Device and method for delivering substance within pre-filled syringe

Abstract

An apparatus includes a housing defining a gas chamber and a balancing bypass, a gas container, a medicament container assembly, and a movable sealing member. A gas container is disposed within the housing and is configured to generate a pressurized gas within the gas chamber when the apparatus is actuated. The movable seal member is configured to move from a first seal position to a second seal position. When the movable sealing member is in the first seal position, the gas chamber is in fluid communication with an external volume around the apparatus via the balancing bypass. The gas chamber is fluidly isolated from the external volume by the movable sealing member when the movable sealing member is in the second seal position.

Description

[0001] Cross - reference to related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 428,557, filed on November 29, 2022, entitled "Devices and Methods for Delivery of Substances Within a Prefilled Syringe", which is incorporated herein by reference in its entirety. Technical field

[0003] The embodiments described herein relate to drug delivery devices, drug compositions, and pharmaceuticals. More particularly, the embodiments described herein relate to drug delivery devices for delivering a drug contained within a prefilled syringe. Background art

[0004] Known prefilled syringes are generally used to contain and inject drugs. Known prefilled syringes include a barrel body, which is typically constructed of glass and contains a drug therein. The distal end portion of certain known prefilled syringes includes a staked needle (i.e., a needle permanently attached to the barrel body during manufacturing), and the end of the needle is located within a needle cap to keep the needle sterile prior to use. Other known prefilled syringes include a Luer fitting or are adapted such that the distal end portion of the barrel body can be coupled with a needle. The proximal end portion of the barrel body of a known prefilled syringe includes a plunger (typically constructed of elastomer), which defines a part of the container closure and can move within the barrel body to inject the drug. The proximal end portion also includes a flange to allow a user to grasp the barrel body and manually apply a force to the piston to move the plunger, thereby causing drug injection.

[0005] Although prefilled syringes can be cost - effective devices for storing and delivering drugs, known methods of using prefilled syringes include manually inserting the needle into the body and subsequently manually applying an injection force. Additionally, upon completion of the injection, known methods also include covering the needle to avoid needle stick. Thus, known prefilled syringes are generally used by healthcare professionals trained in such procedures. To facilitate self - administration of the drug contained within a prefilled syringe, some known auto - injectors have been adapted to accommodate a prefilled syringe. Such known devices provide a source of stored energy for inserting the needle and / or injecting the drug.

[0006] However, known autoinjectors are typically designed for use with drug containers having specific dimensions and / or shapes and are thus generally not configured to receive known prefilled syringes. For example, using a prefilled syringe within a known autoinjector may typically result in a higher force being applied to the flange of the syringe body during the insertion operation, which may cause the syringe flange or body to break. Additionally, since many known prefilled syringes include a stub needle in fluid communication with the drug, it is undesirable to apply a force to the plunger during storage and / or during the insertion operation. For example, applying a force against the plunger during storage (which can be caused, for example, when a spring-loaded member is placed in contact with the plunger) may result in drug leakage. As another example, applying a force against the plunger during a needle insertion event may cause the drug to be injected before the needle has been inserted to the desired location. Similarly, some known autoinjectors are not configured to control the force applied to the plunger within the syringe body during storage and / or needle insertion.

[0007] Known autoinjectors configured to contain a prefilled syringe typically include a spring-based actuation system that moves a piston rod to insert the needle and inject the drug. However, since a piston rod is required, the size (e.g., length) of such known systems may be larger than desired. Additionally, known drugs or therapeutic substances are formulated to include high molecular weight compounds, compounds having complex molecular structures, living cells, and / or biological products. These drugs typically have a very high viscosity (e.g., greater than about 100 centipoise at room temperature), which must be accommodated by the delivery system. For example, the forces and pressures required to overcome the resistance of a spring-based actuation system in an autoinjector may be incompatible with the forces and pressures required to properly deliver a drug or therapeutic substance that includes a high molecular weight compound. Thus, many known autoinjectors configured to receive a prefilled syringe may not be able to provide an appropriate force and / or generate a desired flow rate to effectively deliver such higher viscosity substances. Additionally, even if an autoinjector is able to generate the desired force, such a device may result in undesirable delivery conditions or delivery rates, which may damage the substance being delivered or cause excessive pain or discomfort during delivery. For example, if the delivery rate is too high, the shear forces generated may damage the molecules within the substance, thereby reducing the efficacy. Additionally, known autoinjectors that automatically retract the needle after drug delivery to prevent accidental needle sticks typically include one or more guide shafts or linkages to detect the completion of drug delivery in order to initiate the retraction process. The guide shafts and linkages introduce additional friction during the drug delivery process, which is not conducive to providing the desired delivery rate and delivery conditions. The guide shafts and linkages also require additional internal housing space, thereby increasing the overall size and volume of the autoinjector.

[0008] To address challenges associated with spring-based actuation systems, some known systems use pressurized gas to generate the required insertion and / or drug delivery force. 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 corresponding to the atmospheric pressure at the manufacturing location during manufacture. Thus, in such known systems, a pressure difference may occur between the pressure in the gas chamber and the atmospheric pressure surrounding the device due to changes in the pressure and / or temperature of the environment in which the device is located. The pressure difference may have a negative impact on the device in the stored state and / or on the functionality of the device during actuation. For example, when the device is exposed to an altitude higher than the manufacturing location (e.g., during air transportation), the ambient pressure surrounding the device may be less than the pressure in the gas chamber. In such a case, the greater pressure in the gas chamber may cause drug leakage. Similarly, when the device is exposed to an altitude lower than the manufacturing location, the ambient pressure surrounding the device may be greater than the pressure in the gas chamber. In such a case, the negative pressure difference may prevent complete drug delivery when the device is actuated.

[0009] Accordingly, there is a need for improved methods and devices for delivering a drug contained within a pre-filled syringe. SUMMARY OF THE INVENTION

[0010] A drug delivery device for delivering a drug contained within a pre-filled syringe is described herein. In some embodiments, a device includes a housing, a gas container, a drug container assembly, and a movable seal member. The housing defines a gas chamber and a balance bypass. The gas container is configured to generate pressurized gas within the gas chamber when the device is actuated. 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 is configured to move within the container body to dispense the drug contained therein. The elastomeric member is configured to move within the container body in response to a force applied by the pressurized gas within the gas chamber. The movable seal member is also positioned within the housing. The movable seal member is configured to move from a first seal position to a second seal position. When the movable seal member is in the first seal position, the gas chamber is in fluid communication with the external volume surrounding the housing via the balance 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] In some embodiments, the device includes a system actuator assembly having a release member and a puncturer coupled to the release member. The release member is movable within the housing between a first release member position and a second release member position. When the release member is in the first release member position, the puncturer is spaced from the gas container. When the release member is in the second release member position, the puncturer pierces a portion of the gas container. A movable seal is coupled to the release member. When the release member is in the first release member position, the movable seal is in a first seal position. When the release member is in the second release member position, the movable seal is in a second seal position.

[0012] In some embodiments, the device includes a system actuator assembly having a release member, a puncturer, and an actuation spring disposed within the housing. The release member is movable within the housing. Before the device is actuated, the release member is in a locked configuration and the actuation spring has a stored energy configuration. In response to an actuation force applied by the actuation spring to the release member when the device is actuated, the release member converts to a release configuration. The puncturer is coupled to the release member and is positioned to pierce the gas container in response to the release member converting from the locked configuration toward the release configuration. A movable seal is coupled to the release member and is positioned between the release member and the inner wall of the housing. When the release member is in the locked configuration, the movable seal is in a first seal position, and the movable seal is configured to move to a second seal position in response to the release member converting from the locked configuration toward the release configuration.

[0013] In some embodiments, the system actuator assembly includes a positioning member coupled to the release member. When the release member is in the locked configuration, the positioning member has a first shape; when the release member is in the release configuration, the positioning member has a second shape. When in the second shape, the positioning member engages a receiving portion of the housing. When the positioning member engages the receiving portion of the housing, the movable seal is held at a third seal position. When the movable seal member is in the third seal position, the gas chamber is fluidly isolated from the external volume by the movable seal member. In some embodiments, the third seal position is located along the movement path between the first seal position and the second seal position.

[0014] In some embodiments, the device includes a carrier coupled to the drug container assembly and configured to move within the housing in response to a force applied by the pressurized gas. The proximal surface of the carrier defines a portion of the boundary of the gas chamber.

[0015] In some embodiments, the movable seal is coupled to the carrier and is positioned between the carrier and the inner wall of the housing. Movement of the carrier in response to the force applied by the pressurized gas causes the movable seal to move relative to the housing from the first seal position to the second seal position to isolate the gas chamber from the external volume.

[0016] In some embodiments, the device includes a venting assembly configured to selectively place a gas chamber in fluid communication with an external volume. The venting assembly includes a valve member configured to seal a vent opening defined by a housing. Before the device is actuated, the valve member blocks the vent opening when in a first valve position, and the valve member is configured to move from the first valve position to a second valve position within the housing in response to movement of an elastomeric member. When the valve member is in the second valve position, the gas chamber is in fluid communication with the external volume via the vent opening.

[0017] 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. When the elastomeric member moves within the container body, the expandable assembly is configured to convert from a first configuration to a second configuration. When the expandable assembly converts from the first configuration to the second configuration, the valve member moves from the first valve position to the second valve position to release pressurized gas from the gas chamber to the external volume.

[0018] In some embodiments, the vent opening is sized to maintain the force of the pressurized gas within the gas chamber at a magnitude greater than the force exerted by a retraction spring during the time of drug dispensing, 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] In some embodiments, the vent opening is sized such that the pressurized gas causes the first 20% of the drug to be dispensed within a first duration and causes the last 20% of the drug to be dispensed within a second duration, the second duration being less than twice the first duration.

[0020] 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. The proximal surface of the carrier defines a first portion of the boundary of the gas chamber. A second movable seal member is coupled to the carrier and positioned between the carrier and the inner wall of the housing. The second movable seal member defines a second portion of the boundary of the gas chamber.

[0021] 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 the pressurized gas within the gas chamber. The movable seal is configured to move from the second seal position to a third seal position in response to movement of the elastomeric member, wherein when the movable seal member is in the third seal position, the gas chamber is in fluid communication with the external volume via a balance bypass.

[0022] In some embodiments, the device includes a venting assembly configured to selectively place the gas chamber in fluid communication with the external volume. The venting assembly includes a valve member configured as a movable seal and a vent opening defined by a housing. The valve member is configured to seal the vent opening. When the valve member is in the first seal position, the gas chamber is in fluid communication with the vent opening via a balance bypass.

[0023] 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 an 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. When the elastomeric member moves within the container body, the expandable assembly is configured to convert from a first configuration to a second configuration. When the expandable assembly converts from the first configuration to the second configuration, the valve member moves from a second seal position to a third seal position to release pressurized gas from the gas chamber to the external volume.

[0024] In some embodiments, the container body moves from a first container position to a second container position within the housing in response to a force exerted by the pressurized gas. A movable seal member is coupled to the container body and is positioned between the container body and the inner wall of the housing. The movement of the container body in response to the force exerted by the pressurized gas causes the movable seal to move relative to the housing from a first seal position to a second seal position to isolate the gas chamber from the external volume.

[0025] In some embodiments, the device includes a delivery control mechanism coupled to the drug container assembly. The delivery control mechanism includes a flow restriction member configured to regulate the flow of pressurized gas into the container body that acts on the elastomeric member. The drug 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 restriction member is configured to limit the movement of the elastomeric member before the drug container assembly reaches the second container position.

[0026] In some embodiments, the gas chamber is a first gas chamber. In such embodiments, the flow restriction member is configured to allow pressurized gas to transfer from the first gas chamber to a second gas chamber that is 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] In some embodiments, the device includes a needle coupled to the distal end portion of the container body. Description of the Drawings

[0028] Figure 1A and 1BSchematic diagram of a drug delivery device according to an embodiment, depicting a gas chamber ([ Figure 1A ) in fluid communication with an external volume surrounding the delivery device and a gas chamber ([ Figure 1B ) fluidly isolated from the external volume.

[0029] Figure 2 Front perspective view of a medical syringe according to an embodiment, in a first configuration.

[0030] Figure 3 And 4 Are respectively Figure 2 Front perspective view and rear perspective view of the medical syringe shown, where the electronic circuitry is hidden and the safety lock is removed.

[0031] Figure 5 Is Figure 2 Perspective view of the housing of the medical syringe shown.

[0032] Figure 6 Is Figure 5 Cross-sectional view of the housing shown.

[0033] Figure 7 And 8 Are respectively Figure 2 Perspective view and cross-sectional view of the proximal cap of the medical syringe shown.

[0034] Figure 9 And 10 Is Figure 2 Front view of the drug delivery mechanism of the medical syringe shown.

[0035] Figure 11 Is Figure 2 Front view of the medical syringe shown, in a first configuration.

[0036] Figure 12 Is Figure 2 Front cross-sectional view of the medical syringe shown, in a first configuration.

[0037] Figure 13A Is Figure 12 Enlarged cross-sectional view of a part of the medical syringe shown, in a first configuration.

