. The method further comprises operably coupling a substitute syringe barrel to the first end of the frame member, coupling a first flange extension to a portion of the substitute syringe barrel, and coupling a first plunger rod to the flange extension, whereby the first plunger rod is at least partially movably disposed within the substitute syringe barrel. The first plunger rod comprises a first end, a second end, and a longitudinal length between the first end and the second end. The method further comprises axially moving the drive member toward the second end of the frame member, thereby biasing the first plunger rod toward the second end of the frame member. A maximum biasing force acting on the first plunger rod while moving toward the second end of the frame member is measured.

[0014] The above needs are met, at least in part, by the provision of a plunger rod removal force method and fixture as described in the following detailed description, particularly when considered in conjunction with the drawings. [Brief description of the drawings]

[0015] [Figure 1] 1 illustrates an exemplary test system in accordance with various embodiments. [Diagram 2] 2 illustrates the example test system of FIG. 1 before testing begins, in accordance with various embodiments. [Diagram 3] 3 illustrates a bottom view of an exemplary lift platform for use with the exemplary test system of FIGS. 1 and 2, in accordance with various embodiments. [Figure 4] 1-3 in a pre-test configuration, according to various embodiments. [Diagram 5] 5 shows an enlarged view of a portion of a drug delivery device in the exemplary testing system of FIGS. 1-4, according to various embodiments. [Figure 6] 6 illustrates an exemplary portion of a drug delivery device in the exemplary testing system of FIGS. 1-5 upon completion of testing, according to various embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] Those skilled in the art will appreciate that the elements in the figures are depicted for simplicity and clarity and are not necessarily drawn to scale. For example, the dimensions and / or relative positions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of the various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in commercially feasible embodiments are often not shown in order to not overly distract from the illustrations of these various embodiments. Furthermore, it will be appreciated that certain acts and / or steps may be described or shown in a particular order of occurrence, although those skilled in the art will appreciate that such specificity with respect to the order is not actually required. It will also be appreciated that the terms and expressions used herein have the ordinary technical meaning that those skilled in the art of the above-mentioned art would recognize for such terms and expressions, unless a different specific meaning is otherwise expressly set forth herein.

[0017] Generally, in accordance with these various embodiments, a technique is provided that accurately simulates the loads experienced by a drug delivery device during interaction in a sterilization chamber. The technique includes a test system that biases the delivery device components in a direction that reflects the forces the components experience during the sterilization process. More specifically, the technique simulates the forces experienced by the drug delivery device during an external sterilization process, which, as previously described, includes placing a partially or fully assembled drug delivery device (which may in some instances be filled with a drug product) into a sterilization chamber and exposing the device to a sterilization gas, such as, for example, nitrogen dioxide sterilization, ethylene oxide sterilization, light-based sterilization, and / or any other suitable technique. The test system measures the maximum forces experienced by the device components to aid in the evaluation of their potential use in various drug delivery device designs.

[0018] The drug delivery device delivers a drug, which may be referred to herein as a drug or drug product. The drug may be, but is not limited to, various biological substances, such as peptides, peptibodies, or antibodies. The drug may be in fluid or liquid form, although the present disclosure is not limited to a particular state. Various implementations and configurations of the drug delivery device are possible. For example, the present disclosure describes a drug delivery device in the form of a single-use disposable injector. In other embodiments, the drug delivery device may be configured as a multiple-use reusable injector. The drug delivery device may be operable for self-administration by the patient or administration by a caregiver or formally trained health care provider (e.g., a doctor or nurse). Additionally, the drug delivery device may take the form of an auto-injector or pen-type injector, and thus may be held in the user's hand for the duration of the drug delivery or administration.

[0019] Referring now to the figures, a test system 100 is provided for use with components of a drug delivery device. More specifically, a plunger rod 10 is provided that couples with a flange extension 20. Generally, when used for drug delivery, the plunger rod 10 is disposed within or near a syringe barrel (not shown) that contains a drug (not shown) to be administered to a user. The plunger rod 10 is axially movable within the syringe barrel to urge a plunger toward a delivery member (e.g., a needle and / or cannula) that pierces the user's skin and delivers the drug or agent to the patient's tissue. The plunger rod 10 includes a first end 12 (FIG. 6) that may be coupled to a plunger by any number of suitable techniques, a second end 14, and a longitudinal length 13 therebetween. As shown in FIG. 6, the plunger rod 10 further includes a protruding and / or raised plunger rod interface 16 (FIG. 6) disposed along the longitudinal length 13. In the illustrated example, the plunger rod interface 16 is in the form of a ring extending around the circumference of the longitudinal length 13. The ring 16 may have an outer dimension (e.g., a diameter). It is understood that the plunger rod 10 may include any number of additional features (e.g., additional interfaces, guide mechanisms, coupling mechanisms, etc.) to aid in the operation of the drug delivery device. In some examples, all or a portion of the plunger rod 10 is constructed from a resilient material, such as, for example, a polymeric material. Other examples are possible.

