Device and method for delivery of a substance in a pre-filled syringe

Abstract

The device includes a housing, a gas container, a drug container assembly, and a movable seal member, the housing defining a gas chamber and an equalization bypass. The gas container is disposed within the housing and configured to generate pressurized gas in the gas chamber when the device is activated. The movable seal member is configured to move from a first sealing position to a second sealing position. When the movable seal member is in the first sealing position, the gas chamber is in fluid communication with an external volume surrounding the device via the equalization bypass. When the movable seal member is in the second sealing position, the gas chamber is fluidly isolated from the external volume by the movable seal member.

Description

[Technical Field]

[0001]

[1001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 428,557, entitled "Devices and Methods for Delivery of Substances Within a Prefilled Syringe," filed November 29, 2022, which is incorporated herein by reference in its entirety. [Background technology]

[0002]

[1002] FIELD OF THE INVENTION The embodiments described herein relate to drug delivery devices, pharmaceutical compositions, and drug products. More particularly, the embodiments described herein relate to drug delivery devices for delivery of drugs contained in pre-filled syringes.

[0003]

[1003] Known pre-filled syringes are generally used to fill and inject medications. Known pre-filled syringes include a syringe body (often made of glass) containing a medication. A needle is fixed to the distal end portion of some known pre-filled syringes (i.e., the needle is permanently attached to the syringe body during manufacturing). The end of the needle is disposed within 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 known pre-filled syringes defines a portion of the container closure and includes a plunger (usually made of an elastomer) that can move within the syringe body to inject the medication. The proximal end portion also includes a flange that allows a user to grasp the syringe body and manually apply force to the piston to move the plunger, thereby injecting the medication.

[0004]

[1004] Although pre-filled syringes can be cost-effective devices for storing and delivering medications, known methods for using pre-filled 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 needle punctures. Therefore, known pre-filled syringes are often used by medical professionals trained in such procedures. To facilitate self-administration of medications contained in pre-filled syringes, some known auto-injectors are adapted to accommodate pre-filled syringes. These known devices include a stored energy source for needle insertion and / or medication injection.

[0005]

[1005] However, known auto-injectors are often designed for a specific size and / or shape of medication container and are therefore often not configured to accept known pre-filled syringes. For example, using a pre-filled syringe in a known auto-injector often applies a large force to the flange of the syringe body during an insertion operation, which can lead to damage to the syringe flange or body. Furthermore, many known pre-filled syringes have a fixed needle that is in fluid communication with the medication, making it undesirable to apply force to the plunger during storage and / or insertion. For example, applying force to the plunger during storage can cause medication 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 can cause the medication to be injected before the needle is inserted into the desired location. Similarly, some known auto-injectors are not configured to control the force applied to the plunger within the syringe body during storage and / or needle insertion.

[0006]

[1006] Known autoinjectors configured to incorporate pre-filled syringes often include a spring-based actuation system that moves a piston rod to insert a needle and inject a drug. However, the need to incorporate a piston rod can result in the size (e.g., length) of such known systems being unnecessarily large. Furthermore, known drugs or therapeutic substances are formulated to contain high molecular weight compounds, compounds with complex molecular structures, living cells, and / or biologics. Such drugs often have very high viscosities (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 a spring-based actuation system in an autoinjector may be incompatible with the force and pressure required to properly deliver drugs or therapeutic substances containing high molecular weight compounds. Therefore, many known autoinjectors that accommodate pre-filled syringes may be unable to provide adequate force and / or generate 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 within the substance, thereby reducing its effectiveness. Also, to prevent accidental needle sticks, known autoinjectors that include automatic needle retraction after drug delivery often include one or more guide shafts or linkages to detect the completion of drug delivery and initiate the retraction process. The guide shafts and linkages introduce additional friction into the drug delivery process, which works against providing the desired delivery rate and conditions. Furthermore, the guide shafts and linkages require additional internal housing space, thereby increasing the overall size and bulk of the autoinjector.

[0007]

[1007] To address the challenges associated with spring-based actuation systems, some known systems use pressurized gas to generate the necessary insertion and / or drug delivery forces. Typically, such systems utilize a gas chamber that receives pressurized gas from a gas container when the system is actuated. The gas chamber is typically sealed during manufacture and has an internal pressure that corresponds to the atmospheric pressure at the time of manufacture. Therefore, in such known systems, changes in the pressure and / or temperature of the device's environment can create a pressure differential between the pressure in the gas chamber and the atmospheric pressure surrounding the device. This pressure differential can adversely affect the device during storage and / or the device's functionality during actuation. For example, when a device is exposed to a higher altitude than the location of manufacture (e.g., during air transport), the pressure surrounding the device can be less than the pressure in the gas chamber. In such cases, the greater pressure in the gas chamber can cause leakage of the drug. Similarly, when a device is exposed to a lower altitude than the location of manufacture, the pressure surrounding the device can be greater than the pressure in the gas chamber. In such cases, the negative pressure differential can prevent complete delivery of the drug upon actuation of the device.

[0008]

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

[0009]

[1009] Described herein is a medication delivery device for administration of medication contained within a pre-filled syringe.

[0010] In some embodiments, the device includes a housing, a gas container, a drug container assembly, and a movable seal member. The housing defines a gas chamber and an equalization bypass. The gas container is configured to generate pressurized gas in the gas chamber when the device is activated. The drug container assembly is positioned within the housing and includes a container body and an elastomeric member. The elastomeric member is positioned within the container body and configured to move within the container body to deliver the drug contained therein. The elastomeric member is configured to move within the container body in response to a force exerted by the pressurized gas in the gas chamber. A movable seal member is also positioned within the housing. The movable seal member is configured to move from a first sealing position to a second sealing position. When the movable seal member is in the first sealing position, the gas chamber is in fluid communication with an external volume surrounding the housing via the equalization bypass. However, when the movable seal member is in the second position, the gas chamber is fluidly isolated from the external volume by the movable seal member.

[0011]

[1010] In some embodiments, the device includes a system actuator assembly having an emission member and a perforator coupled to the emission member. The emission member is movable within the housing between a first emission member position and a second emission member position. The perforator is spaced apart from the gas container when the emission member is in the first emission member position. The perforator pierces a portion of the gas container when the emission member is in the second emission member position. A movable seal is coupled to the emission member. The movable seal is in a first sealing position when the emission member is in the first emission member position. The movable seal is in a second sealing position when the emission member is in the second emission member position.

[0012]

[1011] In some embodiments, the device includes a system actuator assembly having an ejection member, a perforator, and an actuation spring disposed within a housing. The ejection member is movable within the housing. Prior to actuation of the device, the ejection member is in a locked configuration and the actuation spring is in a stored energy configuration. Upon actuation of the device, the ejection member moves to the ejection configuration in response to an actuation force provided by the actuation spring on the ejection member. The perforator is coupled to the ejection member and positioned to pierce the gas container in response to the ejection member transitioning from the locked configuration to the ejection configuration. A movable seal is coupled to the ejection member and positioned between the ejection member and an inner wall of the housing. The movable seal is in a first sealing position when the ejection member is in the locked configuration, and the movable seal is configured to move to a second sealing position in response to the ejection member transitioning from the locked configuration to the ejection configuration.

[0013]

[1012] In some embodiments, the system actuator assembly includes a positioning member coupled to the ejection member. The positioning member has a first shape when the ejection member is in the locked configuration and a second shape when the ejection member is in the ejection configuration. The positioning member engages a receiving portion of the housing when in the second shape. The movable seal is maintained in a third sealing position when the positioning member engages the receiving portion of the housing. The gas chamber is fluidly isolated from the exterior volume by the movable seal member when in the third sealing position. In some embodiments, the third sealing position is between the first sealing position and the second sealing position along the path of motion.

[0014]

[1013] In some embodiments, the device includes a carrier configured to couple to the medicament container assembly and move within the housing in response to a force exerted by the pressurized gas, the proximal surface of the carrier defining a portion of the boundary of the gas chamber.

[0015]

[1014] In some embodiments, the movable seal is coupled to the carrier and positioned between the carrier and the interior wall of the housing, such that movement of the carrier in response to a force exerted by the pressurized gas moves the movable seal from a first sealing position to a second sealing position relative to the housing to separate the gas chamber from the exterior volume.

[0016]

[1015] In some embodiments, the device includes a gas vent assembly configured to selectively place the gas chamber in fluid communication with an external volume. The gas vent assembly includes a valve member configured to seal a vent opening defined by the housing. The valve member closes the vent opening when in a first valve position prior to activation of the device, and the valve member is configured to move within the housing from the first valve position to a second valve position in response to movement of the elastomeric member. The gas chamber is in fluid communication with the external volume through the vent opening when the valve member is in the second valve position.

[0017]

[1016] In some embodiments, the device includes an expandable assembly having 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, and 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 container body. The valve member moves from a first valve position to a second valve 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.

[0018]

[1017] In some embodiments, the vent port is sized to maintain the force of the pressurized gas in the gas chamber at a magnitude greater than the force exerted by the retraction spring during the time the drug is dispensed, and the force of the pressurized gas decreases to a magnitude less than the force exerted by the retraction spring upon completion of drug dispensing.

[0019]

[1018] In some embodiments, the vent port is sized so that the pressurized gas dispenses 120% of the medication over a first period of time and the final 20% of the medication over a second period of time that is less than twice the first period of time.

[0020]

[1019] In some embodiments, the movable seal member is a first movable seal member. The device includes a carrier coupled to the drug container assembly and configured to move within the housing in response to a force exerted by the pressurized gas. A proximal surface of the carrier defines a first portion of a boundary of the gas chamber. A second movable seal member is coupled to the carrier and positioned between the carrier and an inner wall of the housing. The second movable seal member defines a second portion of the boundary of the gas chamber.

[0021]

[1020] In some embodiments, the movable seal is configured to move from a first position to a second position in response to a force exerted by pressurized gas in the gas chamber, the movable seal is configured to move from the second sealing position to a third sealing position in response to movement of the elastomeric member, and the gas chamber is in fluid communication with the exterior volume via the equalization bypass when the movable seal member is in the third sealing position.

[0022]

[1021] In some embodiments, the apparatus includes a gas vent assembly configured to selectively fluidly connect the gas chamber to an external volume. The gas vent assembly includes a valve member configured as a movable seal and a vent port defined by a housing. The valve member is configured to seal the vent port. The gas chamber is in fluid communication with the vent port via an equalization bypass when the valve member is in a first sealing position.

[0023]

[1022] In some embodiments, the device includes an expandable assembly. The expandable assembly has 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, and 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 container body. The valve member moves from a second sealing position to a third sealing 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.

[0024]

[1023] In some embodiments, the container body is movable within the housing from a first container position to a second container position in response to a force exerted by the pressurized gas. A movable seal member is coupled to the container body and positioned between the container body and an interior wall of the housing. Movement of the container body in response to the force exerted by the pressurized gas moves the movable seal relative to the housing from the first sealing position to the second sealing position, separating the gas chamber from the exterior volume.

[0025]

[1024] In some embodiments, the device includes a delivery control mechanism coupled to the medicament container assembly. The delivery control mechanism includes a flow restricting member acting on the elastomeric member to regulate the flow of pressurized gas into the container body. The medicament container assembly is configured to move from a first container position to a second container position in response to a force exerted by the pressurized gas, and the flow restricting member is configured to limit movement of the elastomeric member before the medicament container assembly is in the second container position.

[0026]

[1025] In some embodiments, the gas chamber is a first gas chamber. In such embodiments, the flow restricting member is configured to allow pressurized gas to pass from the first gas chamber to a second gas chamber, the second gas chamber being in fluid contact with the elastomeric member. A first portion of the pressurized gas in the first gas chamber has a first pressure magnitude, and a second portion of the pressurized gas in the second gas chamber has a second pressure magnitude. The first pressure magnitude is greater than the second pressure magnitude.