[0038] Figure 13B Is Figure 12 Enlarged cross-sectional view of a part of the medical syringe shown, in a first configuration.

[0039] Figure 14A And 14B Is Figure 12 Perspective view and cross-sectional view of the delivery control mechanism of the medical syringe shown.

[0040] Figure 15 is Figure 14A and 14B a cross-sectional view of the delivery control mechanism shown within the proximal end portion of the drug container.

[0041] Figure 16 and 17 are respectively Figure 12 a perspective view and a cross-sectional view of the carrier assembly of the medical syringe shown.

[0042] Figure 18 is Figure 12 a perspective view of the carrier assembly of the medical syringe shown.

[0043] Figure 19 is Figure 12 a cross-sectional view of the carrier assembly and the drug container of the medical syringe shown.

[0044] Figure 20 is Figure 12 an exploded view of the drug container assembly of the medical syringe shown.

[0045] Figure 21 is Figure 12 a perspective view of the venting assembly of the medical syringe shown.

[0046] Figure 22A 、 22B and 22C are respectively Figure 21 cross-sectional views of the venting assembly of

[0047] Figure 23 and 24 is Figure 2 a perspective view of the safety lock of the medical syringe shown, wherein Figure 23 a needle sheath assembly coupled to the safety lock is shown.

[0048] Figure 25 and 26 is Figure 2 a perspective view of the system actuator of the medical syringe shown.

[0049] Figure 27 is Figure 2 a front cross-sectional view of the medical syringe shown in the second configuration (safety lock removed).

[0050] Figure 28 is Figure 2 a front cross-sectional view of the medical syringe shown in the third configuration (actuated).

[0051] Figure 29 is Figure 2 a front view of the medical syringe shown in the fourth configuration (needle inserted).

[0052] Figure 30 is Figure 2 The front sectional view of the medical syringe shown is in the fourth configuration (needle inserted).

[0053] Figure 31 is Figure 2 The enlarged sectional view of the medical syringe shown is in the fourth configuration (needle inserted).

[0054] Figure 32 is Figure 2 The front view of the medical syringe shown is in the fifth configuration (delivering medicine).

[0055] Figure 33 is Figure 2 The front sectional view of the medical syringe shown is in the fifth configuration (delivering medicine).

[0056] Figure 34 is Figure 2 The perspective sectional view of the medical syringe shown is in the fifth configuration (delivering medicine).

[0057] Figure 35 is Figure 2 The front view of the medical syringe shown is in the sixth configuration (venting the housing gas chamber).

[0058] Figure 36 is Figure 2 The front sectional view of the medical syringe shown is in the sixth configuration (venting the housing gas chamber).

[0059] Figure 37 is Figure 2 The perspective sectional view of the medical syringe shown is in the sixth configuration (venting the housing gas chamber).

[0060] Figure 38 is Figure 2 The front view of the medical syringe shown is in the seventh configuration (needle retracted).

[0061] Figure 39 is Figure 2 The front sectional view of the medical syringe shown is in the seventh configuration (needle retracted).

[0062] Figure 40 is Figure 2 The perspective sectional view of the medical syringe shown is in the seventh configuration (needle retracted).

[0063] Figure 41 The front sectional view of a part of a medical syringe according to an embodiment, wherein the release member of the system actuator assembly is in the first release member position, the movable seal is in the first seal position, and the positioning member has the first shape.

[0064] Figure 42 is a front cross-sectional view of a portion of a medical syringe according to Figure 41 in which the release member is in the second release member position, the movable seal is in the second seal position, and the positioning member has a second shape.

[0065] Figure 43 is a front cross-sectional view of a portion of a medical syringe according to Figure 41 in which the movable seal is in the third seal position and the positioning member is in the second shape.

[0066] Figure 44 is a front cross-sectional view of a portion of a medical syringe according to an embodiment, in which the movable seal is in the first seal position.

[0067] Figure 45 is a front cross-sectional view of a portion of a medical syringe according to an embodiment, in which the movable seal is in the first seal position. DETAILED DESCRIPTION

[0068] A drug delivery device for administering a drug contained in a prefilled syringe is described herein. As described, the drug delivery device (apparatus) uses pressurized gas in a gas chamber to dispense the drug contained in a drug container assembly. When the device is actuated, pressurized gas is introduced from a gas container into the gas chamber. Before actuation, the gas chamber is in fluid communication with the external volume surrounding the device via a balancing bypass. In other words, before actuation, the pressure in the gas chamber corresponds to the ambient pressure affecting the device. The device includes a movable seal member. Before actuation, the movable seal member is in the first seal position, and the gas chamber is in fluid communication with the external volume via the balancing bypass. However, when the device is actuated, the movable seal member moves to the second seal position, at which the movable seal member isolates the gas chamber from the external volume. In other words, when the movable seal is in the second seal position, the gas chamber is sealed.

[0069] In some embodiments, the movable seal is one of a plurality of seal members that together form portions 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 may include a first seal coupled to a release member that is positioned to release pressurized gas from a gas container. A second seal may be coupled to a carrier of the drug container or to the container itself. A third seal may be part of a venting assembly (e.g., a valve member) that is configured to release pressurized gas from the gas chamber. Releasing pressurized gas from the gas chamber may occur, for example, after delivery of the drug to facilitate retraction of the drug container assembly, needle, or other delivery member. In such an embodiment, the first seal coupled to the release member may be the movable seal member, and the gas chamber may be isolated from the external volume by the movable seal member after the device is actuated but before the pressurized gas is released from the gas container. However, in additional embodiments, the movable seal member may be the second seal coupled to the carrier. So long as the carrier can be configured to move in response to the force exerted by the pressurized gas to insert the needle into the patient, movement of the carrier can cause the movable seal member to move to a second seal position, thereby isolating the gas chamber from the external volume. Additionally, in some embodiments, as part of the venting assembly, the third seal may correspond to the movable seal member. In such an embodiment, the force exerted by the pressurized gas may cause the third seal to move from a first seal position to a second seal position, thereby blocking the vent opening of the device. The third seal may be maintained in the second seal position until movement of an elastomeric member of the drug container assembly causes the third seal to transition to a third seal position establishing fluid communication between the gas chamber and the vent opening.

[0070] As used herein, the term "substance" or "drug" includes any ingredient of a therapeutic substance. A drug can include such ingredients regardless of their physical state (e.g., solid, liquid, or gas). Additionally, a drug can include multiple ingredients that can be included in the therapeutic substance in a mixed state, an unmixed state, and / or a partially mixed state. A drug can include both active and inert ingredients of the therapeutic substance. Thus, as used herein, a drug can include inactive ingredients such as, for example, water, coloring agents, or the like.

[0071] The term "about" when used in conjunction with a reference numeral indication refers to the reference numeral indication plus or minus 10% of the reference numeral indication. For example, "about 100" refers to from 90 to 110.

[0072] In a similar manner, the term "substantially" when used in connection with, for example, geometric relationships, numerical values, and / or ranges is intended to mean that the geometric relationship (or structure so described), quantity, and / or range so defined is nominally the recited geometric relationship, quantity, and / or range. For example, two structures described herein as "substantially parallel" are intended to mean that while a parallel geometric relationship is desired, a certain non - parallelism may occur in a "substantially parallel" arrangement. As another example, a structure defining a volume of "substantially 0.50 milliliters (mL)" is intended to mean that while the recited volume is desired, a certain tolerance may occur when the volume is "substantially" the recited volume (e.g., 0.50 mL). Such tolerances may be caused by manufacturing tolerances, measurement tolerances, and / or other practical considerations (e.g., minor imperfections, the lifespan of the structure so defined, the pressure or force applied within the system, and / or similar factors). As noted above, a suitable tolerance may be, for example, ±10% of the recited geometric structure, numerical value, and / or range. Additionally, while a numerical value modified by the term "substantially" may be allowed to account for and / or otherwise cover the tolerance of the recited numerical value, this is not intended to exclude the exact numerical value recited.

[0073] As used herein, the term "group" may refer to multiple features or a single feature having multiple components. For example, when referring to a group of walls, the group of walls may be considered as one wall having multiple parts, or the group of walls may be considered as multiple distinct walls. Thus, an article of manufacture may include a group of walls. Such a group of walls may include, for example, multiple parts that are continuous or discontinuous with each other. A group of walls may also be made from multiple articles that are produced separately and subsequently joined together (e.g., via welding, adhesives, or any suitable method).

[0074] As used in this specification and the appended claims, the words "proximal" and "distal" refer respectively to directions closer to and farther from the operator of the medical device. Thus, for example, the end of a drug delivery device that contacts the patient's body will be the distal end of the drug delivery device, while the end opposite the distal end will be the proximal end of the drug delivery device.

[0075] As used herein, the terms "stiffness" or "rigidity" relate to the ability of an object to resist deflection, deformation, and / or displacement caused by an external force, and are generally understood to be the opposite of the "flexibility" of an object. For example, a gas release member having a greater stiffness is more resistant to deflection, deformation, and / or displacement when exposed to a force than a gas release member having a lower stiffness. Similarly, a gas release member having a higher stiffness can be characterized as being more rigid than a gas release member having a lower stiffness. Stiffness can be characterized based on the amount of force applied to the object and the distance by which a first portion of the object deflects, deforms, and / or displaces relative to a second portion of the object. When characterizing the stiffness of an object, the deflection distance can be measured as the deflection of a portion of the object that is different from the portion of the object to which the force is directly applied. In other words, in some objects, the point of deflection is different from the point at which the force is applied.

[0076] Stiffness (and thus, flexibility) is an extensive property of the object being described and thus depends on the material forming the object as well as certain physical characteristics of the object (e.g., cross-sectional shape, length, boundary conditions, etc.). For example, the stiffness of an object can be increased or decreased by selectively including materials in the object having a desired modulus of elasticity, modulus of flexure, and / or hardness. The modulus of elasticity is an intensive property of the constituent material (i.e., inherent to the material itself) and describes the tendency of an object to elastically (i.e., non-permanently) deform in response to an applied force. In the presence of the same applied stress, a material having a high modulus of elasticity will not deflect as much as a material having a low modulus of elasticity. Thus, for example, the stiffness of an object can be decreased by introducing a material having a relatively low modulus of elasticity into the object and / or constructing the object from a material having a relatively low modulus of elasticity.

[0077] The stiffness of an object can also be increased or decreased by changing the physical characteristics of the object (e.g., the shape or cross-sectional area of the object). For example, an object having a length and a cross-sectional area may have a greater stiffness than an object having the same length but a smaller cross-sectional area. As another example, the stiffness of an object can be decreased by including one or more stress concentration protrusions (or discontinuous boundaries) that cause deformation to occur at a lower stress and / or at a specific location on the object. Thus, the stiffness (or flexibility) of an object can be decreased by reducing and / or changing the shape of the object.

[0078] Thus, an object that is easily deformed under a small force, such as a wire, filament, cord, or the like is referred to as a flexible object.

[0079] The therapeutic compositions described herein can be included in any suitable drug delivery device described herein or in International Patent Publication No. WO2017 / 004345, titled "Auto-Injectors for Administration of a Medicament Within a Prefilled Syringe," filed on June 30, 2016 ("'4345 PCT"), International Patent Publication No. WO2020 / 140040, titled "Devices and Methods for Delivery of Substances Within a Prefilled Syringe," filed on December 27, 2019 ("'0040 PCT"), International Patent Publication No. WO2018 / 136413, titled "Medicament Delivery Devices with Wireless Connectivity and Event Detection," filed on January 16, 2018 ("'6413 PCT"), and / or International Patent Publication No. WO2020 / 018433, titled "Medicament Delivery Devices with Wireless Connectivity and Compliance Detection," filed on July 15, 2019 ("'8433 PCT"), each of these international patent publications being incorporated herein by reference in its entirety. For example, in some embodiments, a drug product configured to be administered by an untrained user (e.g., a person accompanying a patient) can include a dose of icatibant. Such a drug product can include, for example, an auto-injector having a needle length and delivery parameters (e.g., the flow rate of icatibant) to effect subcutaneous injection. In other embodiments, the drug product can include a therapeutic substance comprising a monoclonal antibody. Such a drug product can include, for example, an auto-injector having a plurality of prefilled syringe containers that deliver the drug from each syringe in a single operation to deliver a desired dose. By including multiple syringes, such an arrangement can allow for higher doses while still using the standard fill volume within the prefilled syringe.

[0080] In some embodiments, a gas-powered drug delivery device can result in a compact device in which the external 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 be free of a mechanical linkage that applies or transfers force to an elastomeric member to expel the drug from the drug container therein. Similarly stated, in some embodiments, the drug delivery device can be free of a mechanical linkage (punch, rod) that transfers force to the elastomeric member. Instead, in some embodiments, the elastomeric member can apply force to a member (e.g., an expandable member) to provide control over the delivery. Such a drug delivery device (or drug delivery mechanism) is considered a "pistonless" system. As an example, in a gas-powered pistonless autoinjector, the force applied by the gas can cause the drug container to move relative to the housing and similarly can cause the elastomeric member to move relative to the drug container (e.g., within the drug container). In some embodiments, by not including a movable mechanism, piston, and / or the like, the height of the medical syringe can be reduced relative to the height of a device, for example, that includes a rigid piston of a single length.