[0020] The flange extension 20 is adapted to mate with the plunger rod 10 during use of the drug delivery device. In general, the flange extension 20 may provide a user with an increased surface area to grip before, during, and / or after drug administration. The flange extension 20 includes a body 21 defining an upper opening 22, a floor region 23, and a lower opening 24 extending through the floor region 23, and further includes a flange 26 extending downwardly into the body 21 that at least partially defines the upper opening 22. The lower opening 24 defines an interior dimension. In some examples, all or a portion of the flange extension 20 is constructed from a resilient material, such as, for example, a polymeric material. Other examples are possible.

[0021] The plunger rod 10 is movable axially (i.e., along the longitudinal length 13 of the plunger rod 10) relative to the flange extension 20. Furthermore, a portion of the longitudinal length 13 of the plunger rod is insertable through the upper opening 22 and / or the lower opening 24 of the flange extension 20. In particular and as shown in FIG. 5, before the drug delivery device is used and before sterilization, the ring 16 of the plunger rod 10 is placed above the lower opening 24 of the flange extension 20. In this example, the outer dimension of the ring 16 is larger than the inner dimension of the lower opening 24 of the flange extension 20 (but the remaining portion of the longitudinal length 13 of the plunger rod 10 has a dimension smaller than the inner diameter of the lower opening 24 of the flange extension 20). Thus, in this initial position, the plunger rod 10 is held by the flange extension. This engagement limits the plunger rod 10 from moving downwards.

[0022] The interference between the ring 16 and the lower opening 24 can be overcome by a sufficient axial bias. For example, the ring 16 of the plunger rod can be constructed from a deformable material to compress and / or otherwise deform depending on the characteristics of the plunger rod 10 and the flange extension 20. Additionally and / or alternatively, the lower opening 24 of the flange extension 20 can be constructed from a deformable material to increase in size or otherwise deform with deformation of the body 21. In such an example, the engagement between the ring 16 of the plunger rod 10 and the lower opening 24 of the flange extension 20 can be defined by a retention force, i.e., a maximum force acting on these components before the ring 16 of the plunger rod 10 passes through the lower opening 24 of the flange extension 20. During the (external) sterilization stage, in which a partially and / or fully assembled device that may contain a drug product therein is subjected to sterilization (as well as during other stages such as shipping and other handling), the pressure difference between the interior and exterior of the syringe barrel can cause air bubbles in the syringe barrel to expand, thereby biasing the plunger (and thus the plunger rod) downward. Therefore, to ensure that the plunger rod does not move beyond the desired position, it is advantageous to identify the maximum retention force exhibited between the plunger rod 10 and the flange extension 20 such that this maximum retention force is greater than the peak / maximum biasing force generated by an air bubble.

[0023] The test system 100 is configured to test the engagement between the plunger rod 10 and the flange extension 20 and measure a force corresponding to a maximum retention force experienced before the ring 16 of the plunger rod 10 passes through the lower opening 24 of the flange extension 20. Importantly, the test system 100 is oriented to simulate the relative positions of the components of a drug delivery device during various processes, such as sterilization, and further applies a maximum biasing force in the same direction as the forces experienced by the device during these processes (i.e., "pushing" the first end 12 of the plunger rod 10 rather than "pulling" the second end 14 of the plunger rod 10). The test system 100 includes a frame member 101 having a first end 102 and a second end 103, a substitute syringe barrel 110, and a drive member 120 disposed generally proximate (e.g., above) the first end 102 of the frame member 101 and the substitute syringe barrel 110. In the illustrated example, the first end 102 corresponds to the upper end of the frame member 101 and the second end 103 corresponds to its lower end. Thus, these terms may be used interchangeably throughout this specification. Furthermore, it will be understood that other arrangements and / or orientations are possible. The lower end 103 of the frame member 101 may rest on a horizontal surface or alternatively may be suspended by a shaft or similar component. The frame member 101 includes at least one support post 104 coupled with a lift platform 106 disposed at its upper end 102. As shown in FIG. 3, the one or more support posts 104 may include one or more alignment pins 104a insertable into corresponding support openings 106a formed on or in the platform 106. The platform 106 may further include an opening 108 configured to receive a substitute syringe barrel 110.