[0027]

[1026] In some embodiments, the device includes a needle coupled to a distal end portion of the container body. [Brief explanation of the drawings]

[0028] [Figure 1A]

[1027] A schematic diagram of a drug delivery device according to one embodiment in which the gas chamber is in fluid communication with the external volume surrounding the drug delivery device. [Figure 1B]

[1027] A schematic diagram of a drug delivery device according to one embodiment in which the gas chamber is fluidly isolated from the external volume. [Figure 2]

[1028] FIG. 10 is a front perspective view of a medical injector according to an embodiment, in a first configuration. [Figure 3]

[1029] FIG. 3 is a front perspective view of the medical injector shown in FIG. 2 with the electronic circuit system hidden and the safety lock removed. [Figure 4]

[1029] FIG. 3 is a rear perspective view of the medical injector shown in FIG. 2 with the electronic circuit system hidden and the safety lock removed. [Figure 5]

[1030] FIG. 3 is a perspective view of the housing of the medical injector shown in FIG. [Figure 6]

[1030] FIG. 6 is a cross-sectional view of the housing shown in FIG. [Figure 7]

[1032] FIG. 3 is a perspective view of the proximal cap of the medical injector shown in FIG. 2. [Figure 8]

[1032] FIG. 3 is a cross-sectional view of the proximal cap of the medical injector shown in FIG. [Figure 9]

[1001] FIG. 10 is a front view of the drug delivery mechanism of the medical injector shown in FIG. [Figure 10]

[1001] FIG. 10 is a front view of the drug delivery mechanism of the medical injector shown in FIG. [Figure 11]

[1033] FIG. 3 is a front view of the medical injector shown in FIG. 2 in a first configuration. [Figure 12]

[1034] FIG. 3 is a front cross-sectional view of the medical injector shown in FIG. 2 in a first configuration. [Figure 13A]

[1035] FIG. 13 is an enlarged cross-sectional view of a portion of the medical injector shown in FIG. 12 in a first configuration. [Figure 13B]

[1036] FIG. 13 is an enlarged cross-sectional view of a portion of the medical injector shown in FIG. 12 in a first configuration. [Figure 14A]

[1037] FIG. 13 is a perspective view of a delivery control mechanism of the medical injector shown in FIG. [Figure 14B]

[1037] FIG. 13 is a cross-sectional view of the delivery control mechanism of the medical injector shown in FIG. [Figure 15]

[1038] FIG. 14C is a cross-sectional view of the delivery control mechanism shown in FIGS. 14A and 14B within the proximal end portion of the drug container. [Figure 16]

[1039] FIG. 13 is a perspective view of the carrier assembly of the medical injector shown in FIG. [Figure 17]

[1039] FIG. 13 is a cross-sectional view of the carrier assembly of the medical injector shown in FIG. [Figure 18]

[1040] FIG. 13 is a perspective view of the carrier assembly of the medical injector shown in FIG. [Figure 19]

[1041] FIG. 13 is a cross-sectional view of the carrier assembly and drug container of the medical injector shown in FIG. [Figure 20]

[1042] FIG. 13 is an exploded view of the drug container assembly of the medical injector shown in FIG. [Figure 21]

[1043] FIG. 13 is a perspective view of the gas vent assembly of the medical injector shown in FIG. [Figure 22A]

[1044] FIG. 22 is a cross-sectional view of the gas vent assembly of FIG. 21 in a first configuration. [Figure 22B]

[1044] FIG. 22 is a cross-sectional view of the gas vent assembly of FIG. 21 in a second configuration. [Figure 22C]

[1044] FIG. 22 is a cross-sectional view of the gas vent assembly of FIG. 21 in a third configuration. [Figure 23]

[1045] FIG. 3 is a perspective view of the safety lock of the medical injector shown in FIG. 2, showing a needle sheath assembly coupled with the safety lock. [Figure 24]

[1045] FIG. 3 is a perspective view of a safety lock of the medical injector shown in FIG. 2. [Figure 25]

[1046] FIG. 3 is a perspective view of a system actuator of the medical injector shown in FIG. 2. [Figure 26]

[1046] FIG. 3 is a perspective view of a system actuator of the medical injector shown in FIG. 2. [Figure 27]

[1047] FIG. 3 is a front cross-sectional view of the medical injector shown in FIG. 2 in a second configuration (safety lock removed). [Figure 28]

[1048] FIG. 3 is a cross-sectional front view of the medical injector shown in FIG. 2 in a third configuration (activated). [Figure 29]

[1049] FIG. 10 is a front view of the medical injector shown in FIG. 2 in a fourth configuration (needle inserted). [Figure 30]

[1050] FIG. 10 is a cross-sectional front view of the medical injector shown in FIG. 2 in a fourth configuration (needle inserted). [Figure 31]

[1051] FIG. 10 is an enlarged cross-sectional view of the medical injector shown in FIG. 2 in a fourth configuration (needle inserted). [Figure 32]

[1052] FIG. 10 is a front view of the medical injector shown in FIG. 2 in a fifth configuration (medication being delivered). [Figure 33]

[1053] FIG. 10 is a cross-sectional front view of the medical injector shown in FIG. 2 in a fifth configuration (medication being delivered). [Figure 34]

[1054] FIG. 10 is a perspective cross-sectional view of the medical injector shown in FIG. 2 in a fifth configuration (medication being delivered). [Figure 35]

[1055] FIG. 10 is a front view of the medical injector shown in FIG. 2 in a sixth configuration (the gas chamber of the housing is vented). [Figure 36]

[1056] FIG. 10 is a cross-sectional front view of the medical injector shown in FIG. 2 in a sixth configuration (the gas chamber of the housing is vented). [Figure 37]

[1057] FIG. 10 is a perspective cross-sectional view of the medical injector shown in FIG. 2 in a sixth configuration (the gas chamber of the housing is vented). [Figure 38]

[1058] FIG. 10 is a front view of the medical injector shown in FIG. 2 in a seventh configuration (needle retracted). [Figure 39]

[1059] FIG. 10 is a cross-sectional front view of the medical injector shown in FIG. 2 in a seventh configuration (needle retracted). [Figure 40]

[1060] FIG. 10 is a perspective cross-sectional view of the medical injector shown in FIG. 2 in a seventh configuration (needle retracted). [Figure 41]

[1061] A front cross-sectional view of a portion of a medical injector according to one embodiment, wherein the ejection member of the system actuator assembly is in a first ejection member position, the movable seal is in a first seal position, and the positioning member has a first shape. [Figure 42]

[1062] FIG. 42 is a front cross-sectional view of a portion of the medical injector of FIG. 41, with the ejection member in the second ejection member position, the movable seal in the second sealing position, and the positioning member having a second shape. [Figure 43]

[1063] FIG. 42 is a front cross-sectional view of a portion of the medical injector according to FIG. 41, with the movable seal in a third sealing position and the positioning member having a second shape. [Figure 44]

[1064] FIG. 106 is a cross-sectional front view of a portion of a medical injector according to one embodiment, with the movable seal in a first sealing position. [Figure 45]

[1065] FIG. 106 is a front cross-sectional view of a portion of a medical injector according to one embodiment, with the movable seal in a first sealing position. DETAILED DESCRIPTION OF THE INVENTION

[0029]

[1066] Described herein is a medication delivery device for administering medication contained within a pre-filled syringe. As described above, the medication delivery device (device) uses pressurized gas in a gas chamber to dispense medication contained within a medication container assembly. The pressurized gas is introduced into the gas chamber from the gas container upon activation of the device. Prior to activation, the gas chamber is in fluid communication with an external volume surrounding the device via an equalization bypass. In other words, prior to activation, the pressure in the gas chamber corresponds to the environmental pressure affecting the device. The device includes a movable seal member. Prior to activation, the movable seal member is in a first sealing position, and the gas chamber is in fluid communication with the external volume via the equalization bypass. However, upon activation of the device, the movable seal member moves to a second sealing position, where the movable seal member separates the gas chamber from the external volume. In other words, the gas chamber is sealed when the movable seal is in the second sealing position.

[0030]

[1067] In some embodiments, the movable seal is one of a set of multiple seal members that collectively form part of the boundary of the gas chamber and are configured to move in conjunction with various operations of the device. For example, in some embodiments, the device can include a first seal coupled to a release member positioned to release pressurized gas from the gas container. A second seal can be coupled to the drug container carrier or the container itself. A third seal can be part of a vent assembly (e.g., a valve member) configured to release pressurized gas from the gas chamber. Release of pressurized gas from the gas chamber can occur, for example, after delivery of the drug and can facilitate retraction of the drug container assembly, needle, or other delivery member. In such embodiments, the first seal coupled to the release member can be a movable seal member that can separate the gas chamber from the external volume after activation of the device and before release of pressurized gas from the gas container. However, in additional embodiments, the movable seal member can be a second seal coupled to the carrier. To the extent that the carrier can be configured to move in response to a force exerted by pressurized gas to insert the needle into a patient, movement of the carrier can move the movable seal member to a second sealing position, thereby isolating the gas chamber from the exterior volume. Further, in some embodiments, as part of a vent assembly, a third seal can correspond to the movable seal member. In such embodiments, force exerted by pressurized gas can move the third seal from the first sealing position to the second sealing position, thereby closing the vent port of the device. The third seal can be maintained in the second sealing position until movement of an elastomeric member of the medicament container assembly transitions the third seal to the third sealing position, placing the gas chamber in fluid communication with the vent port.

[0031]

[1068] As used herein, the terms "substance" or "drug" include any component of a therapeutic substance. A drug can include such component regardless of the state of matter (e.g., solid, liquid, or gas). Furthermore, a drug can include multiple components that can be included in a therapeutic substance in a mixed, unmixed, and / or partially mixed state. A drug can include both active and inactive components of a therapeutic substance. Thus, as used herein, a drug can include inactive components such as water, colorants, etc.

[0032]

[1069] When used in connection with a referenced numerical indication, the term "about" means the referenced numerical indication plus or minus up to 10% of the referenced numerical indication. For example, "about 100" means 90 to 110.

[0033]

[1070] 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 nominally conveys the described geometric relationship, number, and / or 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 specifying a volume of "substantially 0.50 milliliters (mL)" is intended to convey that while the recited volume is desired, some tolerance may occur when the volume is "substantially" the recited volume (e.g., 0.50 mL). Such tolerance may result from manufacturing tolerances, measurement tolerances, and / or other practical considerations (e.g., minor imperfections, age of the recited structure, pressure or force exerted within a system, etc.). As previously mentioned, an appropriate tolerance may be, for example, ±10% of the recited geometric structure, numerical value, and / or range. Additionally, values ​​modified by the term "substantially" may allow for tolerances and / or otherwise encompass the stated numerical values, but are not intended to exclude the exact numerical values ​​stated.

[0034]

[1071] 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 portions or as multiple separate walls. Thus, a monolithically made item can include a set of walls. Such a set of walls can include, for example, multiple portions that are contiguous or discontinuous from one another. 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).

[0035]

[1072] 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.

[0036]

[1073] As used herein, the terms "rigidity" or "hardness" refer to an object's resistance to deflection, deformation, and / or displacement produced by an applied force and are generally understood to be the opposite of an object's "flexibility." For example, a more rigid gas-release member is more resistant to deflection, deformation, and / or displacement when subjected to a force than a less rigid gas-release member. Similarly, a more rigid gas-release member can be characterized as being harder than a less rigid gas-release 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 an object's stiffness, the deflected distance may be measured as the deflection of a portion of the object other than the portion of the object directly to which the force is applied. In other words, for some objects, the deflection point is different from the point of force application.

[0037]

[1074] Stiffness (and therefore flexibility) is a broad property of the object being described and therefore depends on the material from which the object is formed and the object's specific physical characteristics (e.g., cross-sectional shape, length, boundary conditions, etc.). For example, the stiffness of an object can be increased or decreased by selectively including materials in the object with desired elastic modulus, flexural modulus, and / or hardness. The elastic modulus is an intensive property (i.e., inherent to the material) of the constituent material and describes the object's tendency to deform elastically (i.e., non-permanently) in response to an applied force. A material with a higher elastic modulus will deflect less than a material with a lower elastic modulus in the presence of the same applied stress. Thus, for example, the stiffness of an object can be decreased by incorporating into the object and / or constructing the object from a material with a relatively lower elastic modulus.

[0038]

[1075] Altering an object's physical characteristics, such as its shape or cross-sectional area, can also increase or decrease the stiffness of the object. For example, an object with a certain 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 altering the shape of an object can decrease the stiffness (or flexibility) of the object.

[0039]

[1076] Therefore, objects that are easily deformed by small forces, such as wires, filaments, cords, etc., are said to be flexible objects.