[0081] For example, any of the drug delivery devices described herein can include any suitable "pistonless" design, such as those described in PCT '4345, PCT '0040, or International Patent Publication No. WO2016 / 154427, titled "DEVICES AND METHODS FORDELIVERING ALYOPHILIZED MEDICAMENT", filed on March 24, 2016, which international patent publication is incorporated herein by reference in its entirety.

[0082] In some embodiments, the properties of the drug, the properties of the drug container, and the properties of the needle are such that it is not possible to achieve the force required for a desired injection via manual injection. Thus, in some embodiments, a device can include an energy storage member configured to generate a desired force (and / or pressure within the drug container) to deliver the drug. For example, in certain cases, the pressure of the drug within the needle-based drug container can be modeled by the Hagen-Poiseuille law, as indicated below:

[0083] (1) P = (8 * μ * L * Q) / (Π * R 4 )

[0084] Wherein, P is the pressure of the drug in the drug container, μ is the viscosity of the drug, L is the length of the needle (not shown), Q is the flow rate of the drug through the needle, and R is the radius of the lumen defined by the needle. Since the pressure (and / or force) required for injecting a highly viscous fluid through a small-bore needle is proportional to the reciprocal of the fourth power of the radius of the lumen of the needle, the pressure of the drug in the drug container required to achieve a desired flow rate may sometimes be relatively high. By including a gas-based energy storage member, a desired pressure can be achieved.

[0085] In some embodiments, the energy storage member can be configurable to include various amounts of stored energy without changing the size of the energy storage member. Thus, in such embodiments, a higher force (e.g., to inject a viscous drug) can be achieved in the same package for a lower-viscosity drug. For example, in some embodiments, the energy storage member can be a compressed gas cylinder having a gas at any desired pressure (and thus, having any desired mass). Thus, regardless of the drug, a pressure and / or force can be achieved to perform the operations described herein.

[0086] In such embodiments, using a non-mechanical energy storage member (e.g., gas, propellant, or the like) can generate a high enough force to create a desired pressure within the drug container to effect a desired injection. For example, in such embodiments having a larger diameter, the amount of force required to create a desired internal pressure increases significantly. In some embodiments, any of the drug delivery devices shown herein can include a gas-based energy storage system configured to generate a gas pressure (e.g., within a gas chamber) between about 200 psi and about 2700 psi. In some embodiments, any of the syringes shown 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 syringes shown herein can include a gas-based energy storage system configured to generate a gas pressure between about 200 psi and 7000 psi. The gas pressure can be generated by any suitable mechanism, such as, for example, by piercing a compressed gas container, releasing a propellant (e.g., hydrofluoroalkane), releasing a refrigerant (e.g., R134a), releasing a liquefied gas, triggering a chemical reaction, or similar operations.

[0087] Figure 1A and1B Schematic diagram of a device (e.g., a drug delivery device) 1000 according to an embodiment. As shown, the device 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 external volume EV. The housing 1100 defines a gas chamber 1460 and a balance bypass 1470. The gas chamber 1460 can be, for example, a part of the volume defined by the housing 1100 in which a part 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 an assembly of multiple parts formed of a plastic material and defines a substantially rectangular shape when assembled. In other embodiments, the housing 1100 can have a substantially cylindrical shape.

[0088] The gas container 1410 is disposed within the housing 1100. The gas container 1410 is configured to generate a pressurized gas PG within the gas chamber 1410 when the device 1000 is actuated. In other words, when the device is actuated, the gas container 1410 can be configured to deliver the pressurized gas into the gas chamber 1460 to generate a force to deliver the contents of the drug container assembly 1200. The gas container 1410 can be any suitable member or device that stores potential energy and generates a pressurized gas when actuated. For example, the gas container 1410 (and any of the gas containers described herein) can be any one of a device containing a 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 that contains a volume of an inert gas at a pressure of at least 900 psi (e.g., 1000 psi or higher).

[0089] The drug container assembly 1200 has a drug container body 1210 that defines a volume for containing (i.e., filled or partially filled with) a drug. The distal end portion of the drug container body 1210 includes a neck or an opening through which the drug can be delivered. In some embodiments, the drug container assembly 1200 can include a delivery member (e.g., a nozzle, a needle, a delivery orifice, a mouthpiece, and / or other similar structures) coupled to the container body 1210 through which the drug is delivered. For example, in some embodiments, the drug container assembly 1200 can be a pre-filled syringe having a needle staked thereon of the type shown and described herein. In other embodiments, the drug container assembly 1200 can be a sealed cartridge that can be selectively coupled to a needle when the device is actuated. For example, in some embodiments, the drug container assembly 1200 can be similar to the multi-chamber cartridge shown and described in U.S. Provisional Application No. 63 / 398,410, filed on August 16, 2022, titled "Devices and Methods for Delivering Reconstituted Medicaments", which is incorporated herein by reference in its entirety. In some embodiments, the drug container assembly 1200 can include or be coupled to a carrier (not shown, but which can be similar to the carrier 4360 described below) that moves the drug container body 1210 within the housing 1100. In this way, the carrier can facilitate the movement of the delivery member out of the housing 1100 in the deployed position, as described below. In some embodiments, one or more surfaces of the carrier can form at least a portion of the boundary of the gas chamber 1460. In some embodiments, the carrier can include one or more seals to fluidly isolate the gas chamber 1460.

[0090] 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 inject 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 the efficacy of the drug that may result from (direct or indirect) contact between the elastomeric member 1217 and the drug. For example, in some embodiments, the elastomeric member 1217 can be formulated to minimize any leaching or outgassing of components that may have an adverse effect on the drug. In other embodiments, the elastomeric member 1217 can be formulated to maintain its chemical stability, flexibility, and / or sealing performance when in (direct or indirect) contact with the drug over a long period of time (e.g., up to six months, one year, two years, five years, or longer).

[0091] The drug container assembly 1200 can include a proximal portion configured to translate within the housing 1100 to move the drug container body 1210 between the positions described herein. Although the drug container assembly 1200 is shown disposed within the housing 1100 without a carrier, in other embodiments, the drug container assembly 1200 can be disposed within or coupled to a carrier to facilitate movement within the housing 1100. The proximal portion of the drug container assembly 1200 and the carrier (if any) can define a portion of the boundary of the gas chamber 1460. Thus, when pressurized gas is delivered into the gas chamber 1460, the pressure within the gas chamber can create a force on the drug container assembly 1200 to move the drug container body 1210, e.g., from a retracted position to a deployed position.

[0092] 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. Thus, the retraction member can be configured to move the drug container assembly 1200 back toward the retracted position after deployment as described in further detail herein. In some embodiments, the retraction member can also be configured to maintain the drug container 1200 in the retracted position prior to supplying gas pressure to the gas chamber 1460. In some embodiments, the device 1000 can be configured to hold the drug 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 lid that moves around the delivery member after delivery is completed).

[0093] As Figure 1A shown, prior to actuation, the gas chamber 1460 is in fluid communication with the external volume EV via the balance bypass 1470. Due to the fluid communication provided by the balance bypass 1470, the pressure within the gas chamber 1460 corresponds to the pressure of the external volume EV. Thus, the fluid communication between the gas chamber 1460 and the external volume EV via the balance bypass 1470 precludes the development of a significant pressure differential between the gas chamber 1460 and the external volume EV that otherwise could affect the condition and / or operation of the device 1000. Similarly, the balance bypass 1470 precludes the development of a significant pressure differential across the elastomeric member 1217 that could cause unwanted movement or jamming of the elastomeric member 1217 within the container body 1210. However, since it may be desirable to increase the pressure within the gas chamber 1460, the device 1000 includes a movable seal member 1480 to selectively isolate the gas chamber 1460 from the external volume EV. Figure 1ADepicts a movable seal member 1480 in a first seal position SP1. When the movable seal member 1480 is in the first seal position SP1, the gas chamber 1460 is in fluid communication with the external volume EV via the balance bypass 1470. After the device 1000 is actuated, as Figure 1B shown, the movable seal member 1480 is in a second seal position SP2, and the gas chamber 1460 is fluidly isolated from the external volume EV. In the case where the gas chamber 1460 is fluidly isolated from the external volume by the movable seal member 1480 in the second seal position, the pressurized gas PG within the gas chamber 1460 exerts a force on the elastomeric member 1217 to cause a desired movement of the elastomeric member 1217 within the container body, thereby dispensing a portion of the drug from the drug container assembly 1200. As described herein, in some embodiments, the movable seal member 1480 may transition from the first seal position SP1 to the second seal position SP2 after the device 1000 is actuated and before the pressurized gas PG is introduced into the gas chamber 1460. In additional embodiments, the force exerted by the pressurized gas PG in the gas chamber 1460 may cause the movable seal member 1480 to transition from the first seal position SP1 to the second seal position SP2 to isolate the gas chamber 1460 from the external volume EV.

[0094] When the device 1000 is actuated, the gas container 1410 is activated and releases the 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 together with the delivery member from a retracted position to a 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, once the gas chamber 1460 is isolated from the external volume EV as Figure 1B shown, pressure builds up within the gas chamber 1460. After the pressure in 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.

[0095] In some embodiments, the drug delivery device may be an auto-injector having a pistonless delivery system, where the force exerted by the gas may cause the drug container to move relative to the housing and the elastomeric member to move relative to the drug container (e.g., within the drug container). For example, Figures 2 - 40FIG. 0 shows a medical syringe 4000 (also referred to as an “auto-injector,” “syringe,” or “device”) according to one embodiment. The medical syringe 4000 is a gas-powered auto-injector configured to deliver a drug contained within a prefilled syringe 4200, as described herein. In some embodiments, the medical syringe 4000 may be configured to be fixed to a patient as an in-body system. After a discussion of the various components of the medical syringe 4000, the operation of the medical syringe 4000 will be discussed. Certain aspects of the medical syringe 4000 may be similar or substantially the same as the medical syringes described in PCT / US2011 / 0244345, PCT / US2011 / 024040, PCT / US2011 / 026413, and U.S. Patent Application Serial No. 13 / 357,935, filed Jan. 25, 2012, entitled “MEDICAMENT DELIVERY DEVICES FOR ADMINISTRATION OF A MEDICAMENT WITHIN A PREFILLED SYRINGE” (now U.S. Pat. No. 9,084,849) (hereinafter referred to as the “‘849 patent”), the disclosures of each of which are incorporated herein by reference in their entirety.

[0096] The medical syringe 4000 includes a housing 4100 (e.g., see Figure 5 and 6 ), a system actuation assembly 4500 (e.g., see Figure 9 and 10 ), a drug container assembly 4200 (see Figure 20 ), a drug delivery mechanism 4300 (e.g., see Figures 16 - 20 ), a base 4510 (or actuator, see Figure 25 and 26 ); and a safety lock 4700 (see Figure 23 and 24 ). As Figures 3 - 6 shown, the housing 4100 has a proximal end portion 4101 and a distal end portion 4102. The housing 4100 defines a first status indicator hole 4130 and a second status indicator hole 4160. The first status indicator hole 4130 defined by the housing 4100 is located on a first side of the housing 4100, and the second status indicator hole 4160 of the housing 4100 is located on a second side of the housing 4100. The status indicator holes 4130, 4160 may allow a patient to monitor the status and / or contents of the drug container 4200, the carrier 4360, and the drug contained within the housing 4100. For example, by visually inspecting the status indicator holes 4130, 4160, a patient can determine whether the drug container 4200 contains a drug and / or whether the drug has been dispensed.

[0097] As Figure 2 , 3As shown in FIGS. 5 and 12, housing 4100 defines a gas container chamber 4151 and a drug chamber 4139. Gas container chamber 4151 is configured to receive gas container 4410 and a portion of system actuator assembly 4500 (e.g., release member 4550 and spring 4576, as shown in FIGS. 12 and 13). The proximal end portion of gas container chamber 4151 is configured to receive gas container retaining member 4180 of proximal cap 4110 of housing 4100, as described in further detail herein. Gas container chamber 4151 is in fluid communication with drug chamber 4139 via gas passage 4135 defined in housing 4100, as described in further detail herein. Drug chamber 4139 is configured to receive drug container assembly 4200 and at least a portion of drug delivery mechanism 4300. In particular, as described below, drug delivery mechanism 4300 includes carrier assembly 4390 (see, e.g., FIGS. 14, 15, 16-19) and venting assembly 4310 (see, e.g., FIGS. 13A, 18, 21, 22A-22C), which are movably disposed within drug chamber 4139. Drug chamber 4139 is in fluid communication with the region external to housing 4100 via needle aperture 4105 and also via vent opening 4112. It should be understood that although a single drug container assembly is shown, in additional embodiments, additional drug container assemblies 4200 may be employed. For example, in some embodiments, housing 4100 may include two drug chambers 4139, each of which contains a separate drug container assembly 4200. As shown in FIGS. 5 and 12, housing 4100 includes an electronic circuitry cavity 4153, which can house any of the electronic devices described herein and / or any of the electronic circuitry described in the '8433 PCT. Although housing 4100 is shown as having an electronic circuitry cavity 4153, in some embodiments, medical syringe 4000 need not include any electronic devices or an electronic circuitry cavity 4153. In some embodiments, housing 4100 may include a label or marking that obscures or otherwise emphasizes status indicator holes 4130, 4160 and / or the contents viewed therethrough. For example, in some embodiments, housing 4100 may include a label (not shown) having a boundary that surrounds at least a portion of status indicator hole 4130, status indicator hole 4160 (or both). In some embodiments, the label may include an indicator color that alerts the user (or helps the user determine) whether the drug is properly colored, whether a portion of carrier 4360 is visible through the window, or the like.

