Devices and methods for delivery of substances within prefilled syringe

Abstract

To provide an improved method and device for delivering a medicament contained in a prefilled syringe.SOLUTION: A device includes a housing 4100, an energy storage member 4410, a carrier 4360, a medicament container 4210, and a delivery control mechanism 4430. The housing defines a gas chamber configured to receive a pressurized gas from the energy storage member to pressurize the gas chamber. The carrier has a proximal surface defining a portion of the gas chamber. The medicament container is coupled to the carrier and a distal end portion is coupled to the delivery member. The medicament container contains a medicament and includes an elastomeric member that seals the medicament within the medicament container. The delivery control mechanism is coupled to the proximal end portion of the medicament container and includes a flow restriction member for regulating the pressure supplied by the gas chamber and entering into the medicament container that acts on the elastomeric member.SELECTED DRAWING: Figure 47

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[1001] This application claims the benefit of priority to U.S. Provisional Application No. 62 / 885,012, entitled “Devices and Methods for Delivery of Substances within a Prefilled Syringe,” filed August 9, 2019, which is incorporated herein by reference in its entirety. [Background technology]

[0002]

[1002] The embodiments described herein relate to a drug delivery device, a pharmaceutical composition, and a drug product. More specifically, the embodiments described herein relate to a drug delivery device for delivery of a drug contained in a pre-filled syringe.

[0003]

[1003] Known pre-filled syringes are generally used to contain and inject medication. Known pre-filled syringes include a syringe body (often made of glass) in which the medication is contained. The distal end portion of some known pre-filled syringes has a needle fixed thereto (i.e., the needle is permanently attached to the syringe body during manufacture). The end of this needle is placed in a needle cover to maintain the sterility of the needle before use. Other known pre-filled syringes include a Luer fitting or are adapted to allow the distal end portion of the syringe body to be attached to a needle. The proximal end portion of the syringe body of the known pre-filled syringe defines a portion of the container closure and includes a plunger (usually made of an elastomer) that can be moved within the syringe body to inject the medication. The proximal end portion also includes a flange that allows a user to grip the syringe body and manually apply force to the piston to move the plunger, thereby injecting the medication.

[0004]

[1004] Although prefilled syringes can be cost-effective devices for storing and delivering medication, known methods for using prefilled syringes include manually inserting a needle into the body and then manually applying an injection force. Furthermore, once the injection is complete, known methods include covering the needle to prevent it from sticking. Thus, known prefilled syringes are often used by medical personnel who are trained in such procedures. To facilitate self-administration of the medication contained in the prefilled syringe, some known autoinjectors are adapted to accommodate the prefilled syringe. Such known devices include a stored energy source for needle insertion and / or injection of the medication.

[0005]

[1005] However, known autoinjectors are often not configured to receive known prefilled syringes because they are often designed for a particular size and / or shape of drug container. For example, the use of a prefilled syringe in a known autoinjector often exerts a large force on the flange of the syringe body during an insertion operation, which may lead to damage to the syringe flange or body. Furthermore, many known prefilled syringes have a fixed needle that is in fluid communication with the drug, so applying force to the plunger during storage and / or insertion operations is undesirable. For example, applying force to the plunger during storage may cause the drug to leak, for example, when a spring-loaded member is in contact with the plunger. As another example, applying force to the plunger during a needle insertion event may cause the drug to be injected before the needle is inserted into the desired location. Similarly, some known autoinjectors are not configured to control the force applied to the plunger in the syringe body during storage and / or needle insertion.

[0006]

[1006] Known autoinjectors that are configured to incorporate a pre-filled syringe often include a spring-based actuation system that moves a piston rod to insert a needle and inject a drug. However, such known systems may be unnecessarily large in size (e.g., length) due to the need to incorporate a piston rod. Furthermore, known drugs or therapeutic substances are formulated to include high molecular weight compounds, compounds with complex molecular structures, living cells, and / or biologics. Such drugs are often highly viscous (e.g., greater than about 100 centipoise at room temperature), which must be accommodated by the delivery system. For example, the force and pressure required to overcome the resistance of the spring-based actuation system in the autoinjector may not be compatible with the force and pressure required to properly deliver drugs or therapeutic substances that include high molecular weight compounds. Thus, many known autoinjectors that contain pre-filled syringes may not be able to provide adequate force and / or produce the desired flow rate for effective delivery of such higher viscosity substances. Furthermore, even if an autoinjector can generate the desired force, such devices may result in undesirable delivery conditions or rates, which may degrade the delivered substance or cause excessive pain or discomfort during the delivery process. For example, if the delivery rate is too fast, the resulting shear forces may damage molecules in the substance, thereby reducing efficacy. Also, to prevent accidental needle pricking, known autoinjectors that include automatic needle retraction after drug delivery often include one or more guide shafts or linkages to detect completion of drug delivery to initiate the retraction process. The guide shafts and linkages introduce additional friction during the drug delivery process that works against providing the desired delivery rate and conditions. The guide shafts and linkages also require additional internal housing space, increasing the overall size and bulk of the autoinjector.

[0007]

[1007] Furthermore, known pre-filled syringes are often filled with a predetermined amount of drug (e.g., enough to deliver a dose of 1 mL). However, some treatment regimens now require larger delivery volumes (e.g., 2 mL or more). Thus, to accommodate available standard filling volumes, known methods and devices for delivering larger volumes can include multiple delivery events (e.g., injections) or infusions (in outpatient clinics or via pumps attached to the body), which is often undesirable for patients.

[0008]

[1008] Thus, there is a need for improved methods and devices for delivering medication contained within a pre-filled syringe. Summary of the Invention

[0009]

[1009] Described herein is a drug delivery device for administration of a drug contained in a pre-filled syringe. In some embodiments, the device includes a housing, an energy storage member, a carrier, a drug container, and a delivery control mechanism. The energy storage member is configured to generate pressurized gas when the energy storage member is activated. The housing defines a gas chamber configured to receive pressurized gas from the energy storage member to pressurize the gas chamber. The carrier has a proximal surface that defines a portion of the boundary of the gas chamber. The drug container is coupled to the carrier and has a distal end portion coupled to the delivery member. The drug container includes an elastomeric member that contains the drug and seals the drug within the drug container. The delivery control mechanism is coupled to a proximal end portion of the drug container. The delivery control mechanism includes a flow restriction member that regulates the pressure provided from the gas chamber into the drug container. Pressurized gas that accumulates in the drug container acts on the elastomeric member. In some embodiments, the flow restriction member includes at least a single-port valve, a multi-port valve, or a porous member. [Brief description of the drawings]

[0010] [Figure 1]

[1010] FIG. 1 is a chart showing the time to deliver 1 mL of a substance as a function of gas pressure and viscosity using a drug delivery device according to an embodiment. [Diagram 2]

[1011] Figure 2 is a schematic diagram of a drug delivery device according to an embodiment in a first configuration. [Diagram 3]

[1011] Figure 3 is a schematic diagram of a drug delivery device according to an embodiment in a second configuration. [Figure 4]

[1011] Figure 4 is a schematic diagram of a drug delivery device according to an embodiment in a third configuration. [Diagram 5]

[1011] Figure 5 is a schematic diagram of a drug delivery device according to an embodiment in a fourth configuration. [Figure 6]

[1012] Figure 6 is a schematic diagram of a drug delivery device according to an embodiment in a first configuration. [Figure 7]

[1012] Figure 7 is a schematic diagram of a drug delivery device according to an embodiment in a second configuration. [Figure 8]

[1012] Figure 8 is a schematic diagram of a drug delivery device according to an embodiment in a third configuration. [Figure 9]

[1012] Figure 9 is a schematic diagram of a drug delivery device according to an embodiment in a fourth configuration. [Figure 10]

[1013] Figure 10 is a schematic diagram of a drug delivery device according to an embodiment in a first configuration. [Figure 11]

[1013] Figure 11 is a schematic diagram of a drug delivery device according to an embodiment in a second configuration. [Figure 12]

[1013] Figure 12 is a schematic diagram of a drug delivery device according to an embodiment in a third configuration. [Figure 13]

[1014] Figure 13 is a schematic diagram of a drug delivery device according to an embodiment in a first configuration. [Figure 14]

[1014] Figure 14 is a schematic diagram of a drug delivery device according to an embodiment in a second configuration. [Figure 15]

[1014] Figure 15 is a schematic diagram of a drug delivery device according to an embodiment in a third configuration. [Figure 16]

[1014] Figure 16 is a schematic diagram of a drug delivery device according to an embodiment in a fourth configuration. [Figure 17]

[1015] FIG. 17 is a front perspective view of a medical injector according to an embodiment in a first configuration. [Figure 18]

[1016] Figure 18 is a front perspective view of the medical injector shown in Figure 17 with the electronic circuit system hidden and the safety lock removed. [Figure 19]

[1016] Figure 19 is a rear perspective view of the medical injector shown in Figure 17 with the electronic circuit system hidden and the safety lock removed. [Figure 20]

[1017] FIG. 20 is a perspective view of the housing of the medical injector shown in FIG. [Figure 21]

[1018] FIG. 21 is a cross-sectional view of the housing shown in FIG. [Figure 22]

[1019] FIG. 22 is a perspective view of the proximal cap of the medical injector shown in FIG. [Diagram 23]

[1019] FIG. 23 is a cross-sectional view of the proximal cap of the medical injector shown in FIG. [Figure 24]

[1001] FIG. 24 is a front view of the drug delivery mechanism of the medical injector shown in FIG. [Diagram 25]

[1001] FIG. 25 is a front view of the drug delivery mechanism of the medical injector shown in FIG. [Figure 26]

[1020] Figure 26 is a front view of the medical injector shown in Figure 17 in a first configuration. [Figure 27]

[1021] Figure 27 is a cross-sectional front view of the medical injector shown in Figure 17 in a first configuration. [Figure 27A]

[1022] Figure 27A is an enlarged cross-sectional view of a portion of the medical injector shown in Figure 27 in a first configuration. [Figure 27B]

[1023] Figure 27B is an enlarged cross-sectional view of a portion of the medical injector shown in Figure 27 in a first configuration. [Figure 28]

[1024] FIG. 28 is a perspective view of a delivery control mechanism of the medical injector shown in FIG. [Figure 28A]

[1024] FIG. 28A is a cross-sectional view of the delivery control mechanism of the medical injector shown in FIG. [Figure 29]

[1025] Figure 29 is a cross-sectional view of the delivery control mechanism shown in Figures 28 and 28A within the proximal end portion of the drug container. [Diagram 30]

[1026] FIG. 30 is a perspective view of the carrier assembly of the medical injector shown in FIG. [Diagram 31]

[1026] FIG. 31 is a cross-sectional view of the carrier assembly of the medical injector shown in FIG. [Diagram 32]

[1027] FIG. 32 is a perspective view of the carrier assembly of the medical injector shown in FIG. [Diagram 33]

[1028] FIG. 33 is a cross-sectional view of the carrier assembly and drug container of the medical injector shown in FIG. [Diagram 34]

[1029] FIG. 34 is an exploded view of the drug container assembly of the medical injector shown in FIG. [Diagram 35]

[1030] FIG. 35 is a perspective view of the gas vent assembly of the medical injector shown in FIG. [Figure 36A]

[1031] Figure 36A is a cross-sectional view of the gas vent assembly of Figure 35 in a first configuration. [Figure 36B]

[1031] FIG. 36B is a cross-sectional view of the gas vent assembly of FIG. 35 in a second configuration. [Figure 36C]

[1031] FIG. 36C is a cross-sectional view of the gas vent assembly of FIG. 35 in a third configuration. [Figure 37]

[1032] FIG. 37 is a perspective view of the safety lock of the medical injector shown in FIG. 17, illustrating a needle sheath assembly coupled to the safety lock. [Figure 38]

[1032] FIG. 38 is a perspective view of the safety lock of the medical injector shown in FIG. [Figure 39]

[1033] FIG. 39 is a perspective view of the system actuator of the medical injector shown in FIG. [Diagram 40]

[1033] FIG. 40 is a perspective view of the system actuator of the medical injector shown in FIG. [Diagram 41]

[1034] Figure 41 is a cross-sectional front view of the medical injector shown in Figure 17 in a second configuration (safety lock removed). [Diagram 42]

[1035] Figure 42 is a cross-sectional front view of the medical injector shown in Figure 17 in a third configuration (actuated). [Diagram 43]

[1036] Figure 43 is a front view of the medical injector shown in Figure 17 in the fourth configuration (needle inserted). [Diagram 44]

[1037] Figure 44 is a cross-sectional front view of the medical injector shown in Figure 17 in the fourth configuration (needle inserted). [Diagram 45]

[1038] Figure 45 is an enlarged cross-sectional view of the medical injector shown in Figure 17 in the fourth configuration (needle inserted). [Diagram 46]

[1039] Figure 46 is a front view of the medical injector shown in Figure 17 in a fifth configuration (medicament being delivered). [Figure 47]

[1040] Figure 47 is a cross-sectional front view of the medical injector shown in Figure 17 in a fifth configuration (medicament being delivered). [Figure 48]

[1041] Figure 48 is a perspective cross-sectional view of the medical injector shown in Figure 17 in a fifth configuration (medicament being delivered). [Figure 49]

[1042] Figure 49 is a front view of the medical injector shown in Figure 17 in a sixth configuration (the gas chamber of the housing is evacuated). [Figure 50]

[1043] Figure 50 is a cross-sectional front view of the medical injector shown in Figure 17 in a sixth configuration (with the gas chamber of the housing evacuated). [Figure 51]

[1044] FIG. 51 is a perspective cross-sectional view of the medical injector shown in FIG. 17 in a sixth configuration (with the gas chamber of the housing vented). [Figure 52]

[1045] Figure 52 is a front view of the medical injector shown in Figure 17 in the seventh configuration (needle retracted). [Diagram 53]

[1046] Figure 53 is a cross-sectional front view of the medical injector shown in Figure 17 in the seventh configuration (needle retracted). [Figure 54]

[1047] Figure 54 is a perspective cross-sectional view of the medical injector shown in Figure 17 in the seventh configuration (needle retracted). [Figure 55]

[1048] FIG. 55 is a cross-sectional view of a portion of a medical injector in accordance with an embodiment. [Figure 56]

[1049] FIG. 56 is an enlarged cross-sectional view of the medical injector shown in FIG. [Figure 57]

[1050] FIG. 57 is an enlarged exploded view of the flow restrictor member of the medical injector shown in FIG. [Figure 58]

[1051] FIG. 58 is a cross-sectional front view of a medical injector according to an embodiment in a first configuration. [Figure 59]

[1052] Figure 59 is a cross-sectional front view of the medical injector of Figure 58 in a second configuration. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011]

[1053] Described herein is a drug delivery device for administration of a drug contained in a pre-filled syringe. In some embodiments, the device includes a housing, an energy storage member, a carrier, a drug container, and a delivery control mechanism. The energy storage member is configured to generate pressurized gas when the energy storage member is activated. The housing defines a gas chamber configured to receive pressurized gas from the energy storage member to pressurize the gas chamber. The carrier has a proximal surface that defines a portion of the boundary of the gas chamber. The drug container is coupled to the carrier and has a distal end portion coupled to the delivery member. The drug container includes an elastomeric member that contains the drug and seals the drug within the drug container. The delivery control mechanism is coupled to a proximal end portion of the drug container. The delivery control mechanism includes a flow restriction member that regulates the pressure provided from the gas chamber into the drug container. Pressurized gas accumulating in the drug container acts on the elastomeric member. In some embodiments, the flow restriction member includes at least a single-port valve, a multi-port valve, or a porous member.

[0012]

[1054] In some embodiments, the delivery member is a needle coupled to a distal end portion of the medicament container. The carrier is configured to move from a first carrier position to a second carrier position in response to pressurized gas being delivered into the gas chamber. Movement of the carrier from the first carrier position to the second carrier position moves the needle from a first needle position, where the needle is disposed within the housing, to a second needle position, where the needle extends from the housing. The flow restricting member is configured to restrict movement of the elastomeric member before the carrier is disposed at the second carrier position.

[0013]

[1055] In some embodiments, the gas chamber is a first gas chamber and a portion of the boundary of the first gas chamber is a first portion of the boundary. A proximal end portion of the flow restricting member defines a second portion of the boundary of the first gas chamber. A distal end portion of the flow restricting member defines a first portion of the boundary of the second gas chamber. A proximal end portion of the elastomeric member defines a second portion of the boundary of the second gas chamber. The flow restricting member is configured such that pressurized gas passes from the first gas chamber through the flow restricting member into the second gas chamber after the carrier is disposed at the second carrier position. In some embodiments, the elastomeric member moves within the drug container in response to pressurized gas being delivered into the second gas chamber. The elastomeric member moves a stroke distance to deliver a dose of drug from the drug container through the needle.

[0014]

[1056] In some embodiments, the delivery control mechanism includes a first body portion and a second body portion. The second body portion extends from the first body portion, the first body portion defining a first axis. The second body portion defines a second axis. The second axis is non-parallel to the first axis. In some embodiments, the drug container defines a third axis. The third axis is parallel to the first axis. In some embodiments, the second body portion of the delivery control mechanism includes a flow-restricting retainer. The flow-restricting member is at least partially supported within the flow-restricting retainer.

[0015]

[1057] In some embodiments, the first body portion of the delivery control mechanism includes a proximal end portion and a distal end portion. The distal end portion of the delivery control mechanism is opposite the proximal end portion of the delivery control mechanism. The distal end portion of the delivery mechanism includes a radially extending flange configured for attachment to at least the proximal end portion of the carrier or medicament container. In some embodiments, the distal end portion of the first body portion extends into the proximal end portion of the medicament container.

[0016]

[1058] In some embodiments, the flow restricting member includes a flow restricting retainer and a flow restricting member disposed within the flow restricting retainer. The flow restricting retainer includes a radially extending flange configured to attach to at least a proximal end portion of the carrier or the drug container. In some embodiments, a distal end portion of the flow restricting retainer extends into the proximal end of the drug container. The flow restricting retainer defines a first axis and the drug container defines a second axis. The second axis is parallel to the first axis.

[0017]

[1059] In some embodiments, the first body portion of the delivery control mechanism includes an annular groove configured to retain a sealing member, hi some embodiments, the sealing member is an O-ring.

[0018]

[1060] In some embodiments, the apparatus further includes a retraction spring coupled to the housing, the retraction spring configured to bias the carrier toward the first carrier position, and the retraction spring configured to move the carrier toward the first carrier position in response to pressurized gas delivered from the gas chamber through the opening in the housing.

[0019]

[1061] In some embodiments, the drug container is a pre-filled syringe having a container body. The delivery member includes a needle, the needle being fixed to a distal end portion of the container body.

[0020]

[1062] In some embodiments, the drug in the drug container comprises a drug and / or a biological product. In some embodiments, the drug in the drug container has a viscosity of 100 centipoise or greater at room temperature. In some embodiments, the drug in the drug container comprises a high molecular weight compound of greater than 5 kDa.

[0021]

[1063] In some embodiments, the carrier is a first carrier, the portion of the boundary of the gas chamber is a first portion of the boundary, the medicament container is a first medicament container, the elastomeric member is a first elastomeric member, the medicament is a first medicament, the delivery control mechanism is a first delivery control mechanism, and the flow restriction member is a first flow restriction member. The device further includes a second carrier disposed within the housing. The second medicament container is coupled to the second carrier. A proximal face of the second carrier defines a second portion of the boundary of the gas chamber. A distal end portion of the second medicament container is configured to couple to the second delivery member. The second medicament container contains a second elastomeric member that seals the second medicament within the second medicament container. A second delivery control mechanism is coupled to a proximal end portion of the second medicament container. The second delivery control mechanism includes a second flow restriction member configured to regulate the flow of pressurized gas into the second medicament container. Pressurized gas accumulating within the second medicament container acts on the second elastomeric member.

[0022]

[1064] In some embodiments, the first delivery member is a first needle coupled to a distal end of the first medicament container. The second delivery member is a second needle coupled to a distal end of the second medicament container. In some embodiments, the first medicament container is non-coaxial with the second medicament container. In some embodiments, the first medicament container and the second medicament container are configured to move simultaneously within the housing in response to pressurized gas being delivered into a gas chamber of the housing. In some embodiments, the first medicament container is non-coaxial with the second medicament container. In some embodiments, the first medicament container and the second medicament container are configured to move simultaneously within the housing in response to pressurized gas being delivered into the gas chamber.

[0023]

[1065] In some embodiments, the device includes a housing, an energy storage member, a carrier, a drug container, a delivery control mechanism, and a valve member. The housing defines a gas chamber and includes a sidewall. The sidewall of the housing defines an opening configured to selectively fluidly connect the gas chamber with an exterior volume. The energy storage member is configured to generate pressurized gas upon actuation of the energy storage member. The carrier is disposed within the housing. A proximal face of the carrier defines a portion of a boundary of the gas chamber. The gas chamber is configured to receive pressurized gas from the energy storage member to pressurize the gas chamber. The drug container is coupled to the carrier. A distal end portion of the drug container is configured to be coupled to the delivery member. The drug container includes an elastomeric member that contains the drug and seals the drug within the drug container. The delivery control mechanism is coupled to a proximal end portion of the drug container. The drug container includes a flow restricting member configured to regulate a flow of pressurized gas into the drug container. The pressurized gas within the drug container acts on the elastomeric member. The valve member is configured to seal the opening in the housing when the valve member is in the first position, and the valve member is configured to unseal the opening in the housing when the valve member is in the second position, such that when the valve member is in the second position, the opening is unsealed such that the gas chamber is in fluid communication with the exterior volume.

[0024]

[1066] In some embodiments, the device further includes an expandable assembly. The expandable assembly includes a first member, a second member, and a third member. The first member is coupled to the elastomeric member. The second member is coupled between the first member and the third member. A portion of the second member is movably disposed within the delivery control mechanism. The third member is coupled to the valve member. The expandable assembly is configured to transition from a first configuration to a second configuration when the elastomeric member moves within the drug container. The valve member moves from a first position to a second position when the expandable assembly transitions from the first configuration to the second configuration to release pressurized gas from the gas chamber to the external volume.

[0025]

[1067] In some embodiments, the delivery control mechanism defines a bore in which a portion of the second member of the expandable assembly is movably disposed. An outer surface of the second member and an inner surface of the bore define an annulus in fluid communication with the flow restricting member. In some embodiments, the annulus is configured to deliver pressurized gas received from the flow restricting member to the drug container.

[0026]

[1068] In some embodiments, the elastomeric member moves a stroke distance within the drug container in response to pressurized gas being delivered into the drug container to deliver a dose of drug from the drug container. In some embodiments, the delivery control mechanism includes a seal member configured to limit pressurized gas received from passage between the second member of the expandable assembly and the bore of the delivery control mechanism.

[0027]

[1069] In some embodiments, the second member of the expandable assembly includes at least a flange portion configured to contact a distal end portion of the delivery control member in the first configuration of the expandable assembly. In some embodiments, the second member and the delivery control mechanism are configured to move together from a first position to a second position in response to pressurized gas being delivered into the gas chamber. In some embodiments, the first member is a flexible member configured to transition when the elastomeric member moves within the drug container. The flexible member transitions from a first length when the flexible member is in a collapsed state to a second length when the flexible member is in an expanded state. The flexible member is configured to exert an ejection force on the second member to move the second member axially relative to the delivery control mechanism when the flexible member transitions from the collapsed state to the expanded state. In some embodiments, the axial movement of the second member transmits an ejection force to a third member to move the valve member relative to the opening.

