Controlled Dispensing Syringe

Abstract

A syringe is described that includes a plunger assembly having a discharge stroke sized to discharge a fluid therapeutic agent without expelling air or headspace from the syringe, the syringe including a plunger rod having a stop mechanism that stops the discharge stroke of the plunger rod at a distance corresponding to the height of air or headspace in the syringe, thereby avoiding an additional air purge step by a medical professional.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Priority is claimed to U.S. Provisional Patent Application No. 62 / 990,819, filed March 17, 2020, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to syringes, and more particularly to pre-filled syringes. [Background technology]

[0003] Some drug ejectors require a healthcare professional to transfer the therapeutic agent from a prefilled syringe into a cartridge or device reservoir designed for that drug ejector. Typically, a prefilled syringe is filled with a predetermined amount of therapeutic agent along with a predetermined amount of air. To transfer the therapeutic agent into the cartridge or device reservoir, a healthcare professional can orient the prefilled syringe so that the air is trapped near the needle and press the prefilled syringe's plunger to remove the air. This air removal action can inadvertently eject some of the therapeutic agent, which can waste expensive medication and can cause the amount of therapeutic agent in the prefilled syringe to be less than the prescribed amount for the patient. Conversely, if air is not fully removed from the prefilled syringe, some of the air can migrate into the cartridge or device reservoir. Air in the fluid flow path of a drug ejection device can adversely affect the operation of the device, for example, by causing uncontrolled forward or backward flow due to changes in air pressure. Summary of the Invention [Means for solving the problem]

[0004] According to a first aspect, the present application discloses a syringe including a barrel having an interior, a discharge opening at a distal end, and an open proximal end, a stopper disposed within the barrel, a plunger rod having a first end configured to at least selectively operatively couple to the stopper, a second end extending through the open proximal end of the barrel, the second end having an outwardly extending flange, a plunger stop member coupled to the plunger rod at a location between the flange and the open proximal end of the barrel, and a stop member assembly including a removable portion coupled to the plunger rod or the barrel, wherein the plunger stop member engages a stop surface adjacent the open proximal end of the barrel to selectively limit displacement of the plunger and the stopper along the interior of the barrel.

[0005] According to one aspect, the plunger stop member and removable portion of the stop member assembly can include first and second main portions pivotable relative to one another and capturing the plunger rod therebetween. In this aspect, the plunger stop member and removable portion of the stop member assembly can be a clip including a hinge pivotally connecting first sides of the first and second main portions and a locking mechanism releasably connecting second sides of the first and second main portions. Alternatively, in this aspect, the plunger stop member and removable portion of the stop member assembly can be a clamp including a biasing mechanism, and the first and second main portions can include jaws at their first ends and handles at their second ends, the biasing mechanism biasing the jaws of the first and second main portions together to capture the plunger rod therebetween.

[0006] According to one aspect, the plunger stop member and removable portion of the stop member assembly can include a main portion defining a cavity having an opening through an end wall thereof, the cavity receiving the plunger rod therein and limiting longitudinal movement of the plunger rod relative to the main portion, and a locking mechanism coupled to the main portion for retaining the plunger rod within the cavity. In this aspect, the locking mechanism can be an adhesive member extending across the cavity. Alternatively, in this aspect, the main portion can include first and second clamshell components having inner surfaces configured to mate and define the cavity therebetween, and the locking mechanism can hold the first and second clamshell components closed with the plunger rod retained within the cavity.

[0007] According to one embodiment, the proximal end of the barrel can include an outwardly protruding flange, and the plunger stop member can be a stop flange extending outward from near the first end of the plunger rod and having a perimeter sized to fit inside the barrel. The removable portion of the stop member assembly can be a blocking member configured to removably engage with the barrel flange, the blocking member having a portion disposed within the path of travel of the stop flange to limit longitudinal movement of the plunger rod. In this embodiment, the blocking member can be a clip having first and second walls spaced apart from one another and connected by an end wall, the clip configured to engage the barrel flange between the first and second walls. Alternatively, in this embodiment, the blocking member can be a tab having a distal end configured complementary to a portion of the horizontal cross-section of the plunger rod, and the barrel flange can include a channel sized to receive the tab therein, the channel configured to guide the tab into engagement with the plunger rod.

[0008] According to another aspect, the plunger stop member and detachable portion of the stop member assembly may be a snap-fit member including first and second walls spaced apart from one another and connected by end walls, the first and second walls defining a channel on their inner surfaces and configured to be bent open to allow the plunger rod to be positioned therebetween and returned to an unbent position to retain a portion of the plunger rod within the channel, or may be a tab connected to the plunger rod along its longitudinal length by a separation mechanism.

[0009] In any of the above configurations, the stop member assembly may include a wall portion having a surface thereon on which information relating to the operation of the stop member is displayed.

[0010] According to a second aspect, a method of ejecting headspace from a syringe containing a liquid therapeutic agent is disclosed, comprising the steps of providing a syringe including: a barrel having an interior, an ejection opening at a distal end, and an open proximal end; a stopper disposed within the barrel; a first end configured to at least selectively operatively couple to the stopper; a plunger rod having a second end extending through the open proximal end of the barrel, the second end having an outwardly extending flange; the fluid therapeutic agent and headspace disposed within the interior of the barrel between the stopper and the ejection opening; and a stop member assembly including a plunger stop member coupled to the plunger rod and a removable portion coupled to the plunger rod or the barrel. The method further includes the steps of driving the plunger rod toward the open proximal end of the syringe barrel to drive the stopper along the interior of the barrel and expel the headspace through the discharge opening, abutting the plunger stop member with a stop member surface adjacent the open proximal end of the barrel, thereby stopping movement of the stopper and preventing the fluid therapeutic agent from being expelled, and removing the detachable portion of the stop member assembly from the plunger rod or the barrel.

[0011] According to some aspects, the method may include the following aspects: the plunger stop member and the removable portion of the stop member assembly may include first and second main portions between which the plunger rod is captured; removing the removable portion of the stop member assembly from the plunger rod or barrel may include pivoting the first and second main portions of the stop member relative to one another; removing the removable portion of the stop member assembly from the plunger rod or barrel may include decoupling a tab from the plunger rod; the plunger stop member and the removable portion of the stop member assembly may include a main portion defining a cavity having an opening through an end wall thereof, the main portion within which the plunger rod is received, and a locking mechanism coupled to the main portion to retain the plunger rod within the cavity; removing the removable portion of the stop member assembly from the plunger rod or barrel may include pivoting the first and second main portions of the stop member relative to one another. The steps may include one or more of: manipulating the main portion and the locking mechanism to release the plunger rod from the cavity; removing the removable portion of the stop member assembly from the plunger rod or barrel may include bending first and second walls of the stop member assembly against each other to release the plunger rod from being trapped therebetween; or the proximal end of the barrel may include an outwardly protruding flange, and the plunger stop member may be a stop flange extending outwardly from the plunger rod, the stop flange having a circumference sized to fit within the interior of the barrel; and removing the removable portion of the stop member assembly from the plunger rod or barrel may include decoupling a blocking member positioned in a path of travel of the stop flange and having a portion that restricts longitudinal movement of the plunger rod from the flange of the barrel.