[0024] The substitute syringe barrel 110 is in the form of a generally hollow cylindrical member that replicates a syringe barrel of a drug delivery device. In the illustrated example, the substitute syringe barrel 110 is a headless member that lacks a connection point for a needle or other component of the drug delivery device. The substitute syringe barrel 110 includes a first end 111, a second end 113, a body 112 disposed between the first end 111 and the second end 113, and a syringe flange 114 disposed at the second end 113. In some examples, the needle of the drug delivery device is disposed at the first end 111. The first end 111 of the substitute syringe barrel 110 is coupled to the mount 106. More specifically, the first end 111 of the substitute syringe barrel 110 may be disposed within an opening 108 of the mount 106. In some examples, the first end 111 of the substitute syringe barrel 110 may frictionally engage the opening 108 of the base 106, and in other examples, the base 106 may be a two-piece or multi-piece member that may be adjusted or tightened to clamp and secure the first end 111 of the substitute syringe barrel 110 therein.

[0025] The drive member 120 is configured to apply a force to the plunger rod 10. More specifically, the drive member 120 includes a load cell 121, a movable coupling 122, and a push pin 124 operably coupled to the movable coupling 122. As shown in FIG. 1, the movable coupling 122 includes a threaded receptacle that receives the push pin 124, which applies a force to the plunger rod 10 during operation. The load cell 121 may be any type of suitable load cell capable of measuring the force acting on the push pin 124. The movable coupling 122 moves axially from an initial upward position (i.e., at or near the top end 102 of the frame member 101) to a downward position (i.e., in a direction toward the bottom end 103 of the frame member 101). Because the push pin 124 is coupled to the movable coupling 122, the push pin 124 also moves axially. As shown in FIGS. 1 and 2, push pin 124 is axially aligned with substitute syringe barrel 110 such that push pin 124 can move axially through substitute syringe barrel 110.

[0026] In use, when the substitute syringe barrel 110 is coupled to the mount 106, the first end 111 of the substitute syringe barrel 110 is axially aligned with the push pin 124. The first end 12 of the plunger rod 10 can be inserted into the second end 113 of the substitute syringe barrel 110, and the flange extension 20 can be coupled to the second end 113 of the substitute syringe barrel 110. More specifically, as shown in FIGS. 4-6, a portion of the body 112 of the substitute syringe barrel 110 can be disposed through the upper opening 22 of the flange extension 20, and the flange 26 of the flange extension 20 rests on the syringe flange 114 of the substitute syringe barrel 110. In this configuration, the syringe flange 114 of the substitute syringe barrel 110 is disposed above the lower opening 24 of the flange extension 20, thus mimicking the configuration of the drug delivery device in an assembled state. As previously mentioned, in this configuration, the ring 16 of the plunger rod 10 is also disposed above the lower opening 24 of the flange extension 20. In some examples, the ring 16 of the plunger rod 10 may be disposed completely and / or partially within the throughbore of the substitute syringe barrel 110, while in other implementations, the ring 16 of the plunger rod 10 may be disposed at or near the syringe flange 114 of the substitute syringe barrel 110. Further, in some examples, the first end 12 of the plunger rod 10 may extend upwardly to the first end 111 of the substitute syringe barrel 110, while in other implementations, the first end 12 of the plunger rod 10 may be disposed a distance within the body 112 of the substitute syringe barrel 110.

[0027] By positioning the drive member 120 axially above the surrogate syringe barrel 110, the plunger rod 10 and the flange extension 20, the movement of the push pin 124 from the upper end 102 of the frame member 101 toward the lower end 103 of the frame member 101 simulates the force acting on the first end 12 of the plunger rod 10 during the expansion of any air or other gas bubbles within the actual syringe barrel of the drug delivery device during the sterilization and / or shipping process. The movable coupling 122 causes the push pin 124 to push the first end 12 of the plunger rod 10 downwards, and the load cell 121 measures this force. This force gradually increases as the drive member 120 moves downwards. As previously described, the ring 16 of the plunger rod 10 engages the lower opening 24 of the flange extension 20 and temporarily holds the plunger rod 10 in this position until the biasing force exerted by the movable coupling 122 is sufficient to overcome the holding force. The maximum value measured by the load cell 121 during this movement is referred to herein as the maximum biasing force. Eventually, the ring 16 of the plunger rod 10 and / or the floor area 23 of the flange extension 20 deform to the point where the ring 16 of the plunger rod 10 passes through the lower opening 24 of the flange extension 20 (FIG. 6). The load cell 121 measures the maximum biasing force, which corresponds to the maximum holding force exhibited between the plunger rod 10 and the flange extension 20. This measurement may be indicative of the maximum internal pressure these components can withstand before exhibiting undesirable relative translation.

[0028] The resulting data can be used to determine whether the retention features of the tested plunger rod and flange extension combination create sufficient interference to adequately withstand internal and / or external forces prior to drug administration. Depending on the particular desired drug, its amount within the syringe barrel, and / or any other additional variables, a maximum internal pressure can be calculated. This value can serve as a minimum threshold (taking into account any desired safety factors) that must be achieved for the desired plunger rod and flange extension to be used with the desired drug. Advantageously, any number of different plunger rods and / or flange extensions having various characteristics (e.g., sizes, materials, features, etc.) can be tested during different stages of implementation (e.g., during the design or development stage, during the design validation stage, and / or during manufacturing). Other examples are possible.