[0028]

[1070] In some embodiments, the second member defines an internal bore. The third member includes a shaft having a proximal end portion and a distal end portion. The proximal end portion of the third member is coupled to the valve member. The distal end portion of the third member includes an end stop member. The internal bore of the second member is configured to slide along the shaft of the third member. The second member slides along the shaft between the valve member and the end stop of the third member in response to pressurized gas delivered into the gas chamber.

[0029]

[1071] In some embodiments, the valve member includes a valve portion defining a gas release path. The valve portion is disposed within the opening of the housing such that when the expandable assembly is in the first configuration, the gas release path is fluidly isolated from the gas chamber via the seal member. In some embodiments, the expandable assembly has a first size in the first configuration and a second size in the second configuration. The second size is sized such that the gas chamber is in fluid communication with the external volume after the valve member is actuated and the drug is delivered from the drug container.

[0030]

[1072] In some embodiments, the first configuration is a collapsed configuration and the second configuration is an expanded configuration. The first member is a flexible member configured to transition from a first length when the expandable member is in a collapsed state to a second length when the expandable member is in an expanded state when the elastomeric member moves within the drug container. The flexible member is configured to exert an ejection force on the valve member to move the valve member relative to the opening when the expandable assembly transitions from the collapsed configuration to the expanded configuration. When the valve member is moved relative to the opening, the gas chamber is in fluid communication with the exterior volume. In some embodiments, the flexible member is at least a filament and / or a band.

[0031]

[1073] In some embodiments, the valve member moves distally when the flexible member transitions from the collapsed configuration to the expanded configuration and as the elastomeric member continues to move distally. In some embodiments, a first member of the expandable assembly is coupled to the elastomeric member via a coupling member. The coupling member includes a retention structure. A third member of the expandable assembly includes a locking protrusion configured to engage the retention structure of the first member when the flexible member is in the collapsed configuration. The locking protrusion is configured to release from the retention structure when gas pressure in the drug container exceeds a threshold pressure value.

[0032]

[1074] In some embodiments, the device includes a housing, a medicament container, an electronic circuit system, a sensing unit, a delivery module, and an output module. The medicament container is disposed within the housing. A distal end portion of the medicament container is configured to be coupled to the delivery member. The medicament container includes an elastomeric member that contains the medicament and seals the medicament within the medicament container. The electronic circuit system is coupled to the housing. The electronic circuit system includes a sensing unit, a delivery module, and an output module. The sensing unit is configured to detect a position of the elastomeric member relative to the medicament container and generate an electronic signal associated with at least one of a position, a velocity, or an acceleration of the elastomeric member. The delivery module is implemented in at least one of a memory or a processing device. The delivery module is configured to receive the electronic signal and determine a movement profile of the elastomeric member based on the electronic signal. The output module is configured to generate at least one of an audio output, a visual output, or a wireless signal associated with the movement profile of the elastomeric member.

[0033]

[1075] In some embodiments, the movement profile includes at least one of a current position of the elastomeric member, a speed of travel of the elastomeric member, a delivery rate of the drug from the drug container, or a time remaining to complete delivery of a dose of the drug from the drug container. In some embodiments, the sensing unit includes an infrared emitter and an infrared receiver.

[0034]

[1076] In some embodiments, the sensing unit includes a plurality of optical emitters and a plurality of detectors. Each of the plurality of detectors is configured to receive a light beam generated by a corresponding one of the plurality of optical emitters. In some embodiments, the drug container extends from a first end portion to a second end portion. The plurality of optical emitters and the plurality of detectors are spaced apart along a length of the drug container between the first end portion and the second end portion.

[0035]

[1077] In some embodiments, the electronic circuit system further includes a prediction module implemented in at least one of the memory or the processing device. The prediction module is configured to determine a remaining time to complete delivery of a dose of the medication based on the received movement profile over a period of time. In some embodiments, an audio output, a visual output, and / or a wireless signal indicates the remaining time to complete delivery of the dose of the medication.

[0036]

[1078] In some embodiments, a computer-implemented method includes emitting a first light beam from a first emitter through a drug container toward a first receiver. The drug container is positioned between the first emitter and the first receiver. The drug container contains an elastomeric member that contains the drug and seals the drug within the drug container. The first receiver is configured to generate a first electronic signal associated with a magnitude of the first light beam. The method includes emitting a second light beam from a second emitter through the drug container toward a second receiver. The drug container is positioned between the second emitter and the second receiver. The second receiver is configured to generate a second electronic signal associated with a magnitude of the second light signal. The method includes detecting at least one of the first electronic signal or the second electronic signal as the elastomeric member advances through the drug container. The method includes determining a position of the elastomeric member within the drug container based on a comparison of the first electronic signal and the second electronic signal. In some embodiments, the first emitter and the second emitter are configured to transmit at least one wavelength in the ultraviolet, visible, and / or infrared spectrum, hi some embodiments, the first emitter and the second emitter are configured to transmit an infrared beam.

[0037]

[1079] In some embodiments, the method includes determining a rate of advancement of the elastomeric member based on a time difference between when the first electronic signal falls below a threshold value and when the second electronic signal falls below a threshold value. In some embodiments, the method includes determining a rate of delivery of the drug from the drug container based on a time difference between when the first electronic signal falls below a threshold value and when the second electronic signal falls below a threshold value. In some embodiments, the method includes determining a remaining completion time to complete delivery of a dose of the drug from the drug container based on a time difference between when the first electronic signal falls below a threshold value and when the second electronic signal falls below a threshold value.

[0038]

[1080] In some embodiments, the device includes a housing, a carrier, a drug container, and a delivery mechanism. The housing defines an opening in which a gas chamber is disposed, and the gas chamber is configured to receive pressurized gas to pressurize the gas chamber. The carrier has a proximal surface that defines a portion of the gas chamber. The drug container is coupled to the carrier and has a distal end portion coupled to the delivery member. The drug container contains an elastomeric member that contains the drug and seals the drug therein. The delivery mechanism includes a flow restricting member coupled to the proximal end portion of the drug container and for regulating pressure provided from the gas chamber to the elastomeric member. In some embodiments, the flow restricting member includes a flow restricting retainer and a flow restricting member disposed within the flow restricting retainer. The flow restricting retainer includes a radially extending flange configured to attach to the carrier. In some embodiments, the drug container is a pre-filled syringe having a drug or biological product. In some embodiments, the drug has a viscosity of 100 centipoise or more at room temperature. In some embodiments, the drug includes a high molecular weight compound of more than 5 kDa.

[0039]

[1081] As used herein, the term "substance" or "medication" includes any component of a therapeutic substance. A medicament can include such components regardless of the state of the substance (e.g., solid, liquid, or gas). Furthermore, a medicament can include multiple components that can be included in the therapeutic substance in a mixed, unmixed, and / or partially mixed state. A medicament can include both active and inactive components of a therapeutic substance. Thus, as used herein, a medicament can include inactive components such as water, colorants, etc.

[0040]

[1082] The term "about" when used in connection with a referenced numerical indication means the referenced numerical indication plus or minus up to 10% of the referenced numerical indication. For example, "about 100" means from 90 to 110.

[0041]

[1083] Similarly, the term "substantially" when used in connection with, for example, a geometric relationship, a numerical value, and / or a range is intended to convey that the geometric relationship (or structure described thereby), the number, and / or the range so defined are nominally the described geometric relationship, the number, and / or the range. For example, two structures described herein as "substantially parallel" are intended to convey that while a parallel geometric relationship is desired, some non-parallelism may occur in a "substantially parallel" arrangement. As another example, a structure defining a volume of "substantially 0.50 milliliters (mL)" is intended to convey that while the described volume is desired, some tolerance may occur when the volume is "substantially" the described volume (e.g., 0.50 mL). Such tolerance may result from manufacturing tolerances, measurement tolerances, and / or other practical considerations (e.g., minute imperfections, age of the described structure, pressure or force exerted within the system, etc.). As previously mentioned, a suitable tolerance may be, for example, ±10% of the described geometric structure, numerical value, and / or range. Additionally, values ​​modified with the term "substantially" may allow for and / or otherwise include a tolerance of the numerical value stated, but are not intended to exclude the exact numerical value stated.

[0042]

[1084] As used herein, the term "set" may refer to multiple features or a single function having multiple parts. For example, when referring to a set of walls, the set of walls can be considered as one wall having multiple parts or as multiple separate walls. Thus, a monolithically made item can include a set of walls. Such a set of walls can include multiple parts that are, for example, continuous or discontinuous from each other. A set of walls can also be fabricated from multiple items that are manufactured separately and later joined together (e.g., via welding, adhesive, or any suitable method).

[0043]

[1085] As used in this specification and the appended claims, the terms "proximal" and "distal" refer to directions toward and away from an operator of a medical device, respectively. Thus, for example, the end of a drug delivery device that contacts a patient's body is the distal end of the drug delivery device, and the end opposite the distal end is the proximal end of the drug delivery device.

[0044]

[1086] As used herein, the term "rigidity" or "hardness" refers to the resistance of an object to deflection, deformation, and / or displacement produced by an applied force, and is generally understood to be the opposite of the "flexibility" of an object. For example, a stiffer gas-releasing member is more resistant to deflection, deformation, and / or displacement when exposed to a force than a less stiff gas-releasing member. Similarly, a stiffer gas-releasing member can be characterized as being harder than a less stiff gas-releasing member. Stiffness can be characterized in terms of the amount of force applied to an object and the resulting distance that a first portion of the object deflects, deforms, and / or displaces relative to a second portion of the object. When characterizing the stiffness of an object, the deflected distance can be measured as the deflection of a portion of the object different from the portion of the object to which the force is directly applied. In other words, in some objects, the deflection point is different from the point of application of the force.

[0045]

[1087] Stiffness (and therefore flexibility) is a broad property of the object being described and thus depends on the material from which the object is formed and the specific physical characteristics of the object (e.g., cross-sectional shape, length, boundary conditions, etc.). For example, the stiffness of an object can be increased or decreased by selectively including in the object a material having a desired elastic modulus, flexural modulus, and / or hardness. The elastic modulus is an intensive property (i.e., inherent to the material of construction) of the material of construction and describes the tendency of the object to deform elastically (i.e., non-permanently) in response to an applied force. A material with a high elastic modulus will not deflect as much as a material with a low elastic modulus in the presence of the same applied stress. Thus, for example, the stiffness of an object can be reduced by introducing into the object a material with a relatively low elastic modulus and / or by making the object from a material with a relatively low elastic modulus.

[0046]

[1088] Changing the physical characteristics of an object, such as its shape or cross-sectional area, can also increase or decrease the stiffness of the object. For example, an object with a length and cross-sectional area may be stiffer than an object of the same length but with a smaller cross-sectional area. As another example, the stiffness of an object can be reduced by including one or more stress concentrating risers (or discontinuous boundaries) that cause deformation under low stress and / or at specific locations of the object. Thus, reducing and / or changing the shape of an object can decrease the stiffness (or flexibility) of the object.

[0047]

[1089] Thus, objects that are easily deformed by small forces, such as wires, filaments, cords, etc., are said to be flexible.

[0048]

[1090] The therapeutic compositions described herein may be any of the compositions described herein or in any of the other applications described in International Patent Publication No. WO2017 / 004345 ("PCT No. 4345"), filed June 30, 2016, and entitled "Auto-Injectors for Administration of a Medicament Within a Prefilled Syringe," International Patent Publication No. WO2020 / 140040 ("PCT No. 0040"), filed December 27, 2019, and entitled "Devices and Methods for Delivery of Substances Within a Prefilled Syringe," International Patent Publication No. WO2018 / 136413 ("PCT No. 6413"), filed January 16, 2018, and entitled "Medicament Delivery Devices with Wireless Connectivity and Event Detection," and / or International Patent Publication No. WO2018 / 136413 ("PCT No. 6413"), filed July 15, 2019, and entitled "Medicament Delivery Devices with Wireless Connectivity and Compliance The drug delivery device may be included within any suitable drug delivery device described in WO 2020 / 018433 ("PCT No. 8433"), entitled "Icatibant Detection," each of which is incorporated herein by reference in its entirety. For example, in some embodiments, a drug product configured for administration by an untrained user (such as a person accompanying a patient) may include a dose of icatibant. Such a drug product may include, for example, an autoinjector having a needle length and delivery profile (e.g., flow of icatibant) sufficient to perform a subcutaneous injection. In other embodiments, the drug product may include a therapeutic agent including a monoclonal antibody. Such a drug product may include, for example, an autoinjector having multiple prefilled syringe containers that can deliver drug from each syringe in a single operation to deliver a desired dose. By including multiple syringes, such an arrangement may allow for higher doses while using the standard fill volume of a prefilled syringe.

[0049]

[1091] In some embodiments, a gas-based drug delivery device can result in a compact device, in which the exterior dimensions of the housing are not substantially larger than the length of the drug container disposed therein. For example, as shown and described herein, in some embodiments, the drug delivery device can be free of a mechanical linkage that exerts or transmits a force to an elastomeric member to expel a drug from an internal drug container. Similarly, in some embodiments, the drug delivery device can be free of a mechanical linkage (ram, rod) that transmits a force to an elastomeric member. More appropriately, in some embodiments, the elastomeric member can exert a force on a member (e.g., an expandable member) to control the delivery. Such a drug delivery device (or drug delivery mechanism) is considered a "piston-less" system. As an example, in a gas-based piston-less autoinjector, the force exerted by the gas can move the drug container relative to the housing, which in turn can move the elastomer member relative to (e.g., within) the drug container. In some embodiments, the lack of a moving mechanism, piston, etc., can reduce the height of the medical injector, for example, compared to the height of a device that includes a rigid single-length piston.

[0050]

[1092] For example, any of the drug delivery devices described herein can include any suitable "pistonless" design, such as those described in PCT No. 4345, PCT No. 0040, or International Patent Publication No. WO2016 / 154427, entitled "DEVICES AND METHODS FOR DELIVERING A LYOPHILIZED MEDICAMENT," filed March 24, 2016, which is incorporated by reference in its entirety.

[0051]

[1093] In some embodiments, the characteristics of the drug, drug container, and needle are such that the force required to achieve the desired injection is not possible via manual injection. Thus, in some embodiments, the device can include an energy storage member configured to generate a desired force (and / or pressure within the drug container) to deliver the drug. For example, in certain circumstances, the pressure of the drug within a needle-based drug container can be modeled by the Hagen-Poiseuille law, as shown below: (1) P = (8 * μ * L * Q) / (π * R 4 )

[0052]

[1094] where P is the pressure of the drug in the drug container, μ is the viscosity of the drug, L is the length of the needle (not shown), Q is the flow rate of the drug through the needle, and R is the radius of the lumen defined by the needle. Because the pressure (and / or force) required to inject a high viscosity fluid through a small diameter needle is proportional to the inverse of the fourth power of the radius of the needle's lumen, the pressure of the drug in the drug container required to achieve the desired flow rate can be relatively high in some cases. The desired pressure can be achieved by including a gas-based energy storage member.

[0053]

[1095] In some embodiments, the energy storage member can be configured to contain various amounts of stored energy without changing the size of the energy storage member. Thus, in such embodiments, high forces (e.g., for injecting viscous drugs) can be achieved with the same packaging used for drugs with low viscosity. For example, in some embodiments, the energy storage member can be a compressed gas cylinder with gas therein at any desired pressure (and therefore mass). Thus, pressures and / or forces can be achieved to complete the operations described herein regardless of drug.

[0054]

[1096] In such embodiments, a non-mechanical energy storage member (gas, propellant, magnetic, electronic, etc.) can be used to generate a force large enough to generate a desired pressure within the drug container to generate the desired injection. For example, in larger diameter embodiments, the amount of force required to generate a desired internal pressure increases significantly. In some embodiments, any drug delivery device described herein can include a gas-based energy storage system configured to generate a gas pressure (e.g., in the gas chamber) of about 200 psi to about 2700 psi. In some embodiments, any injector described herein can include a gas-based energy storage system configured to generate a gas pressure of about 200 psi, 300 psi, 400 psi, 500 psi, 600 psi, 700 psi, 800 psi, 900 psi, 1100 psi, 1200 psi, 1300 psi, 1500 psi, 1700 psi, 1900 psi, 2100 psi, 2300 psi, 2500 psi, or 2700 psi. In some embodiments, any of the injectors described herein can include a gas-based energy storage system configured to generate a gas pressure of between about 200 psi and 7000 psi. The gas pressure can be generated by any suitable mechanism, such as, for example, by puncturing a compressed gas container, releasing a propellant (e.g., a hydrofluoroalkane), releasing a refrigerant (e.g., R134a), releasing a liquefied gas, triggering a chemical reaction, etc.

[0055]

[1097] FIG. 1 is a chart showing the delivery time for delivering 1 mL of a substance using a drug delivery device of the type shown and described herein, and in PCT Nos. 4335 and 0040, as a function of both gas pressure and viscosity of the substance. As shown, the delivery time can be tailored to the desired performance characteristics by adjusting the gas pressure in the device. For example, in some embodiments, any of the devices and drug products described herein can be used to perform a subcutaneous injection method by limiting the gas pressure during the injection event. Limiting the gas pressure can reduce the injection force (and therefore the momentum of the substance leaving the device) to ensure that the substance is delivered subcutaneously and not intramuscularly. Controlling the momentum of the substance leaving the device and the injection rate of the substance can also minimize pain to the patient, especially when the viscosity of the substance is high (e.g., greater than about 100 centipoise at room temperature). As another example, in some embodiments, injection of drugs or therapeutic substances including high molecular weight compounds (e.g., greater than about 5 kDa) may require less injection force than is required to overcome the spring-based actuation system of an autoinjector to prevent shear and therefore damage to the drug or therapeutic substance.

[0056]

[1098] In some embodiments, the gas pressure can be controlled during an injection event by limiting the amount of pressurized gas in the compressed gas container. In other embodiments, the gas pressure can be controlled by selective movement of a gas release valve, such as release valve 4345 described below, during delivery (e.g., injection). Similarly, in some embodiments, any device described herein (or in PCT Nos. 4345, 0040, or 6413) can include a valve and a mechanism for opening the valve a predetermined amount during a delivery event. In yet other embodiments, any device described herein (or in PCT Nos. 4345, 0040, or 6413) can include a porous valve member that allows for some pressure drop during a delivery event.

[0057]

[1099] 2-5 are schematic diagrams of a drug delivery device 1000 according to an embodiment in a first configuration, a second configuration, a third configuration, and a fourth configuration, respectively. The drug delivery device 1000 includes a housing 1100, a drug container assembly 1200, an energy storage member 1400, a flow restricting member 1450, and a retraction member 1351. The housing 1100 defines a gas chamber 1139 that receives pressurized gas from the energy storage member 1400. The gas chamber 1139 can be of any suitable size and shape, and can be, for example, a portion of a volume defined by the housing 1100, within which a portion of the drug container assembly 1200 is disposed. The housing 1100 can be of any suitable size, shape, or configuration, and can be made of any suitable material. For example, in some embodiments, the housing 1100 is a multiple part assembly formed from a plastic material and defines a substantially rectangular shape when assembled. In other embodiments, the housing 1100 can be substantially cylindrical.

[0058]

[1100] The medicament container assembly 1200 has a medicament container body 1210 that defines a volume that contains the medicament (i.e., is filled or partially filled with the medicament). A distal end portion of the medicament container body 1210 includes a neck or opening through which the medicament can be delivered. In some embodiments, the medicament container assembly 1200 includes a delivery member 1216 coupled to the container body 1210 through which the medicament can be delivered. For example, in some embodiments, the delivery member 1216 includes a needle, a nozzle, a mouthpiece, etc. In some embodiments, the medicament container assembly 1200 can be a pre-filled syringe with a fixed needle of the type shown and described herein. In some embodiments, the medicament container assembly 1200 can include or be coupled to a carrier (not shown in FIGS. 2-5, but which can be similar to the carrier 4360 described below) that moves the medicament container body 1210 within the housing 1100. In this manner, the carrier can facilitate removal of the delivery member 1216 from the housing 1100 in the deployed position, as described below. In some embodiments, one or more surfaces of the carrier can form at least a portion of the boundary of the gas chamber 1139. In some embodiments, the carrier can include one or more seals to fluidically isolate the gas chamber 1139.

[0059]

[1101] The drug container assembly 1200 includes an elastomeric member 1217 (i.e., a plunger) that seals the drug within the container body 1210. The elastomeric member 1217 is configured to move within the container body to expel the drug from the drug container assembly 1200. The elastomeric member 1217 can be of any design or formulation suitable for contact with a drug. For example, the elastomeric member 1217 can be formulated to minimize any reduction in drug efficacy that may result from contact (direct or indirect) between the elastomeric member 1217 and the drug. For example, in some embodiments, the elastomeric member 1217 can be formulated to minimize leaching or outgassing of the composition that may have undesirable effects on the drug. In other embodiments, the elastomeric member 1217 can be formulated to maintain chemical stability, flexibility, and / or sealing properties when in contact (direct or indirect) with a drug over an extended period of time (e.g., up to six months, one year, two years, five years or more).

[0060]

[1102] The medicament container assembly 1200 includes a proximal portion 1214 configured to translate within the housing 1100 to move the medicament container body 1210 between a first position and a second position, as described herein. Although the medicament container assembly 1200 is shown as being disposed within the housing 1100 without a carrier, in other embodiments, the medicament container assembly 1200 can be disposed within or coupled to a carrier to facilitate movement within the housing 1100. The proximal portion 1214 of the medicament container assembly 1200, and the carrier, if present, define a portion of the boundary of the gas chamber 1139. In this manner, when pressurized gas is delivered into the gas chamber 1139, the internal pressure generates a force on the proximal portion 1214 to move the medicament container body 1210 (and the delivery member 1216) from the retracted position to the deployed position.

[0061]

[1103] The energy storage member 1400 is disposed within the housing 1100 and is configured to deliver pressurized gas into the gas chamber 1139 when the energy storage member 1400 is actuated to generate a force F1 (see FIG. 2) to deploy the delivery member 1216 and to deliver the contents of the drug container 1200. The energy storage member 1400 may be any suitable member or device that stores potential energy and generates pressurized gas when actuated. For example, the energy storage member 1400 (and any energy storage member described herein) may be any device containing compressed gas, a device including a vapor pressure based propellant, or the like.

[0062]

[1104] The retraction member 1351 may be a retraction spring or any other energy storage member. In this manner, the retraction member 1351 is configured to return the medicament container assembly 1200 to the first position (e.g., retracted position) of the medicament container 1200 after deployment, as described in further detail herein. In some embodiments, the retraction member 1351 may be further configured to maintain the medicament container 1200 in the retracted position before gas pressure is provided to the gas chamber 1139. Although shown as including a retraction member, in other embodiments, the drug delivery device 1000 may not include a retraction member. For example, in some embodiments, the drug delivery device 1000 may be configured to maintain the delivery member 1216 in the deployed position after delivery. In such embodiments, the drug delivery device 1000 may include other suitable mechanisms for covering or shielding the delivery member (e.g., a cover that moves around the delivery member 1216 after delivery is completed).