[0040]

[1077] The therapeutic compositions described herein may be administered orally or in combination with any of the therapeutically effective compositions described herein or in any of the therapeutically effective compositions described in International Patent Publication No. WO 2017 / 004345 ("PCT No. 4345"), filed June 30, 2016, entitled "Auto-Injectors for Administration of a Medicament Within a Prefilled Syringe," International Patent Publication No. WO 2020 / 140040 ("PCT No. 0040"), filed December 27, 2019, entitled "Devices and Methods for Delivery of Substances Within a Prefilled Syringe," International Patent Publication No. WO 2018 / 136413 ("PCT No. 6413"), filed January 16, 2018, entitled "Medicament Delivery Devices with Wireless Connectivity and Event Detection," and / or International Patent Publication No. WO 2018 / 136413 ("PCT No. 6413"), filed July 15, 2019, entitled "Medicament Delivery Devices with Wireless Connectivity and Compliance The drug product may be included within any suitable drug delivery device described in WO 2020 / 018433 ("PCT No. 8433"), entitled "Icatibant Detection." Each of these international patent publications 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 single dose of icatibant. Such a drug product may include, for example, an auto-injector having a needle length and delivery profile (e.g., icatibant flow) sufficient to perform a subcutaneous injection. In other embodiments, the drug product may include a therapeutic agent comprising a monoclonal antibody. Such a drug product may include, for example, an auto-injector having multiple pre-filled 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 pre-filled syringe.

[0041]

[1078] In some embodiments, a gas-powered drug delivery device can provide a compact device in which the exterior dimensions of the housing are not substantially greater than the length of the drug container disposed therein. For example, as shown and described herein, in some embodiments, the drug delivery device can lack 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 lack 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 delivery. Such a drug delivery device (or drug delivery mechanism) is considered a "pistonless" system. As an example, in a gas-powered piston-less auto-injector, the force exerted by the gas can move the drug container relative to the housing, and similarly, the elastomeric member can move relative to (e.g., within) the drug container. In some embodiments, the lack of a moving mechanism, piston, or the like, can reduce the height of the medical injector, for example, compared to the height of a device that includes a rigid, single-length piston.

[0042]

[1079] For example, any of the drug delivery devices described herein may include any suitable "pistonless" design, such as those described in PCT Nos. 4345, 0040, or International Patent Publication No. WO2016 / 154427, filed March 24, 2016, entitled "DEVICES AND METHODS FOR DELIVERING A LYOPHILIZED MEDICAMENT," which are incorporated by reference in their entireties.

[0043]

[1080] In some embodiments, the characteristics of the medicament, the medicament container, and the 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 the desired force (and / or pressure within the medicament container) to deliver the medicament. For example, in certain circumstances, the pressure of the medicament within a needle-based medicament container can be modeled by the Hagen-Poiseuille law, as shown below: (1) P=(8*μ*L*Q) / (π*R 4 )

[1081] where P is the pressure of the drug within 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 within the drug container required to achieve a desired flow rate can be relatively high in some cases. The desired pressure can be achieved by including a gas-based energy storage element.

[0044]

[1082] 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, higher forces (e.g., for injecting viscous drugs) can be achieved with the same packaging used for drugs with lower viscosities. 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 the drug.

[0045]

[1083] In such embodiments, a non-mechanical energy storage member (e.g., gas, propellant) can be used to generate a force large enough to generate the desired pressure within the drug container to produce the desired injection. For example, in larger diameter embodiments, the amount of force required to generate the desired internal pressure increases significantly. In some embodiments, any of the drug delivery devices 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 of the injectors 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 gas pressures 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.

[0046]

[1084] 1A and 1B are schematic diagrams of an apparatus (e.g., a drug delivery device) 1000 according to one embodiment. As shown, the apparatus 1000 includes a housing 1100, a gas container 1410, a drug container assembly 1200, and a movable seal member 1480, and is surrounded by an exterior volume eV. The housing 1100 defines a gas chamber 1460 and an equalization bypass 1470. The gas chamber 1460 can be, for example, a portion of the 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 multi-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.

[0047]

[1085] The gas container 1410 is disposed within the housing 1100. The gas container 1410 is configured to generate pressurized gas PG within the gas chamber 1410 when the device 1000 is actuated. In other words, the gas container 1410 can be configured to deliver pressurized gas to the gas chamber 1460 and generate a force to propel the contents of the drug container assembly 1200 when the device is actuated. The gas container 1410 can be any suitable member or device that stores potential energy and, when actuated, generates pressurized gas. For example, the gas container 1410 (and any of the gas containers described herein) can be any device containing compressed gas, a device containing a vapor pressure-based propellant, or the like. For example, the gas container 1410 can be a sealed gas container containing a quantity of inert gas at a pressure of at least 900 psi (e.g., 1,000 psi or more).

[0048]

[1086] The medicament container assembly 1200 has a medicament container body 1210 that defines a volume containing the medicament (i.e., filled or partially filled with the medicament). A distal end portion of the medicament container body 1210 includes a neck or mouth through which the medicament can be delivered. In some embodiments, the medicament container assembly 1200 can include a delivery member (e.g., a nozzle, a needle, a delivery orifice, a mouthpiece, and / or other similar structure) coupled with the container body 1210 through which the medicament is delivered. For example, 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 other embodiments, the medicament container assembly 1200 can be a cartridge that is sealed and can be selectively coupled to a needle upon activation of the device. For example, in some embodiments, the medicament container assembly 1200 may be similar to the multi-chamber cartridge shown and described in U.S. Provisional Application No. 63 / 398,410, filed August 16, 2022, and entitled "Devices and Methods for Delivering Reconstituted Medicaments." This provisional application is incorporated herein by reference in its entirety. In some embodiments, the medicament container assembly 1200 may include or be coupled to a carrier (not shown, but which may be similar to carrier 4360 described below) that moves the medicament container body 1210 within the housing 1100. In this manner, the carrier may facilitate movement of the delivery member from the housing 1100 in the deployed position, as described below. In some embodiments, one or more surfaces of the carrier may form at least a portion of the boundary of the gas chamber 1460. In some embodiments, the carrier may include one or more seals to fluidly isolate the gas chamber 1460.

[0049]

[1087] The drug container assembly 1200 includes an elastomeric member 1217 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 the 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, which may have an undesirable effect 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 the drug for extended periods of time (e.g., up to six months, one year, two years, five years, or more).

[0050]

[1088] The medicament container assembly 1200 may include a proximal portion configured to translate within the housing 1100 to move the medicament container body 1210 between positions, as described herein. While 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 may be disposed within or coupled to a carrier to facilitate movement within the housing 1100. The proximal portion of the medicament container assembly 1200 and the carrier (if present) may define a portion of the boundary of the gas chamber 1460. In this manner, when pressurized gas is delivered into the gas chamber 1460, the pressure therein may generate a force on the medicament container assembly 1200 to move the medicament container body 1210, for example, from a retracted position to a deployed position.

[0051]

[1089] In some embodiments, the device 1000 can include a retraction member (not shown). The retraction member can be a retraction spring or any other energy storage member. In this manner, the retraction member can be configured to return the medicament container assembly 1200 to the retracted position after it has been deployed, as described in further detail herein. In some embodiments, the retraction member can be further configured to maintain the medicament container 1200 in the retracted position before gas pressure is supplied to the gas chamber 1460. In some embodiments, the device 1000 can be configured to maintain the medicament container assembly 1200 in the deployed position after delivery. In such embodiments, the device 1000 can include other suitable mechanisms for covering or shielding the delivery member (e.g., a cover that moves around the delivery member after delivery is completed).

[0052]

[1090] As shown in FIG. 1A , prior to actuation, the gas chamber 1460 is in fluid communication with the external volume EV via the equalization bypass 1470. The fluid communication provided by the equalization bypass 1470 causes the pressure within the gas chamber 1460 to match the pressure in the external volume EV. Thus, fluid communication between the gas chamber 1460 and the external volume EV via the equalization bypass 1470 prevents large pressure differences from developing between the gas chamber 1460 and the external volume EV that could otherwise affect the state and / or operation of the device 1000. Similarly, the equalization bypass 1470 prevents large pressure differences from developing across the elastomeric member 1217, which could result in undesirable movement or sticking of the elastomeric member 1217 within the container body 1210. However, because it may be desirable to increase the pressure within the gas chamber 1460, the device 1000 includes a movable seal member 1480 for selectively isolating the gas chamber 1460 from the external volume EV. 1A shows the movable seal member 1480 in a first sealing position SP1. When the movable seal member 1480 is in the first sealing position SP1, the gas chamber 1460 is in fluid communication with the external volume EV via the equalization bypass 1470. After actuation of the device 1000, as shown in FIG. 1B, the movable seal member 1480 is in a second sealing position SP2, and the gas chamber 1460 is fluidly isolated from the external volume EV. With the gas chamber 1460 fluidly isolated from the external volume by the movable seal member 1480 in the second sealing position, the pressurized gas PG within the gas chamber 1460 exerts a force on the elastomeric member 1217, causing a desired movement of the elastomeric member 1217 within the container body to dispense a portion of the medicament from the medicament container assembly 1200. As described herein, in some embodiments, after actuation of the device 1000, the movable seal member 1480 can transition from a first sealing position SP1 to a second sealing position SP2 prior to the introduction of pressurized gas PG into the gas chamber 1460. In additional embodiments, a force exerted by the pressurized gas PG within the gas chamber 1460 can transition the movable seal member 1480 from the first sealing position SP1 to the second sealing position SP2 to isolate the gas chamber 1460 from the exterior volume EV.

[0053]

[1091] When the device 1000 is actuated, the gas container 1410 is activated and releases pressurized gas PG into the gas chamber 1460. In some embodiments, the released pressurized gas generates a force that moves the drug container body 1210, along with the delivery member, from the retracted position to the deployed position. In the retracted position, the delivery member is disposed within the housing 1100, and in the deployed position, the delivery member extends from the housing 1100. In some embodiments, the pressurized gas PG is introduced into the gas chamber 1460. Thus, as shown in FIG. 1B , when the gas chamber 1460 is isolated from the external volume EV, pressure increases within the gas chamber 1460. After the pressure within the drug gas chamber 1460 overcomes the resistance of the elastomeric member 1217 against the interior of the drug container body 1210, the elastomeric member 1217 moves away from the gas chamber 1460, thereby expelling the drug from within the drug container body 1210.

[0054]

[1092] In some embodiments, the medication delivery device can be an auto-injector having a piston-less delivery system in which a force exerted by a gas can move a medication container relative to a housing and an elastomeric member relative to (e.g., within) the medication container. For example, FIGS. 2-40 illustrate a medical injector 4000 (also referred to as an "auto-injector," "injector," or "device") according to one embodiment. The medical injector 4000 is a gas-powered auto-injector configured to deliver a medication contained within a pre-filled syringe 4200, as described herein. In some embodiments, the medical injector 4000 can be configured to be attached to a patient as an on-body system. 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 to 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 (now U.S. Pat. No. 9,084,849), entitled "MEDICAMENT DELIVERY DEVICES FOR ADMINISTRATION OF A MEDICAMENT WITHIN A PREFILLED SYRINGE," filed Jan. 25, 2012 (hereinafter referred to as the "'849 patent"), the disclosures of each of which are incorporated herein by reference in their entirety.

[0055]

[1093] The medical injector 4000 includes a housing 4100 (see, e.g., FIGS. 5 and 6), a system actuation assembly 4500 (see, e.g., FIGS. 9 and 10), a drug container assembly 4200 (see, e.g., FIG. 20), a drug delivery mechanism 4300 (see, e.g., FIGS. 16-20), a base 4510 (or actuator, see, e.g., FIGS. 25 and 26), and a safety lock 4700 (see, e.g., FIGS. 23 and 24). As shown in FIGS. 3-6, the housing 4100 has a proximal end portion 4101 and a distal end portion 4102. The housing 4100 defines a first status indicator opening 4130 and a second status indicator opening 4160. The first status indicator opening 4130 defined by the housing 4100 is on a first side of the housing 4100, and the second status indicator opening 4160 defined by the housing 4100 is on a second side of the housing 4100. The status indicator openings 4130, 4160 allow a patient to monitor the status and / or contents of the medication container 4200, the carrier 4360, and the medication contained in the housing 4100. For example, by visually inspecting the status indicator openings 4130, 4160, a patient can determine whether the medication container 4200 contains a medication and / or whether the medication has been dispensed.