[0012] According to a third aspect, a syringe is disclosed that includes a barrel having an interior, a discharge opening at a distal end, and an open proximal end having an end face; a stopper disposed within the barrel; a plunger rod having a first end configured to be at least selectively operatively coupled to the stopper and a second end extending through the open proximal end of the barrel; an outwardly protruding stop member adjacent the second end of the plunger rod; an engagement portion of the second end of the plunger rod spaced from the stop member; and at least one wall portion extending longitudinally between the stop member and the engagement portion and laterally outwardly from the plunger rod, the at least one wall portion being integrally formed with the plunger rod and having a surface on which information regarding operation of the stop member is displayed.

[0013] In some forms, the at least one wall portion may be a wall portion extending laterally outward from an opposite side of the plunger rod.

[0014] According to a fourth aspect, a syringe is disclosed that includes a barrel having an interior, a discharge opening at a distal end, and an open proximal end having an end face, a stopper disposed within the barrel, a plunger rod having a first end configured to at least selectively be operatively coupled to the stopper and a second end extending through the open proximal end of the barrel, an engagement portion at the second end of the plunger rod, a flange adjacent the second end of the plunger and spaced from the engagement portion, and a snap-fit member releasably coupled to the plunger rod. The snap-fit member includes first and second walls spaced from each other and connected by an end wall, the first and second walls configured to be bent open to position the plunger rod therebetween and returned to an unbent position such that the snap-fit member is retained between the engagement portion and the flange on the plunger rod.

[0015] In some embodiments, the first and second walls of the snap-fit member define a channel on an inner surface thereof, the channel being configured to receive a portion of the plunger rod therein when the first and second walls are in an unbent position. [Brief explanation of the drawings]

[0016] [Figure 1] FIG. 1 is a perspective view of a first exemplary syringe complete with a stop assembly showing a fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 2] FIG. 2 is a side view of the syringe of FIG. 1 in its entirety. [Figure 3] FIG. 2 is a side view of the syringe of FIG. 1 in a post-dispensing state, showing the fluid therapeutic agent within the barrel. [Figure 4] 2 is a side view of the syringe of FIG. 1 showing the removable portion of the stop assembly in an open position. [Figure 5] FIG. 10 is a perspective view of a second exemplary syringe complete with a stop assembly showing the fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 6] FIG. 10 is a perspective view of a third exemplary syringe complete with a stop assembly showing the fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 7] 7 is a perspective view of the syringe of FIG. 6 showing the removable portion of the stop member assembly in an open position. [Figure 8] FIG. 10 is a perspective view of a fourth exemplary syringe complete with a stop member assembly showing the fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 9] 9 is a perspective view of the syringe of FIG. 8 showing the removable portion of the stop member assembly in an open position. [Figure 10] FIG. 10 is a perspective view of a fifth exemplary syringe complete with a stop member assembly showing the fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 11] FIG. 10 is a perspective view of a sixth exemplary syringe in its entirety with a stop member assembly showing the fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 12]12 is an exploded view of the syringe of FIG. 11 showing the removable portion of the stop assembly in an open position. [Figure 13] FIG. 10 is a perspective view of a seventh exemplary syringe complete with a stop member assembly showing the fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 14] FIG. 14 is a detailed view of the syringe of FIG. 13. [Figure 15] FIG. 10 is a perspective view of an eighth exemplary syringe complete with a stop member assembly showing the fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 16] 16 is an exploded view of the syringe of FIG. 15 showing the removable portion of the stop member assembly disconnected. [Figure 17] FIG. 13 is a perspective view of a ninth exemplary syringe complete with a stop member assembly showing the fluid therapeutic agent and headspace within the barrel, according to an embodiment of the present disclosure. [Figure 18] FIG. 18 is a front view of the syringe of FIG. 17 in its entirety. [Figure 19] FIG. 18 is a front view of the syringe of FIG. 17 in a post-dispensing state with headspace in the barrel. [Figure 20] FIG. 10 is a perspective view of a tenth exemplary syringe with a stop member assembly in a post-discharge state showing headspace within the barrel, according to an embodiment of the present disclosure. [Figure 21] 21 is an exploded detail view of the syringe of FIG. 20 showing the removable portion of the stop member assembly in a disconnected state. DETAILED DESCRIPTION OF THE INVENTION

[0017] The syringe and syringe assembly include a plunger assembly configured to provide a discharge stroke that controls the headspace within the syringe. Controlling the headspace can include purging the headspace before dispensing the therapeutic agent or dispensing the therapeutic agent without dispensing the headspace. More specifically, the syringe includes a stop member or stop member assembly that stops the discharge stroke of the plunger rod at a predetermined distance corresponding to the height of the headspace within the syringe. This distance can be used to provide controlled discharge of the headspace, or can be configured to leave the headspace within the syringe with one stroke of the plunger rod. Thus, a syringe configured in this manner allows a medical professional to safely perform or skip the step of purging air bubbles from the syringe.

[0018] Referring now to the drawings, a syringe 10 is shown extending along a longitudinal axis X. The syringe 10 is shown in a prefilled state, containing a dose or other predetermined amount of fluid therapeutic agent 12 within a barrel or reservoir 14. The barrel 14 has a tubular configuration oriented along the longitudinal axis X, with an annular sidewall 15 extending between a discharge opening 16 at a distal end 18 and an open proximal end 20. The proximal end 20 may include a radially protruding flange 22, which provides an upwardly facing end face 24. Optionally, the barrel 14 may include measurement marks 26 distributed along its length L to provide a visual indication of the amount of medication 12. The barrel 14 may be fabricated from any suitable material, such as glass or a polymer. At the distal end 18 of the barrel 14, the syringe 10 includes a needle 32 and a needle hub 34 coupled to the barrel 14, thereby fluidly connecting the needle 32 to the interior 36 of the barrel 14. Optionally, syringe 10 may further include a rigid or non-rigid needle shield 33 (FIG. 1) disposed around at least a portion of the distal end of needle 32. Syringe 10 further includes a stopper (plunger stopper) 38 and a plunger rod 40 that at least selectively engages stopper 38 and projects outwardly along longitudinal axis X through open proximal end 20 of barrel 14. Plunger rod 40 includes an elongate main portion 41 coaxial with barrel 14. Main portion 41 engages stopper 38 at a distal end 42 and includes a thumb rest or engagement portion 44 at an opposite, proximal end 46. Plunger rod 40 may be at least selectively operatively coupled to stopper 38 in any suitable manner, such as being embedded therein, having a mating component, abutting an end face, selectively disposed in a recess in stopper 38, etc. For example, plunger rod 40 and stopper 38 can have a retractable or non-retractable configuration as desired. Thus, plunger rod 40 can be coupled to stopper 38 such that as plunger rod 40 is retracted through barrel 14, stopper 38 is also pulled rearward along barrel 14, or plunger rod 40 can be selectively coupled to stopper 38 such that as plunger rod 40 is retracted through barrel 14, stopper 38 is not correspondingly retracted. Plunger rod 40 can beAs shown, engagement portion 44 can include a flange 48 extending outward from main portion 41 generally perpendicular to longitudinal axis X, presenting a flat or contoured upwardly facing engagement surface 50 to a user. Configured in this manner, a user can grasp flange 22 at proximal end 20 of barrel 14 with two fingers and engagement surface 50 with a thumb during an exhalation operation to push and actuate stopper 38 into barrel 14.