[0063]

[1105] Upon actuation of the drug delivery device 1000, the energy storage member 1400 is activated and releases pressurized gas into the gas chamber 1139 as indicated by arrow AA. The released pressurized gas generates a force F1 that moves the drug container body 1210 together with the delivery member 1216 from a first position (e.g., a retracted position) shown in Fig. 2 to a second position (e.g., a deployed position) in a first direction indicated by arrow BB in Fig. 3. As shown, in the retracted position, the delivery member 1216 is disposed within the housing 1100, and in the deployed position, the delivery member 1216 extends from the housing 1100.

[0064]

[1106] When the medicament container body 1210 and the delivery member 1216 are in the deployed position, the released pressurized gas passes (or continues to pass) through the flow restricting member 1450 and into the medicament container gas chamber 1218 of the medicament container 1200, as shown by arrows CC in FIG. 4. The medicament container gas chamber 1218 is defined between the flow restricting member 1450 and the elastomeric member 1217. As the released pressurized gas passes through the flow restricting member 1450, pressure builds up in the medicament container gas chamber 1218. After the pressure in the medicament container gas chamber 1218 overcomes the resistance of the elastomeric member 1217 against the interior of the medicament container body 1210, the elastomeric member 1217 moves from the first elastomeric member position to the second elastomeric member position. As shown in FIGS. 3 and 4, the elastomeric member 1217 moves from a first elastomeric member position to a second elastomeric member position, thereby expelling the medicament from within the medicament container body 1210. As shown in FIG.

[0065]

[1107] Regulating the build-up of pressure in the drug container gas chamber via the flow restrictor 1450 allows the drug container body 1210 and the delivery member 1216 to be fully deployed before any drug is delivered from the drug container body 1210. Also, in embodiments where the drug has a high viscosity (i.e., a viscosity of about 100 centipoise or more at room temperature) and / or the drug includes a high molecular weight compound of more than about 5 kDa, the flow rate of the drug expelled from the drug container body 1210 can be regulated. In other words, the flow restrictor 1450 can control and reduce the force exerted by the pressurized gas released into the drug container gas chamber on the elastomeric member 1217 (compared to applying the gas pressure released from the gas chamber 1139 directly to the elastomeric member 1217). As a result, the pressure regulated by the flow restrictor 1450 can control the speed and movement of the forward stroke of the elastomeric member 1217, thereby preventing shearing of the high molecular weight compounds in the drug and reducing pain felt by the patient.

[0066]

[1108] The flow restricting member 1450 may be any suitable flow restricting member of the type shown and described herein. For example, in some embodiments, the flow restricting member 1450 may be included within a delivery control mechanism (not shown in FIGS. 2-5) coupled to the medicament container assembly 1200. In some embodiments, the flow restricting member 1450 may be at least partially within the container body 1210. Additionally, the flow restricting member 1450 may include any suitable structure for regulating the flow of pressurized gas into (and / or the pressure therein) the medicament container gas chamber 1218. For example, the flow restricting member 1450 may include a porous material through which a portion of the pressurized gas flows. In other embodiments, the flow restricting member 1450 may include a filter element, a diaphragm element, a single port orifice, a series of single port orifices, a sieve plate element, or an adjustable valve. In some embodiments, the flow restricting member 1450 includes a porous metal or porous ceramic material. The porous material provides multiple passages through the flow restricting member 1450, which prevents clogging if there is foreign matter within the housing 1100. In some embodiments, the flow restricting member 1450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.5 to 3 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting member 1450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.75 to 1.5 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting member 1450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 1 standard cubic centimeters per minute (sccm). As described herein, standard temperature is 60° F. (15.6° C.) and standard pressure is 14.696 psia (101.3 kPa).

[0067]

[1109] Although the drug delivery device 1000 is shown as including a flow restricting member 1450 that receives a flow of pressurized gas from the gas chamber 1139, in other embodiments, the drug delivery device 1000 (and any drug delivery device herein) can define one or more gas flow paths such that the flow restricting member (and thus the drug canister gas chamber 1218) receives a flow of pressurized gas directly from the energy storage member 1400, without passing through the gas chamber 1139 of the housing 1100. Similarly, although the gas flow paths from the energy storage member 1400 to the gas chamber 1139 and the drug canister gas chamber 1218 are shown and described as being in series, in other embodiments the gas flow paths can be in parallel.

[0068]

[1110] Once the elastomeric member 1217 has advanced from the first elastomeric member position to the second elastomeric member position to dispense a dose of medicament, the retracting member 1351 is activated to exert a force F2 in a second direction opposite the first direction, as shown by arrow DD in FIG. 5, to return the container body 1210 and the delivery member 1216 to the retracted position. In some embodiments, the retracting member 1351 generates a force F2 that is greater than the force F1 from the pressurized gas released into the gas chamber 1139. In some embodiments, the retracting member 1351 generates a force sufficient to move the medicament container body 1210 and the delivery member 1216 as the released pressurized gas moves out of the gas chamber 1139. For example, the released pressurized gas may be released from the gas chamber 1139 and move to a second gas chamber in the housing 1100, such that the remaining force exerted on the medicament container assembly 1200 in the first direction, as shown by arrow AA, is less than the force F2 exerted by the retracting member 1351. Although the drug delivery device 1000 has been described as maintaining the released pressurized gas within the housing 1100 by either maintaining the released pressurized gas within the gas chamber 1139 or by moving a portion of the released pressurized gas to a second gas chamber within the housing 1100, in other embodiments, the drug delivery device 1000 may include a gas release mechanism that discharges the released pressurized gas to the external environment (i.e., the external environment outside the housing 1100).

[0069]

[1111] 6-9 are schematic diagrams of a drug delivery device 1000' according to an embodiment in a first configuration, a second configuration, a third configuration, and a fourth configuration, respectively. The drug delivery device 1000' includes a housing 1100', a drug container assembly 1200', an energy storage member 1400', and a flow restriction member 1450', which are similar to the corresponding parts of the drug delivery device 1000 described above. The housing 1100' defines a gas chamber 1139' for receiving pressurized gas from the energy storage member 1400'. The housing 1100' further defines an opening 1112' (see FIG. 9) extending through a wall of the housing 1100' to fluidly connect the gas chamber 1139' with an external environment outside the housing 1100'. The drug delivery device 1000' further includes a gas release mechanism 1320' and a retraction member 1351' for returning the drug container assembly 1200' to a retracted (or retracted) position.

[0070]

[1112] The retraction member 1351' may be a retraction spring or any other energy storage member. In this manner, the retraction member 1351' is configured to return the medicament container 1200' to its first position (e.g., the retracted position) after deployment. In some embodiments, the retraction member 1351' may be further configured to maintain the medicament container 1200' in the retracted position before gas pressure is provided to the gas chamber 1139'.

[0071]

[1113] The medicament container assembly 1200 includes an elastomeric member 1217 (i.e., a plunger) that seals the medicament within the container body 1210. In some embodiments, the medicament container assembly 1200' includes a delivery member 1216' coupled to the container body 1210' through which the medicament can be delivered. For example, in some embodiments, the delivery member 1216' includes a needle, a nozzle, a mouthpiece, etc. In some embodiments, the medicament container assembly 1200' can be a pre-filled syringe with a fixed needle of the type shown and described herein. When the medicament container body 1210' moves from the retracted position to the deployed position, the delivery member 1216' is configured to extend from the housing 1100' to dispense the medicament to the user.

[0072]

[1114] The energy storage member 1400' is disposed within the housing 1100' and is configured to deliver pressurized gas into the gas chamber 1139' to generate a force F1 to deploy the delivery member 1216' and deliver the contents of the medicament container 1200' when the energy storage member 1400' is actuated. The energy storage member 1400' may be similar to the energy storage member 1400 (or any energy storage member described herein). The flow restricting member 1450' may be similar to the flow restricting member 1450 (or any flow restricting member or delivery control mechanism described herein) and may regulate the flow of pressurized gas into the medicament container assembly 1200'. For example, in some embodiments, the flow restricting member 1450' may be at least partially within the container body 1210' or may be coupled to the container body 1210' via a delivery control mechanism housing. In some embodiments, the flow restricting member 1450' includes a porous metal or porous ceramic material for restricting flow through the flow restricting member 1450'. In some embodiments, the flow restrictor 1450' is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.5 to 3 standard cubic centimeters per minute (sccm). In some embodiments, the flow restrictor 1450' is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.75 to 1.5 standard cubic centimeters per minute (sccm). In some embodiments, the flow restrictor 1450' is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 1 standard cubic centimeters per minute (sccm).

[0073]

[1115] When the drug delivery device 1000' is actuated, the energy storage member 1400' is activated and releases pressurized gas into the gas chamber 1139' as shown by arrow A in Fig. 7. In this initial state shown in Fig. 6, the gas release mechanism 1320' is in a closed position, such that the opening 1112' of the housing 1100' is sealed and the gas chamber 1139' is isolated from the external environment outside the housing 1100'. As the released pressurized gas fills the gas chamber 1139', pressure builds up and generates a first force F1 that moves the drug container body 1210' of the drug container assembly 1200' from a first position (e.g., a retracted position) to a second position (e.g., a deployed position) in a first direction indicated by arrow BB shown in Fig. 7.

[0074]

[1116] When the medicament container body 1210' and the delivery member 1216' are in the deployed position, the released pressurized gas passes (or continues to pass) through the flow restricting member 1450' and into the medicament container gas chamber 1218' of the medicament container 1200', as shown by arrows CC in FIG. 8. The medicament container gas chamber 1218' is defined between the flow restricting member 1450' and the elastomeric member 1217'. As the released pressurized gas passes through the flow restricting member 1450', pressure builds up in the medicament container gas chamber. After the pressure in the medicament container gas chamber 1218' overcomes the resistance of the elastomeric member 1217' against the interior of the medicament container body 1210', the elastomeric member 1217' moves from the first elastomeric member position to the second elastomeric member position. As shown in Figures 7 and 8, the elastomeric member 1217' moves from the first elastomeric member position to the second elastomeric member position, thereby expelling the medicament from within the medicament container body 1210'.

[0075]

[1117] By regulating the pressure build-up in the drug container gas chamber 1218' via the flow restrictor 1450', the drug container body 1210' and the delivery member 1216' can be fully deployed before any drug is delivered from the drug container body 1210'. Also, in embodiments where the drug has a high viscosity (i.e., a viscosity of about 100 centipoise or more at room temperature) and / or the drug includes a high molecular weight compound of more than about 5 kDa, the flow rate of the drug expelled from the drug container body 1210' can be regulated. In other words, the flow restrictor 1450' can control and reduce the force that the released pressurized gas exerts on the elastomeric member 1217' (compared to applying the pressurized gas released in the gas chamber 1139' directly to the elastomeric member 1217'). As a result, the pressure regulated by the flow restrictor 1450' can control the movement and speed of the forward stroke of the elastomeric member 1217', thereby preventing shearing of the high molecular weight compounds in the drug and reducing pain felt by the patient.

[0076]

[1118] When the elastomeric member 1217' advances from the first elastomeric member position to the second elastomeric member position to dispense a dose of drug, the gas release mechanism 1320' is actuated from a closed position to an open position to unseal the opening 1112' and fluidly connect the gas chamber 1139' to the external environment (e.g., the ambient environment surrounding the user of the drug delivery device 1000'). In some embodiments, the gas release mechanism 1320' is operably coupled to the elastomeric member 1217' such that when the elastomeric member 1217' reaches the end of its stroke at the second elastomeric member position, the gas release mechanism 1320' is disposed in the open position. In some embodiments, the gas release mechanism 1320' is a manually operated valve that can be placed in the open position by the user. For example, in some embodiments, the user can manually press a button or pull the gas release mechanism 1320' upwards after the injection is completed. In some embodiments, the gas release mechanism 1320' is operably coupled to a controller that detects the end of the travel stroke of the elastomeric member 1217', and the gas release mechanism 1320' is configured to actuate to an open position in response to a signal from the controller.

[0077]

[1119] After fluidly connecting the gas chamber 1139' with the external environment, the released pressurized gas is exhausted out of the opening 1112', thereby depressurizing the gas chamber 1139'. Further, the retracting member 1351' can be activated to move the medicament container body 1210' and the delivery member 1216' from the deployed position back to the retracted position. Specifically, the retracting member 1351' generates a force F2 in a second direction opposite to the first direction, as shown by arrow DD in FIG. 9, to return the container body 1210' and the delivery member 1216' to the retracted position. The force F2 applied by the retracting member 1351 is selected to sufficiently act against the frictional forces between the medicament container assembly 1200' and the housing 1100' and / or to act against the released pressurized gas remaining in the gas chamber 1139'.

[0078]

[1120] In some embodiments, any of the drug delivery devices shown and described herein can include a sensing unit that detects the movement and location of the elastomeric member and generates an output (based on the detected movement) related to the delivery rate. In some embodiments, the sensing unit can be included in an electronic circuit system that generates a visual or audible output, such as any of the electronic circuit systems described in PCT 6413. In some embodiments, the sensing unit generates a wireless signal to communicate with an accessory device, a mobile device, a remote server, or a remote network.

[0079]

[1121] 10-12 are schematic diagrams of a drug delivery device 2000 according to an embodiment in a first configuration, a second configuration, and a third configuration, respectively. The drug delivery device 2000 includes a housing 2100, a drug container assembly 2200, an energy storage member 2400, and a flow restricting member 2450, which are similar to the corresponding parts of the drug delivery device 1000 described above. The drug delivery device 2000 also includes an electronic circuit system 2104 coupled to the housing 2100. The electronic circuit system 2104 includes a sensing unit 2105, a delivery module 2106, and an output module 2107. The sensing unit 2105 includes an emitter 2108 and a receiver 2109 to detect the delivery rate of the drug, as described below.

[0080]

[1122] The housing 2100 defines a gas chamber 2139 that receives pressurized gas from the energy storage member 2400. The housing 2100 further includes an opening (not shown) extending through a wall of the housing 2100 to fluidly connect the gas chamber 2139 to an external environment outside the housing 2100. The drug delivery device 2000 further includes a gas release mechanism 2320 and a retraction member 2351 configured to return the drug container assembly 2200 to a retracted position after a dose of drug is dispensed. The gas release mechanism 2320 may be any suitable gas release mechanism described herein and the retraction member 2351 may be any suitable retraction member described herein.

[0081]

[1123] The medicament container assembly 2200 has a medicament container body 2210 that defines a volume that contains the medicament (i.e., is filled or partially filled with the medicament). The medicament container body 2210 includes a transparent or translucent wall configured to transmit a light beam. In some embodiments, the medicament container body 2210 is made of glass or plastic. A distal end portion of the medicament container body 2210 includes a neck or opening through which the medicament can be delivered. In some embodiments, the medicament container assembly 2200 includes a delivery member 2216 coupled to the container body 2210 through which the medicament can be delivered. For example, in some embodiments, the delivery member 2216 includes a needle, a nozzle, a mouthpiece, etc. In some embodiments, the medicament container assembly 2200 can be a pre-filled syringe with a fixed needle of the type shown and described herein.

[0082]

[1124] The medicament container assembly 2200 includes an elastomeric member 2217 (i.e., a plunger) that seals the medicament within the container body 2210. The elastomeric member 2217 is configured to move within the container body to expel the medicament from the medicament container assembly 2200. The elastomeric member 2217 may be of any design or form suitable for contact with a medicament as described herein.

[0083]

[1125] The energy storage member 2400 is disposed within the housing 2100 and is configured to deliver pressurized gas into the gas chamber 2139 upon actuation of the energy storage member 2400 to generate force to deploy the delivery member 2216 and deliver the contents of the medicament container 2200. The energy storage member 2400 may be similar to the energy storage member 1400 (or any energy storage member described herein). The flow restriction member 2450 may be similar to the flow restriction member 1450 (or any flow restriction member or delivery control mechanism described herein) and may regulate the flow of pressurized gas into the medicament container assembly 2200.

[0084]

[1126] Upon actuation of the drug delivery device 2000, the energy storage member 2400 is activated and releases pressurized gas into the gas chamber 2139. The pressurized gas released into the gas chamber 2139 deploys the drug container body 2210 and the delivery member 2216, such that at least a portion of the delivery member 2216 extends from the housing 2100. The released pressurized gas passes (or continues to pass through) the flow restricting member 2450 and into the drug container gas chamber 2218 of the drug container assembly 2200. The drug container gas chamber 2218 is defined between the flow restricting member 2450 and the elastomeric member 2217. As the released pressurized gas passes through the flow restricting member 2450, pressure builds up in the drug container gas chamber. After pressure within the medicament container gas chamber 2218 overcomes the resistance of the elastomeric member 2217 against the interior of the medicament container body 2210, the elastomeric member 2217 moves from the first elastomeric member position (FIG. 10) to the second elastomeric member position (FIG. 12) to dispense a dose of medicament from within the medicament container body 2210. As shown in FIG. 11, the elastomeric member may pass through one or more intermediate positions as it moves from the first elastomeric member position to the second elastomeric member position.

[0085]

[1127] To detect the position of the elastomeric member 2217 within the medicament container body 2210, the medicament delivery device 2000 includes a sensing unit 2105 having an emitter 2108 and a receiver 2109. The emitter 2108 includes a set of emitter modules 2108a, 2108b, 2108c, 2108d operable to generate a light beam. The receiver 2109 includes a set of receiver modules 2109a, 2109b, 2109c, 2109d operable to detect the reception of the light beam. As shown in FIG. 10, the emitter 2108 and receiver 2109 are positioned on either side of the medicament container body 2210 when the medicament container body 2210 and the delivery member 2216 are in a deployed position (e.g., distal to the housing and operable to dispense a medicament to a user). In some embodiments, the medicament container assembly 2200 may include or be coupled to a carrier (not shown in FIGS. 10-12, but may be similar to carrier 4360 described below) that moves the medicament container body 2210 within the housing 2100. In some embodiments, the emitter 2108 and receiver 2109 may be coupled to (or may be within) the carrier. In some embodiments, the emitter 2108 and receiver 2109 extend from a first end portion 2211 to a second end portion 2212 of the medicament container body 2210 along either side of the medicament container body 2210. In some embodiments, the emitter modules 2108a, 2108b, 2108c, 2108d and the receiver modules 2109a, 2109b, 2109c, 2109d are spaced along the length of the medicament container body 2210 between the first end portion 2211 and the second end portion 2212.

[0086]

[1128] To detect the current position of the elastomeric member 2217, each of the plurality of emitter modules 2108a, 2108b, 2108c, 2108d is activated to generate a light beam, and each of the plurality of receiver modules 2109a, 2109b, 2109c, 2109d detects whether it has received a light beam (and / or the magnitude of the light beam) from a corresponding one of the plurality of emitter modules 2108a, 2108b, 2108c, 2108d. For example, as shown in FIG. 11, each of the receiver modules 2109a, 2109b, 2109c, 2109d is activated to generate a light beam, and receiver module 2109c generates a signal indicating that it has not received a light beam from emitter module 2108c (or that the magnitude of the light received by receiver module 2109c is below a predefined threshold). Alternatively, one skilled in the art will appreciate that the light receiving modules 2109a, 2109b, 2109d may be configured to generate a signal indicative of receiving a light beam, while the light receiving module 2109c does not generate a signal. The sensing unit 2105 is configured to receive a signal from each of the light receiving modules 2109a, 2109b, 2109c, 2109d and determine which of the light receiving modules 2109a, 2109b, 2109c, 2109d did not receive a light beam (or received an insufficient amount of light), indicating that the elastomeric member 2217 is blocking the light transmission path. In some embodiments, rather than detecting the presence or absence of a signal indicative of receipt of a light beam, the delivery module 2106 coupled to the sensing unit 2105 is configured to monitor changes in the magnitude of light received by one or more light receiving modules 2109a, 2109b, 2109c, 2109d to determine the current location of the elastomeric member 2217. The emitters 2108 and light receiving modules 2109 are arranged in pairs along the longitudinal axis of the medicament container assembly 2200 such that the position of the elastomeric member 2217 within the container body 2210 can be determined.In some embodiments, the emitter modules 2108a, 2108b, 2108c, 2108d are operable to transmit at least one wavelength in the ultraviolet, visible, or infrared spectrum, and the receiver modules 2109a, 2109b, 2109c, 2109d are operable to receive the at least one wavelength and generate an electronic signal indicative of receipt of the at least one wavelength or an electronic signal indicative of the magnitude of the at least one wavelength received. In some embodiments, the receiver modules 2109a, 2109b, 2109c, 2109d are configured to transmit an infrared beam. In some embodiments, the receiver modules 2109a, 2109b, 2109c, 2109d are configured to transmit a light beam at a wavelength that does not adversely alter the drug stored within the drug container body 2210.

[0087]

[1129] Specifically, the drug delivery device 2000 further includes a delivery module 2106 coupled to the sensing unit 2105 to determine which light receiving module 2109a, 2109b, 2109c, 2109d generated a signal (e.g., received a light beam) and uses this information to determine the current location of the elastomeric member 2217 within the drug container body 2210. In some embodiments, the delivery module 2106 is implemented in at least one of a memory or a processing device. Once the current location of the elastomeric member 2217 is determined, the information may be stored in the memory module 2111 or transmitted to an output module 2107, such as a display or speaker. In some embodiments, the display is an LCD display configured to display text and / or graphic images. In some embodiments, the display is an array of LED lights configured to light up to indicate the current location of the elastomeric member 2217 or to indicate the overall progress of drug delivery. For example, an array of 10 LED lights may be used, with the first 5 LED lights illuminated to indicate that 50% of the medication delivery process is complete. In some embodiments, the output module 2107 includes a speaker operable to generate one or more audible tones or voice notifications. For example, the output module 2107 may be configured to generate a first audible tone while medication is being dispensed and a second audible tone when dispensing is complete. As another example, the output module 2107 may be configured to generate an audio countdown of the time remaining until completion or the current percentage of medication delivered.

[0088]

[1130] In some embodiments, the delivery module 2106 includes a prediction module 2110 to determine a travel profile of the elastomeric member 2217. The travel profile includes at least one of a current position of the elastomeric member, a travel speed of the elastomeric member, a delivery rate of the medicament from the medicament container body 2210, or a time remaining to complete delivery of a dose of the medicament. The prediction module 2110 is configured to calculate a rate of travel (e.g., a travel velocity) of the elastomeric member 2217 based on a time difference between two light receiving modules 2109a, 2109b, 2109c, 2109d that do not receive a light beam (or receive an amount of light below a threshold) and a known distance between the two light receiving modules 2109a, 2109b, 2109c, 2109d. The prediction module 2110 is configured to calculate a delivery rate of the drug based on the rate of advancement of the elastomeric member 2217 and the diameter of the drug container body 2210. In some embodiments, the prediction module 2110 can determine one or more of an elapsed time of the drug delivery process, an estimated time remaining until completion of the drug delivery process, or a remaining percentage of the drug to be dispensed remaining. In some embodiments, the prediction module 2110 is coupled to the memory module 2111 and operable to retrieve stored values ​​related to a stored energy value of the energy storage member 2400, a resistance of the flow restricting member 2450, a stroke advancement distance of the elastomeric member 2217 to complete delivery of a dose of drug in the drug container body 2210, and / or a total amount of drug in the dose of drug in the drug container body 2210. In some embodiments, delivery of the drug may take longer than initially estimated, and the prediction module 2110 is configured to update the time remaining to completion or pause the time remaining to completion until the elastomeric member 2217 reaches a scheduled position associated with the reaming time to completion.