[0098] As Figure 5 , 6 As shown in FIGS. 5, 12 and 12, housing 4100 defines a gas container chamber 4151 and a drug chamber 4139. Gas container chamber 4151 is configured to receive gas container 4410 and a portion of system actuator assembly 4500 (e.g., release member 4550 and spring 4576, as shown in FIGS. 12 and 13). The proximal end portion of gas container chamber 4151 is configured to receive gas container retaining member 4180 of proximal cap 4110 of housing 4100, as described in further detail herein. Gas container chamber 4151 is in fluid communication with drug chamber 4139 via gas passage 4135 defined in housing 4100, as described in further detail herein. Figure 9 and 10 shown). The proximal end portion of gas container chamber 4151 is configured to receive gas container retaining member 4180 of proximal cap 4110 of housing 4100, as described in further detail herein. Gas container chamber 4151 is in fluid communication with drug chamber 4139 via gas passage 4135 defined in housing 4100, as described in further detail herein.

[0099] Drug chamber 4139 is configured to receive drug container assembly 4200 and at least a portion of drug delivery mechanism 4300. In particular, as described below, drug delivery mechanism 4300 includes carrier assembly 4390 (see, e.g., FIGS. 14, 15, 16-19) and venting assembly 4310 (see, e.g., FIGS. 13A, 18, 21, 22A-22C), which are movably disposed within drug chamber 4139. Drug chamber 4139 is in fluid communication with the region external to housing 4100 via needle aperture 4105 and also via vent opening 4112. It should be understood that although a single drug container assembly is shown, in additional embodiments, additional drug container assemblies 4200 may be employed. For example, in some embodiments, housing 4100 may include two drug chambers 4139, each of which contains a separate drug container assembly 4200. Figure 9 , 10 and 16-19) and venting assembly 4310 (see, e.g., FIGS. 13A, 18, 21, 22A-22C), which are movably disposed within drug chamber 4139. Drug chamber 4139 is in fluid communication with the region external to housing 4100 via needle aperture 4105 and also via vent opening 4112. It should be understood that although a single drug container assembly is shown, in additional embodiments, additional drug container assemblies 4200 may be employed. For example, in some embodiments, housing 4100 may include two drug chambers 4139, each of which contains a separate drug container assembly 4200. Figure 7 , 8 and 13A, 21 and 22A-22C), which are movably disposed within drug chamber 4139. Drug chamber 4139 is in fluid communication with the region external to housing 4100 via needle aperture 4105 and also via vent opening 4112. It should be understood that although a single drug container assembly is shown, in additional embodiments, additional drug container assemblies 4200 may be employed. For example, in some embodiments, housing 4100 may include two drug chambers 4139, each of which contains a separate drug container assembly 4200.

[0100] The proximal end portion 4101 of the housing 4100 includes a proximal cap 4110 (see, for example, Figure 7 , 8 and 13). The proximal cap 4110 includes a gas container holding member 4180 configured to receive and / or hold a gas container 4410 containing pressurized gas, as Figures 7 - 10 shown. When the medical syringe 4000 is actuated, the pressurized gas from the gas container 4410 is delivered from the gas container chamber 4151 to the drug chamber 4139 via the gas passage 4135 of the housing 4100. In other words, the gas passage 4135 places the gas container chamber 4151 in fluid communication with the drug chamber 4139. Accordingly, the proximal portion of the drug chamber 4139 may be referred to as (or may act as) a housing gas chamber (e.g., the gas chambers 6460, 7460 as Figure 44 and 45 shown). Similarly, the proximal portion of the drug chamber 4139 is the volume into which pressurized gas is delivered to move the carrier 4360 and serves as a pressurized gas reservoir for injecting the drug, as described herein.

[0101] As Figure 6 , 12 , 27, 28, 30, 31, 33, 34, 36, 37, 39, and 40 show, in some embodiments, the housing 4100 defines a balance bypass 4470. The balance bypass 4470 facilitates a fluid connection between the proximal portion of the drug chamber 4139 and the external volume surrounding the housing. As Figure 27 shown, when a movable seal member (such as the seal member 4574) is in a first seal position, the proximal portion of the drug chamber 4139 is in fluid communication with the external volume via the balance bypass 4470. However, as Figure 28 shown, when the medical syringe is actuated, the movable seal moves from the first seal position to a second seal position. When the movable seal member is in the second seal position, the proximal portion of the drug chamber 4139 is fluidly isolated from the external volume.

[0102] The proximal cap 4110 further includes a cap 4111 that is coupled to the proximal end portion of the proximal cap 4110 while maintaining a gap 4111a between the proximal end portion of the proximal cap 4110 and the cap 4111. The cap 4111 prevents the vent opening 4112 from being in direct contact with the outside and prevents clogging from external debris. The proximal cap 4110 further includes an O-ring 4113 and defines a vent opening 4112. The vent opening 4112 provides a passage through which pressurized gas is delivered from the drug chamber 4139 (or the housing gas chamber portion of the drug chamber 4139) to the volume outside the medical syringe 4000. As Figure 7 and 8As shown, the proximal end portion of the proximal cap 4110 defines a vent passage 4118 that extends laterally away from the vent opening 4112. The vent passage 4118, together with the gap 4111a, forms a plurality of vent passages that allow pressurized gas from within the drug chamber 4139 to escape to the volume external to the medical syringe 4000. In this way, the forces generated by the pressurized gas on the drug delivery mechanism 4300 and / or the drug container assembly 4200 can be reduced to allow retraction of the needle after injection is complete. As Figure 13A shown, the O-ring 4113 selectively seals the vent opening 4112 during needle insertion and drug delivery in combination with the valve portion 4345 of the vent assembly 4310.

[0103] Although the vent opening 4112 is shown as being defined by the proximal cap 4110 and being in its proximal surface, in other embodiments, the vent opening 4112 (and any of the vent openings described herein) can be defined within any suitable portion of the proximal cap or sidewall. For example, in some embodiments, the vent opening 4112 (and any of the vent openings described herein) can be defined by the proximal cap 4110 but can have a centerline that is not parallel to the longitudinal axis of the medical syringe 4000. In other words, in some embodiments, the vent opening 4112 (and any of the vent openings described herein) can open toward one side of the medical syringe rather than toward the proximal end, as shown. In other embodiments, the vent opening 4112 (and any of the vent openings described herein) can be defined by any wall and / or surface of the housing 4100. For example, as Figure 31 shown, in some embodiments, the medical syringe includes both a vent opening 4112 and a separate balance bypass 4470. This arrangement can allow improved operational flexibility. For example, in some embodiments, when the device is actuated, the balance bypass 4470 can be converted from an open configuration to a closed configuration. This process can allow the drug chamber 4139 (and the drug container gas chamber located above the elastomeric member 4217) to maintain a pressure substantially equal to atmospheric pressure prior to actuation. Maintaining this pressure balance can prevent a significant pressure differential from being generated across the elastomeric member 4217. In response to actuation, the balance bypass 4470 can close, allowing gas pressure to accumulate within the drug chamber 4139 (and the drug container gas chamber) to allow needle insertion and then movement of the elastomeric member 4217 to deliver the drug. Conversely, the vent opening 4112 can be such that the vent opening 4112 can be converted from a closed configuration to an open configuration after drug delivery. This results in the release of pressurized gas from the drug chamber 4139, enabling retraction of the needle, as described below.

[0104] The proximal cap 4110 includes a guiding wall 4115 within which the third (or proximal) member 4340 of the venting assembly 4310 moves. In particular, the guiding wall 4115 defines a cylindrical inner wall surface within which the guiding surface 4344 (see, for example Figure 13A and 21 ) of the first member 4340 slides during operation. The proximal cap 4110 also includes an end surface 4117 against which a part of the delivery control mechanism (also referred to as the flow restriction assembly) abuts when the medical syringe 4000 is in its first configuration, i.e., the "storage" state.

[0105] As Figure 6 shown, the distal end portion 4102 of the housing 4100 includes a shoulder 4106 with a contact surface and defines a needle aperture 4105. The distal end portion 4102 also includes a base guide groove 4114 and a base retention recess 4134 (see Figure 4 and 5 ). When the needle 4216 has been inserted the desired distance, the shoulder 4106 is configured to contact a corresponding surface 4365 of the carrier body 4360 (see, for example Figure 6 , 18 , 27 and 40). Thus, the shoulder 4106 can act as an "end stop" or insertion limiting mechanism. The needle aperture 4105 is the opening through which the needle 4216 is disposed when the medical syringe 4000 is actuated, as described in further detail herein.

[0106] The distal end portion 4102 of the housing also includes a release member contact surface 4126 and defines a release member aperture. As Figure 13B shown, the release member aperture 4145 receives the distal end portion 4552 of the release member 4550 such that an extension 4553 of the release member 4550 engages the release member contact surface 4126 to prevent activation of the medical syringe 4000. The safety lock 4700 and its components and functions are described in more detail below.

[0107] The distal base retention recess 4134 (see Figure 5 ) is configured to receive the actuator 4510 (also referred to herein as the "base 4510") when the base 4510 is in a first position relative to the housing 4100 (see, for example Figure 25 and Figure 26) The base is connected to the spherical protrusion 4518. The distal base retaining recess 4134 includes an elongated groove extending in the proximal-to-distal direction to allow the base-connected spherical protrusion 4518 to move and translate within the elongated groove. This allows the base retaining recess 4134 to receive the base-connected spherical protrusion 4518 such that the base 4510 can move proximally relative to the housing 4100 in a first position and can move distally relative to the housing 4100 in a second position. In some embodiments, the base retaining recess 4134 may include a ratchet member that engages the base-connected spherical protrusion 4518 to prevent the base 4510 from moving distally in the backward direction.

[0108] The base guide groove 4114 receives the guide member 4517 of the base 4510 (see Figure 4 , 25 and 26). The guide member 4517 of the base 4510 and the base guide groove 4114 of the housing 4100 engage with each other to allow the guide member 4517 of the base 4510 to slide in the proximal direction and / or the distal direction within the base guide groove 4114 while restricting the lateral movement of the guide member 4517. This arrangement allows the base 4510 to move relative to the housing 4100 in the proximal direction and / or the distal direction but prevents the base 4510 from moving relative to the housing 4100 in the lateral direction.

[0109] Figure 9 and 10 provides an overview of the drug container assembly 4200, the system actuator assembly 4500, the drug delivery mechanism 4300, and the flow restriction assembly 4430 (which serves as a delivery control mechanism) of the medical syringe 4000. Referring to Figure 20 , the drug container assembly 4200 has a container body 4210 that has a distal end portion 4213 and a proximal end portion 4212. The container body 4210 defines a volume that houses (i.e., is filled with or partially filled with) the drug. The distal end portion 4213 of the drug container assembly 4200 includes a neck that is coupled to the needle 4216, as described below. The proximal end portion 4212 of the drug container assembly 4200 includes an elastomeric member 4217 (i.e., a piston) that seals the drug within the container body 4210. The elastomeric member 4217 is configured to move within the container body to inject the drug from the drug container assembly 4200.

[0110] More particularly, as Figure 13AAs shown, the elastomeric member 4217 includes a proximal end portion 4218 and is coupled to the distal member 4320 of the venting assembly 4310. Thus, as described below, when pressurized gas is delivered into the drug chamber 4139 (or “housing gas chamber”), the pressurized gas flows through the flow restriction assembly 4430 and the venting assembly and into the drug container gas chamber (i.e., the second gas chamber) located above the elastomeric member 4217 (i.e., defined between the interior of the flow restriction assembly 4430, the elastomeric member 4217, and the drug container body 4210). The pressure in the drug container gas chamber can have a pressure magnitude that is less than the pressure magnitude in the proximal portion of the drug chamber 4139 (i.e., the first gas chamber). The pressure in the drug container gas chamber exerts a force on the proximal surface 4218 to cause the elastomeric member 4217 to move within the container body 4210 (i.e., to expel the drug therefrom). However, as Figure 30 shown, because the pressure in the drug container gas chamber is less than the pressure in the proximal portion of the drug chamber 4139 (i.e., the first gas chamber, which acts on the carrier 4360 and / or the container body 4210), the flow restriction assembly 4430 restricts movement of the elastomeric member 4217 before the drug container assembly is placed in the deployed configuration (i.e., the second container position).