[0019] As shown, barrel 14 contains headspace 52, e.g., air, along with medication 12. Conventionally, a medical professional holds syringe 10 with needle 32 pointing upward and either pushes plunger rod 40 to actuate stopper 38 within barrel 14 and expel headspace 52 from needle 32, or monitors the level of medication 12 during expulsion to prevent headspace 52 from expelling.

[0020] In a first example shown in Figures 1-16, syringe 10 is prepared for use by the following steps: In a first step, a healthcare professional tilts syringe 10 upward and visually inspects syringe 10 to observe headspace 52 moving toward discharge opening 16 of barrel 14. In a second step, if applicable, the healthcare professional removes needle shield 33 to expose the distal end of needle 32. In a third step, the healthcare professional depresses plunger rod 40 to expel headspace 52.

[0021] As shown, each of the syringes 10 of the embodiments shown in Figures 1-16 includes a stop assembly 100 that limits the distance that the plunger rod 40 can be pushed into the barrel 14. Specifically, the stop assembly 100 allows the plunger rod 40 to be pushed into the barrel 14 only far enough to purge the headspace 52. It should be understood that purging the headspace 52 from the barrel 14 can include expelling a small amount of the medication 12 from the syringe 10 along with the headspace 52 to ensure that the headspace 52 has been completely purged. Advantageously, the stop assembly 100 prevents an excessive amount of medication 12 from being expelled during the headspace purging step. Next, in a fourth step, the healthcare professional removes or disables the detachable portion 101 of the stop assembly 100, and in a fifth step, the medication 12 is administered according to normal operating procedures.

[0022] In each of these examples, the stop member assembly 100 includes a plunger stop member 102 that is, or can be, spaced from the proximal end 20 of the barrel 14 by a distance D corresponding to the length L1 of the headspace 52 within the barrel 14 and a corresponding volume. It should be understood that L1 can be sized to contain a small amount of medication 12, e.g., 2% to 10% of the delivered mL, to ensure that the headspace 52 is completely purged. This configuration allows a user to push the plunger rod 40 to drive the stopper 38 within the barrel 14, and the plunger stop member 102 abuts the barrel 14 or structure associated with the barrel 14 near the open proximal end 20, preventing further movement of the plunger rod 40 and stopper 38. The stop member assembly 100 therefore ensures that the plunger rod 40 travels a sufficient distance to purge the headspace 52 without expelling excess medication 12. In other words, by configuring the plunger rod 40 and stop member assembly 100 so that the plunger rod 40 moves a predetermined length corresponding to a desired portion of the barrel 14, the syringe 10 can be pre-configured to dispense a specific volume within the syringe 10 that corresponds to the headspace 52 within a conventional pre-filled syringe.

[0023] A first exemplary syringe 10 is shown in Figures 1-4. In this configuration, a stop assembly 100, including a removable portion 101 and a plunger stop 102, is provided by a clip 104 having first and second main portions 106, 108 pivotally interconnected by a hinge or other pivot 110. The first and second main portions 106, 108 are pivotable relative to one another to removably attach the clip 104 to the plunger rod 40. As shown, each of the main portions 106, 108 includes a curved portion 112 such that, when the first and second main portions 106, 108 are in a closed position, the curved portions 112 define a throughbore 114 sized to allow the plunger rod 40 to extend through the clip 104. The hole 114 is sized such that the clip 104 is retained between the flange 48 of the engagement portion 44 and the engagement portion 44 of the barrel 14, such that after initial displacement, the upper surface 116 of the clip 104 is configured to abut the flange 48 of the engagement portion 44 and the lower surface 118 of the clip 104 is configured to abut the end surface 24 of the barrel proximal end 20. Thus, in this configuration, the lower surface 118 of the clip 104 provides the plunger stop 102 of the stop member assembly 100. With this configuration, when a user presses the plunger rod 40, the clip 104 limits the full travel of the plunger rod 40 to expel the medicament 12. For example, the hole 114 can have at least one dimension, e.g., a diameter, that is smaller than the flange 48 of the engagement portion 44 such that the upper surface 116 abuts the flange 48, thereby retaining the clip 104 on the plunger rod 40. Additionally, the clip 104 can be prevented from moving into the barrel 14 by the flange 22 abutting against the clip 104 and / or the hole 114 having a smaller size, e.g., diameter, than the barrel 14 so that the lower surface 118 of the clip 104 abuts against the end surface 24 of the barrel 14.

[0024] As shown, the curved portions 112 of the main portions 106, 108 can be disposed on their sides, and the main portions 106, 108 can further include generally flat portions 120 extending laterally from the curved portions 112. When the main portions 106, 108 are in a closed position, the flat portions 120 extend along and abut one another, thereby closing the apertures 114 at their sides by the hinges and the flat portions 120. The clip 104 can include a latch or other fastening mechanism 122, such as a snap fit, having complementary components on the lateral edges 124 of the flat portions 120. The latches 122 allow the clip 104 to be attached to and detached from the plunger rod 40. Additionally, the major surfaces 126 of the flat portions 120 can have instructions, drug-identifying information, or other information displayed thereon for easy viewing by a user. For example, this information can inform a user of the proper operation and use of the clip 104. Information can be printed directly on the flat portion 120 and / or affixed thereto, such as with a sticker.

[0025] Thus, clip 104 can be attached to plunger rod 40, and after a medical professional inspects and points syringe 10 upward, the medical professional can press plunger rod 40, restricting further movement of the plunger rod by clip 104 extending between proximal end 20 of barrel 14 and flange 48 of engagement portion 44. Clip 104 can then be removed by disengaging latch 122 and pivoting main portions 106, 108 away from one another. Once clip 104 is removed, plunger rod 40 is unconstrained, allowing for normal dispensing procedures.

[0026] A second exemplary syringe 10 is shown in FIG. 5. In this configuration, a stop member assembly 100, including a removable portion 101 and a stop flange 102, is provided with a tab 130 that is removably and rigidly secured to the plunger rod 40. The tab 130 extends along the longitudinal length of the plunger rod 40 and is secured thereto along a lateral edge 132. As shown, a lower edge 134 of the tab 130 provides the plunger stop 102 of the stop member assembly 100 for limiting movement of the plunger rod 40. For example, the tab 130 can be secured to the plunger rod 40 such that the lower edge 134 is spaced from the proximal end 20 of the barrel 14 prior to use, and configured to abut the proximal end 20 of the barrel 14 after the plunger rod 40 has moved a distance D relative to the barrel 14 to purge the headspace 52. With this configuration, when a user presses plunger rod 40, tab 130 limits plunger rod 40 from full travel, preventing medication 12 from being dispensed.