[0089]

[1131] In some embodiments, the electronic circuit system 2104 is configured to perform a series of steps to determine the position of the elastomeric member within the medicament container body 2210. The electronic circuit system 2104 is operable to control the emitter 2108 to emit a first light beam using a first emitter module of the emitter modules 2108a, 2108b, 2108c, 2108d through the medicament container body 2210 toward a corresponding first receiver of the light receiving modules 2109a, 2109b, 2109c, 2109d. The first receiver is configured to generate a first electronic signal associated with a magnitude of the received first light beam. The electronic circuit system 2104 is operable to control the emitter 2108 to emit a second light beam through the drug container body 2210 using a second emitter module (different from the first emitter module) of the emitter modules 2108a, 2108b, 2108c, 2108d toward a corresponding second receiver (different from the first receiver) of the light receiving modules 2109a, 2109b, 2109c, 2109d. The second receiver is configured to generate a second electronic signal associated with a magnitude of the received second light beam. The electronic circuit system 2104 detects at least one of the first electronic signal or the second electronic signal and determines a position of the elastomeric member 2217 based on a comparison of the first electronic signal and the second electronic signal. In some embodiments, the electronic circuit system 2104 is operable to determine the rate of advancement of the elastomeric member 2217, the rate of delivery of the drug from the drug container body 2210, and / or the remaining completion time to complete delivery of a dose of the drug from the drug container body 2210 based on the time difference between when the first electronic signal falls below a threshold and when the second electronic signal falls below a threshold.

[0090]

[1132] Although the sensing unit 2105 is shown as including an emitter 2108 (having multiple optical emitters) and a receiver 2109 (having multiple optical receivers), in other embodiments, the sensing unit can include any suitable mechanism to detect the position of the elastomeric member within the medicament container body 2210 and generate an electronic signal associated with at least one of the position, velocity, or acceleration of the elastomeric member 2217 to detect the delivery rate of the medicament. For example, in some embodiments, any of the medicament delivery devices described herein can include a sensing unit that detects the position of the elastomeric member based on inductance. In such a system, the elastomeric member can include a ferromagnetic core and the sensor unit can include a wire coil that detects the movement of the elastomeric member. In other embodiments, any of the medicament delivery devices described herein can include a sensing unit that detects a change in the refractive index of the contents (e.g., medicament, elastomeric member, or released pressurized gas) within the medicament container body 2210 to determine the current position of the elastomeric member.

[0091]

[1133] As described herein, the delivery of highly viscous drugs (i.e., having a viscosity of about 100 centipoise or more at room temperature) can be improved by adjusting the flow to ensure that the flow rate from the delivery member is below a certain threshold to prevent shearing of high molecular weight compounds in the drug and / or reduce pain experienced by the patient. In some embodiments, the flow rate of the drug is less than about 0.2 mL / sec (or, in some embodiments, between 0.05 mL / sec and 0.01 mL / sec). As a result of the reduced flow rate, the drug delivery process takes about 30-60 seconds to complete, and in some cases, about 60-120 seconds. In some embodiments, the drug delivery device can include two or more drug containers, each with a delivery member capable of delivering the drug therein. Such embodiments can accommodate the delivery of viscous drugs, the delivery of large volumes of drugs (e.g., doses greater than 1 mL) by delivering portions of the total dose in parallel, and / or the parallel delivery of two different drugs at the same time. Thus, the use of two or more drug containers operating to dispense in parallel can reduce the overall delivery time of large volumes or highly viscous drugs.

[0092]

[1134] 13-16 are schematic diagrams of a drug delivery device 3000 according to an embodiment in a first, second, third and fourth configuration, respectively. The drug delivery device 3000 includes a housing 3100, a first medicament container assembly 3200A, a first flow restricting member 3450A, a second medicament container assembly 3200B, a second flow restricting member 3450B, an energy storage member 3400 and a retraction member 3351.

[0093]

[1135] The housing 3100 defines a gas chamber 3139 that receives pressurized gas from the energy storage member 3400. The gas chamber 3139 can be of any suitable size and shape, for example, a portion of a volume defined by the housing 3100, within which a portion of the drug container is disposed. The housing 3100 can be of any suitable size, shape, or configuration, and can be made of any suitable material. For example, in some embodiments, the housing 3100 is a multiple part assembly formed from a plastic material and defines a substantially rectangular shape when assembled. In other embodiments, the housing 3100 can have a substantially cylindrical shape.

[0094]

[1136] Each of the medicament container assemblies 3200A, 3200B includes a respective medicament container body 3210A, 3210B. Each of the container bodies 3210A, 3210B defines a volume that contains a medicament (i.e., is filled or partially filled with a medicament). In some embodiments, the medicament in each of the medicament container bodies 3210A, 3210B is of the same medicament dosage form and dose. In some embodiments, the medicament is of a different dosage form and / or has a different dosage (e.g., different amounts of medicament) in each of the medicament container bodies 3210A, 3210B. A distal end portion of each of the medicament container bodies 3210A, 3210B each includes a neck or opening through which the medicament can be delivered. In some embodiments, the medicament container assemblies 3200A, 3200B each include a corresponding delivery member 3216A, 3216B coupled to a respective medicament container body 3210A, 3210B through which the medicament can be delivered. For example, in some embodiments, the delivery member 3216A, 3216B includes a needle, a nozzle, a mouthpiece, etc. In some embodiments, the medicament container assemblies 3200A, 3200B can be a pre-filled syringe with a fixed needle of the type shown and described herein. In some embodiments, the first medicament container body 3210A and the second medicament container body 3210B are positioned in a non-coaxial arrangement within the housing 3100.

[0095]

[1137] The first medicament container assembly 3200A includes a first elastomeric member 3217A (i.e., a plunger) that seals a first medicament within the first medicament container body 3210A. The first elastomeric member 3217A is configured to move within the first medicament container body 3210A to inject the first medicament from the first medicament container assembly 3200A. The second medicament container assembly 3200B includes a second elastomeric member 3217B (i.e., a plunger) that seals a second medicament within the second medicament container body 3210B. The second elastomeric member 3217B is configured to move within the second medicament container body 3210B to inject the second medicament from the second medicament container assembly 3200B. Each of the first elastomeric member 3217A and the second elastomeric member 3217B may be of any design or formulation as described herein.

[0096]

[1138] Each of the medicament container assemblies 3200A, 3200B includes a proximal end portion 3214A, 32214B configured to translate within the housing 3100 to move the corresponding medicament container assembly 3200A, 3200B between a first position and a second position. Although the first medicament container assembly 3200A and the second medicament container assembly 3200B are shown as being disposed within the housing 3100 without a carrier, in other embodiments, the medicament container assemblies 3200A, 3200B can be disposed within or coupled to a carrier to facilitate movement within the housing 3100. For example, in some embodiments, each of the container bodies 3210A, 3210B can be coupled to a separate carrier (not shown in FIGS. 13-16, but which may be similar to the carrier 4360 described below) that independently moves each of the medicament container bodies 3210A, 3210B within the housing 3100. In other embodiments, each of the container bodies 3210A, 3210B can be coupled to a single carrier that moves both medicament container bodies 3210A, 3210B together within the housing 3100. The proximal portions 3214A, 3214B of the medicament container assemblies 3200A, 3200B (and carrier, if any) define a portion of the boundary of the gas chamber 3139. In this manner, when pressurized gas is delivered into the gas chamber 3139, the internal pressure creates a force on the proximal portions 3214A, 3214B to move the medicament container bodies 3210A, 3210B simultaneously from the retracted position to the deployed position.

[0097]

[1139] Specifically, an energy storage member 3400 is disposed within the housing 3100 and configured to deliver pressurized gas into the gas chamber 3139, as shown by arrow AA in Figure 13. Upon actuation of the energy storage member 3400, the released pressurized gas generates a force F1 to deploy the delivery members 3216A, 3216B and deliver the contents from each of the drug containers 3210A, 3210B. The energy storage member 3400 may be any suitable member or device described herein.

[0098]

[1140] The retraction assembly 3351 may be a retraction spring or any other energy storage member. In this manner, the retraction assembly 3351 is configured to return the first medicament container assembly 3200A and the second medicament container assembly 3200B to a first position (e.g., a retracted position) after deployment, as described in further detail herein. In some embodiments, the retraction assembly 3351 may include a first retraction member and a second retraction member. The first retraction member may be coupled to the first medicament container assembly 3200A to maintain the first medicament container assembly 3200A in the retracted position before gas pressure is provided to the gas chamber 3139, and to return the first medicament container assembly 3200A to the retracted position after delivery of the medicament, as described below. A second retraction member can be coupled to the second medicament container assembly 3200B to maintain the second medicament container assembly 3200B in a retracted position before gas pressure is supplied to the gas chamber 3139, and to return the second medicament container assembly 3200B to the retracted position after delivery of the medicament, as described below.

[0099]

[1141] When the medicament container body 3210A, 3210B and the delivery member 3216A, 3216B are in the deployed position, the released pressurized gas passes (or continues to pass) through either the first flow restriction member 3450A or the second flow restriction member 3450B (or both). The released pressurized gas passing through the first flow restriction member 3450A enters the first medicament container gas chamber 3218A of the first medicament container assembly 3200A as shown by arrow CC1 in FIG. 15. The first medicament container gas chamber is defined between the first flow restriction member 3450A and the first elastomeric member 3217A. The released pressurized gas passing through the second flow restriction member 3450B enters the second medicament container gas chamber 3218B of the second medicament container assembly 3200B as shown by arrow CC2 in FIG. 15. A second medicament container gas chamber is defined between the second flow restricting member 3450B and the second elastomeric member 3217B.

[0100]

[1142] As the released pressurized gas accumulates in the first and second medicament container gas chambers, the built up pressure overcomes the resistance associated with the first and second elastomeric members 3217A, 3217B. As shown in Figures 14 and 15, the first elastomeric member 3217A moves from a first elastomeric member position to a second elastomeric member position within the first medicament container body 3210A to expel a first medicament, and the second elastomeric member 3217B moves from a first elastomeric member position to a second elastomeric member position within the second medicament container body 3210B to expel a second medicament.

[0101]

[1143] By regulating the pressure build-up in each of the first and second drug container gas chambers via the flow restricting members 3450A, 3450B, the first and second drug container bodies 3210A, 3210B and the delivery members 3216A, 3216B can be fully deployed prior to delivery of substantially any drug from either of the drug container bodies 3210A, 3210B. Also, in embodiments where the drug has a high viscosity (i.e., has a viscosity of about 100 centipoise or more at room temperature) and / or comprises a high molecular weight compound of greater than about 5 kDa, the flow rate of the drug expelled from the drug container body 1210 can be regulated. In other words, the flow restricting members 3450A, 3450B can control and reduce the force exerted by the released pressurized gas on the elastomeric members 3217A, 3217B, respectively. As a result, the pressure regulated by the flow restricting members 3450A, 3450B can control the movement and speed of the forward stroke of each of the elastomeric members 3217A, 3217B, thereby preventing shearing of high molecular weight compounds in the medication and reducing pain experienced by the patient.

[0102]

[1144] The flow restricting members 3450A, 3450B may be any suitable flow restricting member of the type shown and described herein. For example, in some embodiments, the flow restricting member may be included within a delivery control mechanism (not shown in FIGS. 13-16) coupled to each medicament container assembly 3200A, 3200B. In some embodiments, the flow restricting member may be at least partially within the container body. Furthermore, the flow restricting member may include any suitable structure for regulating the flow of (and / or pressure within) the pressurized gas into the respective medicament container gas chamber. For example, the flow restricting member may include a porous material through which a portion of the pressurized gas flows.

[0103]

[1145] In some embodiments, the flow restricting members 3450A, 3450B can include a filter element, a diaphragm element, a single port orifice, a series of single port orifices, a multi-port element, or an adjustable valve. In some embodiments, the flow restricting members 3450A, 3450B include a porous metal or porous ceramic material. The porous material provides multiple passages through the flow restricting members 3450A, 3450B, which prevents clogging if there is foreign matter within the housing 3100. In some embodiments, the flow restricting members 3450A, 3450B are each calibrated to have a flow rate of approximately 0.5 to 3 standard cubic centimeters per minute (sccm) with nitrogen gas (N2) at 30 psig (inlet side) and atmosphere (outlet side) at standard temperature and pressure. In some embodiments, the flow restrictors 3450A, 3450B are each calibrated with nitrogen gas (N2) at 30 psig (inlet side) to atmosphere (outlet side) at standard temperature and pressure to have a flow rate of about 0.75 to 1.5 standard cubic centimeters per minute (sccm). In some embodiments, the flow restrictors 3450A, 3450B are each calibrated with nitrogen gas (N2) at 30 psig (inlet side) to atmosphere (outlet side) at standard temperature and pressure to have a flow rate of about 1 standard cubic centimeters per minute (sccm).

[0104]

[1146] Additionally, in some embodiments, the flow restrictor 3450A associated with the first medicament container assembly 3200A may be different from the flow restrictor 3450B associated with the second medicament container assembly 3200B. For example, if the medicament in the first medicament container assembly 3200A is different (e.g., different viscosity) from the medicament in the second medicament container assembly 3200B, the characteristics of the two flow restrictors (e.g., nominal pore size, flow rate rating, etc.) may be different. In other embodiments, if the medicament in the first medicament container assembly 3200A is different (e.g., different viscosity) from the medicament in the second medicament container assembly 3200B and it is desired to dispense the two medicaments sequentially (e.g., dispense the second medicament after completion of the first medicament), the second medicament container assembly 3200B may be provided with a flow restrictor 3450B, but the first medicament container assembly 3200A is not provided with a flow restrictor.

[0105]

[1147] As the elastomeric members 3217A, 3217B advance from their respective first elastomeric member positions to their second elastomeric member positions and a dose of medicament is dispensed, the retraction member 3351 is activated to exert a force F2 in a second direction opposite the first direction, as shown by arrow DD in FIG. 16, to return the medicament container body 3210A, 3210B and the delivery member 3216A, 3216B to the retracted position. In some embodiments, the retraction member 3351 generates a force F2 greater than the force F1 generated by the released pressurized gas in the gas chamber 3139. In some embodiments, the retraction member 3351 generates a force sufficient to move the medicament container body 3210A, 3210B and the delivery member 3216A, 3216B as the released pressurized gas moves out of the gas chamber 3139 via the valve portion 3320 coupled to the housing 3100.

[0106]

[1148] In some embodiments, one or both of the elastomeric members 3217A, 3217B may be operably coupled to a gas release mechanism (not shown in FIGS. 10-12, but may be similar to a valve portion coupled to the rocker mechanism 6350, which may also be referred to as a rocker mechanism, described below with reference to FIGS. 58 and 59). The gas release mechanism is configured to release pressurized gas from the gas chamber 3139 to a second chamber of the housing 3100 and / or to the external environment. In this manner, the force F1 may be reduced to a point where the force F2 generated by the retraction member 3351 is greater than the force F1, thereby retracting the medicament container body 3210A, 3210B and the delivery member 3216A, 3216B.

[0107]

[1149] In some embodiments, the drug delivery can be an autoinjector having a piston-less delivery system in which a force exerted by a gas can move the drug container relative to the housing and an elastomeric member relative to (e.g., within) the drug container. For example, FIGS. 17-54 show a medical injector 4000 (also referred to as an "autoinjector," "injector," or "device") according to an embodiment. The medical injector 4000 is a gas-based autoinjector configured to deliver a drug contained within a pre-filled syringe 4200 as described herein. The components of the medical injector 4000 will now be described, followed by a description of the operation of the medical injector 4000. Certain aspects of the medical injector 4000 are similar or substantially the same as the medical injectors described in PCT Nos. 4345, 0040, 6413, and U.S. patent application Ser. No. 13 / 357,935, entitled "MEDICAMENT DELIVERY DEVICES FOR ADMINISTRATION OF A MEDICAMENT WITHIN A PREFILLED SYRINGE" filed on Jan. 25, 2012 (now U.S. Patent No. 9,084,849) (hereinafter referred to as the "'849 Patent"), the disclosures of each of which are incorporated herein by reference in their entireties.

[0108]

[1150] The medical injector 4000 includes a housing 4100 (see, e.g., FIGS. 20 and 21), a system actuation assembly 4500 (see, e.g., FIGS. 24 and 25), a drug container assembly 4200 (see, e.g., FIGS. 34 and 36), a drug delivery mechanism 4300 (see, e.g., FIGS. 30-34), a base 4510 (or actuator, see, e.g., FIGS. 39 and 40), and a safety lock 4700 (see, e.g., FIGS. 37 and 38). As shown in FIGS. 18-21, the housing 4100 has a proximal end portion 4101 and a distal end portion 4102. The housing 4100 defines a first status indicator aperture 4130 and a second status indicator aperture 4160. A first status indicator aperture 4130 defined by the housing 4100 is on a first side of the housing 4100 and a second status indicator aperture 4160 of the housing 4100 is on a second side of the housing 4100. The status indicator apertures 4130, 4160 allow a patient to monitor the status and / or contents of the medication container 4200, the carrier 4360, and the medication contained within the housing 4100. For example, by visually inspecting the status indicator apertures 4130, 4160, a patient can determine whether the medication container 4200 contains a medication and / or whether the medication has been dispensed.

[0109]

[1151] As shown in Figures 17, 18, and 20, the housing 4100 includes an electronics system cavity 4153 that can house any of the electronics described herein and / or any of the electronics systems described in PCT No. 8433. Although the housing 4100 is shown with an electronics system cavity 4153, in some embodiments, the medical injector 4000 may not include an electronics or electronics system cavity 4153. In some embodiments, the housing 4100 can include a label or indicia that hides or otherwise highlights the status indicator apertures 4130, 4160, and / or contents viewed therethrough. For example, in some embodiments, the housing 4100 can include a label (not shown) having a border that surrounds at least a portion of the status indicator aperture 4130, the status indicator aperture 4160 (or both). In some embodiments, the label may include an indicator color that alerts the user (or assists the user in determining) whether the medication has the appropriate color, whether a portion of the carrier 4360 is visible through a window, etc.

[0110]

[1152] As shown in Figures 20, 21 and 27, the housing 4100 defines a gas container cavity 4151 and a medicament cavity 4139. The gas container cavity 4151 is configured to receive the gas container 4410 and a portion of the system actuator assembly 4500 (e.g., the release member 4550 and the spring 4576 as shown in Figures 24 and 25). A proximal end portion of the gas container 4151 is configured to receive the gas container retaining member 4180 of the proximal cap 4110 of the housing 4100, as described in further detail herein. The gas container cavity 4151 is in fluid communication with the medicament cavity 4139 via a gas passageway 4135 defined in the housing 4100, as described in further detail herein.

[0111]

[1153] The medicament cavity 4139 is configured to receive the medicament container assembly 4200 and at least a portion of the medicament delivery mechanism 4300. Specifically, as described below, the medicament delivery mechanism 4300 includes a carrier assembly 4390 (see, e.g., Figures 24, 25, and 30-33) and a gas vent assembly 4310 (see, e.g., Figures 22, 23, and 27A, 35, and 36A-36C) movably disposed within the medicament cavity 4139. The medicament cavity 4139 is in fluid communication with an area outside the housing 4100 via the needle aperture 4105 and the vent opening 4112.

[0112]

[1154] The proximal end portion 4101 of the housing 4100 includes a proximal cap 4110 (see, e.g., FIGS. 22, 23, and 27A). The proximal cap 4110 includes a gas container holding member 4180 configured to receive and / or hold a gas container 4410 containing pressurized gas, as shown in FIGS. 22-25. Upon actuation of the medical injector 4000, pressurized gas from the gas container 4410 is delivered from the gas container cavity 4151 to the medication cavity 4139 via the gas passageway 4135 of the housing 4100. In other words, the gas passageway 4135 places the gas container cavity 4151 in fluid communication with the medication cavity 4139. Thus, the proximal portion of the medication cavity 4139 can be referred to as the housing gas chamber. Similarly, the proximal portion of the cavity 4139 for the medication is a volume into which pressurized gas is delivered to act as a pressurized gas reservoir used to move the carrier 4360 and inject the medication, as described herein.

[0113]

[1155] The proximal cap 4110 also includes a cap cover 4111 coupled to a proximal end portion of the proximal cap 4110 while maintaining a gap 4111a between the proximal end portion of the proximal cap 4110 and the cap cover 4111. The cap cover 4111 prevents the vent opening 4112 from direct external contact and prevents clogging by external foreign objects. The proximal cap 4110 also includes an O-ring 4113 and defines a vent opening 4112. The vent opening 4112 provides a passageway for pressurized gas to be delivered from the medicament cavity 4139 (or a housing gas chamber portion of the medicament cavity 4139) to a volume outside the medical injector 4000. As shown in FIGS. 22 and 23, the proximal end portion of the proximal cap 4110 defines a vent channel 4118 extending laterally away from the vent opening 4112. The vent channel 4118 together with the gap 4111a form a plurality of vent passages that allow the pressurized gas to exit from the drug cavity 4139 to a volume outside the medical injector 4000, thus reducing the force generated by the pressurized gas on the drug delivery mechanism 4300 and / or drug container assembly 4200 to allow the needle to be retracted after injection is completed. As shown in FIG. 27A, the O-ring 4113 in conjunction with the valve portion 4345 of the gas vent assembly 4310 selectively seals the vent opening 4112 during needle insertion and drug delivery.

[0114]

[1156] Although the vent opening 4112 is shown as being defined by and at a proximal face of the proximal cap 4110, in other embodiments, the vent opening 4112 (and any vent openings described herein) may be defined within any suitable portion of the proximal cap or sidewall. For example, in some embodiments, the vent opening 4112 (and any vent openings described herein) may be defined by the proximal cap 4110, but may have a centerline that is non-parallel to the longitudinal axis of the medical injector 4000. In other words, in some embodiments, the vent opening 4112 (and any vent openings described herein) may open toward a side of the medical injector, rather than toward the proximal end as shown. In other embodiments, the vent opening 4112 (and any vent openings described herein) may be defined by any wall and / or surface of the housing 4100.

[0115]

[1157] The proximal cap 4110 includes a guide wall 4115 through which the third (or proximal) member 4340 of the gas vent assembly 4310 moves. Specifically, the guide wall 4115 defines a cylindrical inner wall surface through which the guide surface 4344 (see, e.g., FIGS. 27A and 35) of the first member 4340 slides during operation. The proximal cap 4110 also includes an end surface 4117 against which a portion of the delivery control mechanism (also referred to as a flow restriction assembly) bears when the medical injector 4000 is in the first configuration (i.e., the "storage" state).