[0029] In some arrangements (see, e.g., FIGS. 2 and 3), the end of the push pin 124 may have a concave or similar internal profile positioned to receive a portion of the first end 12 of the plunger rod 10. In such examples, the push pin may have alignment features formed thereon to ensure that the system 100 maintains the correct relative position between these components. Such an arrangement may allow the push pin 124 to apply a uniform downward force to the plunger rod 10, further mimicking the forces experienced within an actual drug delivery device.

[0030] Compared to conventional testing systems that apply a pulling force to the plunger rod, the present testing system 100 pushes or urges the plunger rod 10 downward, thus precisely simulating both the magnitude and direction of the forces experienced by each component during sterilization. In these conventional systems, the use of a pulling force applied to the plunger rod to measure the plunger rod retention force can result in inaccurate measurements due to differences in the behavior of the components / system when under compression versus tension (and / or any internal forces). Thus, the present system provides improved accuracy by precisely simulating the pushing force exerted by the syringe barrel on the plunger rod and associated components.

[0031] Additionally, the present test system 100 provides a technique for holding the syringe barrel above the lower end 103 of the frame member 101 to allow the plunger rod to translate downwards by providing sufficient clearance between its upper end 102 and lower end 103. As previously mentioned, the test system 100 may also be advantageously used to determine retention forces in other environments, such as during shipping. Due to altitude changes during shipping, air bubbles inside the PFS may expand or compress to achieve equilibrium volume, which may further exert different forces on the plunger stopper (and thus the plunger rod). This test measures retention forces to determine if the retention forces are sufficient to maintain the integrity of the sterile barrier of the drug container, and also helps prevent component disassembly.

[0032] The above description describes various devices, assemblies, components, subsystems, and methods of use related to drug delivery devices. The devices, assemblies, components, subsystems, methods, or drug delivery devices may further include or be used with drugs, including, but not limited to, the drugs identified below and their generic and biosimilar equivalents. As used herein, the term drug may be used interchangeably with other similar terms and may be used to refer to any type of drug or therapeutic material, including traditional and non-traditional drugs, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, biological equivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic drugs. Non-therapeutic injectable materials are also included. Drugs may be in liquid form, lyophilized form, or reconstituted from lyophilized form. The following list of exemplary drugs should not be considered exhaustive or limiting.

[0033] The drug is contained within a reservoir. In some cases, the reservoir is a primary container into which the drug is filled or pre-filled for treatment. The primary container may be a vial, cartridge, or pre-filled syringe.

[0034] In some embodiments, the reservoir of the drug delivery device may be loaded with or the device may be used in conjunction with a colony stimulating factor such as granulocyte colony stimulating factor (G-CSF). Such G-CSF formulations include, but are not limited to, Neulasta® (pegfilgrastim, PEGylated filgrastim, PEGylated G-CSF, PEGylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-MetG-CSF), UDENYCA® (pegfilgrastim-cbqv), Ziextenzo® (LA-EP2006; pegfilgrastim-bmez) or FULPHILA (pegfilgrastim-bmez).

[0035] In other embodiments, the drug delivery device may contain or be used with an erythropoietin stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoietin. In some embodiments, an ESA is an erythropoietin stimulating protein. As used herein, "erythropoietin stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to the receptor and causing receptor dimerization. Erythropoietin stimulating proteins include erythropoietin and its variants, analogs or derivatives that bind to and activate the erythropoietin receptor; antibodies that bind to and activate the erythropoietin receptor; or peptides that bind to and activate the erythropoietin receptor. Erythropoietin stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), Epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta and epoetin delta, PEGylated erythropoietin, carbamylated erythropoietin and molecules or variants or analogs thereof.