[0027] The tab 130 can then be detached or removed from the plunger rod 40, allowing the plunger rod 40 to move freely. If desired, the connection 136 between the tab 130 and the plunger rod 40 can be defined by a frangible feature extending between the tab 130 and the plunger rod 40, such as a perforation or tear line in the material. This configuration allows a user, after use, to easily bend the tab 130 relative to the plunger rod 40, severing the connection between the tab 130 and the plunger rod 40, thereby leaving the plunger rod 40 unconstrained for normal dosing procedures. In one example, the plunger rod 40 and the tab 130 can be integrally formed as a single component. Additionally, the major surface 138 of the tab 130 can have instructions, drug-specific information, or other information displayed thereon for easy viewing by the user. For example, the information can inform the user about the proper operation and use of the tab 130. Information may be printed directly on one or both surfaces 138 and / or may be affixed thereto, such as with a sticker.

[0028] A third exemplary syringe 150 is shown in Figures 6 and 7. In this configuration, the stop member assembly 100, including the removable portion 101 and plunger stop member 102, is provided by a block 150 having a main portion 152 with forward and rearward major surfaces 154, 156 defined by side edges 158 and end edges 160, and a locking mechanism 170. A cavity 162 is formed in the main portion 152, and an opening 164 to the cavity 162 extends through the forward major surface 154 and an end wall 168 of the block 150. As shown, the cavity 162 has a shape corresponding to the proximal end of the plunger rod 40, including a rod portion 165 sized to receive the rod 40 therein and a thumb rest portion 166 sized to receive the engagement portion 44 therein. The shape of the cavity 162 limits longitudinal movement of the plunger rod 40 relative to the block 150 by abutting the T-shape against the engagement portion 44. In one form, thumb rest portion 166 of cavity 162 can extend entirely through block 150, thereby reducing the depth of main portion 152. Additionally, if desired, rod portion 165 of cavity 162 can extend entirely through block 150, and block 150 can include a retaining member 167 extending along rear major surface 156 and spanning at least a portion of rod portion 164. Rear major surface 156 or retaining member 167 can have instructions, drug-identifying information, or other information displayed thereon for easy viewing by a user. For example, this information can inform a user about the proper operation and use of block 150. Information can be printed directly on surface 156 or retaining member 167 and / or affixed thereto, such as with a sticker.

[0029] Main portion 152 extends along the length of plunger rod 40, and is sized such that end wall 168 of block 150 provides plunger stop 102 of stop assembly 100 for constraining movement of plunger rod 40. For example, end wall 168 can be configured to be spaced from proximal end 20 of barrel 14 prior to use and to abut proximal end 20 of barrel 14 after plunger rod 40 has moved a distance D relative to barrel 14 to purge headspace 52. With this configuration, when a user presses plunger rod 40, block 150 prevents full movement of plunger rod 40, preventing expulsion of medication 12.

[0030] The plunger rod 40 can be held within the cavity 162 by a securing mechanism 170. In one example, the securing mechanism 170 can be an adhesive member, such as tape or a sticker, that is secured to the block 150 and extends across at least a portion of the opening 164 to the cavity 162, such as the rod portion 165. This configuration allows a user to at least partially remove the adhesive member 170 and remove the plunger rod 40 from the cavity 162 after the headspace 52 has been purged. In another example, the securing mechanism 170 can be a resilient member that extends around the block 150.

[0031] A fourth exemplary syringe 10 is shown in Figures 8 and 9. In this configuration, a stop member assembly 100, including a removable portion 101 and a plunger stop member 102, is provided by a clamshell member 180 and a locking mechanism 198. The clamshell member 180 has first and second main portions 182, 184, the inner surfaces 186 of which are configured to extend along and abut one another when the member 180 is in a closed state. Each of the main portions 182, 184 defines a cavity 188 having an opening 190 extending through the inner surface 186 and end wall 196 of the main portions 182, 184. As shown, the cavity 188 has a shape corresponding to the proximal half of the plunger rod 40, and includes a rod portion 192 sized to receive the rod 40 therein and a thumb rest portion 194 sized to receive the engagement portion 44 therein. The shape of cavity 188 limits longitudinal movement of plunger rod 40 relative to member 180 by the T-shape abutting engagement portion 44. As such, main portions 182, 184 are configured to come together and have inner surfaces 186 abut one another to capture plunger rod 40 within member 180.

[0032] Member 180 is sized to extend along the length of plunger rod 40, with end wall 196 providing plunger stop member 102 of stop member assembly 100 for limiting movement of plunger rod 40. For example, end wall 196 can be configured to be spaced from the proximal end of barrel 14 prior to use and to abut proximal end 20 of barrel 14 after plunger rod 40 has moved distance D relative to barrel 14 to purge headspace 52. With this configuration, when a user presses plunger rod 40, member 180 prevents full movement of plunger rod 40, preventing expulsion of medication 12.

[0033] The member 180 can be held around the plunger rod 40 in the closed position by a securing mechanism 198. In one example, the securing mechanism 198 can be an adhesive member, such as tape or a sticker, that secures the main portions 182, 184 together. In another example, the securing mechanism 198 can be a connecting structure such as a snap-fit mechanism, a tongue and groove mechanism, or the like. If desired, the main portions 182, 184 can be pivotally connected to each other on one side by a hinge or other pivot, and the securing mechanism 198 can connect the other side. Alternatively, the main portions 182, 184 can be separate components, and the securing mechanism 198 can connect the main portions 182, 184 together. With this configuration, after the headspace 52 has been purged, a user can at least partially remove the adhesive member 198 to separate the member 180 from the plunger rod 40. In another example, the securing mechanism 198 can be a resilient member that extends around the member 180.

[0034] A fifth exemplary syringe 10 is shown in FIG. 10 . In this configuration, the stop member assembly 100, including the removable portion 101 and plunger stop member 102, is provided by a clamp 200 having first and second main portions 202, 204 pivotally connected to one another by a pivot 206. The first and second main portions 202, 204 each include a jaw 208 at its distal end 210 and a handle 212 at its proximal end 214. The main portions 202, 204 are held when the jaws 208 are in a closed position by a biasing device 216. This configuration allows a user to squeeze the handle 212 to open the jaws 208. The jaws 208 collectively define a throughbore 218 extending through the clamp 200 when in the closed position, which is sized to allow the plunger rod 40 to extend through the clamp 200. The bore 218 can extend entirely through the clamp 200 or can be defined by an opening in the outer wall of the jaw 208. The jaw 208 is sized so that the clamp 200 is retained between the flange 48 of the engagement portion 44 and the barrel 14, with an upper surface 220 of the clamp 200 configured to abut the flange 48 of the engagement portion 44 and a lower surface 222 of the clamp 200, which in this configuration provides the plunger stop 102, configured to abut the proximal end 20 of the barrel 14. With this configuration, when a user presses the plunger rod 40, the clamp 200 limits the full travel of the plunger rod 40 to expel the medicament 12. For example, the bore 218 can have at least one dimension, e.g., a diameter, that is smaller than the flange 48 of the engagement portion 44 such that the upper surface 220 abuts the flange 48, thereby retaining the clamp 200 on the plunger rod 40. Additionally, the clamp 200 can be prevented from moving into the barrel 14 by the flange 22 abutting the clamp 200 and / or by the hole 218 having a smaller size, e.g., diameter, than the barrel 14 such that the lower surface 222 of the clamp 200 abuts the proximal end 20 of the barrel 14.