[0116]

[1158] As shown in FIG. 21, the distal end portion 4102 of the housing 4100 includes a shoulder portion 4106 having a contact surface and defines a needle aperture 4105. The distal end portion 4102 also includes a base rail groove 4114 and a base retention recess 4134 (see FIGS. 19 and 20). The shoulder portion 4106 is configured to contact a corresponding surface 4365 (see, e.g., FIGS. 21, 32, 41, and 44) ​​of the carrier body 4360 when the needle 4216 is inserted a desired distance. In this manner, the shoulder 4106 can function as an "end stop" or insertion limiting mechanism. The needle aperture 4105 is an opening into which the needle 4216 is disposed when the medical injector 4000 is actuated, as described in further detail herein.

[0117]

[1159] The housing distal end portion 4102 also includes an ejection member contact surface 4126 and defines an ejection member aperture 4145. As shown in FIGURE 27B, the ejection member aperture 4145 receives the distal end portion 4552 of the ejection member 4550 such that an extension 4553 of the ejection member 4550 engages the ejection member contact surface 4126 to prevent activation of the medical injector 4000. The safety lock 4700, its components and functions are described in more detail below.

[0118]

[1160] The distal base retaining recess 4134 (see FIG. 20) is configured to receive the base connection knob 4518 of the actuator 4510 (also referred to herein as the "base 4510"; see, e.g., FIGS. 39 and 40) when the base 4510 is in a first position relative to the housing 4100. The distal base retaining recess 4134 includes an elongated groove extending in a proximal to distal direction such that the base connection knob 4518 can move and translate within the elongated groove. This allows the base retaining recess 4134 to receive the base connection knob 4518 such that the base 4510 can move proximally relative to the housing 4100 in the first position and distally relative to the housing 4100 in the second position. In some embodiments, the base retaining recess 4134 can include a ratchet tooth member that engages the base connection knob 4518 to prevent the base 4510 from moving back in a distal direction.

[0119]

[1161] The base rail groove 4114 receives the guide member 4517 of the base 4510 (see FIGS. 19, 39, and 40). The guide member 4517 of the base 4510 and the base rail groove 4114 of the housing 4100 engage one another to allow the guide member 4517 to slide proximally and / or distally within the base rail groove 4114 while restricting lateral movement of the guide member 4517 of the base 4510. This arrangement allows the base 4510 to move proximally and / or distally relative to the housing 4100 but prevents the base 4510 from moving laterally relative to the housing 4100.

[0120]

[1162] 24 and 25 show an overview of the medicament container assembly 4200, the system actuator assembly 4500, the medicament delivery mechanism 4300, and the flow restriction assembly 4430 (which functions as a delivery control mechanism) of the medical injector 4000. Referring to FIG. 34, the medicament container assembly 4200 includes a container body 4210 having a distal end portion 4213 and a proximal end portion 4212. The container body 4210 defines a volume that contains the medicament (i.e., is filled or partially filled with the medicament). The distal end portion 4213 of the medicament container assembly 4200 includes a neck portion coupled to a needle 4216, as described below. The proximal end portion 4212 of the medicament container assembly 4200 includes an elastomeric member 4217 (i.e., a plunger) that seals the medicament within the container body 4210. The elastomeric member 4217 is configured to move within the container body to inject the medicament from the medicament container assembly 4200.

[0121]

[1163] More specifically, as shown in FIG. 27A, the elastomeric member 4217 includes a proximal end portion 4218 and is coupled to a distal member 4320 of the gas exhaust assembly 4310. In this manner, as described below, when pressurized gas is delivered into the medicament cavity 4139 (or "housing gas chamber"), the pressurized gas flows through the flow restriction assembly 4430 and the gas exhaust assembly into the medicament container gas chamber above the elastomeric member 4217 (i.e., the boundary between the flow restriction assembly 4430, the elastomeric member 4217, and the interior of the medicament container body 4210). Pressure in the medicament container gas chamber exerts a force on the proximal surface 4218 to move the elastomeric member 4217 within the container body 4210 (i.e., to expel the medicament therefrom). Additionally, because the elastomeric member 4217 is coupled to the gas exhaust assembly 4310, movement of the elastomeric member 4217 within the container body 4210 causes movement of at least a portion of the distal member 4320. Similarly, when the elastomeric member 4217 is exposed to a force (e.g., generated by pressurized gas in the medicament container gas chamber 4440 acting directly on the proximal surface 4218), movement of the elastomeric member 4217 exerts a force on the distal member 4320. Specifically, distal movement of the elastomeric member 4217 can generate a tensile force on the distal member 4320.

[0122]

[1164] The distal member 4320 may be coupled to the elastomeric member 4217 in any manner. For example, as shown, the proximal face 4218 receives and / or couples to the protrusion 4323 of the distal member 4320 of the gas exhaust assembly 4310. In some embodiments, the distal member 4320 includes a threaded portion and the proximal end portion 4218 includes a corresponding threaded portion for receiving the distal member 4320. In some embodiments, the threaded portion of the distal member 4320 is a self-tapping threaded portion. In other embodiments, the distal member 4320 may be threadedly engaged to the elastomeric member 4217. In still other embodiments, the distal member 4320 may be bonded to the elastomeric member 4217 via adhesives, a welding process, or the like.

[0123]

[1165] The elastomeric member 4217 may be of any design or formulation suitable for contact with a drug. For example, the elastomeric member 4217 may be formulated to minimize any reduction in efficacy of the drug that may result from contact (direct or indirect) between the elastomeric member 4217 and the drug. For example, in some embodiments, the elastomeric member 4217 may be formulated to minimize leaching or outgassing of the composition that may have undesirable effects on the drug. In other embodiments, the elastomeric member 4217 may be formulated to maintain chemical stability, flexibility, and / or sealing properties when in contact (direct or indirect) with a drug over an extended period of time (e.g., up to 6 months, 1 year, 2 years, 5 years or more).

[0124]

[1166] In some embodiments, the elastomeric member 4217 can be made of a number of different materials. For example, in some embodiments, at least a portion of the elastomeric member 4217 can be coated. Such a coating can include, for example, polydimethylsiloxane. In some embodiments, at least a portion of the elastomeric member 4217 can be coated with a coating of about 0.02 mg / cm 2 ~about 0.80mg / cm 2 The coating may be coated with an amount of polydimethylsiloxane.

[0125]

[1167] The proximal end portion 4212 of the container body 4210 includes a flange 4214 configured to be disposed within a portion of the carrier body 4360, as described in further detail herein. The flange 4214 can be of any suitable size and / or shape. Although the flange 4214 is shown as substantially surrounding the container body 4210, in other embodiments, the flange 4214 may only partially surround the container body 4210.

[0126]

[1168] The drug container assembly 4200 can have any suitable size (e.g., length and / or diameter) and contain any suitable amount of drug. In some embodiments, the drug container assembly 4200 (and any drug container assembly described herein) can be a prefilled (or prefillable) syringe, such as a syringe manufactured by Becton Dickinson, Gerresheimer, Ompi Pharma, or the like. For example, in some embodiments, the drug container assembly 4200 (and any drug container assembly described herein) can be a Becton Dickinson "BD Hypak Physiolis" prefillable syringe containing any drug described herein. The medical injector 4000 can be configured to inject any suitable dose, such as, for example, a dose of up to 4 mL, of any drug described herein. In other embodiments, the medical injector 4000 may be configured to inject up to 2 mL, 3 mL, 4 mL, 5 mL, or more doses of any of the medications described herein.

[0127]

[1169] The container body 4210 can be made of glass and can be attached and / or coupled to any suitable needle. For example, in some embodiments, the container body 4210 can be coupled to a needle of any suitable size. Any of the drug container assemblies and / or pre-filled syringes described herein can be coupled to needles of gauge sizes of 21 gauge, 22 gauge, 23 gauge, 24 gauge, 25 gauge, 26 gauge, 27 gauge, 28 gauge, 29 gauge, 30 gauge, or 31 gauge. Any of the drug container assemblies and / or pre-filled syringes described herein can be coupled to needles of any suitable length, such as, for example, about 0.2 inches, about 0.27 inches, about 0.38 inches, about 0.5 inches, about 0.63 inches, about 0.75 inches, or longer. In some embodiments, for example, any of the drug containers and / or pre-filled syringes described herein can be coupled to a 29 gauge needle of about 0.5 inches in length.

[0128]

[1170] 34, the medicament container assembly 4200 includes a needle sheath assembly 4220 including a sheath body 4230 and a sheath cover 4235. The needle sheath assembly 4220 includes a distal end portion 4221 and a proximal end portion 4222. The sheath body 4230 defines a bore for receiving the needle 4216 and / or the distal end portion 4213 of the medicament container body 4210. The inner portion of the sheath body 4230 defines a friction fit with the distal end portion 4213 of the medicament container body 4210. In this manner, the needle sheath assembly 4220 can protect a user from the needle 4216 and / or maintain the needle 4216 in a sterile condition before the user activates the medical injector 4000.

[0129]

[1171] The sheath cover 4235 is disposed about (and surrounds) the sheath body 4230. The sheath cover 4235 includes a series of ribs 4236 that engage with the tabs 4722 of the safety lock 4700 (see, e.g., FIGS. 27, 27B, 34, 37, and 38). Specifically, the distal end portion of the sheath assembly 4220 is configured to be inserted into a space defined between the tabs 4722 of the engagement members 4721 of the safety lock 4700. The tabs 4722 are angled and / or bent distally to allow the distal end portion of the sheath assembly 4220 to move between the engagement members 4721 in a distal direction, but not in a proximal direction. Similarly, the tabs 4722 include edges that contact the ribs 4236 of the sheath cover 4235 to prevent the safety lock 4700 from moving distally relative to the needle sheath 4220. In this manner, when the safety lock 4700 is moved distally relative to the housing 4100 , the needle sheath assembly 4220 is removed from the needle 4216 .

[0130]

[1172] As shown in FIG. 41, the delivery mechanism 4300 includes a gas vent assembly 4310 (also referred to as an expandable assembly) but does not rely on a piston or rigid member to move the elastomeric member 4217 within the container body 4210 to inject the medicament. Rather, the elastomeric member 4217 moves due to a force generated by the pressurized gas within the gas chamber (or medicament cavity 4139). Thus, the stroke length and / or dose can be set by the expanded length of the gas vent assembly 4310. In this manner, the length of the medicament container assembly 4200 and the length of the gas vent assembly 4310 can be configured to deliver a desired dose. Furthermore, because the gas vent assembly 4310 moves from a collapsed configuration to an expanded configuration, the medicament delivery mechanism 4300 can fit within the same housing 4100 regardless of the loading amount, the delivery amount, and / or the loading amount to delivery amount ratio. In this manner, the same housing and manufacturing tools can be used to manufacture devices with various doses of medicament. For example, in a first embodiment (e.g., a loading to delivery ratio of 0.4), the drug container is a first length and the second movable member is a first length. In a second embodiment (e.g., a loading to delivery ratio of 0.6), the drug container is a second length that is shorter than the first length and the second movable member is a second length that is longer than the first length. In this way, the stroke of the device of the second embodiment is longer than that of the device of the first embodiment, allowing for a larger dose. However, the drug container of the device of the second embodiment is shorter than that of the device of the first embodiment, allowing components of both embodiments to be located within the same housing and / or within housings of the same length.

[0131]

[1173] In some embodiments, the medical injector 4000 has a housing length L H and the length of the container L C (including the needle extending from the end of the container body) is less than about 1.5. H and the length of the container LC In yet another embodiment, the medical injector 4000 is configured such that the ratio of the housing length L H and the length of the container L C The ratio of the

[0132]

[1174] In some embodiments, the medical injector 4000 has a housing length L H and the length of the container L C In another embodiment, the medical injector 4000 is configured such that the ratio of the sum of the housing length L H and the length of the container L C In yet another embodiment, the medical injector 4000 is configured such that the ratio of the sum of the housing length L H and the length of the container L C , carrier distance, and stroke sum ratio is configured to be less than about 0.9.

[0133]

[1175] As shown in Figures 24, 25 and 45, the system actuator assembly 4500 includes a base 4510, an ejection member 4550, and a spring 4576. Figure 25 illustrates certain internal components of the medical injector 4000 without the base 4510 and the safety lock 4700 so that the ejection member 4550 can be more clearly seen. The ejection member 4550 has a proximal end portion 4551 and a distal end portion 4552 and is movably disposed within the distal end portion of the gas container cavity 4151. The proximal end portion of the ejection member 4550 includes a sealing member 4574 and a perforator 4575. The sealing member 4574 is configured to engage a side wall of the housing 4100 that defines the gas container cavity 4151 such that the proximal end portion of the gas container cavity 4151 is fluidly isolated from the distal end portion of the gas container cavity 4151. In this manner, when gas is released from the gas canister 4410, gas contained in the proximal end portion of the gas-canister cavity 4151 is unable to enter the distal end portion of the gas-canister cavity 4151. The perforator 4575 of the release member 4550 is configured to contact and pierce the frangible seal 4413 of the gas canister 4410 as the release member 4550 moves proximally within the gas-canister cavity 4151.

[0134]

[1176] The distal end portion 4552 of the ejection member 4550 includes an extension 4553. The extension 4553 has a protrusion that includes a tapered surface and an engagement surface. Additionally, the extensions 4553 define an opening between adjacent extensions 4553. As shown in FIG. 42, the engagement surface is configured to extend through the ejection member aperture and contact the ejection member contact surface of the housing 4100. In this manner, the engagement surface limits proximal movement of the ejection member 4550.

[0135]

[1177] The opening defined by the extension 4553 is configured to receive the safety lock protrusion 4702 (see, e.g., FIGS. 27 and 27B) of the safety lock 4700 when the safety lock 4700 is coupled to the housing 4100 and / or base 4510. The safety lock protrusion 4702 is configured to keep the extensions 4553 from approaching one another. In other words, the safety lock protrusion 4702 is configured such that the extensions 4553 remain spaced apart and the engagement surface remains in contact with the ejection member contact surface of the housing 4100. In some embodiments, for example, the ejection member 4550 and / or the extension 4553 can be made of any suitable material configured to resist deformation that may occur when exposed to loads over an extended period of time.

[0136]

[1178] The tapered surface of the extension 4553 is configured to contact a corresponding tapered surface 4557 of the base 4510 when the base 4510 is moved proximally relative to the housing 4100. Thus, as the base 4510 moves proximally relative to the housing 4100, the extension 4553 moves along with it by virtue of the tapered surface. The inward movement of the extension 4553 disengages the ejection member 4550 from the ejection member contact surface 4126 of the housing 4100, which allows the ejection member 4550 to move proximally along its longitudinal axis as the spring 4576 expands (see FIG. 45).

[0137]

[1179] The gas container 4410 includes a distal end portion 4411 and a proximal end portion 4412 and is configured to contain and / or generate pressurized gas. The distal end portion 4411 of the gas container 4410 includes a frangible seal 4413 configured to break when a perforator 4575 of the discharge member 4550 contacts the frangible seal 4413. The gas container retaining member 4180 of the proximal cap 4110 of the housing 4100 is configured to receive and / or retain the proximal end portion 4412 of the gas container 4410. In other words, the position of the gas container 4410 within the gas container cavity 4151 is maintained by the gas container retaining member 4180. As shown in FIGS. 24 and 25, the length of the gas container retaining member 4180 and the length of the discharge member 4550 collectively determine the distance between the perforator 4575 and the frangible seal 4413 when the medical injector 4000 is in the storage configuration. This distance is therefore the distance traveled by the perforator 4575 when the medical injector 4000 is actuated and can be adjusted by varying the length of the gas container retaining member 4180 and / or the length of the release member 4550. In some embodiments, by varying the distance between the perforator 4575 and the frangible seal 4413, the actuation time and / or the force that the perforator 4575 exerts on the frangible seal 4413 can be adjusted.

[0138]

[1180] As generally shown in FIG. 24, the drug delivery mechanism 4300 includes a carrier assembly 4390, a flow restriction assembly 4430 (also referred to as a delivery control mechanism), and a gas vent assembly 4310. The carrier assembly 4390 and the gas vent assembly 4310 are each movably disposed within the drug cavity 4139 of the housing 4100. As shown in FIGS. 30-34, the carrier assembly 4390 includes a carrier body 4360 and a retraction spring 4380. The carrier body 4360 includes a distal end portion 4361 and a proximal end portion 4362. The proximal end portion 4362 of the carrier body 4360 defines an opening into which the drug container body 4210 is disposed. The proximal end portion 4362 also includes a proximal surface 4376 and forms a portion of the boundary of the housing gas chamber (i.e., a portion of the medicament cavity 4139 through which the pressurized gas flows during a first stage of expansion when the medicament container body 4210 is actuated within the housing 4100). In this manner, the pressurized gas creates a force on the proximal surface 4376 that moves the carrier assembly 4390 distally within the housing 4100.

[0139]

[1181] The inner surface of the proximal end portion 4362 defines grooves in which a first O-ring 4371 and a second O-ring 4372 are disposed. The first O-ring 4371 and the second O-ring 4372 are disposed between an upper surface of the carrier body 4360 and the flange 4214 of the medicament container body 4210. In this manner, the first O-ring 4371 and the second O-ring 4372 form a substantially fluid-tight seal. Thus, when pressurized gas flows into the proximal portion of the medicament cavity 4139 (i.e., the housing gas chamber), the area between the inner surface of the carrier body 4360 and the medicament container body 4210 is sealed. The first O-ring 4371 and the second O-ring 4372 also cushion the flange 4214.

[0140]

[1182] The outer surface of the carrier body 4360 defines an O-ring groove and includes an outer O-ring 4370. The outer surface is configured to slide against a sidewall 4139a (see FIG. 21) within the medicament cavity 4139, such that the O-ring 4370 and the inner surface of the housing 4100 define a type of substantially fluid-tight seal. Thus, when pressurized gas flows into the proximal portion of the medicament cavity 4139, the area between the outer surface of the carrier body 4360 and the inner surface of the housing 4100 is sealed. The outer O-ring 4370 is in a fixed location relative to each of the inner O-rings 4371, 4372. However, in other embodiments, the carrier assembly can include components that move relative to each other such that the outer seal member moves relative to the inner seal member.

[0141]

[1183] The distal end portion 4361 of the carrier body 4360 has an open end. Thus, as shown in FIGS. 30-33, the distal end portion 4213 of the medicament container body 4210 extends beyond the carrier body 4360. Additionally, the distal end portion 4361 of the carrier body 4360 includes two extensions (i.e., "legs") that collectively define an opening 4375. The opening is configured to align with the stator apertures 4130, 4160 of the housing to allow viewing of the medicament, the elastomeric member 4217, etc., within the medicament container assembly. The distal end portion 4361 also includes an end surface 4365 configured to contact the shoulder portion 4106 of the housing 4100 (see, e.g., FIG. 44) when the needle 4216 is inserted a desired distance.

[0142]

[1184] The retraction spring 4380 is disposed within a spring pocket 4363 defined by the exterior surface of the carrier body 4360, as shown in FIG. 32. The retraction spring 4380 is disposed about a spring pin 4381 that limits buckling or other lateral movement of the retraction spring 4380 during use. The delivery control mechanism 4430 (also referred to as a flow limiting assembly) is configured to adjust the pressure applied to the elastomeric member 4217 to control the rate at which the elastomeric member 4217 moves within the medicament container body 4210. In this manner, the rate at which the medicament is dispensed from the medicament container body 4210 through the needle 4216 as the elastomeric member 4217 moves through its forward stroke can be controlled. Controlling the flow rate of the medicament leaving the device can minimize pain or discomfort, especially when the viscosity of the medicament is high (e.g., greater than about 100 centipoise at room temperature). Furthermore, when the agent includes a high molecular weight compound (e.g., greater than about 5 kDa), a reduced injection force, less than the force required to overcome the retraction spring 4380, prevents shear and therefore damage to the agent or therapeutic substance.

[0143]

[1185] As shown in FIGS. 28, 28A, and 29, the delivery control mechanism includes a first body portion 4431 and a second body portion 4432. The second body portion 4432 extends from the first body portion 4431. The second body portion 4432 includes a flow restricting retainer 4433 configured to support at least a portion of the flow restricting member 4450. As shown in FIG. 28A, the flow restricting retainer 4433 includes a cylindrical inner surface 4433a and an end surface 4433b. The end surface 4433b defines a through hole 4433c that extends into an interior portion of the first body portion 4431. In this manner, the interior of the first body portion 4431 is in fluid communication with the second body portion 4432. Although the through hole 4433c is shown as being non-coaxial with the center of the flow restricting member 4450, in some embodiments, the through hole 4433c is coaxial with the flow restricting member 4450. In some embodiments, at least a portion of the flow restricting element 4450b of the flow restricting member 4450 overlaps a portion of the through hole 4433c. In some embodiments, at least 50% of the flow restricting element 4450b overlaps with the through hole 4433c. In some embodiments, the flow restricting member 4450 is press fit or screwed into the flow restricting retainer 4433.

[0144]

[1186] The flow restricting member 4450 includes a sleeve member 4450a and a flow restricting element 4450b, with the flow restricting element 4450b supported within the sleeve member 4450a. In some embodiments, the sleeve member 4450a is a metal sleeve. In some embodiments, the metal sleeve is made of stainless steel or brass. In some embodiments, the flow restricting element 4450b is a porous material. In some embodiments, the porous material is a sintered porous metal. In some embodiments, the flow restricting member 4450b is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of approximately 0.5 to 3 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting member 4450b is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.75 to 1.5 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting member 4450b is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 1 standard cubic centimeters per minute (sccm). As described herein, the standard temperature is 60° F. (15.6° C.) and the standard pressure is 14.696 psia (101.3 kPa).

[0145]

[1187] In some embodiments, the compressed gas provided from the gas container 4410 is argon gas and the flow restricting element 4450b has a flow rate rating of about 0.75 and 1.5 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas provided from the gas container 4410 is argon gas and the flow restricting element 4450b has a flow rate rating of about 1 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas in the gas container 4410 has a molecular weight greater than that of argon. For example, in some embodiments, the compressed gas provided from the gas container 4410 is R134a (tetrafluoroethane) and the flow restricting element 4450b has a flow rate rating of about 10-100 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas provided from the gas container 4410 is R134a (tetrafluoroethane) and the flow restricting element 4450b has a flow rate rating of about 20-40 sccm based on the nitrogen gas calibration described above.

[0146]

[1188] In some embodiments, gas pressure initially supplied to the drug cavity 4139 and through the flow restricting member 4450 can be used to reduce the drug flow rate to less than 0.2 mL / sec (or in some embodiments, 0.05 mL / sec to 0.01 mL / sec). Lower injection force and / or slower delivery (compared to pressure directly supplied from the drug cavity 4139 to the elastomeric member) can create a laminar flow of the drug through the needle, preventing shearing of high molecular weight compounds in the drug and / or reducing pain experienced by the patient, especially when the viscosity of the drug being delivered is very high (e.g., greater than about 100 centipoise at room temperature). In some embodiments, a screen or mesh protection member can be provided proximal to the flow restricting member 4450 to prevent particles or foreign objects from clogging the flow restricting element 4450b during operation.

[0147]

[1189] The first body portion 4431 includes a proximal end portion 4431a and a distal end portion 4431b. The proximal end portion 4431a includes a first cylindrical inner surface 4431c that is configured to support an O-ring 4436. The O-ring 4436 contacts a portion of the gas vent assembly 4310 and seals the interior of the first body portion 4431 from a housing gas chamber portion of the medication cavity 4139, as described in further detail herein.