[0111] In the case where the elastomeric member 4217 is coupled to the venting assembly 4310, movement of the elastomeric member 4217 within the container body 4210 results in movement of at least a portion of the distal member 4320. Similarly, when the elastomeric member 4217 is exposed to a force (e.g., a force generated by pressurized gas within the drug body gas chamber 4440 that directly acts on the proximal surface 4218), movement of the elastomeric member 4217 exerts a force on the distal member 4320. In particular, distal movement of the elastomeric member 4217 can generate a tensile force on the distal member 4320.

[0112] 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 is coupled to the protrusion 4323 of the distal member 4320 of the venting assembly 4310. In some embodiments, the distal member 4320 includes a threaded portion and the proximal end portion 4218 includes a corresponding threaded portion to receive 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 by an adhesive, a welding process, or the like.

[0113] 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 the efficacy of the drug that may result from (direct or indirect) contact between the elastomeric member 4217 and the drug. For example, in some embodiments, the elastomeric member 4217 can be formulated to minimize any leaching or outgassing of components that may have an adverse effect on the drug. In other embodiments, the elastomeric member 4217 can be formulated to maintain its chemical stability, flexibility, and / or sealing properties when in (direct or indirect) contact with the drug for an extended period of time (e.g., up to six months, one year, two years, five years, or longer).

[0114] In some embodiments, the elastomeric member 4217 can be constructed of a variety of different materials. For example, in some embodiments, at least a portion of the elastomeric member 4217 can be coated. Such a coating can include, for example, polydimethylsiloxane. In some embodiments, at least a portion of the elastomeric member 4217 can be coated with an amount of polydimethylsiloxane between about 0.02 mg / cm 2 and about 0.80 mg / cm 2 2.

[0115] 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 shown as substantially surrounding the container body 4210, in other embodiments, the flange 4214 can only partially surround the container body 4210.

[0116] The drug container assembly 4200 can be of any suitable size (e.g., length and / or diameter) and can contain any suitable volume of drug. In some embodiments, the drug container assembly 4200 (and any of the drug container assemblies described herein) can be a pre-filled (or pre-fillable) syringe, such as those manufactured by Becton Dickinson, Gerresheimer, Ompi Pharma, or other companies. 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" pre-fillable syringe containing any of the drugs described herein. The medical syringe 4000 can be configured to inject any suitable dose of any of the drugs described herein, such as a dose of up to 4 mL. In other embodiments, the medical syringe 4000 can be configured to inject a dose of up to 2 mL, 3 mL, 4 mL, 5 mL, or higher of any of the drugs described herein.

[0117] The container body 4210 can be constructed of glass and can be assembled 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. Either the drug container assembly and / or the pre-filled syringe described herein can be coupled to a needle having a gauge size of 21G, 22G, 23G, 24G, 25G, 26G, 27G, 28G, 29G, 30G, or 31G. Either the drug container assembly and / or the pre-filled syringe described herein can be coupled to a needle having any suitable length, for example, a length of 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 greater. In some embodiments, for example, either the drug container and / or the pre-filled syringe described herein can be coupled to a 29G needle having a length of about 0.5 inches.

[0118] As Figure 20 As shown, the drug container assembly 4200 includes a needle sheath assembly 4220, which includes a sheath body 4230 and a sheath cap 4235. The needle sheath assembly 4220 includes a distal end portion 4221 and a proximal end portion 4222. The sheath body 4230 defines a bore for receiving the distal end portion 4213 of the needle 4216 and / or the drug container body 4210. The inner portion of the sheath body 4230 defines a friction fit with the distal end portion 4213 of the drug container body 4210. Thus, prior to user actuation of the medical syringe 4000, the needle sheath assembly 4220 can protect the user from the needle 4216 and / or can keep the needle 4216 sterile.

[0119] The sheath cap 4235 is disposed around (and encloses) the sheath body 4230. The sheath cap 4235 includes a series of ribs 4236 that engage tabs 4722 of the safety lock 4700 (see, for example Figure 12 , 13B , 20, 23, and 24). In particular, the distal end portion of the needle sheath assembly 4220 is configured to be inserted into the space defined between the tabs 4722 of the engagement member 4721 of the safety lock 4700. The tabs 4722 are inclined and / or curved in the distal direction to allow the distal end portion of the sheath assembly 4220 to move distally between the engagement members 4721, but not proximally. Similarly, the tabs 4722 include edges that contact the ribs 4236 of the sheath cap 4235 to prevent the safety lock 4700 from moving distally relative to the needle sheath 4220. Thus, when the safety lock 4700 moves distally relative to the housing 4100, the needle sheath assembly 4220 is removed from the needle 4216.

[0120] As Figure 27As shown, the delivery mechanism 4300 includes a venting assembly 4310 (also referred to as an expandable assembly), but does not rely on a piston or a rigid member to move the elastomeric member 4217 within the container body 4210 for drug injection. Instead, the elastomeric member 4217 is moved by a force generated by pressurized gas within a gas chamber (or drug chamber 4139). Thus, the stroke length and / or the amount of the dose can be set by the expansion length of the venting assembly 4310. In this way, the length of the drug container assembly 4200 and the length of the venting assembly 4310 can be configured such that a desired amount of the dose is delivered. Additionally, since the venting assembly 4310 moves from a collapsed configuration to an expanded configuration, the drug delivery mechanism 4300 can be assembled within the same housing 4100 regardless of the fill volume, the delivery volume, and / or the ratio of the fill volume to the delivery volume. In this way, the same housing and production tools can be used to produce devices with various doses of drugs. For example, in a first embodiment (e.g., having a fill volume to delivery volume ratio of 0.4), the drug container has a first length, and the second movable member has a first length. In a second embodiment (e.g., having a fill volume to delivery volume ratio of 0.6), the drug container has a second length shorter than the first length, and the second movable member has a second length longer than the first length. In this way, the stroke of the device of the second embodiment is longer than the stroke of the device of the first embodiment, thereby allowing a larger dose. However, the drug container of the device of the second embodiment is shorter than the drug container of the device of the first embodiment, thereby allowing the components of both embodiments to be arranged within the same housing and / or within a housing of the same length.

[0121] In some embodiments, the medical syringe 4000 is configured such that the housing length L H to the container length L C (which includes the needle extending from the end of the container body) is less than about 1.5. In other embodiments, the medical syringe 4000 is configured such that the housing length L H to the container length L C is less than about 1.25. In still other embodiments, the medical syringe 4000 is configured such that the housing length L H to the container length L C is less than about 1.1.

[0122] In some embodiments, the medical syringe 4000 is configured such that the housing length L H to the sum of the container length L C , the carrier distance, and the stroke is less than about 1.1. In other embodiments, the medical syringe 4000 is configured such that the housing length L H to the container length L C, the ratio of the sum of the carrier distance and the stroke is less than about 1.0. In yet other embodiments, the medical syringe 4000 is configured such that the housing length L H to the container length L C , the ratio of the sum of the carrier distance and the stroke is less than about 0.9.

[0123] As Figure 9 , 10 and 31 show, the system actuator assembly 4500 includes a base 4510, a release member 4550, and a spring 4576. Figure 10 Shows certain internal components of the medical syringe 4000 without the base 4510 and the safety lock 4700, such that the release member 4550 can be more clearly shown. The release 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 chamber 4151. The proximal end portion of the release member 4550 includes a seal member 4574 and a piercer 4575. The seal member 4574 is configured to engage the sidewall of the housing 4100 that defines the gas container chamber 4151, such that the proximal end portion of the gas container chamber 4151 is fluidly isolated from the distal end portion of the gas container chamber 4151. Thus, when gas is released from the gas container 4410, the gas contained in the proximal end portion of the gas container chamber 4151 cannot enter the distal end portion of the gas container chamber 4151. The piercer 4575 of the release member 4550 is configured to contact and pierce the frangible seal 4413 on the gas container 4410 when the release member 4550 moves proximally within the gas container chamber 4151.

[0124] The distal end portion 4552 of the release member 4550 includes an extension 4553. The extension 4553 has a protrusion that includes a tapered surface and a mating surface. In addition, the extension 4553 defines an opening between adjacent extensions 4553. The mating surface is configured to extend through the release member aperture and contact the release member contact surface of the housing 4100, as Figure 28 shown. Thus, the mating surface restricts the proximal movement of the release member 4550.

[0125] The opening defined by the extension 4553 is configured to receive the safety locking protrusion 4702 of the safety lock 4700 when the safety lock 4700 is coupled to the housing 4100 and / or the base 4510 (e.g., see Figure 12 and 13B)。The safety locking projections 4702 are configured to prevent the extensions 4553 from moving closer to each other. In other words, the safety locking projections 4702 are configured to ensure that the extensions 4553 remain spaced apart from the release member contact surface of the housing 4100 and the engagement surfaces remain in contact with the release member contact surface. In some embodiments, for example, the release member 4550 and / or the extensions 4553 may be constructed of any suitable material configured to withstand deformation that may occur when exposed to a load over an extended period of time.

[0126] When the base 4510 moves proximally relative to the housing 4100, the tapered surfaces of the extensions 4553 are configured to contact the corresponding tapered surfaces 4557 of the base 4510. Thus, when the base 4510 moves proximally relative to the housing 4100, the extensions 4553 move together via the tapered surfaces. The inward movement of the extensions 4553 causes the release member 4550 to disengage from the release member contact surface 4126 of the housing 4100, thereby allowing the release member 4550 to move proximally along its longitudinal axis as the spring 4576 expands (see Figure 31 ).

[0127] 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 piercer 4575 of the release 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 Figure 9 and 10 shown, when the medical syringe 4000 is in the stored configuration, the length of the gas container retaining member 4180 and the length of the release member 4550 together determine the distance between the piercer 4575 and the frangible seal 4413. Thus, this distance is the distance that the piercer 4575 travels when the medical syringe 4000 is actuated, and this distance can be adjusted by changing 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 force applied by the piercer 4575 to the frangible seal 4413 can be adjusted by changing the distance between the piercer 4575 and the frangible seal 4413.

[0128] As Figure 9Generally, the drug delivery mechanism 4300 includes a carrier assembly 4390, a flow restriction assembly 4430 (also referred to as a delivery control mechanism), and a venting assembly 4310. The carrier assembly 4390 and the venting assembly 4310 are both movably disposed within the drug chamber 4139 of the housing 4100. For example, the carrier assembly 4390 (along with the drug container assembly 4200) is configured to move between a retracted position (i.e., the first position as shown in Figure 12 ), and a deployed position (i.e., the second position as shown in Figure 30 ) in response to a force applied by pressurized gas in the proximal portion of the drug chamber 4139. As shown in Figures 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 within which the drug container body 4210 is disposed. The proximal end portion 4362 also includes a proximal surface 4376 that forms a part of the boundary of the housing gas chamber (i.e., the portion of the drug chamber 4139 through which pressurized gas flows during a first expansion phase when the drug container body 4210 is actuated within the housing 4100). Thus, the pressurized gas generates a force on the proximal surface 4376 that causes the carrier assembly 4390 to move distally within the housing 4100.

[0129] The inner surface of the proximal end portion 4362 defines a groove within 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 top surface of the carrier body 4360 and the flange 4214 of the drug container body 4210. Thus, the first O-ring 4371 and the second O-ring 4372 form a substantially fluid-tight seal. Accordingly, when pressurized gas flows into the proximal portion of the drug chamber 4139 (i.e., the housing gas chamber), the region between the inner surface of the carrier body 4360 and the drug container body 4210 is sealed. The first O-ring 4371 and the second O-ring 4372 also dampen any impact on the flange 4214.

[0130] The outer surface of the carrier body 4360 defines an O-ring groove and includes an outer O-ring 4370. This outer surface is configured to slide against the sidewall 4139a within the drug chamber 4139 (see Figure 6), and the O-ring 4370 and the inner surface of the housing 4100 define a substantially fluid-impermeable sealed form. Thus, when pressurized gas flows into the proximal portion of the drug chamber 4139, the region 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 position relative to each of the inner O-rings 4371, 4372. However, in other embodiments, the carrier assembly may include components that move relative to each other such that the outer sealing member moves relative to the inner sealing member.

[0131] The distal end portion 4361 of the carrier body 4360 has an open end. Thus, as Figures 16 - 19 shown, the distal end portion 4213 of the drug container body 4210 extends beyond the carrier body 4360. Additionally, the distal end portion 4361 of the carrier body 4360 includes two extensions (or "legs") that together define an opening 4375. The opening is configured to align with the status holes 4130, 4160 of the housing to allow viewing of the drug, the elastomeric member 4217, or the like within the drug container assembly. The distal end portion 4361 also includes an end surface 4365 configured to contact the shoulder 4106 of the housing 4100 when the needle 4216 has been inserted the desired distance (see, for example, Figure 30 ).