[0036] Particularly exemplary proteins include the specific proteins listed below, including fusions, fragments, analogs, variants or derivatives thereof: OPGL-specific antibodies (also referred to as RANKL-specific antibodies, peptibodies, etc.), peptibodies, related proteins, etc., including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies; myostatin-binding proteins, peptibodies, related proteins, etc., including myostatin-specific peptibodies; IL-4 receptor-specific antibodies, peptibodies, related proteins, etc., which particularly inhibit activities mediated by binding of IL-4 and / or IL-13 to its receptor; Interleukin 1-receptor 1 ("IL1-R1") specific antibodies, peptibodies, related proteins, etc.; Ang2 specific antibodies, peptibodies, related proteins, etc.; NGF specific antibodies, peptibodies, related proteins, etc.; CD22 specific antibodies, peptibodies, related proteins, etc., especially dimers of human-mouse monoclonal hLL2 gamma chain disulfide bound to human-mouse monoclonal hLL2 kappa chain, e.g., epratuzumab (CAS Registry Number 501423-23-0). human CD22 specific antibodies, such as, but not limited to, humanized and fully human antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, including, but not limited to, human CD22 specific IgG antibodies, particularly including, but not limited to, the human CD22 specific fully humanized antibody of HuMax; IGF-1 receptor specific antibodies, including, but not limited to, anti-IGF-1R antibodies, peptibodies and related proteins; B-7 related protein 1 specific antibodies, peptibodies, related proteins and the like, including, but not limited to, those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, on activated T cells, including, but not limited to, the B7RP specific fully human monoclonal IgG2 antibody, including, but not limited to, the fully human IgG2 monoclonal antibody that binds to an epitope in the first immunoglobulin-like domain of B7RP-1 (also referred to as "B7RP-1" and B7H2, ICOSL, B7h and CD275); e.g., 145c7, HuMax IL-15 specific antibodies, such as humanized monoclonal antibodies, peptibodies, related proteins, and the like, including, but not limited to, IL-15 antibodies and related proteins;IFN gamma specific antibodies, including but not limited to, human IFN gamma specific antibodies, including but not limited to, fully human anti-IFN gamma antibodies; TALL-1 specific antibodies, peptibodies, related proteins, etc., as well as other TALL specific binding proteins; parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, etc.; thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies, related proteins, etc.; fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter factor (HGF / SF) hepatocyte growth factor ("HGF") specific antibodies, peptibodies, related proteins, and the like, including those that target the HGF / SF:cMet axis (HGF / SF:c-Met), such as monoclonal antibodies; TRAIL-R2 specific antibodies, peptibodies, related proteins, and the like; activin A specific antibodies, peptibodies, proteins, and the like; TGF-beta specific antibodies, peptibodies, related proteins, and the like; amyloid-beta protein specific antibodies, peptibodies, related proteins, and the like; and proteins that bind to c-Kit and / or other stem cell factor receptors, including, but not limited to, including, but not limited to, c-Kit specific antibodies, peptibodies, related proteins, etc.; OX40L specific antibodies, peptibodies, related proteins, etc., including, but not limited to, proteins that bind OX40L and / or other ligands of the OX40 receptor; Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa), erythropoietin [30-asparagine, 32-threonine, 87-valine, 88-asparagine, 90-threonine], darbepoetin alfa, stimulating de novo erythropoiesis Protein (NESP); Epogen® (epoetin alfa or erythropoietin); GLP-1, Avonex® (interferon beta-1a); Bexxar® (tositumomab, an anti-CD22 monoclonal antibody); Betaseron® (interferon-beta); Campath® (alemtuzumab, an anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokine receptor mAb);Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker); Eprex® (epoetin alfa); Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1); Genotropin® (somatropin, human growth hormone); Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb); Kanjinti™ (trastuzumab-anns) anti-HER2 monoclonal antibody, a biosimilar of Herceptin® or another product containing trastuzumab for the treatment of breast or gastric cancer; Humatrope® (somatropin, human growth hormone); Humira® (adalimumab); Vectibix (registered ® (panitumumab), Xgeva® (denosumab), Prolia® (denosumab), immunoglobulin G2 human monoclonal antibody against RANK ligand, Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumab, conatumumab, brodalumab, insulin in solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human B-type natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™ (eculizumab); pexelizumab (anti-complement C5); Numax® (MEDI-524); Lucentis® (ranibizumab);Panorex® (17-1A, edrecolomab); Trabio® (lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (vigilizumab); cantuzumab mertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega® (oprelvekin, human interleukin-11); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody); Procrit® (epoetin alpha); Remicade® (infliximab, anti-TNFα monoclonal antibody); Reopro® (abciximab, anti-GP lIb / Ilia receptor monoclonal antibody; Actemra® (anti-IL6 receptor mAb); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Mvasi™ (bevacizumab-awwb); Rituxan® (rituximab, anti-CD20 mAb);Tarceva® (erlotinib);Roferon-A®-(interferon alpha-2a);Simulect® (basiliximab);Prexige® (lumiracoxib);Synagis® (palivizumab);145c7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507);Tysabri® (natalizumab, anti-α4 integrin mAb);Valortim® (MDX-1303, anti-B. anthracis protective antigen mAb);ABthrax®;Xolair® (omalizumab);ETI211 (anti-MRSA mAb);IL-1 trap (Fc portion of human IgG1 and extracellular domain of both IL-1 receptor components (type I receptor and receptor accessory protein));VEGF trap (IgG1 Ig domain of VEGFR1 fused to Fc; Zenapax® (daclizumab); Zenapax® (daclizumab, an anti-IL-2Rα mAb);Zevalin® (ibritumomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFα mAb); HGS-ETR1 (mapatuzumab; human anti-TRAIL receptor-1 mAb); HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab); M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAbs; anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388; anti-CD22 dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-Cripto mAb; anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019); anti-CTLA4 mAb; anti-eotaxin 1 mAb (CAT-213); anti-FGF8 mAb; anti-ganglioside GD2 mAb;Anti-ganglioside GM2 mAb;Anti-GDF-8 human mAb (MYO-029);Anti-GM-CSF receptor mAb (CAM-3001);Anti-HepC mAb (HuMax HepC);Anti-IFNα mAb (MEDI-545, MDX-198);Anti-IGF1R mAb;Anti-IGF-1R mAb (HuMax-Inflam);Anti-IL12 mAb (ABT-874); anti-IL12 / IL23 mAb (CNTO 1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5 receptor mAb; anti-integrin receptor mAb (MDX-018, CNTO 95);Anti-IP10 ulcerative colitis mAb (MDX-1100);BMS-66513;Anti-mannose receptor / hCGβ mAb (MDX-1307); anti-mesothelin dsFv-PE38 conjugate (CAT-5001); anti-PD1 mAb (MDX-1106 (ONO-4538)); anti-PDGFRα antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL receptor-2 human mAb (HGS-ETR2); anti-TWEAK mAb; anti-V; EGFR / Flt-1 mAb; and anti-ZP3 mAb (HuMax-ZP3).