[0148]

[1190] The distal end portion 4431b extends into the proximal end portion of the medicament container body 4210. The distal end portion 4431b also includes a second cylindrical inner surface 4431d and a cylindrical outer groove 4431e configured to support an O-ring 4437. The O-ring 4437 contacts and seals with the medicament container body 4210 interior wall. The first cylindrical inner surface 4431c and the second cylindrical inner surface 4431d define a bore extending from the proximal end portion 4431a to the distal end portion 4431b. The bore allows the gas vent assembly 4310 to extend into and through the first body portion 4431. A portion of the bore further defines a gas passageway between the second body portion 4432 and the medicament body gas chamber 4440, as described in more detail below. 28A, the inner diameter of the first cylindrical inner surface 4431c is greater than the inner diameter of the second cylindrical inner surface 4431d. The first body portion 4431 further includes a flange portion 4431f extending radially from an outer surface of the first body portion 4431. The flange portion 4431f is configured to attach to a flange 4214 of the medicament container body 4210 or a proximal end portion of the carrier 4360.

[0149]

[1191] As shown in FIG. 29, the first body portion 4431 defines a first axis A1 and the second body portion 4432 defines a second axis A2, the first axis being non-parallel to the second axis. In some embodiments, the first axis A1 and the second axis A2 are perpendicular to each other. In other embodiments, the first axis and the second axis define an acute angle therebetween. In some embodiments, the drug container body 4210 defines a third axis A3, and the first axis of the first body portion 4431 is parallel to the third axis A3. In some embodiments, the second body portion 4432 includes a guide surface 4432a (see FIG. 28A) that contacts a wall or guide member 4135a (see FIG. 21) of the housing 4100 to prevent the delivery control mechanism 4430 from rotating about the first axis A1 during operation.

[0150]

[1192] The gas vent assembly 4310 is configured to expand and / or change configuration during operation of the medical injector 4000 to selectively create a passageway through which pressurized gas exits the drug cavity 4139 following delivery of the drug. Releasing or removing force from the carrier body 4360, the delivery control mechanism 4430, and / or the drug container assembly 4200 can cause the retraction spring 4380 to move the carrier body 4360 proximally to retract the needle 4216. Notably, the gas vent assembly 4310 does not exert a distal force on the elastomeric member 4217, but is instead carried distally by the elastomeric member 4217 during delivery of the drug. This arrangement is therefore considered a "pistonless" delivery system. This is because, as described herein, the force for insertion and drug delivery is provided either by pressurized gas acting directly on the drug container assembly 4200 (e.g., the proximal surface 4218 of the elastomeric member 4217), the delivery control mechanism 4430 (e.g., the first body portion 4431 and the second body portion 4432 of the delivery control mechanism extending from the drug container body 4210), and / or the carrier assembly 4390 (e.g., the proximal surface 4376 of the carrier body 4360), or indirectly by gas pressure supplied from the drug cavity 4139 through the delivery control mechanism 4430 via a flow restricting member.

[0151]

[1193] As shown in Figures 35, 36A, 36B, and 36C, the gas vent assembly 4310 includes a first (or distal) member 4320, a second (or central) member 4330, and a third (or proximal) member 4340. These components are nested such that the gas vent assembly 4310 can transition from a collapsed configuration (Figures 27, 27A, and 42) to an expanded configuration (Figures 47 and 48, just before delivery of the drug is completed) and a series of partially expanded configurations in between (see, for example, Figure 44). The gas vent assembly 4310 reaches the expanded configuration just before a full dose of drug is delivered. Once the gas vent assembly 4310 is in the expanded configuration, the elastomeric member 4217 continues to travel the final distance to deliver the remaining amount from the full dose. This pulls the valve portion 4345 at least partially out of the opening 4112. In other words, the length of the gas vent assembly 4310 in the expanded configuration is selected to expand to and reach the expanded configuration before continuing to the end of travel of the elastomeric member 4217. When the gas vent assembly 4310 is in the expanded configuration and continues to travel with the elastomeric member 4217 a final distance to complete delivery of a full dose (FIGS. 50 and 51, after drug delivery is complete), the opening 4112, O-ring 4113, and passageway 4346 collectively allow pressurized gas from the housing gas chamber of the drug cavity 4139 to exit the drug cavity 4139 as the needle is retracted.

[0152]

[1194] The first member 4320 includes a proximal end portion 4322 and a distal end portion 4321. The distal end portion 4321 includes a protrusion 4323 configured to matingly engage the elastomeric member 4217. In this manner, distal movement of the elastomeric member 4217 results in distal movement of the first member 4320. In some embodiments, the protrusion 4323 is a threaded portion that matingly engages the elastomeric member 4217. The proximal end portion 4322 includes a pair of retaining walls 4324 configured to engage a corresponding distal end surface 4333 of the second (or central) member 4330. In some embodiments, the pair of retaining walls 4324 each include a pin or tab that loosely couples the proximal end portion 4322 of the first member 4320 to the distal end surface 4333 of the second member 4330 to aid in assembly of the device, but separates upon application of pressure in a distal direction to the elastomeric member 4217. The proximal end portion 4322 further includes a flexible expansion member 4325 secured at a first end 4325a to the proximal end portion 4322 of the first member 4320 and secured at a second end 4325b to the distal end surface 4333 of the second member 4330. During the second stage of expansion (i.e., movement of the elastomeric member 4217 as the device transitions from the fourth configuration to the fifth configuration), the elastomeric member 4217 moves distally within the medicament container body 4210. As the elastomeric member 4217 moves, the first end 4325a and the second end 4325b move away from each other as the flexible extension member 4325 expands. As shown in FIG. 35 and FIGS. 36A-C, the flexible extension member 4325 is folded in an accordion-like manner. In some embodiments, the flexible extension member 4325 is a filament or band. In some embodiments, the flexible extension member 4325 is overmolded with a plastic material. In some embodiments, the flexible extension member 4325 is a cable that is initially coiled or spooled between the proximal end portion 4322 of the first member 4320 and the distal end surface 4333 of the second member 4330.

[0153]

[1195] The second member 4330 includes a distal end portion 4331 and a proximal end portion 4332. The distal end portion 4331 includes a distal end surface 4333 that engages the first member 4320. The second member 4330 includes a sidewall 4334 extending from the distal end portion 4331 to the proximal end portion 4332. The proximal end portion 4332 includes a shoulder portion 4335 extending toward a center of the second member 4330, the shoulder portion 4335 defining an opening 4336. The distal end portion 4331, the proximal end portion 4332, and the sidewall 4334 define an interior volume 4337.

[0154]

[1196] The third member 4340 includes a distal end portion 4341 and a proximal end portion 4342. The distal end portion 4341 extends through the opening 4336 of the second member 4330. The distal end portion 4341 travels within the interior volume 4337 and includes a distal protrusion 4343 configured to engage the shoulder portion 4335 of the second member 4320 when the second member 4320 extends away from the third member 4340. In this manner, the distal protrusion 4343 limits the movement of the second member 4340 as it extends away from the third member 4340 during a first stage of expansion, as described herein. The proximal end portion 4342 includes a guide surface 4344 and a valve portion 4345. The guide surface 4344 engages the O-ring 4113 and slides within the proximal cap 4110 guide wall 4115 (FIG. 27A). The valve portion 4345 defines a passageway 4346 that bypasses the O-ring 4113 when the valve portion 4345 is in an open configuration (see FIGS. 53 and 54). As shown in FIG. 35, the passageway 4346 is a recessed portion that extends into the proximal end portion 4342.

[0155]

[1197] 27, 37 and 38, the safety lock 4700 includes a safety lock protrusion 4702 and an engagement portion 4720. As previously described, when the safety lock 4700 is in a first (locked) position, the safety lock protrusion 4702 is configured to be disposed in an opening defined by the extensions 4553 of the release member 4550. Thus, the safety lock protrusion 4702 is configured to prevent the extensions 4553 from approaching one another, thereby preventing proximal movement of the release member 4550 and / or delivery of the medicament.

[0156]

[1198] The engagement portion 4720 of the safety lock 4700 includes a proximally extending engagement member 4721. The engagement member 4721 has a tab 4722 extending from a surface of the engagement member. As previously described, the tab 4722 engages a rib 4236 of the sheath cover 4235 to limit relative movement between the safety lock 4700 and the needle sheath assembly 4220. In this manner, the needle sheath assembly 4220 can protect the user from the needle 4216 and / or maintain the needle 4216 in a sterile condition before the user activates the medical injector 4000, and the needle sheath assembly 4220 can be removed from the needle 4216 once the safety lock 4700 is removed.

[0157]

[1199] On the exterior surface of the safety lock 4700 are gripping portions (recessed finger grips) and indicia. The recessed finger grips provide an area for a user to grasp and / or remove the safety lock 4700 from the housing 4100. The indicia provide a method of removal of the safety lock 4700. In some embodiments, for example, the indicia can indicate the direction a user should pull the safety lock 4700 to remove it.

[0158]

[1200] 39 and 40 show the base (or actuator) 4510 of the medical injector 4000. The base 4510 includes a proximal (or inner) surface 4511, a distal (or outer) surface 4523, and a base connection knob 4518. During use of the injector 4000, the distal surface 4523 is positioned against a target surface (not shown). As described below, the housing 4100 is moved distally relative to the base 4510 and / or the distal surface 4523, which causes the base 4510 to move proximally relative to the housing 4100 to actuate the medical injector 4000. The base 4510 defines a needle aperture 4513 and a safety lock protrusion aperture 4514. The needle aperture 4513 is configured to receive the needle 4216 when the medical injector 4000 is actuated. The safety lock protrusion aperture 4514 of the base 4510 receives the safety lock protrusion 4702 of the safety lock 4700 when the safety lock 4700 is coupled to the housing 4100 and / or the base 4510 .

[0159]

[1201] The proximal surface 4511 of the base 4510 includes a guide member 4517 and a protrusion 4515. As described above, the guide member 4517 of the base 4510 engages and / or slides within the base rail groove 4114 of the housing 4100. The protrusion 4515 of the base 4510 engages a tapered surface of the extension 4553 of the release member 4550. As described in further detail herein, when the safety lock 4700 is removed and the base 4510 moves proximally relative to the housing 4100, the protrusion 4515 of the base 4510 is configured to move the extension 4553 of the release member 4550 closer together to actuate the drug delivery mechanism 4300. In some embodiments, the base connection knob 4518 engages the base retention recess 4134 to allow proximal movement of the base 4510 but limit distal movement of the base 4510.

[0160]

[1202] The medical injector 4000 can be moved from a first configuration (FIGS. 26 and 27) to a second configuration (FIG. 42) by moving the safety lock 4700 from the first position to the second position. The safety lock 4700 is moved from the first position to the second position by moving the safety lock 4700 distally and / or disengaging it relative to the housing 4100. Moving the safety lock 4700 from the first position to the second position disengages the safety lock protrusion 4702 from between the extensions 4553 of the release member 4550, thereby enabling the drug delivery mechanism 4300. As shown in FIG. 26, prior to actuation, a portion of the drug container assembly 4200 is viewable through the status aperture 4130. In particular, the drug container body 4210 and its contents (e.g., drug) are viewable. As previously mentioned, in some embodiments, the housing 4100 can include a label or other indicia providing a color strip (against which the drug can be compared), a method of viewing, or the like. Although not shown in FIG. 26, in some embodiments, a portion of the elastomeric member 4217 is visible through the stator aperture 4130.

[0161]

[1203] After the safety lock 4700 has been moved from the first position to the second position, the medical injector 4000 can be moved from the second configuration (FIG. 42) to the third configuration (FIG. 43) by moving the base 4510 from the first position to the second position. Similarly, the medical injector 4000 can be actuated by the system actuator assembly 4500 by moving the base 4510 proximally relative to the housing 4100. The base 4510 is moved from the first position to the second position by placing the medical injector 4000 against the patient's body and moving the base 4510 relative to the housing 4100. Specifically, as discussed above, the base includes a "contact portion" (i.e., distal surface 4523) that can be placed against and / or contact a target location. As the base 4510 is moved from the first position to the second position, the base 4510 engages the extension 4553 of the ejection member 4550, thereby moving the extension 4553 with it. Inward movement of the extensions 4553 disengages the engagement surface of the ejection member 4550 from the housing 4100, thereby allowing the ejection member 4550 to move proximally along its longitudinal axis as the spring 4576 expands.

[0162]

[1204] Moving the base 4510 from the first position to the second position causes the system actuator assembly 4500 to actuate the drug delivery mechanism 4300, which places the medical injector 4000 in a fourth configuration (i.e., a needle insertion configuration), as shown in Figures 43-45. More specifically, when the medical injector 4000 is in the fourth configuration, the perforator 4575 of the discharge member 4550 is in contact with and / or disposed through the frangible seal 4413 of the gas container 4410.

[0163]

[1205] After the frangible seal 4413 is pierced, an actuated portion of compressed gas flows from the gas container 4410 through the gas passageway 4135 into the medicament cavity 4139, initiating the first stage of expansion (i.e., movement of the carrier assembly 4390 as the device transitions from the third configuration to the fourth configuration). The gas exerts gas pressure on the flange 4214 of the medicament container, the delivery control mechanism 4430, and / or the top surface of the carrier body 4360. Because the seals 4371, 4372 of the medicament container assembly 4200, the outer seal 4370 of the carrier assembly 4390, and the seals of the delivery control mechanism 4430 keep the medicament cavity 4139 fluidly isolated from the exterior of the device, the gas pressure exerts a force that moves the carrier assembly 4390 distally within the medicament cavity 4139, as shown in FIGS. 44 and 45. The medicament container body 4210 and the delivery control mechanism 4430 also move distally together with the carrier assembly 4390. In this manner, distal movement of the needle 4216 causes the distal end portion of the needle 4216 to exit the housing 4100 and enter the patient's body prior to administration of the medicament. In some embodiments, the gas container 4410 can contain approximately 1000 psi of pressurized gas prior to piercing the frangible seal 4413. When the frangible seal 4413 is pierced, the pressurized gas released into the medicament cavity 4139 is pressurized to approximately 500 psi at the start of the third configuration (i.e., before the gas vent assembly 4310 and the carrier assembly 4390 are activated). In some embodiments, the compressed gas provided by the gas container 4410 is argon gas. In some embodiments, the compressed gas provided by the gas container 4410 is a refrigerant, such as R134a.

[0164]

[1206] As the device moves from the third configuration to the fourth configuration, as shown in Figures 44 and 45, the gas vent assembly 4310 expands from the collapsed configuration (Figures 36A and 42) to a partially expanded configuration. In particular, in the partially expanded configuration, gas pressure within the agent cavity 4139 acts on the underside of the proximal end portion 4342, and the valve portion 4345 is maintained in a sealed position within the opening 4112 and O-ring 4113. Thus, the agent cavity 4139 is maintained in a fluid isolated state.

[0165]

[1207] Once the needle 4216 has extended a desired distance, the distal surface 4365 of the carrier body 4360 contacts the shoulder portion 4106 of the housing 4100 to limit further distal movement of the carrier assembly 4390 within the housing 4100. Once distal movement of the carrier assembly 4390 is prevented, the first stage of expansion is complete. Gas within the drug cavity 4139 (i.e., the housing gas chamber) continues to travel through the delivery control mechanism 4430 to exert gas pressure on the elastomeric member 4217 to initiate the second stage of expansion. In the first stage of expansion, the flow restriction provided by the delivery control mechanism 4430 prevents movement of the elastomeric member 4217 before the carrier body 4360 contacts the shoulder portion 4106. In some embodiments, in the first stage of expansion, the flow delivery control mechanism 4430 allows gas to pass through the flow restriction member 4450, but does not build up enough pressure to move the elastomeric member 4217. In some embodiments, at the end of the fourth configuration (i.e., when the housing 4100 and shoulder portion 4106 restrict the carrier assembly 4390 from moving further distally), the pressurized gas in the drug cavity 4139 drops to approximately 90-100 psi.

[0166]

[1208] As generally shown in FIG. 27A, gas from the medicament cavity 4139 passes through and is regulated by the flow restricting member 4450. Gas passing through the flow restricting member 4450 passes through the through hole 4433c and along the internal passageway 4438 between the second cylindrical inner surface 4431d and the sidewall 4334 of the second member 4330. The internal passageway 4438 between the second member 4330 and the first body portion 4431 defines an annular passageway. In some embodiments, the second member 4330 and / or the first body portion 4431 can include one or more dimples or bumper portions extending along the axis A1 to maintain separation between the second member 4330 and / or the first body portion 4431 and to prevent the internal passageway 4438 (see FIG. 29) from being sealed or restricted. In some embodiments, the surface of the distal end portion 4331 facing the first body portion 4431 includes one or more grooves or ridges. In some embodiments, the surface of the distal end portion 4331 facing the first body portion 4431 includes a textured surface.

[0167]

[1209] After passing through the internal passageway 4438, the gas enters the drug body gas chamber 4440 sealed between the distal side of the O-ring 4437 and the proximal side of the elastomeric member 4217. This causes the elastomeric member 4217 (and thus the first member 4320 of the gas vent assembly 4310) to move distally within the drug container body 4210. The distal movement of the elastomeric member 4217 creates pressure on the drug contained within the drug container assembly 4200. This allows at least a portion of the drug to flow out of the drug container 4200 and through the needle 4216. The drug is delivered to the user's body via a drug delivery pathway defined by the drug container 4200 and the needle 4216. As the elastomeric member 4217 advances to dispense the drug, the gas vent assembly 4310 expands from a partially expanded configuration to a fully expanded configuration and the medical injector is in the fifth configuration (FIGS. 47 and 48). In some embodiments, the drug body gas chamber 4440 is pressurized to approximately 10-20 psi to initiate actuation of the elastomeric member 4217 .

[0168]

[1210] As shown in FIG. 46, a portion of the medicament container assembly 4200, a portion of the carrier body 4360, and a portion of the gas vent assembly 4310 are visible through the status aperture 4130 when the medical injector 4000 is in the fifth configuration and / or transitioning to the sixth configuration. As previously mentioned, in some embodiments, the housing 4100 may include a label providing a color strip or other indicia to assist a user in identifying the carrier, providing a way to view, etc. Although not shown in FIG. 11, in some embodiments, a portion of the elastomeric member 4217 is visible through the status aperture 4130 when the medical injector 4000 is in the fifth configuration or in the sixth configuration to indicate that delivery of the medicament is nearing completion or has been completed.

[0169]

[1211] 47 and 48, as the elastomeric member 4217 moves distally, the gas vent assembly 4310 moves with the elastomeric member 4217 in a fully expanded configuration. Once the gas vent assembly 4310 is in the fully expanded configuration and begins to pull on the valve portion 4345, the medical injection 4000 is in a sixth configuration. In this sixth configuration, the elastomeric member 4217 continues to move a predetermined distance (corresponding to a desired dose remaining) within the medicament container body 4210, causing the valve portion 4345 to move out from within the opening 4112, thereby allowing the pressurized gas contained within the housing gas chamber (i.e., the volume within the medicament cavity 4139 between the proximal end of the housing 4100 and the surface of the carrier 4360) to exit via the passageway 4346 and the opening 4112. More specifically, the pressure exerted by the gas in the drug body gas chamber 4440 on the elastomeric member 4217 is greater than the pressure exerted by the gas on the underside of the proximal end portion 4342 and the frictional force acting on the guide surface 4344. In some embodiments, the drug body gas chamber 4440 is pressurized to approximately 30-50 psi to actuate the valve portion 4345.

[0170]

[1212] When the gas pressure in the medicament cavity 4139 falls below a certain level, the force exerted by the retraction spring 4380 on the carrier body 4360 is sufficient to move (i.e., retract) the carrier body 4360 proximally within the housing 4100. This places the medical injector in the seventh configuration (FIGS. 53 and 54). As shown in FIGS. 27A, 28A, 53, and 54, the inner diameter of the first cylindrical inner surface 4431c is greater than the outer diameter of the guide surface 4344. In this manner, as the carrier assembly 4390, gas vent assembly 4310, and flow restrictor assembly 4430 move back toward the proximal end of the housing 4100, the first body portion 4431 bypasses the guide surface 4344 to prevent the valve portion 4345 from contacting and closing the opening 4112.

[0171]

[1213] As shown in FIG. 52, a portion of the medicament container assembly 4200 is visible through the status aperture 4130 when the medical injector 4000 is in the seventh configuration. Specifically, as shown, a portion of the medicament container body 4210 and the elastomeric member 4217 are visible through the status aperture 4130. As previously mentioned, in some embodiments, the housing 4100 can include a label providing a color strip or other indicia to assist a user in identifying, providing a way to view, etc. the elastomeric member. Although not shown in FIG. 52, in some embodiments, a portion of the carrier 4360 is visible through the status aperture 4130 when the medical injector 4000 is in the seventh configuration.

[0172]

[1214] As mentioned above, the drug delivery mechanism 4300 is considered a "piston-less" system. In a gas-based piston-less autoinjector, the force exerted by the gas can move the drug container relative to the housing, which in turn can move the elastomeric member 4217 relative to (e.g., within) the drug container body 4210. In some embodiments, not including a moving mechanism, piston, etc. can reduce the height of the medical injector 4000, for example, relative to the height of a device including a rigid single-length piston.

[0173]

[1215] Although the medical injector 4000 is shown as including a gas vent assembly 4310 that releases pressurized gas in response to the elastomeric member 4217 reaching a predetermined position, in other embodiments the medical injector can include any suitable mechanism for releasing pressurized gas. For example, FIG. 55 illustrates a medical injector 4000' in which the drug delivery mechanism 4300 described above has been replaced with a drug delivery mechanism 5300, as described in more detail below. The drug delivery mechanism 5300 includes a carrier assembly 5390 and a gas vent assembly 5310. The gas vent assembly 5310 includes a valve actuator 5320 and a valve portion 5345. The valve actuator 5320 is coupled to the valve portion 5345 and is operable to seal the opening 4112 during storage throughout the drug delivery process and to allow gas to be released at the end of injection so that the needle 4216 can be retracted. In some embodiments, the valve actuator 5320 is configured to detect lift-off or separation of the base 4510 from the patient after injection. In some embodiments, the medical injector 4000' can include an electronic circuit system as described in connection with the drug delivery device 2000 above to detect the location of the elastomeric member and / or to detect completion of drug delivery. In some embodiments, the medical injector 4000' and any of the devices described herein can include an electronic circuit system as described in PCT No. 8433.

[0174]

[1216] Once completion is detected, the valve actuator 5320 actuates the valve portion 5345 to an open position to vent the high pressure gas from the drug cavity 4139. This causes the needle 4216 to retract due to the force of the retraction spring, as described above. In some embodiments, the valve actuator 5320 can be an electronically controlled actuator that actuates the valve portion 5345 based on input received from the electronic circuit system described above. In some embodiments, the valve actuator 5320 can be an electronically controlled actuator with one or more sensors to detect lift-off of the base 4510 and / or completion of delivery of the desired dose of drug. In other embodiments, the valve actuator 5320 is mechanically coupled to the base 4510 such that the valve actuator 5320 actuates the valve portion 5345 upon movement of the base 4510 in a distal direction following actuation of the medical injector (e.g., this may occur when a user removes the injector from the target location). In yet other embodiments, the valve actuator 5320 is a manually operated valve. In this manner, the user can push, pull, slide, or rotate the valve actuator 5320 to the open position. As described herein, the user can detect completion by viewing a status indicator (such as the status indicator 4130 described herein) and / or after receiving an audible or visual alert (such as from the output module 2107 described herein).