[0035] Additionally, a user can open the jaws 208 by squeezing the handle 212 and position the jaws 208 on either side of the plunger rod 40. A biasing device 216 closes the jaws 208 around the plunger rod 40 and attaches the clamp 200 thereto. After the medical practitioner inspects and points the syringe 10 up, the medical practitioner can push the plunger rod 40 until the clamp 200 restricts it from further movement by extending between the proximal end 20 of the barrel 14 and the flange 48 of the engagement portion 44. The clamp 200 can then be removed by opening the jaws 208. After the clamp 200 is removed, the plunger rod 40 is unconstrained and the normal dispensing procedure can be performed.

[0036] A sixth exemplary syringe 10 is shown in FIGS. 11 and 12. In this configuration, the stop member assembly 100, including the removable portion 101 and plunger stop member 102, is provided by a snap-fit member 220 having opposing first and second walls 222, 224 joined together by an end wall 226 and having opposite open ends 227. The first and second walls 222, 224 are spaced apart from one another to releasably receive and retain the plunger rod 40 therebetween. In the illustrated configuration, the plunger rod 40 has a cross-shaped horizontal cross section with intersecting walls 41 a. With this configuration, the inner surfaces 228 of the walls 222, 224 can include a longitudinal channel 230 defined therein, and the walls 222, 224 can be spaced apart a distance such that one of the walls 41 a of the plunger rod 40 is received in and retained by the channel 230. Additionally, the snap-fit member 220 can be fabricated from a material that allows the first and second walls 222, 224 to resiliently bend against one another, thereby allowing the plunger rod 40 to be inserted between the walls 222, 224 and removed from a storage position where it is held therebetween.

[0037] The snap-fit member 220 is sized to be retained between the flange 48 of the engagement portion 44 and the barrel 14, with an upper surface 232 of the member 220 configured to abut the flange 48 of the engagement portion 44 and a lower surface 234 of the member 220 configured to abut the proximal end 20 of the barrel 14, in this configuration providing the plunger stop member 102. With this configuration, when a user presses the plunger rod 40, the snap-fit member 220 restricts the plunger rod 40 from full travel to expel the medicament 12. For example, the flange 48 of the engagement portion 44 can have a dimension larger than the space between the walls 222, 224, such that the snap-fit member 220 is retained on the plunger rod 40 by the upper surface 232 abutting the flange 48. Additionally, the snap-fit member 220 can be prevented from moving into the barrel 14 by the flange 48 or another surface of the proximal end 20 of the barrel 14 abutting the lower surface 234.

[0038] Thus, a user can bend the walls 222, 224 against one another to position the plunger rod 40 to be received within the channel 230. The snap-fit member 220 resiliently returns to its unbent position, thereby retaining the snap-fit member 220 on the plunger rod 40. The snap-fit member 220 is sized to allow the plunger rod 40 to be pushed into the barrel 14 a distance D, which purges the headspace 52 from the syringe 10. After the healthcare professional inspects and turns the syringe 10 upside down, the healthcare professional can push the plunger rod 40 until the snap-fit member 220 restricts it from further movement by extending between the proximal end 20 of the barrel 14 and the flange 48 of the engagement portion 44. The snap-fit member 220 can then be removed by bending the walls 222, 224 against one another and removing the plunger rod 40. After the snap fit member 220 is removed, the plunger rod 40 is left unconstrained and the normal administration procedure can be performed.

[0039] Seventh and eighth exemplary syringes 10 are shown in FIGS. 13-16. In these configurations, the stop member assembly 100 includes a flange 250 on the plunger rod 40 that provides this configuration of plunger stop member 102, which interacts with a blocking member 252 that provides this configuration of removable portion 101 that is detachably coupled to the barrel 14. In one example, the plunger rod main section 41 has an x-shaped cross section formed by intersecting walls 41a. In another example, the plunger rod main section 41 can have a circular cross section or the like that has a dimension smaller than the inner diameter of the barrel 14. As will be apparent, in either configuration, the cross-sectional width of the plunger rod main section 41 is smaller than the inner diameter of the barrel 14, thereby allowing the plunger rod 40 to be inserted into the barrel 14. As shown, at least a portion 254 of the distal end 42 of the plunger rod main section 41 has a free space 256 between the structure of the plunger rod main section 41 and a radial dimension corresponding to the inner diameter of the barrel 14. Flange 250 extends at least partially into this space 256 while being sized to fit within barrel 14 and allow normal movement of plunger rod 40. In this configuration, flange 250 moves through a different path than distal end portion 254 when plunger rod 40 is pushed into barrel 14. Blocking member 252 is coupled to proximal end 20 of barrel 14 and extends at least partially into the path of flange 250, thereby preventing further movement of plunger rod 40. In these configurations, flange 250 provides plunger stop member 102 of stop member assembly 100 spaced a distance D from an upper surface 257 of blocking member 252 associated with proximal end 20 of barrel 14. After headspace 52 has been purged by driving flange 250 into contact with blocking member 252, the user can remove blocking member 252 from barrel 14, thereby leaving plunger rod 40 unconstrained and allowing a normal dosing procedure to occur.

[0040] In a seventh exemplary syringe 10 shown in FIGS. 13 and 14 , the blocking member 252 is a clip 258 having spaced-apart first and second walls 260, 262 connected by an end wall 264 and having opposite open ends 265. The first and second walls 260, 262 are spaced apart a distance sized to receive the flange 22 of the barrel proximal end 20 therebetween. In one form, the distance between the walls 260, 262 can be sized to frictionally retain the clip 258 on the flange 22. Alternatively, a snap fit, tongue and groove, or similar complementary structure can be utilized. So configured, the clip 258 can be removably attached to the flange 22, thereby coupling the clip 258 to the barrel 14. In the illustrated form, first, upper wall 260 includes a distal slot 263 that receives a portion of wall 41 a of plunger rod 40 therein, and second, lower wall 262 is configured to extend adjacent flange 22 around barrel 14. As described above, when clip 258 is attached to flange 22, a portion of upper surface 266 of clip 258 is located within the path of flange 250, thereby limiting travel of plunger rod 40 after plunger rod 40 has been driven a distance D sufficient to purge headspace 52 within barrel 14. After headspace 52 has been purged, the user can simply slide clip 258 off flange 48.