[0132] As Figure 18 shown, a retraction spring 4380 is disposed within a spring sleeve 4363 defined by the outer surface of the carrier body 4360. The retraction spring 4380 is disposed about a spring pin 4381 that restricts buckling or other lateral movement of the retraction spring 4380 during use. The delivery control mechanism 4430 (also referred to as the flow restriction assembly) is configured to regulate the pressure applied to the elastomeric member 4217 to control the rate at which the elastomeric member 4217 moves within the drug container body 4210. In this way, the flow rate at which the drug is dispensed from the drug container body 4210 via the needle 4216 as the elastomeric member 4217 moves through its stroke can be controlled. Controlling the flow rate of the drug leaving the device can minimize pain or discomfort, particularly when the drug has a high viscosity (e.g., greater than about 100 centipoise at room temperature). Additionally, in cases where the drug includes high molecular weight compounds (e.g., greater than about 5 kDa), a reduced injection force less than the force required to overcome the retraction spring 4380 prevents shearing and thus prevents damage to the drug or therapeutic substance.

[0133] As Figure 14A 、 14BAs shown in FIGS. 14 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 restriction retainer 4433 configured to support at least a portion of the flow restriction member 4450. As Figure 14B shown, the flow restriction retainer 4433 includes a cylindrical inner surface 4433a and an end surface 4433b. The end surface 4433b defines a through hole 4433c that extends into an interior portion of the first body portion 4431. Thus, 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 restriction member 4450, in some embodiments, the through hole 4433c is coaxial with the flow restriction member 4450. In some embodiments, at least a portion of the flow restriction element 4450b of the flow restriction member 4450 overlaps a portion of the through hole 4433c. In some embodiments, at least 50% of the flow restriction element 4450b overlaps the through hole 4433c. In some embodiments, the flow restriction member 4450 is press - fit or threaded into the flow restriction retainer 4433.

[0134] The flow restriction member 4450 includes a sleeve member 4450a and a flow restriction element 4450b, and the flow restriction element 4450b is 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 restriction element 4450b is a porous material. In some embodiments, the porous material is sintered porous metal. In some embodiments, the flow restriction element 4450b is calibrated with nitrogen (N2) at standard temperature and pressure from 30 psig (inlet side) to atmosphere (outlet side) to have a flow rate between 0.5 and 3 standard cubic centimeters per minute (sccm). In some embodiments, the flow restriction element 4450b is calibrated with nitrogen (N2) at standard temperature and pressure from 30 psig (inlet side) to atmosphere (outlet side) to have a flow rate between approximately 0.75 and 1.5 standard cubic centimeters per minute (sccm). In some embodiments, the flow restriction element 4450b is calibrated with nitrogen (N2) at standard temperature and pressure from 30 psig (inlet side) to atmosphere (outlet side) to have a flow rate of approximately 1 standard cubic centimeter per minute (sccm). As described herein, the standard temperature is 60°F (15.6°C) and the standard pressure is 14.696 psia (101.3 kPa).

[0135] In some embodiments, the compressed gas supplied by the gas container 4410 is argon, and the flow rate limiting element 4450b has a flow rate rating of about 0.75 to 1.5 sccm calibrated based on the above-mentioned nitrogen. In some embodiments, the compressed gas supplied by the gas container 4410 is argon, and the flow rate limiting element 4450b has a flow rate rating of about 1 sccm calibrated based on the above-mentioned nitrogen. In some embodiments, the molecular weight of the compressed gas in the gas container 4410 is greater than that of argon. For example, in some embodiments, the compressed gas supplied by the gas container 4410 is R134a (tetrafluoroethane), and the flow rate limiting element 4450b has a flow rate rating of about 10 to 100 sccm calibrated based on the above-mentioned nitrogen. In some embodiments, the compressed gas supplied by the gas container 4410 is R134a (tetrafluoroethane), and the flow rate limiting element 4450b has a flow rate rating of about 20 to 40 sccm calibrated based on the above-mentioned nitrogen.

[0136] In some embodiments, the flow rate of the drug can be reduced to less than 0.2 mL / sec (or in some embodiments, between 0.05 mL / sec and 0.01 mL / sec) using the gas pressure initially supplied to the drug chamber 4139 and passing through the flow rate limiting member 4450. (Compared with the pressure directly supplied from the drug chamber 4139 to the elastomeric member), the lower injection force and / or slower delivery can produce a laminar flow of the drug through the needle, prevent shear of high molecular weight compounds in the drug, and / or reduce the pain felt by the patient, especially if the drug being delivered has a very high viscosity (e.g., greater than about 100 centipoise at room temperature). In some embodiments, a screen or mesh protective member can be provided on the proximal portion of the flow rate limiting member 4450 to prevent any particles or debris from clogging the flow rate limiting element 4450b during operation.

[0137] The first body portion 4431 includes a proximal end portion 4431a and a distal end portion 4431b. The proximal end portion 4431a includes a first cylindrical inner surface 4431c configured to support an O-ring 4436, which in turn contacts a portion of the ventilation assembly 4310 to seal the interior of the first body portion 4431 from the housing gas chamber portion of the drug chamber 4139, as described in further detail herein.

[0138] The distal end portion 4431b extends into the proximal end portion of the drug container body 4210. The distal end portion 4431b further includes a second cylindrical inner surface 4431d and a cylindrical outer groove 4431e configured to support an O-ring 4437, which contacts and seals against the inner wall of the drug 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 venting assembly 4310 to extend into and through the first body portion 4431. A portion of the bore also defines a gas passage between the second body portion 4432 and the drug body gas chamber 4440, as described in detail below. As Figure 14B shown, the inner diameter of the first cylindrical inner surface 4431c is greater than the inner diameter of the second cylindrical inner surface 4431d. The first body portion 4431 further includes a flange portion 4431f that extends radially from the outer surface of the first body portion 4431. The flange portion 4431f is configured to be mounted onto the flange 4214 of the drug container body 4210 or onto the proximal end portion of the carrier 4360.

[0139] As Figure 15 shown, the first body portion 4431 defines a first axis A1, the second body portion 4432 defines a second axis A2, and the first axis is not parallel to the second axis. In some embodiments, the first axis A1 and the second axis A2 are perpendicular to each other. In other embodiments, the first axis and the second axis define an acute angle therebetween. In some embodiments, the drug container body 4210 defines a third axis A3, and the first axis of the first body portion 4431 is parallel to the third axis A3. In some embodiments, the second body portion 4432 includes a guiding surface 4432a (see Figure 14B ) to contact the wall of the housing 4100 or a guiding member 4135a (see Figure 6 ) to prevent the delivery control mechanism 4430 from rotating about the first axis A1 during operation.

[0140] The venting assembly 4310 is configured to expand and / or change configuration during operation of the medical syringe 4000 and selectively create a path through which pressurized gas escapes the drug chamber 4139 after drug delivery. By releasing or removing force from the carrier body 4360, the delivery control mechanism 4430, and / or the drug container assembly 4200, the retraction spring 4380 can move the carrier body 4360 proximally to retract the needle 4216. Notably, during drug delivery, the venting assembly 4310 does not apply a distally directed force on the elastomeric member 4217, but is carried distally by the elastomeric member 4217. Thus, this arrangement is considered a "pistonless" delivery system because the force for inserting and delivering the drug 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 chamber 4139 through the delivery control mechanism 4430 via a flow restricting member, as described herein.

[0141] As Figure 21 , 22A , shown in FIGS. 22B and 22C, the venting assembly 4310 includes a first (or distal) member 4320, a second (or central) member 4330, and a third (or proximal) member 4340. These components are nested such that the venting assembly 4310 can be converted from a collapsed configuration ( Figure 12 , 13A and 28) to an expanded configuration ( Figure 33 and 34 , just prior to complete drug delivery), as well as a series of partially expanded configurations between these two configurations (see, e.g., Figure 30 ). The venting assembly 4310 reaches the expanded configuration just prior to delivering a full dose of the drug. Once the venting assembly 4310 has been placed in the expanded configuration, the elastomeric member 4217 continues to travel a final distance to deliver the remaining amount from the full dose, which in turn pulls the valve portion 4345 to seat it at least partially away from the opening 4112. In other words, the length of the venting assembly 4310 in the expanded configuration is selected to expand and reach the expanded configuration prior to the end of the travel of the elastomeric member 4217. When the venting assembly 4310 is in the expanded configuration and continues to travel a final distance with the elastomeric member 4217 to complete delivery of the full dose ( Figure 36 and 37, when drug delivery is completed), the opening 4112, the O-ring 4113, and the passage 4346 together allow the pressurized gas in the housing gas chamber of the drug chamber 4139 to escape from the drug chamber 4139, enabling needle retraction to occur.

[0142] 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. Thus, distal movement of the elastomeric member 4217 causes the first member 4320 to move distally. 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, each of the pair of retaining walls 4324 includes 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 assist in the assembly of the device, but separates once pressure is applied to the elastomeric member 4217 in the distal direction. The proximal end portion 4322 also includes a flexible expansion member 4325 that is fixed 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 expansion stage (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 drug 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 Figure 21 and 22A shown in -22C, the flexible expansion member 4325 collapses with a bellows-like fold. In some embodiments, the flexible expansion member 4325 is a filament or strip. 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 initially wound or wrapped between the proximal end portion 4322 of the first member 4320 and the distal end surface 4333 of the second member 4330.

[0143] 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 side wall 4334 that extends from the distal end portion 4331 to the proximal end portion 4332. The proximal end portion 4332 includes a shoulder 4335 that extends toward the center of the second member 4330, and the shoulder 4335 defines an opening 4336. The distal end portion 4331, the proximal end portion 4332, and the side wall 4334 define an internal volume 4337.

[0144] 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 includes a distal protrusion 4343 that is configured to travel within the internal volume 4337 and engage the shoulder 4335 of the second member 4320 when the second member 4320 extends away from the third member 4340. Thus, the distal protrusion 4343 restricts the movement of the second member 4340 as it extends away from the third member 4340 during the first expansion phase, 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 of the proximal cap 4110 ( Figure 13A ). The valve portion 4345 defines a passageway 4346 that bypasses the O-ring 4113 when the valve portion 4345 is in the open configuration (see Figure 39 and 40 ). As Figure 21 shown, the passageway 4346 is a recessed portion that extends into the proximal end portion 4342.

[0145] In some embodiments, the venting assembly 4310 is configured (e.g., the venting opening 4112 is sized and / or shaped) to maintain the force generated by the compressed gas on the drug container assembly 4200 at a magnitude greater than the force exerted by the retraction spring 4380 during the time of the last portion of the delivered dose. In other words, the venting assembly 4310 is adjusted such that the force of the compressed gas within the proximal portion (e.g., the gas chamber) of the drug chamber 4139 remains greater than the retraction force during the time period required to complete the delivery of the last portion of the dose. In some embodiments, the venting duration begins with the actuation of the valve member 4345 of the venting assembly 4310 and may terminate at the delivery of the last portion of the dose. It should be understood that the venting duration may correspond to the desired time required to deliver the last portion of the dose and may thus be determined based on the delivery properties of the composition. It should also be understood that maintaining the force of the compressed gas at a magnitude greater than the retraction force beyond the completion of the delivery of the last portion of the dose may cause the needle to remain in the patient for a longer time than required to deliver the dose. However, venting the compressed gas too quickly may be undesirable as it may allow the force of the compressed gas to drop below the retraction force before the last portion is fully delivered. In addition to the time at which venting begins, the venting rate also affects the time and accuracy of the delivery of the last portion of the dose.

[0146] In some embodiments, the venting assembly 4310 (including the venting opening size and / or the movement of the valve body within the opening and / or the moment of starting venting) may be configured such that the force generated by the compressed gas within the proximal portion of the drug chamber 4139 decreases to a magnitude less than the force exerted by the retraction spring 4380 at the end of the delivery of the last portion of the dose. For example, the venting assembly 4310 is configured (e.g., adjusted) by selecting the venting opening size, venting opening shape, valve body size, and / or valve body shape to achieve a desired rate of decrease of the force within the internal volume. For example, the desired rate of decrease of the force may be based on the desired delivery properties of the composition, the characteristics of the pressurized gas, and / or environmental parameters. For example, in some embodiments, the venting opening is configured (e.g., sized) to establish a venting duration of at least 0.5 seconds and less than 1.5 seconds. In some other embodiments, the venting opening is sized to establish a venting duration of at least 5 seconds and less than or equal to 15 seconds.

[0147] In some embodiments, the initial pressure within the proximal portion of the drug chamber 4139 is about 100 psi. After the entire drug (e.g., 10 mL) has been delivered, the final pressure within the proximal portion of the drug chamber 4139 is substantially higher than 80 psi. Additionally, the average transit time for the first 20% of the drug delivered is about 17 seconds, the average transit time for the second 20% of the drug delivered is about 19 seconds, the average transit time for the third 20% of the drug delivered is about 21 seconds, the average transit time for the fourth 20% of the drug delivered is 25 seconds, and the average transit time for the fifth and final 20% of the drug delivered is about 31 seconds. The flow restriction assembly 4430 and / or the venting assembly 4310 are configured to restrict and moderate the delivery of the drug such that the delivery of the first 20% of the delivery volume is no more than twice as fast as the delivery of the last 20% of the delivery volume. In other words, the delivery of the first 20% of the delivery volume is less than twice as fast as the delivery of the last 20% of the delivery volume (i.e., about 17 seconds vs. about 31 seconds). In some embodiments, the transit time for dispensing the last 20% of the delivery volume is between about one and two times the transit time for dispensing the first 20% of the delivery volume. For example, if the transit time for dispensing the first 20% of the delivery volume is about 15 seconds, the transit time for dispensing the last 20% of the delivery volume is between about 15 seconds and about 30 seconds. In some embodiments, the transit time for dispensing the last 20% of the delivery volume is between about 100% and about 195% of the transit time for dispensing the first 20% of the delivery volume.