[0037] In some embodiments, the drug delivery device may contain or be used with sclerostin antibodies, such as, but not limited to, romosozumab, brosozumab, BPS 804 (Novartis), Evenity™ (romosozumab-aqqg), another product containing romosozumab for the treatment of postmenopausal osteoporosis and / or fracture healing, and in other embodiments, monoclonal antibodies (IgG) that bind to human proprotein convertase subtilisin / kexin type 9 (PCSK9). Such PCSK9-specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab). In other embodiments, the drug delivery device may contain or be used with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, or panitumumab. In some embodiments, the reservoir of the drug delivery device may be loaded with or the device may be used in conjunction with IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers, including but not limited to OncoVEXGALV / CD; OrienX010; G207, 1716; NV1020; NV12023; NV1034; and NV1042. In some embodiments, the drug delivery device may contain or be used in conjunction with an endogenous tissue inhibitor of metalloproteinases (TIMP), such as but not limited to TIMP-3. In some embodiments, the drug delivery device may contain or be used in conjunction with Aimovig® (erenumab-aooe), anti-human CGRP-R (calcitonin gene-related peptide type 1 receptor), or another product containing erenumab for the treatment of migraines. Antagonistic antibodies to the human calcitonin gene-related peptide (CGRP) receptor, such as, but not limited to, erenumab, and bispecific antibody molecules targeting the CGRP receptor and other headache targets, may also be delivered using the drug delivery devices of the present disclosure.In addition, bispecific T cell-engaging (BiTE®) molecules, such as but not limited to BLINCYTO® (blinatumomab), can be used in or with the drug delivery device of the disclosure. In some embodiments, the drug delivery device can contain or be used with an APJ large molecule agonist, such as but not limited to apelin or an analogue thereof. In some embodiments, a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody is used in or with the drug delivery device of the disclosure. In some embodiments, the drug delivery device can contain or be used with Avsola™ (infliximab-axxq), an anti-TNFα monoclonal antibody, a biosimilar of Remicade® (infliximab) (Janssen Biotech, Inc.) or another product containing infliximab for the treatment of autoimmune diseases. In some embodiments, the drug delivery device may contain or be used in conjunction with Kyprolis® (carfilzomib), (2S)-N-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide, or another product containing carfilzomib for the treatment of multiple myeloma. In some embodiments, the drug delivery device may contain or be used in conjunction with Otezla® (apremilast), N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide, or another product containing apremilast for the treatment of various inflammatory diseases. In some embodiments, the drug delivery device may contain or be used in conjunction with Parsabiv™ (etelcalcetide HCl, KAI-4169), or another product containing etelcalcetide HCl for the treatment of secondary hyperparathyroidism (sHPT), such as in patients with chronic kidney disease (KD) undergoing hemodialysis.In some embodiments, the drug delivery device may contain or be used with ABP 798 (rituximab), a biosimilar candidate of Rituxan® / MabThera™, or another product containing an anti-CD20 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used with a VEGF antagonist, such as a non-antibody VEGF antagonist, and / or a VEGF trap, such as aflibercept (Ig domain 2 from VEGFR1 and Ig domain 3 from VEGFR2 fused to the Fc domain of IgG1). In some embodiments, the drug delivery device may contain or be used with ABP 959 (eculizumab), a biosimilar candidate of Soliris®, or another product containing a monoclonal antibody that specifically binds to complement protein C5. In some embodiments, the drug delivery device may contain or be used with rogivafusp alfa (formerly AMG 570), a novel bispecific antibody-peptide conjugate that simultaneously blocks ICOSL and BAFF activity. In some embodiments, the drug delivery device may contain or be used with omecamtiv mecarbil, a small molecule selective cardiac myosin activator or myotrope that directly targets the contractile mechanism of the heart, or another product containing a small molecule selective cardiac myosin activator. In some embodiments, the drug delivery device may contain or be used with sotorasibe (formerly known as AMG 510), a KRASG12C small molecule inhibitor, or another product containing a KRASG12C small molecule inhibitor. In some embodiments, the drug delivery device may contain or be used with tezepelumab, a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), or another product