[0175]

[1217] The carrier assembly 5390 and the gas vent assembly 5310 are each movably disposed within the medicament cavity 4139 of the housing 4100. The carrier assembly 5390 includes a carrier body 5360 and a retraction spring (not shown). The carrier body 5360 includes a distal end portion 5361 and a proximal end portion 5362. The proximal end portion 5361 of the carrier body 5360 defines an opening within which the medicament container body 4210 is disposed. The proximal end portion 5361 also includes a proximal face 5376, which forms a portion of the boundary of the gas chamber (i.e., a portion of the medicament cavity 4139 through which the pressurized gas flows). In this manner, the pressurized gas generates a force on the proximal face 5376 that moves the carrier assembly 5390 distally within the housing 4100.

[0176]

[1218] In some embodiments, the inner surface of the proximal end portion 5361 defines a groove in which the first O-ring 5371 and the second O-ring 5372 are disposed. The first O-ring 5371 and the second O-ring 5372 are disposed between the upper surface of the carrier body 5360 and the flange 4214 of the medicament container body 4210. In this manner, the first O-ring 5371 and the second O-ring 5372 form a substantially fluid-tight seal. Thus, when pressurized gas flows into the proximal portion of the medicament cavity 4139 (i.e., gas chamber), the area between the inner surface of the carrier body 5360 and the medicament container body 4210 is sealed. The first O-ring 5371 and the second O-ring 5372 can also cushion the flange 4214.

[0177]

[1219] In some embodiments, the drug delivery mechanism 5300 includes a flow restricting member 5430. The flow restricting member 5430 can be inserted into the proximal end portion 4212 of the drug container assembly 4200 to define a drug control cavity 4239 within the drug container assembly 4200 between the flow restricting member 5430 and the elastomeric member 4217. As shown, the flow restricting member 5430 includes a flow restricting retainer 5440 and a flow restricting element 5450, the flow restricting element 5450 being at least partially retained within the flow restricting retainer 5440.

[0178]

[1220] 56 and 57, the flow restricting retainer 5440 includes a proximal end portion 5441 and a distal end portion 5442. The flow restricting retainer 5440 includes a first cylindrical inner portion 5443 and a second cylindrical inner portion 5444, where the diameter of the first cylindrical inner portion 5443 is greater than the diameter of the second cylindrical inner portion 5444. The first and second cylindrical inner portions extend parallel to a longitudinal axis of the flow restricting retainer 5440 between the proximal and distal end portions. In some embodiments, the proximal end portion of the flow restricting retainer 5440 includes a flange portion 5445 that extends radially away from the longitudinal axis of the flow restricting retainer 5440. The flange portion 5445 includes at least an upper surface 5445a and a bottom surface 5445b, the upper surface 5445a being configured to abut against the guide wall 4115 of the proximal cap 4110 (described above) and the bottom surface 5445b being operable to attach to and abut against the proximal end of the carrier body 5360 to prevent the flow limiting retainer 5440 from moving relative to the carrier body 5360.

[0179]

[1221] The flow limiting retainer 5440 includes an outer circumferential surface 5446 extending between a proximal end portion 5441 and a distal end portion 5442. The outer circumferential surface 5446 of the flow limiting retainer 5440 is configured to be inserted into the drug container body 4210, as shown in FIG. 56. In some embodiments, the outer circumferential surface 5446 can include a groove 5447 for securing a seal or O-ring 5448 to prevent pressurized gas from bypassing a flow restricting element 5450 between the outer circumferential surface of the flow limiting retainer 5440 and the carrier body 5360.

[0180]

[1222] In some embodiments, the flow restricting element 5450 can be a reduced pressure filter element, a diaphragm element, a single port orifice, a series of single port orifices, a sieve plate element, an adjustable valve, a single port valve, a multi-port valve, or a porous member to allow for a reduction in pressure during a delivery event. For example, the size and porosity of the ports of the flow restricting element 5450 can be selected to allow gas pressure to build up in the drug cavity 4139 and / or the gas chamber to deploy the needle 4216 before the elastomeric member 4217 is actuated. The size and porosity of the ports of the flow restricting element 5450 can also be selected to control the rate of advancement of the elastomeric member 4217 and therefore the rate of drug infused into the patient. In particular, the flow restricting element 5450 allows the drug delivery mechanism 5300 to rapidly deploy the needle 4216 via high pressure gas delivered from the gas container 4410 to the drug cavity 4139, but then regulate and reduce the pressure delivered to the drug control cavity 4239. By limiting the pressure supplied from the drug cavity 4139 to the drug control cavity 4239 via the flow restricting element 5450, a slow and gradual build-up of pressure within the drug control cavity 4239 can be promoted, controlling the actuation of the elastomeric member 4217 to enable lower injection forces and / or slower drug delivery.

[0181]

[1223] In some embodiments, gas pressure initially supplied to the drug cavity 4139 and through the flow restricting element 5450 can be used to reduce the flow rate of the drug to less than 0.2 mL / sec (or in some embodiments, 0.05 mL / sec to 0.01 mL / sec). Lower injection force and / or slower delivery (compared to pressure directly supplied from the drug cavity 4139 to the elastomeric member) can create a laminar flow of the drug through the needle, preventing shearing of high molecular weight compounds in the drug and / or reducing pain experienced by the patient, especially when the viscosity of the drug being delivered is very high (e.g., greater than about 100 centipoise at room temperature). In some embodiments, a screen or mesh protection member can be provided proximal to the flow restricting element 5450 to prevent particles or foreign objects from clogging the flow restricting element 5450 during operation. In some embodiments, the flow restricting element 5450 comprises a porous metal or porous ceramic material. The porous material provides multiple passages through the flow restricting element 5450, which prevents clogging if there is foreign matter within the housing 4100. In some embodiments, the flow restricting element 5450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.5 to 3 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting element 5450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.75 to 1.5 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting member 5450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 1 standard cubic centimeters per minute (sccm).

[0182]

[1224] In some embodiments, the compressed gas provided from the gas container 4410 is argon gas and the flow restricting member 5450 has a flow rate rating of about 0.75 and 1.5 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas provided from the gas container 4410 is argon gas and the flow restricting member 5450 has a flow rate rating of about 1 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas in the gas container 4410 has a molecular weight greater than that of argon. For example, in some embodiments, the compressed gas provided from the gas container 4410 is R134a (tetrafluoroethane) and the flow restricting member 5450 has a flow rate rating of about 10-100 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas provided from the gas container 4410 is R134a (tetrafluoroethane) and the flow restricting member 5450 has a flow rate rating of about 20-40 sccm based on the nitrogen gas calibration described above.

[0183]

[1225] Similar to the medical injector 4000, the medical injector 4000' can be moved from a first configuration (i.e., a "storage" state) to a second configuration by moving the safety lock 4700, as described above. From the second configuration (see, e.g., FIG. 41), the medical injector 4000' can be moved from the second configuration to a third configuration (see, e.g., FIG. 42) by moving the base 4510 from the first position to the second position.

[1204] Moving the base 4510 from the first position to the second position causes the system actuator assembly 4500 to actuate the drug delivery mechanism 5300 to place the medical injector 4000' in the fourth configuration (i.e., a needle insertion configuration).

[1204] When the base 4510 moves from the first position to the second position, the system actuator assembly 4500 actuates the drug delivery mechanism 5300, which causes the medical injector 4000' to be in the fourth configuration (ie, the needle insertion configuration), as shown in FIG. 44.

[0184]

[1226] More specifically, as shown in FIG. 55, when the medical injector 4000′ is in the fourth configuration, the perforator 4575 of the discharge member 4550 is in contact with and / or disposed through the frangible seal 4413 of the gas container 4410. After the frangible seal 4413 is pierced, an actuated portion of the compressed gas flows from the gas container 4410 through the gas passageway into the medicament cavity 4139. The gas exerts gas pressure on the flange 4214 of the medicament container and / or the proximal face 5376 of the carrier body 5360. Because the seals 5371, 5372, and the outer seal 4370 maintain the medicament cavity 4139 fluidly isolated from the exterior of the device, the gas pressure exerts a force that moves the carrier assembly 5390 distally within the medicament cavity 4139, as shown in FIGS. 55-57. In this manner, distal movement of the needle 4216 causes a distal portion of the needle 4216 to exit the housing 4100 and enter the patient's body prior to administration of the medication.

[0185]

[1227] As compressed gas flows from the gas container 4410 into the medication cavity 4139 and exerts pressure on the flange 4214 and / or proximal face 5376 of the medication container to extend the needle 4216, a portion of the compressed gas passes through the flow restricting member 5430. When the needle 4216 has been extended a desired distance, the distal face of the carrier body 5360 contacts the shoulder portion 4106 of the housing 4100 to limit further distal movement of the carrier assembly 5390 within the housing 4100. While distal movement of the carrier assembly 5390 is prevented, gas within the medication cavity 4139 (i.e., gas chamber) continues to pass through the flow restricting element 5450 into the medication control cavity 4239.

[0186]

[1228] As gas pressure builds up within the drug control cavity 4239 and overcomes the frictional force of the elastomeric member 4217 against the drug container body 4210, the elastomeric member 4217 begins to move distally within the drug container body 4210. The distal movement of the elastomeric member 4217 creates pressure on the drug contained within the drug container assembly 4200. This allows at least a portion of the drug to flow out of the drug container 4200 and through the needle 4216. The drug is delivered to the user's body via a drug delivery pathway defined by the drug container 4200 and the needle 4216. At the end of the injection, the medical injector is in the fifth configuration.

[0187]

[1229] In some embodiments, the flow restricting element 5450 is sized and configured to prevent movement of the elastomeric member 4217 while the needle 4216 is extended from the housing 4100. When the needle 4216 is fully extended, the flow restricting element 5450 is configured to build up sufficient pressure within the drug control cavity 4239 to allow movement of the elastomeric member 4217. In some embodiments, the gas pressure within the drug control cavity 4239 remains lower than the gas pressure in the drug cavity 4139 throughout the drug injection process.

[0188]

[1230] After the elastomeric member 4217 has moved a predetermined distance (corresponding to a desired dose) within the medicament container body 4210 to place the medical injector in the sixth configuration, or after the base 4510 has been lifted from the injection site, the valve portion 5345 moves out from within the opening 4112, thereby allowing the pressurized gas contained within the gas chamber (i.e., the volume within the medicament cavity 4139 between the proximal end of the housing 4100 and the surface of the carrier body 5360) to exit via the passageway 5345 and the opening 4112. When the gas pressure within the medicament cavity 4139 falls below a certain level, the force exerted by the retraction spring on the carrier body 5360 is sufficient to cause the carrier body 5360 to move proximally (i.e., retract) within the housing 4100. This places the medical injector in the seventh configuration (FIG. 53).

[0189]

[1231] Although the medical injector 4000 is shown as including a single drug container assembly 4200, in other embodiments the medical injector may include two or more drug container assemblies to deliver a larger dose of drug (e.g., a dose greater than 1 mL) or to deliver two different dosage forms of drug as previously described with reference to the drug delivery device 3000. For example, Figs. 58 and 59 show a medical injector 6000 having a housing 6100 that replaces the housing 4100. Corresponding components in the medical injector 6000 that are similar to those provided in the medical injector 4000 are identified with the same reference numerals. The housing 6100 includes a proximal end portion 6101, a distal end portion 6102, and a drug cavity 6139 sized to accommodate the two drug delivery mechanisms 4300, the two carrier assemblies 4390, and the two delivery control mechanisms 4430. Additionally, the third member 4340 of the gas vent assembly 4310 is modified to be coupled to a coupling actuation member 6350 (also referred to as a rocker mechanism) to form a modified gas vent assembly 4310' including a modified third member 4340'.

[0190]

[1232] The housing 6100 includes a proximal cap 6110 having a vent opening 6112 in fluid communication with an area outside the housing 6100. The proximal cap 6110 further includes a guide wall 6115 into which the O-ring 6113 and the valve portion 4345 are seated when the valve portion 4345 is in a closed configuration. Similar to the medical injector 4000, each of the drug delivery mechanisms 4300 of the medical injector 6000 is coupled to a delivery control mechanism 4430 as described herein to regulate the flow rate of the drug dispensed. Each of the gas vent assemblies 4310' is coupled to a coupling actuation member 6350 to prevent premature draining and retraction of the drug cavity 6139 when dispensing of the drug from the first drug container is complete but not the second drug container. The combined actuation member 6350 requires that each of both gas vent assemblies 4310 ′ move a predetermined distance before the combined actuation member 6350 actuates the valve portion 4345 .

[0191]

[1233] 36B with FIG. 59, the combined actuation member 6350 is an intermediate member connected between the distal portion 4341 of the third (proximal) member 4340 shown in FIG. 36B and the valve portion 4345. The combined actuation member 6350 includes a first arm portion 6351 and a second arm portion 6352. The first arm portion 6351 is coupled to the third member 4340' associated with the first gas vent assembly 4310'. The second arm portion 6352 is coupled to the third member 4340' associated with the second gas vent assembly 4310'. In this manner, the combined actuation member 6350 is configured to actuate the valve portion 4345 to the open position only when both sets of gas vent assemblies 4310 are fully extended and both elastomeric members 4217 have completed their entire travel stroke. In other words, the combined actuation member 6350 is operable to actuate the valve portion 4345 upon application of force to both the first arm portion 6351 and the second arm portion 6352 as a result of both sets of the drug delivery mechanism 4300 transitioning to the sixth configuration, as described above.

[0192]

[1234] The center of the coupled actuation member 6350 includes a guide member (not shown) configured to interact with a guide rail or groove 6104 of the housing 6100. The guide member allows the coupled actuation member 6350 to rotate (e.g., similar to a seesaw) when forces are applied unequal to the first arm portion 6351 and the second arm portion 6352. The coupled actuation member 6350 translates axially along the guide rail or groove 6104 upon receiving force input from both the first arm portion 6351 and the second arm portion 6352. As described herein, when both sets of drug delivery mechanisms 4300 transition to the sixth configuration, sufficient force is applied via the coupled actuation member 6350 to unseat the valve member 4345, placing the drug cavity 6139 in fluid communication with the external environment. Retraction of the carrier assembly 4390 and drug delivery mechanism 4300 can be performed in the same manner as described above for the medical injector 4000. In some embodiments, the guide member is a pin member or a rounded protrusion, hi some embodiments, the guide member is a guide rail or groove that translates along a fixed guide pin or guide protrusion in the housing 6100.

[0193]

[1235] 58 and 59 show the same flow restricting member 4450 installed in each of the delivery control mechanisms 4430, in some embodiments, different flow restricting members can be used to vary the gas pressure applied to each drug container gas chamber 4440. For example, in some embodiments, different doses and / or dosage forms of drug can be provided in each of the drug container bodies 4210, and the flow restricting characteristics can be adjusted to regulate the desired flow rate for each drug to prevent damage to the drug or minimize discomfort to the patient.

[0194]

[1236] In some embodiments, the flow restricting member 4450 comprises a porous material. In some embodiments, the porous material is a sintered porous metal. In some embodiments, the flow restricting member 4450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.5 to 3 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting member 4450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 0.75 to 1.5 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting member 4450 is calibrated to atmosphere (outlet side) at standard temperature and pressure with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of about 1 standard cubic centimeters per minute (sccm).

[0195]

[1237] In some embodiments, the compressed gas provided from the gas container 4410 is argon gas and the flow restricting member 4450 has a flow rate rating of about 0.75 and 1.5 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas provided from the gas container 4410 is argon gas and the flow restricting member 4450 has a flow rate rating of about 1 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas in the gas container 4410 has a molecular weight greater than that of argon. For example, in some embodiments, the compressed gas provided from the gas container 4410 is R134a (tetrafluoroethane) and the flow restricting member 4450 has a flow rate rating of about 10-100 sccm based on the nitrogen gas calibration described above. In some embodiments, the compressed gas provided from the gas container 4410 is R134a (tetrafluoroethane) and the flow restricting member 4450 has a flow rate rating of about 20-40 sccm based on the nitrogen gas calibration described above.

[0196]

[1238] In some embodiments, gas pressure initially supplied to the drug cavity 6139 and through the flow restricting member 4450 can be used to reduce the drug flow rate to less than 0.2 mL / sec (or in some embodiments, 0.05 mL / sec to 0.01 mL / sec). Lower injection force and / or slower delivery (compared to pressure directly supplied from the drug cavity 6139 to the elastomeric member) can create a laminar flow of the drug through the needle, preventing shearing of high molecular weight compounds in the drug and / or reducing pain experienced by the patient, especially when the viscosity of the drug being delivered is very high (e.g., greater than about 100 centipoise at room temperature). In some embodiments, a screen or mesh protection member can be provided proximal to the flow restricting member 4450 to prevent particles or foreign objects from clogging the flow restricting element 4450b during operation.

[0197]

[1239] While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation. Where the methods above indicate that certain events occur in a particular order, the order of the certain events may be modified. Also, some of the events may occur simultaneously in parallel processes where possible, or may occur sequentially as described above.

[0198]

[1240] For example, in some embodiments, the drug delivery device may include two or more drug containers, each with a delivery member capable of delivering the drug therein. Such embodiments may accommodate delivery of viscous drugs and / or large volumes of drugs (e.g., greater than 1 mL) by delivering portions of the total dose in parallel. Specifically, as explained above with respect to Equation 1, the needle length (L) and needle gauge (identified as the radius R of the needle's lumen) may significantly affect the pressure required to deliver a desired amount of drug. Thus, the use of a "parallel delivery" device of the type shown and described herein may facilitate delivery of viscous drugs, such as certain large or macromolecular injectables, including carbohydrate-derived dosage forms, lipids, nucleic acids, hyaluronidase, proteins / peptides (e.g., monoclonal antibodies), and other biotechnology-derived drugs. Any of the gas venting mechanisms, electronic circuit systems, or other components described herein may be included in a dual container device of the type shown and described in PCT No. 4345 or PCT No. 0040.

[0199]

[1241] For example, any of the elastomeric members described herein can be made of any suitable material or combination of different materials. For example, in some embodiments, at least a portion of any of the elastomeric members described herein can be coated. Such a coating can include, for example, polydimethylsiloxane. In some embodiments, at least a portion of any of the elastomeric members described herein can be coated with a coating having a viscosity of about 0.02 mg / cm. 2 ~about 0.80mg / cm 2 The coating may be coated with an amount of polydimethylsiloxane.

[0200]

[1242] Any of the drug container assemblies described herein can have any suitable size (e.g., length and / or diameter) and contain any suitable amount of drug. In some embodiments, any of the drug container assemblies described herein can be a prefilled (or prefillable) syringe, such as a syringe manufactured by Becton Dickinson, Gehresheim, Ompipharma, or the like. For example, in some embodiments, the drug container assembly 4200 (and any of the drug container assemblies described herein) can be a Becton Dickinson "BD Hypak Physiolis" prefillable syringe containing any of the drugs described herein. Additionally, any of the drug delivery devices and / or medical injectors described herein can be configured to inject any suitable dose, such as, for example, a dose of up to 1 mL, of any of the drugs described herein. In other embodiments, any of the drug delivery devices and / or medical injectors described herein can be configured to inject up to 2 mL, 3 mL, 4 mL, 5 mL, or more doses of any of the drugs described herein.

[0201]

[1243] Any of the container bodies described herein can be made of glass and can be attached to and / or coupled to any suitable needle. For example, in some embodiments, any of the container bodies described herein (including the container body 4210) can be coupled to any suitable size needle. Any of the drug container assemblies and / or pre-filled syringes described herein can be coupled to needles with gauge sizes of 21 gauge, 22 gauge, 23 gauge, 24 gauge, 25 gauge, 26 gauge, 27 gauge, 28 gauge, 29 gauge, 30 gauge, or 31 gauge. Any of the drug container assemblies and / or pre-filled syringes described herein can be coupled to needles of any suitable length, such as, for example, about 0.2 inches, about 0.27 inches, about 0.38 inches, about 0.5 inches, about 0.63 inches, about 0.75 inches, or longer. In some embodiments, any of the drug containers and / or pre-filled syringes described herein can be coupled to a 29 gauge needle with a length of about 0.5 inches. Additionally, any of the medication containers and / or pre-filled syringes described herein may include a needle secured to a distal end thereof.

[0202]

[1244] For example, any of the medical injectors shown and described herein may include a base (or distal actuator) having a mechanism for cooling a surface at a target injection site. Cooling the target injection site may increase patient comfort during the injection procedure. Such cooling mechanisms may include, for example, an electronic cooler (e.g., a thermoelectric cooler) that is triggered when a safety guard is removed, a chemical or spray that is released from the base when the safety guard is removed, or any other suitable mechanism.

[0203]

[1245] Any of the medical injectors shown and described herein may include a base (or distal actuator) having a mechanism for expanding, stretching, or otherwise tauting the patient's skin at or near the injection site. In other embodiments, the base (or distal actuator) of any of the injectors described herein may include a mechanism for increasing the surface area of ​​the base (or distal actuator) that contacts the injection site. For example, in some embodiments, the base may include a series of grips, protrusions, microneedles, etc. that allow the base to expand to grip the skin and stretch the surface prior to actuation and / or injection, or allow a large contact surface area that contacts the skin to add stability for administration of the injection fluid. In other embodiments, the base may include a series of grips, protrusions, microneedles, etc. that allow the base to grip the skin together and pinch the surface prior to actuation and / or injection. Such a base may include a dome or other structure to pinch a particular portion of the anatomy, such as the abdomen, for example.

[0204]

[1246] Although the medical injectors shown and described above include a delivery mechanism (e.g., 4300) that includes the release of pressurized gas, in other embodiments, the drug delivery device can include any suitable method of delivery of a drug disposed therein. For example, in some embodiments, any of the devices described herein can include a mechanical energy storage member (e.g., springs, gears, racks, pinions, pulleys, etc.) rather than a compressed gas container. In other embodiments, any of the devices described herein can include any other suitable energy storage member (e.g., magnetic, electrical, propellant-based, chemical reaction-based, etc.).

[0205]

[1247] Although the medical injector is described herein as a "pistonless" gas-powered autoinjector, in other embodiments, any medical injector may include any suitable energy storage member configured to generate a force directly on the drug container and / or carrier (e.g., as described in the '849 patent). For example, in some embodiments, the medical injector may include one or more biasing members, springs, and / or any other suitable mechanical drive (as discussed above) configured to exert a force on one or more drug containers. By way of example, the medical injector may include a first spring configured to generate a force on a first drug container and a second spring configured to generate a force on a second drug container substantially equal to the force generated by the first spring. Additionally, the first and second springs may be actuated substantially simultaneously and / or via the same actuation event such that the first and second springs move the first and second drug containers substantially simultaneously.

[0206]

[1248] Although particular injection events, mechanisms, devices, and / or components are described herein, it should be understood that these are presented by way of example and not limitation, that is, an autoinjector can include two or more drug containers and can be configured to deliver at least one dose of drug to a patient in response to any suitable actuation event, etc.