[0056]

[1094] 2, 3, and 5, 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 Publication No. 8433. While the housing 4100 is shown with the 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 labels or indicia that conceal or otherwise highlight the status indicator openings 4130, 4160 and / or contents viewable 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 opening 4130, the status indicator opening 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.

[0057]

[1095] As shown in Figures 5, 6, and 12, the housing 4100 defines a gas canister cavity 4151 and a medicament cavity 4139. The gas canister cavity 4151 is configured to receive the gas canister 4410 and a portion of the system actuator assembly 4500 (e.g., the release member 4550 and spring 4576, as shown in Figures 9 and 10). A proximal end portion of the gas canister cavity 4151 is configured to receive the gas canister retention member 4180 of the proximal cap 4110 of the housing 4100, as described in further detail herein. The gas canister 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.

[0058]

[1096] 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., FIGS. 9, 10, and 16-19) and a gas vent assembly 4310 (see, e.g., FIGS. 7, 8, 13A, 21, and 22A-22C) 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 opening 4105 and also via the vent port 4112. It should be understood that while a single medicament container assembly is depicted, additional embodiments may employ additional medicament container assemblies 4200. For example, in some embodiments, the housing 4100 may include two medicament cavities 4139, each containing an individual medicament container assembly 4200.

[0059]

[1097] The proximal end portion 4101 of the housing 4100 includes a proximal cap 4110 (see, e.g., FIGS. 7, 8, and 13). The proximal cap 4110 includes a gas canister retaining member 4180 configured to receive and / or retain a gas canister 4410 containing pressurized gas, as shown in FIGS. 7-10. When the medical injector 4000 is actuated, pressurized gas from the gas canister 4410 is delivered from the gas canister cavity 4151 to the medicament cavity 4139 via a gas passageway 4135 in the housing 4100. In other words, the gas passageway 4135 places the gas canister cavity 4151 in fluid communication with the medicament cavity 4139. Thus, the proximal portion of the medicament cavity 4139 can be referred to as (or can function as) a housing gas chamber (e.g., gas chambers 6460, 7460 shown in FIGS. 44 and 45). Similarly, the proximal portion of the medication cavity 4139 is the 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.

[0060]

[1098] As shown in Figures 6, 12, 27, 28, 30, 31, 33, 34, 36, 37, 39, and 40, in some embodiments, the housing 4100 defines an equalization bypass 4470. The equalization bypass 4470 facilitates fluid coupling between a proximal portion of the medicament cavity 4139 and an external volume surrounding the housing. As shown in Figure 27, when a movable seal member, such as sealing member 4574, is in a first sealing position, the proximal portion of the medicament cavity 4139 is in fluid communication with the external volume through the equalization bypass 4470. However, as shown in Figure 28, when the medical injector is actuated, the movable seal moves from the first sealing position to a second sealing position. When the movable seal member is in the second sealing position, the proximal portion of the medicament cavity 4139 is fluidly isolated from the external volume.

[0061]

[1099] The proximal cap 4110 also includes a cap cover 4111 coupled to the proximal end portion of the proximal cap 4110, 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 port 4112 from direct external contact and prevents clogging by external foreign matter. The proximal cap 4110 also includes an O-ring 4113 and defines the vent port 4112. The vent port 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. 7 and 8 , the proximal end portion of the proximal cap 4110 defines a vent channel 4118 extending laterally away from the vent port 4112. The vent channel 4118, together with the gap 4111a, form a plurality of vent passageways that allow pressurized gas to exit the medicament cavity 4139 to a volume outside the medical injector 4000. In this manner, the force generated by the pressurized gas on the medicament delivery mechanism 4300 and / or medicament container assembly 4200 is reduced, allowing the needle to be retracted after an injection is completed. As shown in FIG. 13A , the O-ring 4113, in conjunction with the valve portion 4345 of the gas vent assembly 4310, selectively seals the vent port 4112 during needle insertion and medicament delivery.

[0062]

[1100] Although the vent orifice 4112 is shown as being defined by the proximal cap 4110 and at its proximal face, in other embodiments, the vent orifice 4112 (and any of the vent orifices described herein) can be defined within any suitable portion of the proximal cap or side wall. For example, in some embodiments, the vent orifice 4112 (and any of the vent orifices described herein) can be defined by the proximal cap 4110 but have a centerline that is non-parallel to the longitudinal axis of the medical injector 4000. In other words, in some embodiments, the vent orifice 4112 (and any of the vent orifices described herein) can open toward the side of the medical injector rather than toward the proximal end as shown. In other embodiments, the vent orifice 4112 (and any of the vent orifices described herein) can be defined by any wall and / or surface of the housing 4100. As shown in FIG. 31 , for example, in some embodiments, the medical injector includes both a vent port 4112 and a separate equalization bypass 4470. This arrangement can provide increased operational flexibility. For example, in some embodiments, the equalization bypass 4470 can transition from an open configuration to a closed configuration when the device is actuated. This sequence can allow the medicament cavity 4139 (and the medicament container gas chamber above the elastomeric member 4217) to be maintained at a pressure substantially equal to atmospheric pressure prior to actuation. Maintaining this equalization can avoid large pressure differentials across the elastomeric member 4217. In response to actuation, the equalization bypass 4470 can close, allowing gas pressure to build up in the medicament cavity 4139 (and the medicament container gas chamber) to move the elastomeric member 4217 after needle insertion to deliver the medicament. Conversely, the vent port 4112 can transition from a closed configuration to an open configuration after medicament delivery. This releases pressurized gas from the medication cavity 4139, thereby allowing the needle to retract as described below.

[0063]

[1101] The proximal cap 4110 includes a guide wall 4115 within 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 within which the guide surface 4344 of the first member 4340 (see, e.g., FIGS. 13A and 21 ) 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 restrictor assembly) bears when the medical injector 4000 is in the first configuration (i.e., the “storage” state).

[0064]

[1102] As shown in FIG. 6, the distal end portion 4102 of the housing 4100 includes a shoulder portion 4106 having a contact surface and defining a needle opening 4105. The distal end portion 4102 also includes a base rail groove 4114 and a base retention recess 4134 (see FIGS. 4 and 5). The shoulder portion 4106 is configured to contact a corresponding surface 4365 of the carrier body 4360 (see, e.g., FIGS. 6, 18, 27, and 40) 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 opening 4105 is an opening in which the needle 4216 is disposed when the medical injector 4000 is actuated, as described in further detail herein.

[0065]

[1103] The housing distal end portion 4102 also includes an ejection member contact surface 4126 and defines an ejection member opening. As shown in FIGURE 13B, the ejection member opening 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 its function are described in more detail below.

[0066]

[1104] The distal base retention recess 4134 (see FIG. 5 ) 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. 25 and 26 ) when the base 4510 is in a first position relative to the housing 4100. The distal base retention recess 4134 includes an elongated groove extending from a proximal to a distal direction such that the base connection knob 4518 can move and translate within the elongated groove. This allows the base retention 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 retention recess 4134 can include a ratchet tooth member that engages the base connection knob 4518 to prevent the base 4510 from moving distally.

[0067]

[1105] The base rail groove 4114 receives the guide member 4517 (see FIGS. 4, 25, and 26) of the base 4510. The guide member 4517 of the base 4510 and the base rail groove 4114 of the housing 4100 engage with one another in a manner that limits lateral movement of the guide member 4517 of the base 4510 while allowing the guide member 4517 to slide proximally and / or distally within the base rail groove 4114. 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.

[0068]

[1106] 9 and 10 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. 20, 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 containing the medicament (i.e., filled or partially filled with the medicament). The distal end portion 4213 of the medicament container assembly 4200 includes a neck that couples with 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.

[0069]

[1107] 13A , the elastomeric member 4217 includes a proximal end portion 4218 and couples to the distal member 4320 of the gas evacuation 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 evacuation assembly into a medicament container gas chamber (i.e., the second 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). The pressure in the medicament container gas chamber can have a magnitude of pressure that is less than the magnitude of the pressure in the proximal portion of the medicament cavity 4139 (i.e., the first gas chamber). The pressure in the medicament container gas chamber exerts a force on the proximal face 4218 to move the elastomeric member 4217 within the container body 4210 (i.e., to expel the medicament therefrom). However, as shown in FIG. 30 , because the pressure in the medicament container gas chamber is less than the pressure (acting on the carrier 4360 and / or container body 4210) in the proximal portion of the medicament cavity 4139 (i.e., first gas chamber), the flow restrictor assembly 4430 restricts movement of the elastomeric member 4217 before the medicament container assembly is in the deployed configuration (i.e., second container position).

[0070]

[1108] As long as the elastomeric member 4217 is coupled to the gas evacuation 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 subjected to a force (e.g., generated by pressurized gas in the medicament body 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.

[0071]

[1109] The distal member 4320 can be coupled to the elastomeric member 4217 in any suitable manner. For example, as shown, the proximal surface 4218 receives and / or couples to the protrusion 4323 of the distal member 4320 of the gas evacuation 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 can be threadedly coupled to the elastomeric member 4217. In still other embodiments, the distal member 4320 can be bonded to the elastomeric member 4217 via an adhesive, a welding process, or the like.

[0072]

[1110] The elastomeric member 4217 can be of any design or formulation suitable for contact with a drug. For example, the elastomeric member 4217 can be formulated to minimize any reduction in drug efficacy 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 can be formulated to minimize leaching or outgassing of the composition, which may have an undesirable effect on the drug. In other embodiments, the elastomeric member 4217 can be formulated to maintain chemical stability, flexibility, and / or sealing properties when in contact (direct or indirect) with a drug for extended periods of time (e.g., up to six months, one year, two years, five years or more).

[0073]

[1111] In some embodiments, the elastomeric member 4217 can be made of multiple 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 can be made with an amount of polydimethylsiloxane.

[0074]

[1112] 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. While 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.

[0075]

[1113] The drug container assembly 4200 can have any suitable size (e.g., length and / or diameter) and can contain any suitable amount of drug. In some embodiments, the drug container assembly 4200 (and any of the drug container assemblies 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 of the drug container assemblies described herein) can be a Becton Dickinson "BD Hypak Physiolis" prefillable syringe containing any of the drugs described herein. The medical injector 4000 can be configured to inject any suitable dose, such as, for example, a single dose of up to 4 mL, of any of the drugs described herein. In other embodiments, the medical injector 4000 can be configured to inject a single dose of up to 2 mL, 3 mL, 4 mL, 5 mL, or more of any of the drugs described herein.

[0076]

[1114] The container body 4210 can be made of glass and can be fitted with 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 that is about 0.5 inches long.

[0077]

[1115] 20 , 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 that receives the needle 4216 and / or the distal end portion 4213 of the medicament container body 4210. An 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 a user activates the medical injector 4000.

[0078]

[1116] 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. 12, 13B, 20, 23, and 24). 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 distal movement of the safety lock 4700 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 .

[0079]

[1117] As shown in FIG. 27 , 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 and inject the medicament. Rather, the elastomeric member 4217 is moved by a force generated by 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 fill volume, delivery volume, and / or ratio of fill volume to delivery volume. 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 ratio of loaded volume to delivered volume of 0.4), the drug reservoir has a first length and the second movable member has a first length. In a second embodiment (e.g., a ratio of loaded volume to delivered volume of 0.6), the drug reservoir has a second length that is shorter than the first length and the second movable member has a second length that is longer than the first length. In this manner, the stroke of the device in the second embodiment is longer than the stroke of the device in the first embodiment, thereby allowing for a larger dose. However, because the drug reservoir in the device in the second embodiment is shorter than the drug reservoir in the device in the first embodiment, components of both embodiments can be disposed within the same housing and / or within housings of the same length.

[0080]

[1118] In some embodiments, the medical injector 4000 has a housing length L H The length of the container L C In another embodiment, the medical injector 4000 is configured such that the ratio of the housing length L to the needle length (including the needle extending from the end of the container body) is less than about 1.5. H The length of the container L CIn yet another embodiment, the medical injector 4000 is configured such that the ratio of the housing length L H The length of the container L C to less than about 1.1.