[0041] In the eighth exemplary syringe 10 shown in FIGS. 15 and 16 , the blocking member 252 is a tab 270, which can be flat as shown. In one form, the tab 270 can have an elongated configuration that provides a user-friendly grip. The distal end 272 of the tab 270 has a configuration complementary to a portion of the cross-section of the plunger rod 40. For example, by having an x-shaped cross-section as shown, the distal end 272 includes a slot 274 that receives a portion of the protruding wall of the plunger rod 40 and a lateral space 276 that receives a lateral wall therein, thereby allowing the tab 270 to slide into engagement with the plunger rod 40. Of course, the distal end 272 can alternatively include a recessed edge or other configuration complementary to the plunger rod 40. As shown, the flange 22 can include a channel 278 formed therein to receive and align the tab 270 with the plunger rod 40. In one form, the channel 278 can be sized to frictionally receive the tab 270 and hold the tab 270 in engagement with the plunger rod 40. Alternatively, or in addition, the slot 274 and / or the lateral space 276 can be sized to frictionally engage the plunger rod 40.

[0042] With this configuration, when tab 270 engages plunger rod 40, upper surface 280 of tab 270 enters the path of flange 250, thereby limiting the movement of plunger rod 40, after plunger rod 40 has been driven a distance D sufficient to purge headspace 52 within barrel 14. After headspace 52 has been purged, the user can simply pull tab 270 off plunger rod 40 and disengage it from flange 22.

[0043] In a second example shown in FIGS. 17-21 , the syringe 10 is prepared for use in the following steps. In a first step, if applicable, the healthcare professional removes the needle shield 33, exposing the distal end of the needle 32. In a second step, the healthcare professional orients the syringe 10 generally vertically, e.g., within 45 degrees vertical, preferably within 20 degrees vertical, so that the engagement portion 44 is positioned above the barrel 14 and the needle 32 points upward, and observes that the headspace 52 moves toward the proximal end 20 of the barrel 14. As shown, each of the syringes 10 in the embodiments shown in FIGS. 17-21 includes a stop member 300 that limits the distance the plunger rod 40 can be pushed into the barrel 14. For example, the stop member 300 can extend outward from the plunger rod main portion 41 in a generally perpendicular direction relative to the longitudinal axis of the plunger rod 40 a sufficient distance to engage the end face 24 of the barrel proximal end 20 during an ejection operation. In this regard, stop member 300 can have at least one radial dimension that is greater than the corresponding radius of the opening in barrel proximal end 20. In a third step, the medical professional can push plunger rod 40 to drive stopper 38 within barrel 14. Advantageously, plunger rod 40 moves until stop member 300 abuts end face 24 of barrel 14, halting movement of stopper 38 within barrel 14. As shown in FIG. 19 , plunger rod 40 and barrel 14 are positioned such that a headspace 52 remains within barrel 14 in this position of plunger rod 14 and stopper 38 during expulsion of a predetermined dose of medication 12.

[0044] With this configuration, stop member 300 prevents further displacement of plunger rod 40, and therefore stopper 38, through barrel 14, causing the dispensing action to dispense a predetermined volume. In other words, by configuring plunger rod 40 to have a predetermined length between distal end 42 and stop member 54 that corresponds to a desired portion of barrel 14, syringe 10 can be pre-configured to dispense a particular volume of fluid. Advantageously, this can be used to avoid issues with headspace in conventional pre-filled syringes by limiting the dispensing action to a volume that prevents headspace 52 from being expelled.

[0045] The predetermined distance between the distal end 42 of the plunger rod 40 and the stop member 300, together with the length of the stopper 38, corresponds to a portion L2 of the length L of the barrel 14. This length L2 is shown in FIG. 19 with the plunger rod 40 fully inserted into the barrel 14, with the stop member 300 abutting the end face 24. Thus, during preparation of the syringe 10, the barrel 14 can be filled with a desired amount or dose of the medication 12, and the stopper 38 can be positioned within the barrel 14 so that the length, and corresponding volume, of the headspace 52 is generally equal to the remaining portion L2 of the length L of the barrel 14.

[0046] Of course, the fluid in medication 12 may interact with barrel 14 and have a meniscus rather than a flat top surface. To ensure that no headspace 52 is ejected, the value of length L2 may be equal to or greater than the length of medication 12 at its elevated perimeter adjacent barrel 14.

[0047] 17-19, the stop member 300 is provided by a flange 302 extending from the plunger rod main portion 41 in a direction generally perpendicular, e.g., about 1-5 degrees, relative to the longitudinal axis of the plunger rod 40. In one example, the flange 302 can extend radially outward from the entire circumference of the plunger rod main portion 41, e.g., in a circular or polygonal configuration. Alternatively, the flange 302 can extend outward from only a portion of the circumference.

[0048] Additionally, as shown, the plunger rod 40 can include one or more wall portions 304 extending longitudinally between the stop flange 302 and the flange 48 of the engagement portion 44 and providing a major surface 306 that is visible along the longitudinal axis of the syringe 10. If desired, the wall portion 304 can extend laterally outward from the plunger rod main portion 41 a greater distance than the flanges 302, 48, thereby providing the major surface 306 with an extended surface area for providing instructions, drug-identifying information, or other information thereon that is easily visible to a user. For example, this information can inform the user about the proper operation and use of the syringe 10. The information can be printed directly on the major surface 306 and / or affixed thereto with a sticker or the like.

[0049] In a second exemplary syringe 10 of this configuration, shown in FIGS. 20 and 21 , the stop member 300 is provided by a snap-fit member 320 having opposing first and second walls 322, 324 joined together by an end wall 326 and having an open, opposite end 327. The first and second walls 322, 324 are spaced apart a distance to removably receive and retain the plunger rod 40 therebetween. In the illustrated configuration, the plunger rod 40 has a cross-shaped horizontal cross section with intersecting walls 41 a. With this configuration, the inner surfaces 328 of the walls 322, 324 can include a vertical channel 330 defined therein, and the walls 322, 324 can be spaced apart a distance to allow one of the walls 41 a of the plunger rod 40 to be received in and retained by the channel 330. Additionally, snap-fit member 320 may be fabricated from a material that allows first and second walls 322, 324 to resiliently flex against one another, thereby allowing plunger rod 40 to be inserted between walls 322, 324 and removed from a storage position where it is held therein. If desired, plunger rod 40 may include a flange 331, the periphery of which is sized to fit within barrel 14 and which is spaced from engagement portion 44 by a distance substantially equal to the height of snap-fit member 320 to retain snap-fit member 320 on the discrete portion of plunger rod 40.

[0050] The snap-fit member 320 is sized to be retained between the flange 48 of the engagement portion 44 and the barrel 14, with an upper surface 332 of the member 320 configured to abut the flange 48 of the engagement portion 44 and a lower surface 334 of the member 320 configured to abut the proximal end 20 of the barrel 14. In this configuration, when a user presses the plunger rod 40, the snap-fit member 320 restricts the plunger rod 40 from full travel, allowing the healthcare professional to expel the desired dose of medication 12. For example, the flange 48 of the engagement portion 44 can have a dimension larger than the space between the walls 322, 324, such that the snap-fit member 320 is retained on the plunger rod 40 by the upper surface 332 abutting the flange 48. Additionally, the flange 48 or other surface of the proximal end 20 of the barrel 14 abutting the lower surface 334 can prevent the snap-fit member 320 from moving into the barrel 14.