[0207]

[1249] Any of the devices and / or drug containers shown and described herein can be made of any suitable material, including glass, plastic (including thermoplastics such as cyclic olefin copolymers), or any other material used in the manufacture of pre-filled syringes containing drugs.

[0208]

[1250] Any of the devices and / or drug containers shown and described herein can accommodate and / or deliver a wide range of large or macromolecular injectables, including carbohydrate-derived dosage forms, lipids, nucleic acids, nucleic acids, hyaluronidase, proteins / peptides (e.g., monoclonal antibodies), and other biotechnology-derived drugs. For example, anti-tumor necrosis factor formulations such as infliximab, etanercept, adalimumab, golimumab, natalizumab, vedolizumab, and certolizumab can be administered using the autoinjectors described herein. Other macromolecular injectable drugs that can be administered using the devices and / or drug containers shown and described herein include viscous drugs that target inflammatory cytokines (e.g., IL-1, IL-2, IL-4, IL-5, IL-6, IL-12, IL-13, IL-23, IL-17, IL-21, IL-23A, and associated receptors), including dupilumab, sarilumab, mepolizumab, benralizumab, reslizumab, lebrikizumab, ustekinumab, anrunkinzumab, bertilimumab, tralokinumab, and risankizumab. Large anti-adhesion molecules for treating various diseases, including etrolizumab and batelizumab, can be administered using the devices and / or drug containers shown and described herein. Still other large and viscous monoclonal antibodies that can be administered using the devices and / or drug containers shown and described herein include tezepelumab, anifrolumab, omalizumab, and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors, including alirocumab and evolocumab.

[0209]

[1251] Any of the devices and / or drug containers shown and described herein may contain any suitable drug or therapeutic agent. In some embodiments, the drug contained in any of the drug containers shown herein may be a vaccine, such as, for example, influenza vaccine, hepatitis vaccine, influenza type B (HiB) vaccine, measles vaccine, mumps vaccine, rubella vaccine, or combination vaccine (e.g., measles, mumps, and rubella, quadrivalent, or hexavalent vaccine), polio vaccine, human papillomavirus (HPV) vaccine, tetanus vaccine, diphtheria vaccine, whooping cough vaccine, bubonic plague vaccine, yellow fever vaccine, cholera vaccine, malaria vaccine, smallpox vaccine, pneumococcal vaccine, rotavirus vaccine, chickenpox vaccine, dengue vaccine, rabies vaccine, and / or meningococcal vaccine. In other embodiments, the drug contained in any of the drug containers shown herein may be a catecholamine, such as epinephrine. In other embodiments, the medication contained in the medication containers depicted herein may be an opioid receptor antagonist, such as naloxone, including any of the naloxone formulations described in U.S. Patent No. 8,627,816, filed February 28, 2011, entitled "Medicament Delivery Device for Administration of Opioid Antagonists Including Formulation for Naloxone."In still other embodiments, the pharmaceutical agent contained in any of the pharmaceutical containers provided herein can include peptide hormones (such as insulin or glucagon), human growth hormone (HGH), sumatriptan, corticosteroids (such as dexamethasone), ondansetron, opioid agonist receptor modulators (such as fentanyl), partial agonist opioid receptor modulators (such as buprenorphine), mixed agonist / antagonist opioid receptor modulators (such as nalbuphine), benzodiazepines (such as diazepam, midazolam, or lorazepam), erythropoietin stimulating agents (ESAs) (such as darbepoetin alfa), immunoglobulins (such as dual variable domain immunoglobulins), interferons, anti-cancer, recombinant human granulocyte colony stimulating factors (GCSFs) (such as pegfilgrastim), icatibant, and other therapies suitable for infusion into a mammal. In still other embodiments, the medication contained in any medication container provided herein may be a placebo substance (ie, a substance that does not contain an active ingredient), such as water.

[0210]

[1252] The drug container and / or drug delivery device disclosed herein can contain any suitable amount of any drug. For example, in some embodiments, as shown herein, the drug delivery device can be a single dose device containing about 0.4 mg, 0.8 mg, 1 mg, 1.6 mg, or 2 mg of drug to be delivered. As previously described, the loading amount can be such that the ratio of the delivered amount to the loading amount is any suitable value (e.g., 0.4, 0.6, etc.). In some embodiments, the electronic circuit system can include a "configuration switch" that, when actuated during assembly of the delivery device, can select an electronic output that corresponds to a dose contained in the drug container.

[0211]

[1253] In some embodiments, the medical injector can include two pre-filled syringes, each containing up to 1 mL (or more) of a drug and also carrying a needle. Such devices (e.g., "dual container devices") are shown and described in PCT No. 4345, which is incorporated herein by reference. Upon actuation of the device (as described above), a single energy storage member (e.g., compressed gas container) can release energy to move the two containers in the housing in substantially the same operation to inject the two needles. The force generated by the energy storage member can further inject a drug from each container. In such embodiments, the two containers can contain the same drug or two different drugs. For example, the dual container device can be filled and / or used to inject methotrexate (from one container) and tocilizumab (from the other container) for the treatment of rheumatoid arthritis.In some embodiments, the dual container device is configured to administer tocilizumab and methotrexate for the treatment of rheumatoid arthritis, adalimumab and methotrexate for the treatment of psoriasis or rheumatoid arthritis, etanercept and methotrexate for the treatment of psoriatic arthritis, belimumab and rituximab for the treatment of primary Sjogren's syndrome, lanreotide autogel and pegvisomant for the treatment of acromegaly, narlaprevir and ritonavir for the treatment of chronic hepatitis C, alemtuzumab and rituximab for the treatment of chronic lymphocytic leukemia, pertuzumab and trastuzumab for the treatment of HER2 positive early breast cancer, long acting insulin glargine and rapid acting insulin lispro for the treatment of type 2 diabetes, ribavirin and ribavirin for the treatment of type 1 diabetes, ribavirin and ribavirin for the treatment of type 2 ... and insulin for the treatment of type 1 diabetes, insulin glargine and insulin lispro for the treatment of type 1 diabetes, mosunetuzumab and anzolizumab for the treatment of neoplasms, nivolumab and tumor infiltrating lymphocytes with interleukin 2 for the treatment of metastatic melanoma, pertuzumab and trastuzumab for the treatment of HER2 positive early breast cancer, ocrelizumab and recombinant human hyaluronidase for the treatment of multiple sclerosis, daratumumab and recombinant human hyaluronidase for the treatment of multiple myeloma, nivolumab and recombinant human hyaluronidase for the treatment of metastatic tumors, and insulin lispro and recombinant human hyaluronidase for the treatment of diabetes mellitus.

[0212]

[1254] Any of the drug containers described herein may include any suitable elastomeric member and / or plunger. For example, the elastomeric member may be made to be compatible with the drug contained in the drug container. Additionally, the drug container may include any number of elastomeric members. For example, in some embodiments, the drug container may include a dry portion of the drug and a fluid portion of the drug configured to be mixed prior to injection. The piston portion of the drug delivery mechanism may be configured to engage multiple elastomeric members associated with the portions of the drug. In this manner, the multiple elastomeric members may be engaged to mix the dry and fluid portions of the drug prior to completing the injection event. In some embodiments, for example, any of the devices shown and described herein may include a mixing actuator similar to the mixing actuator shown and described in U.S. Patent No. 9,173,999, entitled "Devices and Methods for Delivering Medicaments from a Multi-Chamber Container," filed on January 25, 2012, which is incorporated herein by reference in its entirety.

[0213]

[1255] Although the injectors described herein are shown and described as including a mechanism for needle retraction, in other embodiments, any of the injectors shown and described herein can include a needle shield that extends distally after injection to cover the exposed needle. Such designs can be used, for example, in the "pistonless" designs described above. For example, in some embodiments, the base of the medical injector (e.g., base 4510) can be (or can include) an extension that extends distally to cover the needle once injection is complete. In some such embodiments, the gas vent assembly can redirect all or a portion of the pressurized gas into a volume within the housing. The redirected gas can then exert a force on the base (or a portion of the base) to extend the base (or a portion of the base) to cover the needle. In other such embodiments, a spring, biasing member, or retraction member can urge the base (or a portion of the base) distally.

[0214]

[1256] Although the gas vent assembly 4310 is shown and described herein as moving a valve portion relative to a seal to selectively fluidly connect the internal gas chamber with the exterior volume, in other embodiments, any gas vent assembly disclosed herein may be operable to vent all or a portion of the pressurized gas to a second region within the housing. Additionally, any gas vent assembly disclosed herein may include any suitable valve arrangement. For example, in some embodiments, the gas vent assembly and / or a portion of the housing may include a tear-through seal that is pierced or torn when a portion of the medication carrier or a portion of the elastomeric member moves past a particular point during a delivery event. In other embodiments, the gas vent assembly and / or a portion of the housing may include a movable valve member (e.g., a poppet, ball, etc.) that moves to release pressure when a portion of the medication carrier or a portion of the elastomeric member moves past a particular point during a delivery event.

[0215]

[1257] Although various embodiments have been described as having particular combinations of features and / or components, other embodiments are possible having combinations of any features and / or components from any of the embodiments, where appropriate. For example, any of the devices shown and described herein may include the electronic circuitry systems described herein.

Claims

1. a housing defining a gas chamber; an energy storage member configured to generate pressurized gas when the energy storage member is actuated; a carrier disposed within the housing, a proximal surface of the carrier defining a portion of a boundary of the gas chamber, the gas chamber configured to receive the pressurized gas to pressurize the gas chamber; and a medicament container coupled to the carrier, a distal end portion of the medicament container configured to couple to a delivery member, the medicament container containing a medicament and including an elastomeric member that seals the medicament within the medicament container; a delivery control mechanism coupled to a proximal end portion of the drug container, the delivery control mechanism including a flow restricting member acting on the elastomeric member and configured to regulate the flow of the pressurized gas into the drug container.

2. The apparatus of claim 1 , wherein the flow restricting member comprises at least one of a single port valve, a multi-port valve, or a porous member.

3. the delivery member being a needle coupled to the distal end portion of the medicament container; the carrier is configured to move from a first carrier position to a second carrier position in response to the pressurized gas being delivered into the gas chamber such that the needle moves from a first needle position, where the needle is disposed within the housing, to a second needle position, where a portion of the needle extends from the housing; The apparatus of claim 1 , wherein the flow restricting member is configured to restrict movement of the elastomeric member before the carrier is disposed at the second carrier location.

4. the gas chamber is a first gas chamber; the portion of the boundary of the gas chamber defined by the carrier is a first portion of the boundary of the first gas chamber; a proximal end portion of the flow restricting member defining a second portion of the boundary of the first gas chamber; a distal end portion of the flow restricting member defining a first portion of a boundary of a second gas chamber; a proximal end portion of the elastomeric member defining a second portion of the boundary of the second gas chamber; 4. The apparatus of claim 3, wherein the flow restricting member is configured to allow pressurized gas to pass from the first gas chamber through the flow restricting member and into the second gas chamber after the carrier is positioned at the second carrier position.

5. 5. The device of claim 4, wherein the elastomeric member moves a stroke distance within the drug container in response to the pressurized gas being delivered into the second gas chamber to deliver a dose of the drug from the drug container through the needle.

6. 2. The device of claim 1, wherein the delivery control mechanism includes a first body portion and a second body portion, the second body portion extending from the first body portion, the first body portion defining a first axis and the second body portion defining a second axis, the second axis being non-parallel to the first axis.

7. The device of claim 6 , wherein the medicament container defines a third axis, the third axis of the medicament container being parallel to the first axis of the first body portion.

8. The device of claim 6 , wherein the second body portion of the delivery control mechanism includes a flow restricting retainer, the flow restricting member being at least partially supported within the flow restricting retainer.

9. 7. The device of claim 6, wherein the first body portion of the delivery control mechanism includes a proximal end portion and a distal end portion, the distal end portion being opposite the proximal end portion, the distal end portion including a radially extending flange configured to attach to at least one of the proximal end portion of the carrier or the drug container.

10. The device of claim 9 , wherein the distal end portion of the first body portion extends into the proximal end portion of the drug container.

11. 2. The device of claim 1, wherein the flow restricting member comprises a flow restricting retainer and a flow restricting member disposed within the flow restricting retainer, the flow restricting retainer comprising a radially extending flange configured to attach to at least one of the proximal end portion of the carrier or the drug container.

12. 12. The device of claim 11, wherein a distal end portion of the flow-restricting retainer extends into the proximal end portion of the drug container, the flow-restricting retainer defining a first axis, and the drug container defining a second axis, the second axis being parallel to the first axis.

13. An apparatus according to any one of claims 8 to 12, wherein the first body portion includes an annular groove configured to retain a seal member.

14. The apparatus of claim 13 , wherein the sealing member is an O-ring.

15. The apparatus of any one of claims 3 to 5, further comprising a retraction spring coupled to the housing, the retraction spring configured to bias the carrier toward the first carrier position.

16. 6. The apparatus of claim 3, further comprising a retraction spring coupled to the housing, the retraction spring configured to move the carrier toward the first carrier position in response to the pressurized gas being delivered from the gas chamber through an opening in the housing.

17. the delivery member comprises a needle; The device according to any one of claims 1 to 12, wherein the drug container is a pre-filled syringe, and the needle is fixed to a distal end portion of a container body of the pre-filled syringe.

18. The device of any one of claims 1 to 12, wherein the medicament in the medicament container is one of a drug or a biological product.

19. The device of any one of claims 1 to 12, wherein the drug in the drug container has a viscosity of 100 centipoise or greater at room temperature.

20. The device of any one of claims 1 to 12, wherein the drug in the drug container comprises a high molecular weight compound of greater than 5 kDa.

21. the carrier is a first carrier, the portion of the boundary of the gas chamber is a first portion of the boundary, the medicament container is a first medicament container, the elastomeric member is a first elastomeric member, the medicament is a first medicament, the delivery member is a first delivery member, the delivery control mechanism is a first delivery control mechanism, and the flow restriction member is a first flow restriction member; The device further comprises a second carrier disposed within the housing and a second medicament container coupled to the second carrier; a proximal surface of the second carrier defines a second portion of the boundary of the gas chamber; a distal end portion of the second medicament container configured to be coupled to a second delivery member, the second medicament container containing a second medicament and including a second elastomeric member sealing the second medicament within the second medicament container; 2. The device of claim 1, wherein a second delivery control mechanism is coupled to a proximal end portion of the second drug container, the second delivery control mechanism including a second flow restricting member acting on the second elastomeric member and configured to regulate the flow of the pressurized gas into the second drug container.

22. the first delivery member being a first needle coupled to the distal end portion of the first medicament container; 22. The device of claim 21, wherein the second delivery member is a second needle coupled to the distal end portion of the second medicament container.

23. 22. The device of claim 21, wherein the first medicament container is non-coaxial with the second medicament container.

24. 22. The device of claim 21, wherein the first medicament container and the second medicament container are configured to move simultaneously within the housing in response to the pressurized gas being delivered into the gas chamber.

25. a housing defining a gas chamber, a sidewall of the housing defining an opening configured to selectively fluidly connect the gas chamber to an exterior volume; an energy storage member configured to generate pressurized gas when the energy storage member is actuated; and a carrier disposed within the housing, a proximal surface of the carrier defining a portion of a boundary of the gas chamber, the gas chamber configured to receive the pressurized gas to pressurize the gas chamber; and a medicament container coupled to the carrier, a distal end portion of the medicament container configured to couple to a delivery member, the medicament container containing a medicament and including an elastomeric member that seals the medicament within the medicament container; a delivery control mechanism coupled to a proximal end portion of the medicament container, the delivery control mechanism including a flow restricting member acting on the elastomeric member and configured to regulate the flow of the pressurized gas into the medicament container; a valve member configured to seal the opening in the housing when the valve member is in a first position and to unseal the opening in the housing when the valve member is in a second position to place the gas chamber in fluid communication with the exterior volume.

26. the expandable assembly further comprising a first member, a second member, and a third member, the first member coupled to the elastomeric member, the second member coupled between the first member and the third member, a portion of the second member movably disposed within the delivery control mechanism, and the third member coupled to the valve member, the expandable assembly configured to transition from a first configuration to a second configuration when the elastomeric member moves within the medicament container; 26. The device of claim 25, wherein the valve member moves from the first position to the second position when the expandable assembly transitions from the first configuration to the second configuration to release the pressurized gas from the gas chamber to the exterior volume.

27. the delivery control mechanism defines a bore within which the portion of the second member of the expandable assembly is movably disposed; 27. The apparatus of claim 26, wherein an outer surface of the second member and an inner surface of the bore define an annulus in fluid communication with the flow restricting member.

28. 28. The device of claim 27, wherein the annulus is configured to deliver pressurized gas received from the flow restricting member to the drug container.

29. 30. The device of claim 28, wherein the elastomeric member moves a stroke distance within the drug container to expel a dose of the drug from the drug container in response to the pressurized gas being delivered into the drug container.

30. 28. The device of claim 27, wherein the delivery control mechanism includes a seal member configured to limit pressurized gas received from passage between the second member of the expandable assembly and the bore of the delivery control mechanism.

31. 27. The device of claim 26, wherein the second member of the expandable assembly includes at least a flange portion configured to contact a distal end portion of the delivery control mechanism in the first configuration of the expandable assembly.

32. 32. The device of claim 31, wherein the second member and the delivery control mechanism are configured to move together from a first position to a second position in response to pressurized gas being directed into the gas chamber.

33. the first member is a flexible member configured to transition from a first length when the flexible member is in a collapsed state to a second length when the flexible member is in an expanded state when the elastomeric member moves within the medicament container; 33. The device of claim 32, wherein the flexible member is configured to exert an ejection force on the second member to move the second member axially relative to the delivery control mechanism when the flexible member transitions from the collapsed state to the expanded state.

34. 34. The device of claim 33, wherein axial movement of the second member transmits the ejection force to the third member to move the valve member relative to the opening.

35. The second member defines an internal bore; the third member includes a shaft member having a proximal end portion and a distal end portion; the proximal end portion of the third member is coupled to the valve member; the distal end portion of the third member includes an end stop member; 27. The apparatus of claim 26, wherein the internal bore of the second member is configured to slide along the shaft member between the valve member and the end stop member in response to pressurized gas being delivered into the gas chamber.

36. 27. The apparatus of claim 26, wherein the valve member includes a valve portion defining a gas release path, the valve portion being disposed within the opening of the housing such that the gas release path is fluidly isolated from the gas chamber via a seal member when the expandable assembly is in the first configuration.

37. 27. The device of claim 26, wherein the expandable assembly has a first size when in the first configuration and a second size when in the second configuration, the second size being sized to place the gas chamber in fluid communication with the external volume after the valve member is actuated and drug is delivered from the drug container.

38. the first configuration is a folded configuration; the second configuration is an expanded configuration; the first member is a flexible member configured to transition from a first length when the flexible member is in a collapsed state to a second length when the flexible member is in an expanded state when the elastomeric member moves within the medicament container; 27. The apparatus of claim 26, wherein the flexible member is configured to exert an ejection force on the valve member to move the valve member relative to the opening when the expandable assembly transitions from the collapsed configuration to the expanded configuration placing the gas chamber in fluid communication with the exterior volume.

39. 40. The device of claim 38, wherein the flexible member is at least one of a filament or a band.

40. 40. The device of claim 38 or 39, wherein the valve member moves in the distal direction when the flexible member transitions from the collapsed configuration to the expanded configuration and as the elastomeric member continues to move in the distal direction.

41. the first member of the expandable assembly is coupled to the elastomeric member via a coupling member, the coupling member including a retention structure; 40. The device of claim 38 or 39, wherein the third member of the expandable assembly includes a locking projection configured to engage the retaining structure of the first member when the flexible member is in the collapsed configuration, the locking projection configured to release from the retaining structure when gas pressure within the drug container exceeds a threshold pressure value.

42. Housing and a medicament container disposed within the housing, a distal end portion of the medicament container configured to couple to a delivery member, the medicament container containing a medicament and including an elastomeric member that seals the medicament within the medicament container; an electronic circuit system coupled to the housing; The electronic circuit system includes: a sensing unit configured to detect a position of the elastomeric member relative to the medicament container and generate an electronic signal associated with at least one of a position, a velocity, or an acceleration of the elastomeric member; a delivery module implemented in at least one of a memory or a processing device, the delivery module configured to receive the electronic signal and determine a movement profile of the elastomeric member based on the electronic signal; and and an output module configured to generate at least one of an audio output, a visual output, or a wireless signal associated with the movement profile of the elastomeric member.

43. 43. The device of claim 42, wherein the movement profile includes at least one of a current position of the elastomeric member, a speed of travel of the elastomeric member, a delivery rate of the drug from the drug container, or a time remaining to complete delivery of a dose of the drug from the drug container.

44. 43. The apparatus of claim 42, wherein the sensing unit includes an infrared emitter and an infrared receiver.

45. 43. The apparatus of claim 42, wherein the sensing unit includes a plurality of light emitters and a plurality of detectors, each of the plurality of detectors configured to receive a light beam generated by a corresponding one of the plurality of light emitters.

46. The medicament container extends from a first end portion to a second end portion; 46. ​​The apparatus of claim 45, wherein the plurality of optical emitters and the plurality of detectors are spaced along a length of the drug container between the first end portion and the second end portion.

47. The electronic circuit system further comprises:

43. The apparatus of claim 42, further comprising a prediction module implemented in at least one of the memory or the processing device, the prediction module configured to determine a remaining time to complete delivery of a dose of the medication based on the movement profile received over a period of time.

48. 48. The device of claim 47, wherein the audio output, the visual output, or the wireless signal indicates the time remaining to complete delivery of the dose of the medication.

49. 1. A computer-implemented method comprising: emitting a first light beam from a first emitter, through a medicament container, toward a first receiver, the medicament container being positioned between the first emitter and the first receiver, the medicament container including an elastomeric member that contains a medicament and seals the medicament within the medicament container, the first receiver configured to generate a first electronic signal associated with a magnitude of the first light beam; emitting a second light beam from a second emitter, through the medicament container, toward a second receiver, the medicament container being positioned between the second emitter and the second receiver, the second receiver being configured to generate a second electronic signal associated with a magnitude of the second light beam; detecting at least one of the first electronic signal or the second electronic signal as the elastomeric member advances within the medicament container; and determining a position of the elastomeric member within the medicament container based on a comparison of the first electronic signal and the second electronic signal.

50. 50. The computer-implemented method of claim 49, further comprising determining a speed of advancement of the elastomeric member based on a time difference between when the first electronic signal falls below a threshold and when the second electronic signal falls below the threshold.

51. 50. The computer-implemented method of claim 49, further comprising determining a delivery rate of the medication from the medication container based on a time difference between when the first electronic signal falls below a threshold and when the second electronic signal falls below the threshold.

52. 50. The computer-implemented method of claim 49, further comprising determining a remaining completion time to complete delivery of a dose of the medication from the medication container based on a time difference between when the first electronic signal falls below a threshold and when the second electronic signal falls below the threshold.

53. 50. The computer-implemented method of claim 49, wherein the first emitter and the second emitter are configured to transmit at least one wavelength in the ultraviolet, visible, or infrared spectrum.

54. 50. The computer-implemented method of claim 49, wherein the first emitter and the second emitter are configured to transmit infrared beams.

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