[0081]

[1119] In some embodiments, the medical injector 4000 has a housing length L H The length of the container L C , carrier distance, and stroke sum ratio is less than about 1.1. H The length of the container L C , carrier distance, and stroke sum ratio is less than about 1.0. H The length of the container L C , carrier distance, and stroke to sum ratio is configured to be less than about 0.9.

[0082]

[1120] 9, 10, and 31, the system actuator assembly 4500 includes a base 4510, an ejection member 4550, and a spring 4576. FIG. 10 shows certain internal components of the medical injector 4000 without the base 4510 and 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 sidewall 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 prevented from entering 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.

[0083]

[1121] 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 openings between adjacent extensions 4553. As shown in FIG. 28 , the engagement surface is configured to extend through the ejection member opening 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.

[0084]

[1122] The opening defined by the extension 4553 is configured to receive the safety lock protrusion 4702 (see, e.g., FIGS. 12 and 13B ) of the safety lock 4700 when the safety lock 4700 is mated with the housing 4100 and / or base 4510. The safety lock protrusion 4702 is configured to prevent the extensions 4553 from approaching each other. In other words, the safety lock protrusion 4702 is configured so 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 subjected to loads over an extended period of time.

[0085]

[1123] 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 due to 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, thereby allowing the ejection member 4550 to move proximally along its longitudinal axis as the spring 4576 expands (see FIG. 31 ).

[0086]

[1124] 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 rupture when the 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. 9 and 10 , the lengths of the gas container retaining member 4180 and 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. Thus, this distance is 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, the actuation time and / or the force that the perforator 4575 exerts on the frangible seal 4413 can be adjusted by varying the distance between the perforator 4575 and the frangible seal 4413.

[0087]

[1125] As generally shown in FIG. 9 , the medication 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 medication cavity 4139 of the housing 4100. For example, the carrier assembly 4390, together with the medication container assembly 4200, is configured to move between a retracted position (i.e., the first position shown in FIG. 12 ) and a deployed position (the second position shown in FIG. 30 ) in response to a force exerted by pressurized gas in a proximal portion of the medication cavity 4139. As shown in FIGS. 16-20 , 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 in which the medicament container body 4210 is disposed. The proximal end portion 4362 also includes a proximal face 4376 and forms a portion of the boundary of the housing gas chamber (i.e., a portion of the medicament cavity 4139 through which 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 generates a force on the proximal face 4376 that moves the carrier assembly 4390 distally within the housing 4100.

[0088]

[1126] 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 the 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.

[0089]

[1127] 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 the sidewall 4139a (see FIG. 6) within the medicament cavity 4139, such that the O-ring 4370 and the inner surface of the housing 4100 define a 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.

[0090]

[1128] The distal end portion 4361 of the carrier body 4360 has an open end. Thus, as shown in FIGS. 16-19 , 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. This opening is configured to align with the state openings 4130, 4160 of the housing to permit 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. 30 ) when the needle 4216 is inserted a desired distance.

[0091]

[1129] The retraction spring 4380 is disposed within a spring pocket 4363 defined by the outer surface of the carrier body 4360, as shown in FIG. 18 . The retraction spring 4380 is disposed about a spring pin 4381, which 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 can be controlled as the elastomeric member 4217 moves through its forward stroke. Controlling the rate at which the medicament leaves the device can minimize pain or discomfort, especially when the medicament has a high viscosity (e.g., greater than about 100 centipoise at room temperature). Furthermore, if the drug contains a high molecular weight compound (e.g., greater than about 5 kDa), a reduced injection force less than that required to overcome the retraction spring 4380 prevents shearing and therefore damage to the drug or therapeutic substance.

[0092]

[1130] 14A, 14B, and 15, the delivery control mechanism 4430 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. 14B, the flow-restricting retainer 4433 includes a cylindrical inner surface 4433a and an end face 4433b. The end face 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 flow restricting element 4450b of flow restricting member 4450 overlaps a portion of through hole 4433c. In some embodiments, at least 50% of flow restricting element 4450b overlaps through hole 4433c. In some embodiments, flow restricting member 4450 is press fit or screwed onto flow restricting retainer 4433.

[0093]

[1131] 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 atmospheric air at standard temperature and pressure (outlet side) 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 element 4450b is calibrated to atmospheric air at standard temperature and pressure (outlet side) with nitrogen gas (N2) at 30 psig (inlet side) to have a flow rate of approximately 0.75 to 1.5 standard cubic centimeters per minute (sccm). In some embodiments, the flow restricting element 4450b is calibrated to have a flow rate of approximately 1 standard cubic centimeter per minute (sccm) using nitrogen gas (N2) at 30 psig (inlet side) and atmosphere (outlet side) at standard temperature and pressure. As described herein, standard temperature is 60°F (15.6°C) and standard pressure is 14.696 psia (101.3 kPa).

[0094]

[1132] In some embodiments, the compressed gas supplied from the gas container 4410 is argon gas, and the flow restricting element 4450b has a flow rate rating of approximately 0.75 and 1.5 sccm, based on the nitrogen gas calibration described above. In some embodiments, the compressed gas supplied from the gas container 4410 is argon gas, and the flow restricting element 4450b has a flow rate rating of approximately 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 supplied from the gas container 4410 is R134a (tetrafluoroethane), and the flow restricting element 4450b has a flow rate rating of approximately 10-100 sccm, based on the nitrogen gas calibration described above. In some embodiments, the compressed gas supplied from the gas container 4410 is R134a (tetrafluoroethane), and the flow restricting element 4450b has a flow rate rating of approximately 20-40 sccm, based on the nitrogen gas calibration described above.

[0095]

[1133] In some embodiments, gas pressure initially supplied to the medication cavity 4139 and delivered through the flow restricting element 4450 can be used to reduce the flow rate of the medication to less than 0.2 mL / sec (or in some embodiments, 0.05 mL / sec to 0.01 mL / sec). Lower injection forces and / or slower delivery (compared to pressure delivered directly from the medication cavity 4139 to the elastomeric element) can create a laminar flow of the medication through the needle, preventing shearing of high molecular weight compounds in the medication and / or reducing pain experienced by the patient, particularly when the viscosity of the medication 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 4450b to prevent particles or foreign objects from clogging the flow restricting element 4450b during operation.

[0096]

[1134] First body portion 4431 includes a proximal end portion 4431 a and a distal end portion 4431 b. Proximal end portion 4431 a includes a first cylindrical inner surface 4431 c that is configured to support an O-ring 4436. O-ring 4436 contacts a portion of gas vent assembly 4310 and seals the interior of first body portion 4431 from a housing gas chamber portion of medication cavity 4139, as described in further detail herein.

[0097]

[1135] 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 interior wall of the medicament container body 4210. 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. 14B, the inner diameter of the first cylindrical inner surface 4431c is larger 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 the outer surface of the first body portion 4431. The flange portion 4431f is configured to attach to the flange 4214 of the medicament container body 4210 or the proximal end portion of the carrier 4360.

[0098]

[1136] 15, the first body portion 4431 defines a first axis A1 and the second body portion 4432 defines a second axis A2, where the first axis is non-parallel to the second axis. In some embodiments, the first axis A1 and the second axis A2 are perpendicular to one another. 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, where 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. 14B) that contacts a wall of the housing 4100 or a guide member 4135a (see FIG. 6) to prevent the delivery control mechanism 4430 from rotating about the first axis A1 during operation.

[0099]

[1137] 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 medicament cavity 4139 after delivery of the medicament. Releasing or removing force from the carrier body 4360, the delivery control mechanism 4430, and / or the medicament 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 rather is carried distally by the elastomeric member 4217 during delivery of the medicament. This arrangement is therefore considered a "pistonless" delivery system. This is because, as described herein, the force for insertion and drug delivery is provided 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.

[0100]

[1138] As shown in FIGS. 21 , 22A, 22B, and 22C, 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 to allow the gas vent assembly 4310 to transition from a collapsed configuration ( FIGS. 12, 13A, and 28 ) to an expanded configuration ( FIGS. 33 and 34 , just before delivery of the drug is complete), and a series of partially expanded configurations in between (see, e.g., FIG. 30 ). 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 a 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 so that it expands to 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 the final distance with the elastomeric member 4217 to complete delivery of a full dose (FIGS. 36 and 37, after delivery of the drug 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 so that the needle is retracted.

[0101]

[1139] 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 corresponding distal end surfaces 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 when pressure is applied distally 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 at a second end 4325b to the distal end surface 4333 of the second member 4330. During the second stage of expansion (i.e., the 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 expansion member 4325 expands. As shown in FIG. 21 and 22A-22C, the flexible expansion member 4325 is folded in an accordion-like manner. In some embodiments, the flexible expansion member 4325 is a filament or band. In some embodiments, the flexible expansion member 4325 is overmolded with a plastic material. In some embodiments, the flexible expansion 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.

[0102]

[1140] 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 that extends from the distal end portion 4331 to the proximal end portion 4332. The proximal end portion 4332 includes a shoulder portion 4335 that extends toward the 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.

[0103]

[1141] 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 the 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 guide wall 4115 ( FIG. 13A ) of the proximal cap 4110. When the valve portion 4345 is in the open configuration (see FIGS. 39 and 40), the valve portion 4345 defines a passageway 4346 that bypasses the O-ring 4113. As shown in FIG. 21 , the passageway 4346 is a recessed portion that extends into the proximal end portion 4342.

[0104]

[1142] In some embodiments, the gas vent assembly 4310 is configured (e.g., the vent port 4112 is sized or shaped) to maintain the force generated by the compressed gas on the medicament container assembly 4200 greater than the force exerted by the retraction spring 4380 at the time of delivery of the final portion of the dose. In other words, the gas vent assembly 4310 is adjusted so that the force of the compressed gas within the proximal portion of the medicament cavity 4139 (e.g., gas chamber) remains greater than the retraction force for the period of time required for complete delivery of the final portion of the dose. In some embodiments, the exhaust period may begin with actuation of the valve member 4345 of the gas vent assembly 4310 and end with delivery of the final portion of the dose. It should be understood that the exhaust period may correspond to the desired time to deliver the final portion of the dose and, therefore, may be determined based on the delivery characteristics of the composition. Furthermore, it should be understood that maintaining the compressed gas force at a magnitude greater than the retraction force past the completion of delivery of the last portion may undesirably maintain the needle within the patient longer than necessary to deliver the dose. However, expelling the compressed gas too early may be undesirable in that it may allow the compressed gas force to fall below the retraction force before the last portion is fully delivered. In addition to when expulsion begins, the rate of expulsion may also affect the timing and accuracy of delivery of the last portion of the dose.

[0105]

[1143] In some embodiments, the gas vent assembly 4310 can be configured to include a vent port size and / or movement of the valve body within the opening, and / or the moment expulsion is initiated, such that the force generated by the compressed gas within the proximal portion of the medicament cavity 4139 decreases to a magnitude less than the force applied by the retraction spring 4380 upon completion of delivery of the last portion of the dose. For example, the gas vent assembly 4310 is configured (e.g., adjusted) by selecting a vent port size, a vent port shape, a valve body size, and / or a valve body shape to achieve a desired rate of force decrease within the internal volume. For example, the desired rate of force decrease can be based on the desired delivery characteristics of the composition, the characteristics of the pressurized gas, and / or environmental parameters. For example, in some embodiments, the vent port is configured (e.g., sized) to establish an expulsion duration of at least 0.5 seconds to less than 1.5 seconds. In some additional embodiments, the vent port is sized to establish an expulsion duration of at least 5 seconds to less than 15 seconds.