containing a human monoclonal antibody that inhibits the action of TSLP. In some embodiments, the drug delivery device may contain or be used with AMG 714, a human monoclonal antibody that binds to interleukin-15 (IL-15), or another product containing a human monoclonal antibody that binds to interleukin-15 (IL-15).In some embodiments, the drug delivery device may contain or be used with AMG 890, a small interfering RNA (siRNA) that reduces lipoprotein(a), also known as Lp(a), or another product that contains small interfering RNA (siRNA) that reduces lipoprotein(a). In some embodiments, the drug delivery device may contain or be used with ABP 654 (a human IgG1 kappa antibody), a biosimilar candidate for Stelara®, or another product that contains a human IgG1 kappa antibody and / or binds to the p40 subunit of the human cytokines interleukin (IL)-12 and IL-23. In some embodiments, the drug delivery device may contain or be used with Amjevita™ or Amgevita™ (formerly ABP501) (monoclonal antibody anti-TNF human IgG1), a biosimilar candidate for Humira®, or another product that includes the human monoclonal antibody anti-TNF human IgG1. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 160 or a half-life extended (HLE) anti-prostate specific membrane antigen (PSMA) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 119 or a delta-like ligand 3 (DLL3) CAR T (chimeric antigen receptor T cell) cell therapy. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 119 or a delta-like ligand 3 (DLL3) CAR T (chimeric antigen receptor T cell) cell therapy. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 133 or a gastric inhibitory polypeptide receptor (GIPR) antagonist and a GLP-1R agonist. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 171 or a growth differentiation factor 15 (GDF15) analog.In some embodiments, the drug delivery device may contain or be used with another product containing AMG 176 or a small molecule inhibitor of myeloid cell leukemia 1 (MCL-1). In some embodiments, the drug delivery device may contain or be used with another product containing AMG 199 or a half-life extended (HLE) bispecific T cell engager construct (BiTE®). In some embodiments, the drug delivery device may contain or be used with AMG 256 or another product containing an anti-PD-1 x IL21 mutein and / or an IL-21 receptor agonist designed to selectively activate the interleukin 21 (IL-21) pathway in programmed cell death-1 (PD-1) positive cells. In some embodiments, the drug delivery device may contain or be used with AMG 330 or another product containing an anti-CD33 x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 404 or another product containing a human anti-programmed cell death-1 (PD-1) monoclonal antibody being investigated as a treatment for patients with solid tumors. In some embodiments, the drug delivery device may contain or be used with AMG 427 or another product containing a half-life extended (HLE) anti-fms-like tyrosine kinase 3 (FLT3) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with AMG 430 or another product containing an anti-Jagged-1 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used with AMG 506 or another product containing a multispecific FAP x 4-1BB targeted DARPin® biologic being investigated as a treatment for solid tumors. In some embodiments, the drug delivery device may house or be used in conjunction with AMG 509 or another product containing a bivalent T cell engager and designed using XmAb® 2+1 technology.In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 562 or another product containing a half-life extended (HLE) CD19xCD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with efavalukin alfa (formerly AMG 592) or another product containing an IL-2 mutein Fc fusion protein. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 596 or CD3xEpidermal Growth Factor Receptor vIII (EGFRvIII) BiTE®. In some embodiments, the drug delivery device may contain or be used with another product containing a half-life extended (HLE) anti-human CD33 x anti-anti-human CD3 BiTE® (bispecific T cell engager) molecule. In some embodiments, the drug delivery device may contain or be used with another product containing a half-life extended (HLE) anti-B cell maturation antigen (BCMA) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with another product containing a half-life extended (HLE) anti-B cell maturation antigen (BCMA) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used with another product containing a half-life extended (HLE) anti-delta-like ligand 3 (DLL3) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may house or be used in conjunction with AMG 910 or another product containing the half-life extended (HLE) epithelial cell tight junction component protein claudin 18.2 x CD3 BiTE® (bispecific T cell engager) construct.