[0051] Thus, a user can bend walls 322, 324 away from one another to position plunger rod 40 for receipt within channel 330. Snap-fit member 320 resiliently returns to an unbent position, thereby retaining snap-fit member 320 on plunger rod 40. Snap-fit member 320 has a height sufficient to press plunger rod 40 into barrel 14 a distance L2 sufficient to dispense medication 12 and leave headspace 52 in syringe 10.

[0052] The disclosure provided herein can be utilized with any desired dosage and syringe size, ensuring accurate delivery of the dose. It is suitable for both pre-filled syringes for patient self-injection and injections administered by healthcare professionals. The components of the syringe 10, such as the barrel 14 and plunger rod 40, can be constructed of any suitable material, such as plastic or glass. In one example, the syringe 10 described herein can provide a desired accuracy of injection of a fluid therapeutic agent of + / - 10 microliters. For a 1 mL syringe, plunger travel can be controlled to + / - 0.3 mm, achieving this desired accuracy.

[0053] Those skilled in the art will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been 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 improve understanding of 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 so as to unduly distract from the views of these various embodiments. The same reference numerals may be used to describe like or similar parts. Furthermore, while several examples have been disclosed herein, any feature of any example may be combined with or substituted for other features of other examples. Furthermore, while several examples have been disclosed herein, changes may be made to the disclosed examples without departing from the scope of the claims.

[0054] 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 in conjunction 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 pharmaceutical or therapeutic substance, including traditional and non-traditional medicines, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic drugs. Non-therapeutic injectable materials are also encompassed. 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.

[0055] The drug is contained in a reservoir. Optionally, the reservoir is a primary container that is either filled or pre-filled with the drug for treatment. The primary container can be a vial, cartridge, or pre-filled syringe.

[0056] 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 agents include, but are not limited to, Neulasta® (pegfilgrastim, PEGylated filgastim, PEGylated G-CSF, PEGylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-Met-G-CSF), UDENYCA® (pegfilgrastim-cbqv), Ziextenzo® (LA-EP2006; pegfilgrastim-bmez), or FULPHILA (pegfilgrastim-bmez).

[0057] In other embodiments, the drug delivery device may contain or be used in conjunction with an erythropoiesis-stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoiesis. In some embodiments, the ESA is an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" refers to any protein that directly or indirectly activates the erythropoietin receptor, for example, by binding to the receptor and causing it to dimerize. Erythropoiesis-stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof 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. Erythropoiesis-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 alpha, 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.

[0058] Among certain exemplary proteins are the specific proteins described 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; and antibodies directed against receptors for IL-4 and / or IL-13, particularly those directed against receptors for IL-4 and / or IL-13. IL-4 receptor-specific antibodies, peptibodies, related proteins, etc., which inhibit binding-mediated activity; 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., particularly dimers of human-mouse monoclonal hLL2 gamma chain disulfide bound to human-mouse monoclonal hLL2 kappa chain. human CD22-specific antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, particularly including, but not limited to, human CD22-specific IgG antibodies, such as the human CD22-specific fully humanized antibody epratuzumab (CAS Registry Number 501423-23-0); IGF-1 receptor-specific antibodies, peptibodies, and related proteins, including, but not limited to, anti-IGF-1R antibodies; B7RP-specific fully human monoclonal IgG2 B-7 related protein 1 specific antibodies, peptibodies, related proteins, etc. (also referred to as "B7RP-1" and B7H2, ICOSL, B7h, and CD275), including but not limited to, antibodies that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, on activated T cells, including but not limited to, fully human IgG2 monoclonal antibodies that bind to an epitope in the first immunoglobulin-like domain of B7RP-1; IL-15 specific antibodies, peptibodies, related proteins, etc., particularly humanized monoclonal antibodies, including but not limited to, HuMax IL-15 antibodies and related proteins, such as 145c7;IFN gamma-specific antibodies, peptibodies, related proteins, and the like, including but not limited to, human IFN gamma-specific antibodies, and fully human anti-IFN gamma antibodies; TALL-1-specific antibodies, peptibodies, related proteins, and the like, as well as other TALL-specific binding proteins; parathyroid hormone ("PTH")-specific antibodies, peptibodies, related proteins, and the like; thrombopoietin receptor ("TPO-R")-specific antibodies, peptibodies, related proteins, and the like; fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter factor (HGF / SF) Hepatocyte growth factor ("HGF")-specific antibodies, peptibodies, related proteins, etc., including those that target the HGF / SF:c-Met axis (HGF / SF:c-Met), such as clonal antibodies; TRAIL-R2-specific antibodies, peptibodies, related proteins, etc.; activin A-specific antibodies, peptibodies, proteins, etc.; TGF-beta-specific antibodies, peptibodies, related proteins, etc.; amyloid beta protein-specific antibodies, peptibodies, related proteins, etc.; proteins that bind to c-Kit and / or other stem cell factor receptors, including, but not limited to, those c-Kit-specific antibodies, peptibodies, related proteins, etc., including but not limited to; OX40L-specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind to 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, de novo hematopoietic stimulating protein 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® ® (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 alfa); Remicade® (infliximab, anti-TNFα monoclonal antibody); Reopro® (abciximab, anti-GP IL6 / IL6 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 (the Fc portion of human IgG1 and the extracellular domains 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, 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-VEGFR / Flt-1 mAb; and anti-ZP3 mAb (HuMax-ZP3).