[0106]

[1144] In some embodiments, the initial pressure in the proximal portion of the medication cavity 4139 is approximately 100 psi. After the entire medication (e.g., 10 mL) has been delivered, the final pressure in the proximal portion of the medication cavity 4139 is generally greater than 80 psi. Furthermore, the average elapsed time to deliver 120% of the medication is approximately 17 seconds, the average elapsed time to deliver 220% of the medication is approximately 19 seconds, the average elapsed time to deliver 320% of the medication is approximately 21 seconds, the average elapsed time to deliver 420% of the medication is approximately 25 seconds, and the average elapsed time to deliver the fifth and final 20% of the medication is approximately 31 seconds. The flow restriction assembly 4430 and / or gas vent assembly 4310 are configured to limit and manage medication delivery such that the first 20% of the delivery volume is not delivered more than twice as fast as the last 20% of the delivery volume. In other words, the first 20% of the delivered dose is delivered less than twice as fast as the last 20% of the delivered dose (i.e., about 17 seconds versus about 31 seconds). In some embodiments, the elapsed time for dispensing the last 20% of the delivered dose is about 1 to 2 times the elapsed time for dispensing the first 20% of the delivered dose. For example, if the elapsed time for dispensing the first 20% of the delivered dose is about 15 seconds, the elapsed time for dispensing the last 20% of the delivered dose is about 15 seconds to about 30 seconds. In some embodiments, the elapsed time for dispensing the last 20% of the delivered dose is about 100% to about 195% of the elapsed time for dispensing the first 20% of the delivered dose.

[0107]

[1145] 12, 23, and 24, 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 the 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 each other, thereby preventing proximal movement of the release member 4550 and / or delivery of the medicament.

[0108]

[1146] 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 thereof. As previously described, the tab 4722 engages with a rib 4236 on 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 when the safety lock 4700 is removed.

[0109]

[1147] The exterior surface of the safety lock 4700 has a gripping portion (recessed finger grip) and indicia. The recessed finger grip provides an area for a user to grasp and / or remove the safety lock 4700 from the housing 4100. The indicia provides a method for removing 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.

[0110]

[1148] 25 and 26 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 disposed against a target surface (not shown). As described below, the housing 4100 moves 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 opening 4513 and a safety lock protrusion opening 4514. The needle opening 4513 is configured to receive the needle 4216 when the medical injector 4000 is actuated. The safety lock protrusion opening 4514 in the base 4510 receives the safety lock protrusion 4702 of the safety lock 4700 when the safety lock 4700 is mated with the housing 4100 and / or the base 4510 .

[0111]

[1149] 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 is moved proximally relative to the housing 4100, the protrusion 4515 of the base 4510 is configured to move the extensions 4553 of the release member 4550 closer together to activate 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.

[0112]

[1150] The medical injector 4000 can be moved from a first configuration (FIGS. 11 and 12) to a second configuration (FIG. 28) 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 distally moving and / or disengaging the safety lock 4700 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 ejection member 4550, thereby enabling the drug delivery mechanism 4300. As shown in FIG. 11 , prior to actuation, a portion of the drug container assembly 4200 is visible through the state opening 4130. Specifically, the drug container body 4210 and its contents (e.g., drug) are visible. As mentioned above, in some embodiments, the housing 4100 can include a color strip (against which the drug can be compared), a label or other indicia providing a viewing method, etc. Although not shown in FIG. 11, in some embodiments, a portion of the elastomeric member 4217 is visible through the state opening 4130.

[0113]

[1151] 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. 28 ) to the third configuration ( FIG. 29 ) 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 applying the medical injector 4000 to a patient's body and moving the base 4510 relative to the housing 4100. Specifically, as described above, the base includes a “contact portion” (i.e., distal surface 4523) that can rest 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 discharge member 4550, thereby moving the extension 4553 with it. Inward movement of extensions 4553 disengages the engagement surfaces of ejection member 4550 from housing 4100, thereby allowing ejection member 4550 to move proximally along its longitudinal axis as spring 4576 expands.

[0114]

[1152] 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 29-31. 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.

[0115]

[1153] After the frangible seal 4413 is pierced, an actuated portion of compressed gas flows from the gas container 4410 through the gas passageway 4135 and 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 applies gas pressure to the medicament container flange 4214, 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 maintain 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. 30 and 31 . The medicament container body 4210 and the delivery control mechanism 4430 also move distally with the carrier assembly 4390. In this manner, moving the needle 4216 distally causes a distal end portion of the needle 4216 to exit the housing 4100 and enter the patient's body before administering the medicament. In some embodiments, the gas container 4410 can contain pressurized gas at approximately 1000 psi before piercing the frangible seal 4413. Once 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 supplied from the gas container 4410 is argon gas. In some embodiments, the compressed gas supplied from the gas container 4410 is a refrigerant, such as R134a.

[0116]

[1154] As the device moves from the third configuration to the fourth configuration, as shown in Figures 30 and 31, the gas vent assembly 4310 expands from the collapsed configuration (Figures 22A and 28) to a partially expanded configuration. In particular, in the partially expanded configuration, gas pressure within the medication cavity 4139 acts on the underside of the proximal end portion 4342, maintaining the valve portion 4345 in a sealing position within the opening 4112 and O-ring 4113. Thus, the medication cavity 4139 is maintained in a fluid-isolated state.

[0117]

[1155] When the needle 4216 extends a desired distance, the distal surface 4365 of the carrier body 4360 contacts the shoulder portion 4106 of the housing 4100, limiting 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 medication cavity 4139 (i.e., the housing gas chamber) continues through the delivery control mechanism 4430, applying gas pressure to the elastomeric member 4217 and initiating the second stage of expansion. During 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, during the first stage of expansion, the 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 further distal movement), the pressurized gas in the medication cavity 4139 drops to approximately 90-100 psi.

[0118]

[1156] As generally shown in FIG. 13A , gas from the medication 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. 15 ) 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.

[0119]

[1157] After passing through the internal passageway 4438, the gas enters the medicament body gas chamber 4440, which is 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 therefore the first member 4320 of the gas vent assembly 4310) to move distally within the medicament container body 4210. The distal movement of the elastomeric member 4217 creates pressure on the medicament contained within the medicament container assembly 4200. This allows at least a portion of the medicament to flow out of the medicament container 4200 and through the needle 4216. The medicament is delivered to the body of the user via the medicament delivery pathway defined by the medicament container 4200 and the needle 4216. As the elastomeric member 4217 advances to dispense the medicament, the gas vent assembly 4310 expands from a partially expanded configuration to a fully expanded configuration, and the medical injector is in its fifth configuration (FIGS. 33 and 34). In some embodiments, the drug body gas chamber 4440 is pressurized to approximately 10-20 psi to initiate actuation of the elastomeric member 4217 .

[0120]

[1158] 32, 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 state opening 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 or other indicia providing a color strip to assist a user in identifying the carrier, providing a way to view it, etc. Although not shown in FIG. 11, in some embodiments, a portion of the elastomeric member 4217 is visible through the state opening 4130 when the medical injector 4000 is in the fifth configuration or in the sixth configuration to indicate that medicament delivery is nearing completion or has been completed.

[0121]

[1159] 33 and 34, as the elastomeric member 4217 moves distally, the gas vent assembly 4310 moves with the elastomeric member 4217 in the 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 infusion 4000 is in the sixth configuration. In this sixth configuration, the elastomeric member 4217 continues to move a predetermined distance within the medicament container body 4210 (corresponding to the remaining desired dose) and the valve portion 4345 moves 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.

[0122]

[1160] When the gas pressure within the medication cavity 4139 falls below a certain level, the force exerted by the carrier body 4360 by the gas vent assembly 4310 is sufficient to cause the carrier body 4360 to move proximally (i.e., retract) within the housing 4100, thereby placing the medical injector in the seventh configuration (FIGS. 39 and 40). As shown in FIGS. 13, 14B, 39, and 40, 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, preventing the valve portion 4345 from contacting and closing the opening 4112.

[0123]

[1161] As shown in FIG. 38 , a portion of the medicament container assembly 4200 is visible through the state opening 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 state opening 4130. As mentioned above, in some embodiments, the housing 4100 can include a label or other indicia providing a color strip to assist a user in identifying, providing a way to view, etc. the elastomeric member. Although not shown in FIG. 38 , in some embodiments, a portion of the carrier 4360 is visible through the state opening 4130 when the medical injector 4000 is in the seventh configuration.

[0124]

[1162] As mentioned above, the drug delivery mechanism 4300 is considered a "pistonless" system. In a gas-powered pistonless auto-injector, forces provided by 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, the lack of a moving mechanism, piston, or the like can reduce the height of the medical injector 4000, for example, relative to the height of a device that includes a rigid, single-length piston.

[0125]

[1163] 41-43 show cross-sectional views of an apparatus 5000 including an equalization bypass 5470 and a movable seal member 5480 in three sealing positions. In some embodiments, the apparatus 5000 may be a drug delivery device, such as the medical injector 4000 described herein. Accordingly, the apparatus 5000 may optionally include any of the elements, structures, and / or features described herein with reference to the medical injector 4000.

[0126]

[1164] In some embodiments, the device 5000 includes a housing 5100, a gas container 5410, a medicament container assembly (e.g., medicament container assembly 4200), and a movable seal member 5480. The housing 5100 defines a gas chamber 5460 configured to receive pressurized gas from the gas container 5410 when the device 5000 is actuated. The movable seal member 5480 is also configured to move from a first sealing position SP1 ( FIG. 41 ) to a second sealing position SP2 ( FIG. 42 ) when the device 5000 is actuated. In addition to the gas chamber 5460, the housing 5100 also defines an equalization bypass 5470. The equalization bypass 5470 can facilitate fluid communication between the gas chamber 5460 and an external volume surrounding the housing 5100 when the movable seal member 5480 is in the first sealing position SP1. For example, as shown in FIG. 41 , fluid communication between the gas chamber 5460 and the external volume can occur along the path indicated by arrows AA1-AA3. Thus, a volume of gas can flow from the gas chamber 5460, bypassing the movable seal member 5480 via the equalization bypass 5470, distally between the housing 5100 and the discharge member 5550, and through the base (e.g., base 4510) of the device 5000, or vice versa. However, as shown in FIG. 42 , when the movable seal member 5480 is in the second sealing position SP2, the gas chamber 5460 is fluidly isolated from the external volume by the movable seal member 5480. In other words, the movable seal member 5480 in the second sealing position SP2 seals the gas chamber 5460, thereby facilitating an increase in gas pressure within the gas chamber 5460.

[0127]

[1165] As shown in FIGS. 41-43 , in some embodiments, the device 5000 includes a system actuator assembly 5500. The system actuator assembly 5500 may include any of the features described herein with reference to the system actuator assembly 4500. In particular, the system actuator assembly 5500 includes an ejection member 5550, a perforator 5575 coupled to the ejection member 5550, and an actuation spring 5576. The ejection member 5550 is movable within the housing 5100 between a first ejection member position shown in FIG. 41 and a second ejection member position shown in FIG. 42. When the ejection member 5550 is in the first ejection member position, the perforator 5575 is spaced apart from the gas canister 5410. The actuation spring 5576 is positioned between a portion of the ejection member 5550 and the housing 5100 and is configured to move the ejection member 5550 from the first ejection member position to the second ejection member position. Prior to actuation of the device 5000, the ejection member 5550 is in the locked configuration and the actuation spring 5576 is in the stored energy configuration. When the device 5000 is actuated, the ejection member is in the ejection configuration in response to an actuation force provided by the actuation spring 5576, and the perforator 5575 pierces a portion of the gas canister 5410 when the ejection member 5550 is in the second ejection member position. In other words, the perforator 5575 is positioned to pierce the gas canister 5410 in response to the ejection member 5550 transitioning from the locked configuration to the ejection configuration.

[0128]

[1166] In some embodiments, a movable seal member 5480 (e.g., similar to sealing member 4574) is coupled to the emission member 5550. In some embodiments, the movable seal member 5480 can be an O-ring that surrounds the emission member 5550. However, in some embodiments, the movable seal member 5480 can be a sealing structure (e.g., a protrusion, lip, or other similar structure) that is monolithically formed as part of the emission member 5550. When the emission member 5550 is in the first emission member position shown in FIG. 41 , the movable seal member 5480 is in a first sealing position SP1. When the emission member 5550 is in the second emission member position shown in FIG. 42 , the movable seal member 5480 is in a second sealing position SP2. In other words, the movable seal member 5480 is coupled to the emission member 5550 and is positioned between the emission member 5550 and the inner wall of the housing 5100. The movable seal member 5480 is in a first sealing position SP1 when the ejection member is in the locked state and is configured to move to a second sealing position SP2 in response to the ejection member transitioning from the locked configuration to the ejection configuration. The movable seal member 5480 thus fluidly isolates the gas chamber 5460 from the external volume after actuation of the device 5000 and prior to puncturing the gas container 5410. Thus, when pressurized gas is released from the gas container, it is contained within the sealed gas chamber 5460 and the ability of the pressurized gas to deliver the medicament is not affected by loss of gas.