[0038] The drug delivery devices, assemblies, components, subsystems and methods have been described in terms of, but not limited to, exemplary embodiments. The detailed description should be construed as merely exemplary and does not describe all possible embodiments of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, but such embodiments still fall within the scope of the claims that define the invention disclosed herein.

[0039] Those skilled in the art will understand that various modifications, alterations and combinations may be made to the above-described embodiments without departing from the spirit and scope of the present invention disclosed herein, and that such modifications, alterations and combinations are to be construed as falling within the scope of the concept of the present invention.

Claims

1. 1. A testing system for a drug delivery device, comprising: a frame member having a first end and a second end; a drive member disposed adjacent to the frame member, the drive member being axially movable between the first end of the frame member and the second end of the frame member; a substitute syringe barrel operably coupled to the frame member; a flange extension adapted to mate with a portion of the substitute syringe barrel; a plunger rod coupled to the flange extension and adapted to be at least partially disposed within the substitute syringe barrel while being movable within the substitute syringe barrel, the plunger rod including a first end, a second end, and a longitudinal length between the first end and the second end, the first end being disposed adjacent a portion of the drive member; wherein the drive member is adapted to measure a maximum biasing force acting on the plunger rod as the drive member moves axially toward the second end of the frame member.

2. 2. The test system of claim 1, wherein the plunger rod includes a plunger rod interface disposed along the longitudinal length of the plunger rod, the plunger rod interface adapted to engage a floor region of the flange extension to hold the plunger rod in an initial position.

3. The test system of claim 2 , wherein the plunger rod interface includes a ring having an outer dimension.

4. 4. The test system of claim 2 or 3, wherein the floor area of ​​the flange extension includes an opening having an interior dimension.

5. 5. The test system of claim 4, wherein the outer dimension of the ring of the plunger rod is greater than the inner dimension of the opening of the flange extension portion so as to prevent axial movement of the plunger rod toward the second end of the frame member.

6. 4. The test system of claim 2 or 3, wherein at least one of the plunger rod interface or the floor area of ​​the flange is constructed at least in part from a deformable material.

7. 4. The test system of claim 1, wherein the surrogate syringe barrel includes a syringe flange, and the flange extension includes a flange adapted to rest on the syringe flange of the surrogate syringe barrel.

8. 4. The test system of claim 1, wherein the frame member includes a platform disposed at the first end of the frame member, the platform adapted to hold and suspend the substitute syringe barrel from the first end of the platform.

9. The test system of claim 8 , wherein the plunger rod and the flange extension are subjected to a gravitational force in the axial direction when the drive member is moved toward the second end of the frame member.

10. The test system of any one of claims 1 to 3, wherein the drive member comprises a push pin adapted to be at least partially insertable and movable within the substitute syringe barrel.

11. The test system of claim 10 , wherein the push pin includes a recessed area adapted to align with the first end of the plunger rod.

12. The test system of any one of claims 1 to 3, wherein the drive member is positioned above the first end of the frame member.

13. 1. A method for measuring a maximum biasing force experienced by a portion of a drug delivery device, comprising: disposing a drive member adjacent a first end of a frame member, the drive member being axially movable between the first end of the frame member and a second end of the frame member; operably coupling a substitute syringe barrel to the first end of the frame member; coupling a first flange extension to a portion of the substitute syringe barrel; coupling a first plunger rod with the flange extension, whereby the first plunger rod is at least partially movably disposed within the substitute syringe barrel, the first plunger rod including a first end, a second end, and a longitudinal length between the first end and the second end; moving the drive member axially toward the second end of the frame member, thereby urging the first plunger rod toward the second end of the frame member; measuring a maximum biasing force acting on the first plunger rod while moving toward the second end of the frame member; A method comprising:

14. 14. The method of claim 13, wherein the plunger rod includes a plunger rod interface disposed along the longitudinal length of the plunger rod, the plunger rod interface adapted to engage a floor region of the flange extension to retain the plunger rod in an initial position.

15. 15. The method of claim 13 or 14, further comprising the step of placing a flange of the flange extension onto a syringe flange of the substitute syringe barrel.

16. 15. The method of claim 13 or 14, further comprising holding and suspending the replacement syringe barrel from a frame member lift platform located at the first end of the frame member.

17. 17. The method of claim 16, wherein the step of moving the drive member toward the second end of the frame member further comprises subjecting the plunger rod and the flange extension to a gravity force in the axial direction.

18. 15. The method of claim 13 or 14, wherein the step of axially moving the drive member comprises moving a push pin within the substitute syringe barrel.

19. 20. The method of claim 18, further comprising aligning a recessed area of ​​the push pin with the first end of the plunger rod.

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