[0059] In some embodiments, the drug delivery device may contain or be used in conjunction with a sclerostin antibody, such as, but not limited to, romosozumab, brosozumab, BPS 804 (Novartis), Evenity™ (romosozumab-aqqg), or another product containing romosozumab for the treatment of postmenopausal osteoporosis and / or fracture healing, and in other embodiments, a monoclonal antibody (IgG) that binds 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 in conjunction 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, OncoVEX GALV / 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), an anti-human CGRP-R (calcitonin gene-related peptide type 1 receptor), or another product containing erenumab for the treatment of migraines. Antagonistic antibodies of the human calcitonin gene-related peptide (CGRP) receptor, such as, but not limited to, erenumab, and bispecific antibody molecules that target the CGRP receptor and other headache targets, may also be delivered using the drug delivery devices of the present disclosure.Additionally, bispecific T-cell engager (BiTE®) antibodies, such as, but not limited to, BLINCYTO® (blinatumomab), can be used in or with the drug delivery devices of the present disclosure. In some embodiments, the drug delivery device may contain or be used in conjunction with an APJ large molecule agonist, such as, but not limited to, apelin or an analog 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 present disclosure. In some embodiments, the drug delivery device may contain or be used in conjunction 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) on hemodialysis. In some embodiments, the drug delivery device may contain or be used in conjunction with ABP 798 (rituximab), a biosimilar candidate for Rituxan® / MabThera™, or another product containing an anti-CD20 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used in conjunction with a VEGF antagonist, such as a non-antibody VEGF antagonist, and / or a VEGF-Trap (Ig domain 2 from VEGFR1 and Ig domain 3 from VEGFR2 fused to the Fc domain of IgG1), such as aflibercept. In some embodiments, the drug delivery device may contain or be used in conjunction with ABP 959 (eculizumab), a biosimilar candidate for 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 in conjunction with rozivacsp 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 in conjunction with omecamtib mecarbil, a small molecule selective cardiac myosin activator or myotrope that directly targets the cardiac contractile machinery, or another product containing a small molecule selective cardiac myosin activator. In some embodiments, the drug delivery device may contain sotorasib (formerly known as AMG 510), a KRAS inhibitor. G12C Small molecule inhibitors, or KRAS G12CThe drug delivery device may contain or be used in conjunction with another product containing a small molecule inhibitor. In some embodiments, the drug delivery device may contain or be used in conjunction 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 in conjunction 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 in conjunction with AMG 890, a small interfering RNA (siRNA) that reduces lipoprotein(a), also known as Lp(a), or another product containing a small interfering RNA (siRNA) that reduces lipoprotein(a). In some embodiments, the drug delivery device may contain or be used in conjunction with ABP 654 (a human IgG1 kappa antibody), a biosimilar candidate for Stelara®, or another product containing a human IgG1 kappa antibody and / or binding 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 in conjunction with Amjevita™ or Amgevita™ (formerly ABP 501) (a mab anti-TNF human IgG1), a biosimilar candidate for Humira®, or another product containing a human mab anti-TNF human IgG1. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 160, or another product containing 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 AMG 133 or a product containing 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 AMG 171 or a product containing a growth differentiation factor 15 (GDF15) analog. In some embodiments, the drug delivery device may contain or be used with AMG 176 or a product containing a small molecule inhibitor of myeloid cell leukemia 1 (MCL-1). In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 199 or another product containing a half-life extended (HLE) bispecific T-cell engager construct (BiTE®). In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 256 or another product containing an anti-PD-1 x IL21 mutein and / or 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 in conjunction 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 in conjunction with AMG 404, 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 in conjunction with AMG 427, 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 in conjunction with AMG 430, an anti-Jagged-1 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 506, a multispecific FAPx4-1BB-targeted DARPin® biologic being investigated as a treatment for solid tumors. In some embodiments, the drug delivery device may house AMG 509 or another product containing a bivalent T cell engager and engineered 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) CD19 x anti-CD3 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 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 another product containing a CD3 x epidermal growth factor receptor vIII (EGFRvIII) BiTE® (bispecific T-cell engager) molecule. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 673 or another product containing a half-life extended (HLE) anti-human CD33 x anti-human CD3 BiTE® (bispecific T-cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 701 or 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 in conjunction with AMG 757 or 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 contain or be used in conjunction with AMG 910 or another product containing a half-life extended (HLE) epithelial cell tight junction component protein claudin 18.2 x anti-CD3 BiTE® (bispecific T cell engager) construct.

[0060] The drug delivery devices, assemblies, components, subsystems, and methods have been described in terms of exemplary, but not limited to, embodiments. This detailed description should be construed as exemplary only and does not describe every possible embodiment of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and such embodiments would still fall within the scope of the claims that define the invention disclosed herein.

[0061] Those skilled in the art will understand that various modifications, variations and combinations can be made to the above-described embodiments without departing from the spirit and scope of the present invention disclosed herein, and that such modifications, variations and combinations should be construed as being within the scope of the present invention.

Claims

1. a barrel having an interior, a discharge opening at a distal end, and an open proximal end; a stopper disposed within the barrel; a plunger rod having a first end configured to at least selectively operatively couple to the stopper and a second end extending through the open proximal end of the barrel, the second end including an outwardly extending flange; a plunger stop member coupled to the plunger rod at a location between the flange and the open proximal end of the barrel; and a stop member assembly including a removable portion coupled to the plunger rod or the barrel, the plunger stop member configured and dimensioned to engage a stop surface adjacent the open proximal end of the barrel to selectively limit displacement of the plunger rod and stopper along the interior of the barrel; the plunger rod and stop member assembly are configured to allow the plunger rod to move a predetermined length corresponding to the plunger rod expelling at least a specified volume of headspace within the flange. Syringe.

2. 2. The syringe of claim 1, wherein the plunger stop and the removable portion of the stop assembly include first and second main portions pivotable relative to one another and capturing the plunger rod therebetween.

3. 3. The syringe of claim 2, wherein the plunger stop member and the removable portion of the stop member assembly include a hinge pivotally connecting first sides of the first and second main portions and a clip including a securing mechanism releasably connecting second sides of the first and second main portions.

4. 3. The syringe of claim 2, wherein the plunger stop member and the removable portion of the stop member assembly include a clamp including a biasing mechanism, the first and second main portions include a jaw at a first end thereof and a handle at a second end thereof, and the biasing mechanism biases the jaws of the first and second main portions together to capture the plunger rod therebetween.

5. 10. The syringe of claim 1, wherein the plunger stop and the removable portion of the stop assembly include tabs coupled to the plunger rod along its longitudinal length by a breakaway mechanism.

6. the plunger stop member and the detachable portion of the stop member assembly a main portion defining a cavity having an opening through an end wall thereof, the cavity configured to receive the plunger rod therein and limit longitudinal movement of the plunger rod relative to the main portion; a locking mechanism coupled to the main portion to retain the plunger rod within the cavity; Including, The syringe of claim 1 .

7. The syringe of claim 6 , wherein the securing mechanism includes an adhesive member extending across the cavity.

8. 7. The syringe of claim 6, wherein the main body includes first and second clamshell-like components having inner surfaces configured to mate and define the cavity therebetween, and the locking mechanism captures the first and second clamshell-like components in a closed state with the plunger rod captured within the cavity.

9. 2. The syringe of claim 1, wherein the plunger stop member and the removable portion of the stop member assembly comprise snap-fit members including first and second walls spaced apart from one another and connected by an end wall, the first and second walls defining a channel on their inner surfaces and configured to be bent open to position the plunger rod therebetween and returned to an unbent position to retain a portion of the plunger rod within the channel.

10. 2. The syringe of claim 1, wherein the proximal end of the barrel includes an outwardly protruding flange, the removable portion of the stop member assembly includes a blocking member configured to removably engage the flange of the barrel, the plunger stop member of the stop member assembly includes a stop flange extending outward from the plunger rod at the first end thereof, the stop flange having a circumference sized to fit within the interior of the barrel, and the blocking member is disposed within the path of travel of the stop flange and has a portion that limits longitudinal movement of the plunger rod.

11. 11. The syringe of claim 10, wherein the blocking member includes a clip having first and second walls spaced apart from one another and connected by an end wall, the clip configured to engage the flange of the barrel between the first and second walls.

12. 11. The syringe of claim 10, wherein the blocking member includes a tab having a distal end configured complementary to a portion of a horizontal cross section of the plunger rod, and the flange of the barrel includes a channel sized to receive the tab therein, the channel configured to guide the tab into engagement with the plunger rod.

13. A syringe according to any preceding claim, wherein the stop member assembly includes a wall portion having a surface thereon displaying information relating to operation of the stop member assembly.

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