[0129]

[1167] As shown in FIGS. 41-43 , in some embodiments, the system actuator assembly 5500 includes a positioning member 5560. The positioning member 5560 can be coupled to the ejection member 5550. As shown in FIG. 41 , the positioning member 5560 can have a first shape when the ejection member 5550 is in the locked configuration. The positioning member 5560 can have a second shape when the ejection member 5550 is in the ejection configuration shown in FIG. 42 . The first shape can be, for example, a compressed configuration in which the positioning member 5560 stores potential energy (e.g., elastic energy), and the second shape can be an expanded configuration resulting from the release of the potential energy. However, in some embodiments, the first shape can be an expanded configuration in which the positioning member 5560 is compressed to transition to the second shape. In some embodiments, the positioning member 5560 can include, for example, at least one leg 5562. The at least one leg 5562 can have a distal end portion 5564. The distal end portion 5564 may have a first radial position in the first shape (FIG. 41) and a second radial position in the second shape (FIGS. 42 and 43). The second radial position may be radially outward from the first radial position. In other words, the positioning member 5560 may have a first circumference in the first shape that is smaller than a second circumference in the second shape.

[0130]

[1168] As shown in FIG. 43 , when in the second shape, the positioning member 5560 engages with a receiving portion 5566 of the housing 5100. The engagement between the positioning member 5560 and the receiving portion 5566 prevents the ejection member 5550 from moving. For example, the engagement can prevent the ejection member 5550 from moving back from the second ejection member position to the first ejection member position. In other words, the engagement between the positioning member 5560 and the receiving portion 5566 can limit movement (e.g., distal movement) along the axis of motion (e.g., along the longitudinal axis of the device 5000). In some embodiments, as shown in FIG. 43 , when the positioning member 5560 engages with the receiving portion 5566 of the housing 5100, the movable seal member 5480 is maintained in a third seal position SP3. In some embodiments, the third seal position SP3 is between the first seal position SP1 and the second seal position SP2 along the axis of motion. The gas chamber 5460 is fluidly isolated from the external volume by the movable seal member 5480 when the movable seal member 5480 is in the third sealing position SP3. It should be understood that, without the positioning member 5560, the force provided by the release of pressurized gas from the gas container 5410 would overcome the force provided by the actuation spring 5576, thereby returning the release member 5550 and the movable seal member 5480 to the first release member position, first sealing position SP1. In such an event, fluid communication between the gas chamber 5460 and the external volume would be re-established, affecting operation of the device 5000.

[0131]

[1169] In some embodiments, movable seal member 5480 is a first movable seal member. In such embodiments, device 5000 can include a second movable seal member coupled to the carrier (e.g., outer O-ring 4370 coupled to carrier 4360). Additionally, device 5000 can include a third movable seal member (e.g., valve member 4345 configured as a movable seal).

[0132]

[1170] 44 shows a cross-sectional view of apparatus 6000 including an equalization bypass 6470 and a movable seal member 6480 in a first sealing position SP1. In some embodiments, apparatus 6000 may be a drug delivery device, such as medical injector 4000 or apparatus 5000 described herein. Accordingly, apparatus 6000 may optionally include any of the elements, structures, and / or features described herein with reference to medical injector 4000 or apparatus 5000.

[0133]

[1171] In some embodiments, the device 6000 includes a housing 6100, a gas canister 6410, a medicament container assembly 6200 (e.g., medicament container assembly 4200), and a movable seal member 6480. The medicament container assembly 6200 includes a container body 6210 and an elastomeric member 6217 disposed within the container body 6210. The elastomeric member 6217 is configured to move within the container body 6210 to deliver the medicament contained therein. The housing 6100 defines a gas chamber 6460 configured to receive pressurized gas from the gas canister 6410 when the device 6000 is actuated. The movable seal member 6480 is also configured to move from a first sealing position SP1 to a second sealing position (e.g., a distal sealing position) when the device 6000 is actuated. In addition to the gas chamber 6460, the housing 6100 also defines an equalization bypass 6470. The equalization bypass 6470 can facilitate fluid communication between the gas chamber 6460 and an external volume surrounding the housing 6100 when the movable seal member 6480 is in the first sealing position SP1. For example, as shown, fluid communication between the gas chamber 6460 and the external volume can occur along the path indicated by arrow BB. Thus, a volume of gas can flow from the gas chamber 6460, via the equalization bypass 6470, around the movable seal member 6480, distally between the housing 6100 and the carrier 6360 or medicament container assembly 6200, and through the base (e.g., base 4510) of the device 6000, or vice versa. However, when the movable seal member 6480 is in the second sealing position, the gas chamber 6460 is fluidly isolated from the external volume by the movable seal member 6480. In other words, the movable sealing member 6480 in the second sealing position seals the gas chamber 6460, thereby facilitating an increase in gas pressure within the gas chamber 6460.

[0134]

[1172] As shown, in some embodiments, device 6000 includes carrier 6360. Carrier 6360 can include any of the features described herein with reference to carrier 4360. Accordingly, as described herein with reference to carrier 4360, carrier 6360 can be configured to couple to medicament container assembly 6200 and to move (e.g., move distally) within housing 6100. Movement of carrier 6360 can be in response to forces exerted by pressurized gas within gas chamber 6460 following actuation of device 6000. Accordingly, a proximal surface of carrier 6360 can define a portion of the boundary of gas chamber 6460.

[0135]

[1173] In some embodiments, the movable sealing member 6480 (e.g., outer O-ring 4370) is coupled to the carrier 6360 and positioned between the carrier 6360 and an interior wall of the housing 6100. Movement of the carrier 6360 in response to a force exerted by the pressurized gas moves the movable sealing member 6480 relative to the housing 6100 from a first sealing position SP1 to a second sealing position, thereby isolating the gas chamber 6460 from the exterior volume.

[0136]

[1174] In some embodiments, the carrier 6360 can be omitted and the movable seal member 6480 can be directly coupled to the container body 6210 and positioned between the container body 6210 and an interior wall of the housing 6100. The container body 6210 can be moved within the housing 6100 from a first container position to a second container position in response to a force exerted by the pressurized gas in the gas chamber 6460. Movement of the container body 6210 in response to the force exerted by the pressurized gas moves the movable seal member 6480 relative to the housing 6100 from the first sealing position SP1 to the second sealing position SP2 to isolate the gas chamber 6460 from the exterior volume.

[0137]

[1175] In some embodiments, the movable seal member 6480 is a first movable seal member. In such embodiments, the device 6000 can include a second movable seal member coupled to the ejection member of the system actuator assembly (e.g., sealing member 4574 coupled to ejection member 4550). Additionally, the device 6000 can include a third movable seal member (e.g., valve member 4345 configured as a movable seal).

[0138]

[1176] 45 shows a cross-sectional view of apparatus 7000 including an equalization bypass 7470 and a movable seal member 7480 in a first sealing position SP1. In some embodiments, apparatus 7000 may be a drug delivery device, such as medical injector 4000, apparatus 5000, or apparatus 60000 described herein. Accordingly, apparatus 7000 may optionally include any of the elements, structures, and / or features described herein with reference to medical injector 4000, apparatus 5000, or apparatus 6000.

[0139]

[1177] In some embodiments, the device 7000 includes a housing 7100, a gas canister 7410, a medicament container assembly 7200 (e.g., medicament container assembly 4200), and a movable seal member 7480. The medicament container assembly 7200 includes a container body 7210 and an elastomeric member 7217 disposed within the container body 7210. The elastomeric member 7217 is configured to move within the container body 7210 to deliver the medicament contained therein. The housing 7100 defines a gas chamber 7460 configured to receive pressurized gas from the gas canister 7410 when the device 7000 is actuated. The movable seal member 7480 is also configured to move from a first sealing position SP1 to a second sealing position (e.g., a distal sealing position) when the device 7000 is actuated. In addition to the gas chamber 7460, the housing 7100 also defines an equalization bypass 7470. The equalization bypass 7470 can facilitate fluid communication between the gas chamber 7460 and an external volume surrounding the housing 7100 when the movable seal member 7480 is in the first sealing position SP1. For example, as shown, fluid communication between the gas chamber 7460 and the external volume can occur along the path indicated by arrow CC. Thus, a volume of gas can flow from the gas chamber 7460, bypass the movable seal member 7480 through the equalization bypass 7470, and proximally out of the housing 7100 through the vent port 7112, or vice versa. However, when the movable seal member 7480 is in the second sealing position, the gas chamber 7460 is fluidly isolated from the external volume by the movable seal member 7480. In other words, the movable seal member 7480 in the second sealing position seals the gas chamber 7460, thereby facilitating an increase in gas pressure within the gas chamber 7460. In some embodiments, the movable seal member 7480 is configured to move from the first position SP1 to the second position in response to a force exerted by pressurized gas in the gas chamber 7460.

[0140]

[1178] In some embodiments, the apparatus 7000 includes a gas vent assembly 7310. The gas vent assembly may include any of the features described herein with reference to the gas vent assembly 4310. The gas vent assembly 7310 is configured to selectively fluidly connect the gas chamber 7460 with the external volume. The movable seal member 7480 is configured as a valve member (e.g., valve member 4345). The movable seal member 7480 is configured to close and / or seal both the equalization bypass 7470 and the vent port 7112 defined by the housing 7100. Prior to actuation, the movable seal member 7480 (i.e., the valve member) is in a first sealing position SP1. In response to a force exerted by the pressurized gas in the gas chamber 7460, the movable seal member 7480 is configured to move to (e.g., move proximal to) a second sealing position, thereby sealing the vent port 7112 and fluidly isolating the gas chamber 7460 from the external volume. The movable seal member 7480 (i.e., valve member) is operatively coupled to an elastomeric member of the medicament container assembly 7200 via an expandable assembly (e.g., first member 4320, second member 4330, and third member 4340). The expandable assembly is configured to transition from a first configuration to a second configuration as the elastomeric member moves within the container body. In response to the movement of the elastomeric member, the movable seal member 7480 (i.e., valve member) moves from the second sealing position to the third sealing position as the expandable assembly transitions from the first configuration to the second configuration. Movement of the movable seal member 7480 to the third sealing position releases pressurized gas from the gas chamber 7460 to the exterior volume, as described herein.

[0141]

[1179] In other words, prior to actuation, the movable sealing member 7480 is in the first sealing position SP1, and the gas chamber 7460 is in fluid communication with the external volume via the equalization bypass 7470 and the vent port 7112. Upon actuation of the device 7000, pressurized gas is released from the gas container 7410. An initial portion of the pressurized gas enters the gas chamber 7460 and exerts a force on the movable sealing member 7480, causing it to move to the second sealing position. In the second sealing position, the movable sealing member 7480 fluidly isolates the gas chamber 7460 from the external volume. The pressurized gas also exerts a force on the elastomeric member, moving it to dispense a portion of the medicament contained in the medicament container assembly 7200. After the elastomeric member has moved sufficiently, the movable sealing member 7480 moves from the second sealing position to a third sealing position (which may be the same as the first sealing position SP1) to release the pressurized gas from the gas chamber 7460 to the external volume.

[0142]

[1180] In some embodiments, movable seal member 7480 is the first movable seal member. In such embodiments, apparatus 70000 can include a second movable seal member coupled to the ejection member of the system actuator assembly (e.g., sealing member 4574 coupled to ejection member 4550). Additionally, apparatus 7000 can include a third movable seal member coupled to the carrier (e.g., outer O-ring 4370 coupled to carrier 4360).

[0143]

[1181] 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.

[0144]

[1182] For example, in some embodiments, a 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 and / or large volumes of drug (e.g., greater than 1 mL) by delivering portions of the total dose in parallel. Specifically, as explained above with respect to Equation 1, needle length (L) and needle gauge (identified as the radius R of the needle's lumen) can 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 can facilitate the 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 can be included in dual-container devices of the type shown and described in PCT No. 4345 or PCT No. 0040.

[0145]

[1183] 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 of about 0.02 mg / cm. 2 ~about 0.80mg / cm 2 The coating can be made with an amount of polydimethylsiloxane.