[0148] As Figure 12 , 23 and as shown in 24, the safety lock 4700 includes a safety lock protrusion 4702 and an engagement portion 4720. As described above, when the safety lock 4700 is in the first (locked) position, the safety lock protrusion 4702 is configured to be disposed within an opening defined by an extension 4553 of the release member 4550. Thus, the safety lock protrusion 4702 is configured to prevent the extensions 4553 from moving closer to each other, thereby preventing proximal movement of the release member 4550 and / or preventing drug delivery.

[0149] The engagement portion 4720 of the safety lock 4700 includes an engagement member 4721 that extends in the proximal direction. The engagement member 4721 has a tab 4722 that extends from the surface of the engagement member. The tab 4722 engages a rib 4236 of the sheath cap 4235 to limit relative movement between the safety lock 4700 and the needle sheath assembly 4220, as described above. In this way, prior to user actuation of the medical syringe 4000, the needle sheath assembly 4220 can protect the user from the needle 4216 and / or can keep the needle 4216 sterile, and when the safety lock 4700 is removed, the needle sheath assembly 4220 can be removed from around the needle 4216.

[0150] The outer surface of the safety lock 4700 includes a gripping portion (a recessed finger grip) and markings thereon. The recessed finger grip provides an area for a user to grip the safety lock 4700 and / or remove the safety lock from around the housing 4100. The markings provide guidance on how to remove the safety lock 4700. In some embodiments, for example, the markings may indicate the direction in which the user should pull the safety lock 4700 to remove it.

[0151] Figure 25 and 26 The base (or actuator) 4510 of the medical syringe 4000 is shown. The base 4510 includes a proximal (or inner) surface 4511, a distal (or outer) surface 4523, and a base connection spherical protrusion (knob) 4518. During use of the syringe 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, causing the base 4510 to move proximally relative to the housing 4100 to actuate the medical syringe 4000. The base 4510 defines a needle aperture 4513 and a safety lock protrusion aperture 4514. The needle aperture 4513 is configured to receive the needle 4216 when the medical syringe 4000 is actuated. When the safety lock 4700 is coupled to the housing 4100 and / or the base 4510, the safety lock protrusion aperture 4514 of the base 4510 receives the safety lock protrusion 4702 of the safety lock 4700.

[0152] 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 track groove 4114 of the housing 4100. The protrusion 4515 of the base 4510 engages the tapered surface of the extension 4553 of the release member 4550. As described in further detail herein, when the safety lock 4700 is removed and the base 4510 moves proximally relative to the housing 4100, the protrusion 4515 of the base 4510 is configured to move the extensions 4553 of the release member 4550 closer to each other, thereby actuating the drug delivery mechanism 4300. In some embodiments, the base connection spherical protrusion 4518 engages the base retention recess 4134 in a manner that allows the base 4510 to move proximally but restricts the base 4510 from moving distally.

[0153] The medical syringe 4000 can be moved from a first configuration ( Figure 11 and 12 ) to a second configuration ( Figure 28)。The safety lock 4700 is moved from the first position to the second position by moving distally and / or removing the safety lock 4700 relative to the housing 4100. When the safety lock 4700 is moved from the first position to the second position, the safety lock protrusion 4702 is removed from between the extensions 4553 of the release member 4550, thereby enabling the drug delivery mechanism 4300. As Figure 11 shown, prior to actuation, a portion of the drug container assembly 4200 can be observed through the status aperture 4130. In particular, the drug container body 4210 and the contents therein (e.g., the drug) can be observed. As described above, in some embodiments, the housing 4100 can include a label or other markings providing a color bar (to which the drug can be compared), instructions for viewing, and the like. Although not Figure 11 shown in

[0154] , in some embodiments, a portion of the elastomeric member 4217 is visible through the status aperture 4130. Figure 28 ), it can be moved to a third configuration ( Figure 29 ) by moving the base 4510 from the first position to the second position. Similarly, the medical syringe 4000 can be actuated by the system actuator assembly 4500 by moving the base 4510 proximally relative to the housing 4100. By placing the medical syringe 4000 against the patient's body and moving the base 4510 relative to the housing 4100, the base 4510 moves from its first position to its second position. In particular, as described above, the base includes a “contact portion” (i.e., the distal surface 4523), which can be placed against and / or in contact with the target location. Moving the base 4510 from the first position to the second position causes the base 4510 to engage the extension 4553 of the release member 4550, causing the extension 4553 to move together. The inward movement of the extension 4553 causes the engagement surface of the release member 4550 to become disengaged from the housing 4100, allowing the release member 4550 to move proximally along its longitudinal axis as the spring 4576 expands.

[0155] When the base 4510 is moved from the first position to the second position, the system actuator assembly 4500 actuates the drug delivery mechanism 4300, thereby placing the medical syringe 4000 in its fourth configuration (i.e., the needle insertion configuration), as Figures 29 - 31 shown. More particularly, when the medical syringe 4000 is in its fourth configuration, the piercer 4575 of the release member 4550 contacts and / or passes through the frangible seal 4413 of the gas container 4410.

[0156] After the frangible seal 4413 is punctured, the actuating portion of the compressed gas flows out of the gas container 4410 via the gas passage 4135 and into the drug chamber 4139 to initiate the first expansion phase (i.e., the 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 flange 4214 of the drug container, the delivery control mechanism 4430, and / or the top surface of the carrier body 4360. Since the seals 4371, 4372 of the drug container assembly 4200, the outer seal 4370 of the carrier assembly 4390, and the seal of the delivery control mechanism 4430 maintain fluid isolation between the drug chamber 4139 and the exterior of the device, the gas pressure applies a force to move the carrier assembly 4390 distally within the drug chamber 4139, as Figure 30 and 31 shown. The drug container body 4210 and the delivery control mechanism 4430 also move distally with the carrier assembly 4390. Thus, the movement of the needle 4216 in the distal direction causes the distal end portion of the needle 4216 to exit the housing 4100 and enter the patient's body before the drug is administered. In some embodiments, the gas container 4410 may contain pressurized gas at approximately 1000 psi before the frangible seal 4413 is punctured. Once the frangible seal 4413 has been punctured, the pressurized gas is released into the drug chamber 4139 and is pressurized to approximately 500 psi at the start of the third configuration (i.e., before the venting assembly 4310 and the carrier assembly 4390 are actuated). In some embodiments, the compressed gas provided by the gas container 4410 is argon. In some embodiments, the compressed gas provided by the gas container 4410 is a refrigerant, such as R134a.

[0157] As Figure 30 and 31 shown, when the device transitions from the third configuration to the fourth configuration, the venting assembly 4310 expands from its collapsed configuration ( Figure 22A and 28 ) to a partially expanded configuration. Notably, in the partially expanded configuration, the gas pressure within the drug chamber 4139 acts on the lower side of the proximal end portion 4342, and the valve portion 4345 maintains a sealed position within the opening 4112 and the O-ring 4113. Thus, the drug chamber 4139 remains fluidly isolated.

[0158] When the needle 4216 has extended the desired distance, the distal surface 4365 of the carrier body 4360 contacts the shoulder 4106 of the housing 4100 to limit further distal movement of the carrier assembly 4390 within the housing 4100. When the distal movement of the carrier assembly 4390 is blocked, the first expansion phase is complete. The gas within the drug chamber 4139 (i.e., the housing gas chamber) continues to travel through the delivery control mechanism 4430 to apply gas pressure to the elastomeric member 4217, thereby initiating the second expansion phase. During the first expansion phase, the flow restriction provided by the delivery control mechanism 4430 prevents the elastomeric member 4217 from moving before the carrier body 4360 contacts the shoulder 4106. In some embodiments, the delivery control mechanism 4430 may allow gas to pass through the flow restriction member 4450 during the first expansion phase but 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 the shoulder 4106 limit any further distal movement of the carrier assembly 4390), the pressurized gas in the drug chamber 4139 drops to approximately 90 - 100 psi.

[0159] As Figure 13A Generally shown, gas from the drug chamber 4139 passes through the flow restriction member 4450 and is regulated by the flow restriction member. The gas passing through the flow restriction member 4450 travels through the through - hole 4433c and along the internal passage 4438 located between the second cylindrical inner surface 4431d and the side wall 4334 of the second member 4330. The internal passage 4438 between the second member 4330 and the first body portion 4431 defines an annular passage. In some embodiments, the second member 4330 and / or the first body portion 4431 may include one or more pits or buffer portions extending along the axis A1 to maintain the separation between the second member 4330 and / or the first body portion 4431 and prevent the internal passage 4438 (see Figure 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.

[0160] After passing through the internal passage 4438, the gas enters the drug body gas chamber 4440 sealed between the distal portion of the O-ring 4437 and the proximal portion of the elastomeric member 4217. This causes the elastomeric member 4217 (and thus the first member 4320 of the venting assembly 4310) to move distally within the drug container body 4210. The distal movement of the elastomeric member 4217 creates pressure on the drug contained within the drug container assembly 4200, allowing at least a portion of the drug to flow out of the drug container 4200 via the needle 4216. The drug is delivered to the user's body via the drug delivery path defined by the drug container 4200 and the needle 4216. As the elastomeric member 4217 travels to dispense the drug, the venting assembly 4310 expands from a partially expanded configuration to a fully expanded configuration, and the medical syringe is in its fifth configuration ( Figure 33 and 34 ). In some embodiments, the drug body gas chamber 4440 is pressurized to about 10 to 20 psi to initiate actuation of the elastomeric member 4217.

[0161] As Figure 32 shown, when the medical syringe 4000 is in its fifth configuration and / or is converted to its sixth configuration, a portion of the drug container assembly 4200, a portion of the carrier body 4360, and a portion of the venting assembly 4310 can be observed via the status hole 4130. As described above, in some embodiments, the housing 4100 can include labels or other markings that provide color bars to assist the user in identifying the carrier, provide instructions for viewing, and so on. Although not shown in Figure 11 , in some embodiments, when the medical syringe 4000 is in its fifth configuration or its sixth configuration, a portion of the elastomeric member 4217 is visible via the status hole 4130 to indicate that the delivery of the drug is about to be completed or has been completed.

[0162] As Figure 33 and 34As shown, as the elastomeric member 4217 moves distally, the venting assembly 4310 moves with the elastomeric member 4217 to its fully expanded configuration. Once the venting assembly 4310 is in its fully expanded configuration and begins to pull on the valve portion 4345, the medical syringe 4000 is in its sixth configuration. In this sixth configuration, the elastomeric member 4217 continues to move within the drug container body 4210 a predetermined distance (corresponding to the remainder of the desired dose), and the valve portion 4345 moves out of the opening 4112, thereby allowing the pressurized gas contained within the housing gas chamber (i.e., the volume within the drug chamber 4139 between the proximal end of the housing 4100 and the surface of the carrier 4360) to escape via the passage 4346 and the opening 4112. More particularly, the pressure exerted on the elastomeric member 4217 by the gas in the drug body gas chamber 4440 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 about 30 to 50 psi to actuate the valve portion 4345.

[0163] After the gas pressure within the drug chamber 4139 drops below a certain level, the force exerted on the carrier body 4360 by 4 4380 is sufficient to cause the carrier body 4360 to move proximally (i.e., retract) within the housing 4100. This causes the medical syringe to be in its seventh configuration ( Figure 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. Thus, when the carrier assembly 4390, the venting assembly 4310, and the flow restriction assembly 4430 move proximally back towards the proximal end of the housing 4100, the first body portion 4431 bypasses the guide surface 4344 to prevent the valve portion 4345 from contacting the opening 4112 and closing the opening back up.

[0164] As Figure 38 shown, when the medical syringe 4000 is in its seventh configuration, a portion of the drug container assembly 4200 can be viewed via the status hole 4130. In particular, as shown, a portion of the elastomeric member 4217 and the drug container body 4210 are visible via the status hole 4130. As described above, in some embodiments, the housing 4100 can include labels or other markings that provide colored stripes to assist the user in identifying the elastomeric member, provide instructions for viewing, and so forth. Although not shown in Figure 38 , in some embodiments, a portion of the carrier 4360 is visible via the status hole 4130 when the medical syringe 4000 is in its seventh configuration.

[0165] As described above, the drug delivery mechanism 4300 is considered a "pistonless" system. For a gas-powered pistonless autoinjector, the force exerted by the gas can move the drug container relative to the housing and, similarly, can move the elastomeric member 4217 relative to the drug container body 4210 (e.g., within the drug container body). In some embodiments, by not including a movable mechanism, piston, and / or similar components, the height of the medical syringe 4000 can be reduced relative to the height of, for example, a device including a rigid single-length piston.