[0146]

[1184] 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, Gerresheimer, Ompi Pharma, 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. Furthermore, 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 single 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 a single dose of up to 2 mL, 3 mL, 4 mL, 5 mL, or more of any of the drugs described herein.

[0147]

[1185] Any of the container bodies described herein can be made of glass and can be fitted with and / or coupled to any suitable needle. For example, in some embodiments, any of the container bodies described herein (including 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 that is about 0.5 inches long. Additionally, any of the medication containers and / or pre-filled syringes described herein may include a needle secured to its distal end.

[0148]

[1186] For example, any of the medical injectors shown and described herein may include a base (or distal actuator) having a mechanism for cooling the surface of a target injection site. Cooling the target injection site may improve patient comfort during the injection procedure. Such a cooling mechanism 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.

[0149]

[1187] Any of the medical injectors shown and described herein may include a base (or distal actuator) having a mechanism for expanding, stretching, or otherwise tautening a 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 it to expand to grip and stretch the surface against the skin prior to actuation and / or injection, or that allow a larger contact surface area against 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 it to grip and pinch the skin together prior to actuation and / or injection. Such a base may include a dome or other structure for pinching a particular portion of the anatomy, such as the abdomen.

[0150]

[1188] 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., a spring, gear, rack, pinion, pulley, 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.).

[0151]

[1189] 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 a 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 described 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. Furthermore, 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.

[0152]

[1190] While particular injection events, mechanisms, devices, and / or components are described herein, it should be understood that these are offered by way of example and not limitation, i.e., an auto-injector 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.

[0153]

[1191] Any of the devices and / or medication 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 medication syringes.

[0154]

[1192] Any of the devices and / or drug containers shown and described herein can contain and / or deliver a wide variety of large or macromolecular injectable substances, including carbohydrate-derived dosage forms, lipids, nucleic acids, hyaluronidase, proteins / peptides (e.g., monoclonal antibodies), and other biotechnology-derived drugs. For example, anti-tumor necrosis factor drugs 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.

[0155]

[1193] Any of the devices and / or medication containers shown and described herein can contain any suitable medication or therapeutic agent. In some embodiments, the medication contained in any of the medication containers shown herein can 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, pertussis vaccine, bubonic plague vaccine, yellow fever vaccine, cholera vaccine, malaria vaccine, smallpox vaccine, pneumococcal vaccine, rotavirus vaccine, varicella vaccine, dengue fever vaccine, rabies vaccine, and / or meningococcal vaccine. In other embodiments, the medication contained in any of the medication containers shown herein can be a catecholamine, such as epinephrine. In other embodiments, the medication contained in the medication containers provided 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 medication contained in any of the medication 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), erythropoiesis-stimulating agents (ESAs) (such as darbepoetin alfa), immunoglobulins (such as dual variable region immunoglobulins), interferons, anti-cancer drugs, 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 of the medication containers provided herein can be a placebo substance (i.e., a substance without an active ingredient), such as water.

[0156]

[1194] The drug containers and / or drug delivery devices 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 approximately 0.4 mg, 0.8 mg, 1 mg, 1.6 mg, or 2 mg of drug to be delivered. As previously mentioned, the load can be such that the ratio of delivered amount to load is any suitable value (e.g., 0.4, 0.6, etc.). In some embodiments, the electronic circuitry system can include a "configuration switch" that, when activated during assembly of the delivery device, can select an electronic output corresponding to the dose contained in the drug container.

[0157]

[1195] In some embodiments, a medical injector can include two prefilled syringes, each containing up to 1 mL (or more) of medication and equipped with a needle. Such devices (e.g., "dual-container devices") are shown and described in PCT Publication No. 4345, incorporated herein by reference. Upon actuation of the device (as described above), a single energy storage member (e.g., a compressed gas container) can release energy to move two containers within the housing in substantially the same operation to inject two needles. The force generated by the energy storage member can further inject medication from each container. In such embodiments, the two containers can contain the same medication or two different medications. For example, a 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, 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.

[0158]

[1196] Any of the medication containers described herein can include any suitable elastomeric member and / or plunger. For example, the elastomeric member can be tailored to be compatible with the medication contained in the medication container. Additionally, the medication container can include any number of elastomeric members. For example, in some embodiments, the medication container can include a dry portion of the medication and a fluid portion of the medication configured to be mixed prior to injection. The piston portion of the medication delivery mechanism can be configured to engage multiple elastomeric members associated with the portions of the medication. In this manner, the multiple elastomeric members can be engaged to mix the dry and fluid portions of the medication before the injection event is completed. In some embodiments, for example, any of the devices shown and described herein can 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 January 25, 2012. This patent is incorporated herein by reference in its entirety.

[0159]

[1197] 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, with 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 then exerts a force on the base (or portion of the base) to extend it and cover the needle. In other such embodiments, a spring, biasing member, or retraction member can urge the base (or portion of the base) distally.

[0160]

[1198] Although the gas vent assembly 4310 is shown and described herein as moving a valve portion relative to a seal to selectively place the internal gas chamber in fluid communication with the external 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. Furthermore, 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 punctured 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, a 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.

[0161]

[1199] Although various embodiments are described as having particular combinations of features and / or components, other embodiments are possible that have any combination of 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. 1. An apparatus comprising: a housing defining a gas chamber and an equalization bypass, the housing being surrounded by an external volume; a gas bottle disposed within the housing, the gas bottle configured to generate pressurized gas within the gas chamber when the device is activated; and a medicament container assembly disposed within the housing, the medicament container assembly including a container body and an elastomeric member disposed within the container body, the elastomeric member configured to move within the container body to advance a medicament contained therein in response to a force exerted by the pressurized gas in the gas chamber; a movable seal member disposed within the housing, the movable seal member configured to move from a first sealing position to a second sealing position; Equipped with the gas chamber is in fluid communication with the external volume through the equalization bypass when the movable sealing member is in the first sealing position; The apparatus, wherein the gas chamber is fluidly isolated from the exterior volume by the movable sealing member when the movable sealing member is in the second sealing position.

2. a system actuator assembly including an ejection member and a perforator coupled to the ejection member; the emitting member is movable within the housing between a first emitting member position and a second emitting member position; the perforator is spaced from the gas container when the discharge member is in the first discharge member position, and the perforator penetrates a portion of the gas container when the discharge member is in the second discharge member position; 2. The device of claim 1, wherein the movable seal member is coupled to the ejection member, the movable seal member being in the first sealing position when the ejection member is in the first ejection member position, and the movable seal member being in the second sealing position when the ejection member is in the second ejection member position.

3. a system actuator assembly including an ejection member disposed within the housing, a perforator, and an actuation spring; the ejection member is movable within the housing; prior to actuation of the device, the ejection member is in a locked configuration and the actuation spring is in a stored energy configuration, and upon actuation of the device, the ejection member is in the ejection configuration in response to an actuation force exerted by the actuation spring on the ejection member; the perforator is coupled to the discharge member and is positioned to pierce the gas container in response to the discharge member transitioning from the locked configuration to the discharge configuration; the movable seal member is coupled to the discharge member and positioned between the discharge member and an inner wall of the housing; the movable sealing member is in the first sealing position when the ejection member is in the locked configuration; The device of claim 1 , wherein the movable sealing member is configured to move to the second sealing position in response to the ejection member transitioning from the locked configuration to the ejection configuration.

4. the system actuator assembly includes a positioning member coupled to the ejection member; the positioning member has a first shape when the ejection member is in the locked configuration and a second shape when the ejection member is in the ejection configuration, the positioning member engaging a receiving portion of the housing when in the second shape; the movable sealing member is maintained in a third sealing position when the positioning member engages the receiving portion of the housing; The apparatus of claim 3 , wherein the gas chamber is fluidly isolated from the exterior volume by the movable sealing member when the movable sealing member is in the third sealing position.

5. The apparatus of claim 4 , wherein the third seal position is between the first seal position and the second seal position along a path of motion.

6. 10. The device of claim 1, further comprising a carrier coupled to the drug container assembly and configured to move within the housing in response to the force exerted by the pressurized gas, a proximal surface of the carrier defining a portion of the boundary of the gas chamber.

7. the movable seal member is coupled to the carrier and positioned between the carrier and an inner wall of the housing; 7. The apparatus of claim 6, wherein movement of the carrier in response to the force exerted by the pressurized gas moves the movable sealing member relative to the housing from the first sealing position to the second sealing position to isolate the gas chamber from the exterior volume.

8. a gas vent assembly configured to selectively place the gas chamber in fluid communication with the exterior volume, the gas vent assembly including a valve member configured to seal a vent opening defined by the housing; the valve member closes the vent port when in a first valve position prior to operation of the device; the valve member is configured to move within the housing from the first valve position to a second valve position in response to movement of the elastomeric member; The apparatus of claim 1 , wherein the gas chamber is in fluid communication with the external volume through the vent port when the valve member is in the second valve position.

9. an expandable assembly having 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, 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 members move within the drug container; 9. The device of claim 8, wherein the valve member moves from the first valve position to the second valve 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 external volume.

10. 9. The device of claim 8, wherein the vent port is sized to maintain the force of the pressurized gas in the gas chamber at a magnitude greater than the force exerted by the retraction spring during the time the medication is dispensed, and wherein the force of the pressurized gas decreases to a magnitude less than the force exerted by the retraction spring upon completion of the dispensing of the medication.

11. 11. The device of claim 10, wherein the vent port is sized so that the pressurized gas dispenses a first 20% of the medication over a first period of time and a last 20% of the medication over a second period of time that is less than twice the first period of time.

12. the movable seal member is a first movable seal member, and the apparatus comprises: a carrier coupled to the medicament container assembly and configured to move within the housing in response to the force exerted by the pressurized gas, a proximal surface of the carrier defining a portion of a boundary of the gas chamber; 9. The apparatus of claim 8, further comprising a second movable seal member coupled to the carrier and positioned between the carrier and an inner wall of the housing, the second movable seal member defining a second portion of the boundary of the gas chamber.

13. the movable sealing member is configured to move from the first sealing position to the second sealing position in response to a force exerted by the pressurized gas in the gas chamber; 2. The apparatus of claim 1, wherein the movable sealing member is configured to move from the second sealing position to a third sealing position in response to the movement of the elastomeric member, and the gas chamber is in fluid communication with the external volume via the equalization bypass when the movable sealing member is in the third sealing position.

14. 14. The apparatus of claim 13, further comprising a gas vent assembly configured to selectively fluidly connect the gas chamber with the external volume, the gas vent assembly including a valve member configured as the movable sealing member and a vent opening defined by the housing, the valve member configured to seal the vent opening, and the gas chamber being in fluid communication with the vent opening through the equalization bypass when the valve member is in the first sealing position.

15. an expandable assembly having 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, 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 members move within the drug container; 15. The device of claim 14, wherein the valve member moves from the second sealing position to the third sealing 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.

16. the container body is movable within the housing from a first container position to a second container position in response to the force exerted by the pressurized gas; the movable seal member is coupled to the container body and positioned between the container body and an inner wall of the housing; 2. The device of claim 1, wherein movement of the container body in response to the force exerted by the pressurized gas moves the movable sealing member relative to the housing from the first sealing position to the second sealing position, isolating the gas chamber from the exterior volume.

17. a delivery control mechanism coupled to the medicament container assembly, the delivery control mechanism including a flow restriction member acting on the elastomeric member and configured to regulate the flow of the pressurized gas into the container body; the medicament container assembly is configured to move from a first container position to a second container position in response to the force exerted by the pressurized gas; 10. The device of claim 1, wherein the flow restricting member is configured to restrict movement of the elastomeric member before the medicament container assembly assumes the second container position.

18. the gas chamber is a first gas chamber; the flow restricting member is configured to allow pressurized gas to pass from the first gas chamber to a second gas chamber, the second gas chamber being in fluid contact with the elastomeric member; a first portion of the pressurized gas in the first gas chamber having a first pressure magnitude; a second portion of the pressurized gas in the second gas chamber having a second pressure magnitude; 18. The apparatus of claim 17, wherein the magnitude of the first pressure is greater than the magnitude of the second pressure.

19. The device of claim 1 , further comprising a needle coupled to a distal end portion of the container body.

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