[0166] Figures 41 - 43 A cross-sectional view of a device 5000 including a balance bypass 5470 and a movable seal member 5480 is shown, where the movable seal member is in three seal positions. In some embodiments, the device 5000 can be a drug delivery device, such as the medical syringe 4000 described herein. Thus, the device 5000 can optionally include any of the elements, structures, and / or features described herein with reference to the medical syringe 4000.

[0167] In some embodiments, the device 5000 includes a housing 5100, a gas container 5410, a drug container assembly (e.g., drug container assembly 4200), and a movable seal member 5480. The housing 5100 defines a gas chamber 5460 that is configured to receive pressurized gas from the gas container 5410 when the device 5000 is actuated. Moreover, when the device 5000 is actuated, the movable seal member 5480 is configured to move from a first seal position SP1 ( Figure 41 ) to a second seal position SP2 ( Figure 42 ). In addition to the gas chamber 5460, the housing 5100 also defines a balance bypass 5470. When the movable seal member 5480 is in the first seal position SP1, the balance bypass 5470 can facilitate fluid communication between the gas chamber 5460 and the external volume surrounding the housing 5100. For example, as Figure 41 shown, the fluid communication between the gas chamber 5460 and the external volume can occur along a path described by arrows AA1 - AA3. Thus, a certain volume of gas can be transmitted from the gas chamber 5460, bypass the movable seal member 5480 via the balance bypass 5470, flow distally between the housing 5100 and the release member 5550, and pass through the base of the device 5000 (e.g., base 4510), and vice versa. However, when as Figure 42 shown the movable seal member 5480 is in the second seal 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 seal position SP2 seals the gas chamber 5460, thereby facilitating an increase in the gas pressure within the gas chamber 5460.

[0168] As Figures 41 - 43 shown, in some embodiments, device 5000 includes system actuator assembly 5500. System actuator assembly 5500 may include any of the features described herein with reference to system actuator assembly 4500. In particular, system actuator assembly 5500 includes release member 5550, a piercer 5575 coupled to release member 5550, and actuation spring 5576. Release member 5550 may move within housing 5100 between a first release member position as Figure 41 shown and a second release member position as Figure 42 shown. When release member 5550 is in the first release member position, piercer 5575 is spaced apart from gas container 5410. Actuation spring 5576 is positioned between a portion of release member 5550 and housing 5100 and is configured to move release member 5550 from the first release member position to the second release member position. Before device 5000 is actuated, release member 5550 is in a locked configuration and actuation spring 5576 has an energy storage configuration. When device 5000 is actuated, the release member is in a released configuration in response to the actuation force applied by actuation spring 5576, and when release member 5550 is in the second release member position, piercer 5575 pierces a portion of gas container 5410. In other words, piercer 5575 is positioned to pierce gas container 5410 in response to the conversion of release member 5550 from the locked configuration to the released configuration.

[0169] In some embodiments, a movable seal member 5480 (e.g., similar to seal member 4574) is coupled to release member 5550. Movable seal member 5480 may be an O-ring surrounding release member 5550 in some embodiments. However, in some embodiments, movable seal member 5480 may be a seal structure (e.g., a protrusion, a lip, or other similar structure) integrally formed as part of release member 5550. When release member 5550 is in the first release member position as Figure 41 shown, movable seal member 5480 is in a first seal position SP1. When release member 5550 is in the second release member position as Figure 42When in the second release member position shown, the movable seal member 5480 is in the second seal position SP2. In other words, the movable seal member 5480 is coupled to the release member 5550 and positioned between the release member 5550 and the inner wall of the housing 5100. When the release member is in the locked state, the movable seal member 5480 is in the first seal position SP1 and is configured to move to the second seal position SP2 in response to the release member transitioning from the locked configuration towards the release configuration. Thus, the movable seal member 5480 fluidly isolates the gas chamber 5460 from the external volume after the device 5000 is actuated but before the gas container 5410 is punctured. Accordingly, when discharged from the gas container, the pressurized gas is contained within the sealed gas chamber 5460, and the ability of the pressurized gas to deliver the drug is not affected by gas loss.

[0170] As Figures 41 - 43 shown, in some embodiments, the system actuator assembly 5500 includes a positioning member 5560. The positioning member 5560 may be coupled to the release member 5550. As Figure 41 shown, when the release member 5550 is in the locked configuration, the positioning member 5560 may have a first shape. When the release member 5550 is in the release configuration as Figure 42 shown, the positioning member 5560 may have a second shape. For example, the first shape may be a compressed configuration in which the positioning member 5560 stores potential energy (e.g., elastic potential energy), and the second shape may be an expanded configuration caused by the release of the potential energy. However, in some embodiments, the first shape may be an expanded configuration that is compressed to convert to the second shape. In some embodiments, the positioning member 5560 may include, for example, at least one leg 5562. The leg 5562 may have a distal end portion 5564. The distal end portion 5564 may have a first radial position ( Figure 41 ) in the first shape, and may have a second radial position ( Figure 42 and 43 ) in the second shape. The second radial position may be radially outside the first radial position. In other words, the positioning member 5560 may have a first perimeter that is less than a second perimeter in the second shape.

[0171] As Figure 43As shown, when in the second shape, the positioning member 5560 engages the receiving portion 5566 of the housing 5100. The engagement between the positioning member 5560 and the receiving portion 5562 prevents movement of the release member 5550. For example, this engagement can prevent the release member 5550 from returning from the second release member position to the first release member position. In other words, the engagement between the positioning member 5560 and the receiving portion 5566 can limit movement (e.g., movement in the distal direction) along the movement axis (e.g., along the longitudinal axis of the device 5000). In some embodiments, when the positioning member 5560 engages the receiving portion 5566 of the housing 5100, the movable sealing member 5480 is maintained at the third seal position SP3 as shown in Figure 43 . In some embodiments, the third seal position SP3 is located between the first seal position SP1 and the second seal position SP2 along the movement axis. When the movable sealing member 5480 is in the third seal position SP3, the gas chamber 5460 is fluidically isolated from the external volume by the movable sealing member 5480. It should be understood that without the positioning member 5560, the force exerted by releasing the pressurized gas from the gas container 5410 may overcome the force exerted by the actuation spring 5576, causing the release member 5550 and the movable sealing member 5480 to return to the first release member position and the first seal position SP1, respectively. When this occurs, the fluid connection between the gas chamber 5460 and the external volume may be re-established, and the operation of the device 5000 may be affected.

[0172] In some embodiments, the movable sealing member 5480 is a first movable sealing member. In such embodiments, the device 5000 may include a second movable sealing member that is coupled to a carrier (e.g., the outer O-ring 4370 is coupled to the carrier 4360). Additionally, the device 5000 may include a third movable sealing member (e.g., the valve member 4345 configured as a movable seal).

[0173] Figure 44 A cross-sectional view of a device 6000 including a balanced bypass 6470 and a movable sealing member 6480 in the first seal position SP1 is shown. In some embodiments, the device 6000 can be a drug delivery device, such as the medical syringe 4000 or the device 5000 described herein. Thus, the device 6000 can optionally include any of the elements, structures, and / or features described herein with reference to the medical syringe 4000 or the device 5000.

[0174] In some embodiments, device 6000 includes a housing 6100, a gas container 6410, a drug container assembly 6200 (e.g., drug container assembly 4200), and a movable seal member 6480. The drug 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 drug contained therein. The housing 6100 defines a gas chamber 6460 that is configured to receive pressurized gas from the gas container 6410 when the device 6000 is actuated. Moreover, when the device 6000 is actuated, the movable seal member 6480 is configured to move from a first seal position SP1 to a second seal position (e.g., a distal seal position). In addition to the gas chamber 6460, the housing 6100 also defines a balance bypass 6470. When the movable seal member 6480 is in the first seal position SP1, the balance bypass 6470 can facilitate fluid communication between the gas chamber 6460 and the external volume surrounding the housing 6100. For example, as shown, the fluid communication between the gas chamber 6460 and the external volume can occur along a path described by arrow BB. Thus, a volume of gas can be transferred from the gas chamber 6460, bypass the movable seal member 6480 via the balance bypass 6470, flow distally between the housing 6100 and the carrier 6360 or the drug container assembly 6200, and through the base of the device 6000 (e.g., base 4510), and vice versa. However, when the movable seal member 6480 is in the second seal position, the gas chamber 6460 is fluidly isolated from the external volume by the movable seal member 6480. In other words, the movable seal member 6480 in the second seal position seals the gas chamber 6460, thereby facilitating an increase in the gas pressure within the gas chamber 6460.

[0175] As shown, in some embodiments, device 6000 includes a carrier 6360. The carrier 6360 can include any of the features described herein with reference to carrier 4360. Thus, as described herein with reference to carrier 4360, the carrier 6360 can be coupled to the drug container assembly 6200 and configured to move (e.g., distally) within the housing 6100. The movement of the carrier 6360 can be responsive to a force exerted by the pressurized gas within the gas chamber 6460 after the device 6000 is actuated. Thus, the proximal surface of the carrier 6360 can define a portion of the boundary of the gas chamber 6460.

[0176] In some embodiments, a movable seal member 6480 (e.g., outer O-ring 4370) is coupled to a carrier 6360 and positioned between the carrier 6360 and the inner wall of the housing 6100. Movement of the carrier 6360 in response to a force applied by pressurized gas causes the movable seal member 6480 to move relative to the housing 6100 from a first seal position SP1 to a second seal position, thereby isolating the gas chamber 6460 from the external volume.

[0177] In some embodiments, the carrier 6360 may be omitted, and the movable seal member 6480 may be directly coupled to the container body 6210 and positioned between the container body 6210 and the inner wall of the housing 6100. The container body 6210 may move within the housing 6100 from a first container position to a second container position in response to a force applied by pressurized gas within the gas chamber 6460. Movement of the container body 6210 in response to a force applied by pressurized gas causes the movable seal member 6480 to move relative to the housing 6100 from a first seal position SP1 to a second seal position to isolate the gas chamber 6460 from the external volume.

[0178] In some embodiments, the movable seal member 6480 is a first movable seal member. In such embodiments, the device 6000 may include a second movable seal member that is coupled to a release member of the system actuator assembly (e.g., seal member 4574 is coupled to release member 4550). Additionally, the device 6000 may further include a third movable seal member (e.g., valve member 4345 configured as a movable seal).

[0179] Figure 45 A cross-sectional view of a device 7000 including a balance bypass 7470 and a movable seal member 7480 in a first seal position SP1 is shown. In some embodiments, the device 7000 may be a drug delivery device, such as the medical syringe 4000, device 5000, or device 6000 described herein. Thus, the device 7000 may optionally include any of the elements, structures, and / or features described herein with reference to the medical syringe 4000, device 5000, or device 6000.

[0180] In some embodiments, device 7000 includes a housing 7100, a gas container 7410, a drug container assembly 7200 (e.g., drug container assembly 4200), and a movable seal member 7480. The drug 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 drug contained therein. The housing 7100 defines a gas chamber 7460 that is configured to receive pressurized gas from the gas container 7410 when the device 7000 is actuated. Moreover, when the device 7000 is actuated, the movable seal member 7480 is configured to move from a first seal position SP1 to a second seal position (e.g., a distal seal position). In addition to the gas chamber 7460, the housing 7100 also defines a balance bypass 7470. When the movable seal member 7480 is in the first seal position SP1, the balance bypass 7470 can facilitate fluid communication between the gas chamber 7460 and the external volume surrounding the housing 7100. For example, as shown, the fluid communication between the gas chamber 7460 and the external volume can occur along a path described by arrow CC. Thus, a volume of gas can be transmitted from the gas chamber 7460, bypass the movable seal member 7480 via the balance bypass 7470, and flow proximally out of the housing 7100 via a vent opening 7112, and vice versa. However, when the movable seal member 7480 is in the second seal 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 seal position seals the gas chamber 7460, thereby facilitating an increase in the 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 applied by the pressurized gas within the gas chamber 7460.

[0181] In some embodiments, device 7000 includes a venting assembly 7310. The venting assembly may include any of the features described herein with reference to venting assembly 4310. The venting assembly 7310 is configured to selectively place gas chamber 7460 in fluid communication with an external volume. A movable seal member 7480 is configured as a valve member (e.g., valve member 4345). The movable seal member 7480 is configured to block and / or seal both a balance bypass 7470 and a vent opening 7112 defined by housing 7100. Prior to actuation, the movable seal member 7480 (i.e., the valve member) is in a first seal position SP1. In response to a force exerted by pressurized gas within gas chamber 7460, the movable seal member 7480 is configured to move (e.g., proximally) to a second seal position, thereby sealing the vent opening 7112 and fluidly isolating the gas chamber 7460 from the external volume. The movable seal member 7480 (i.e., the valve member) is operatively coupled via an expandable assembly (e.g., first member 4320, second member 4330, and third member 4340) to an elastomeric member of a drug container assembly 7200. The expandable assembly is configured to transition from a first configuration to a second configuration when the elastomeric member moves within the container body. In response to movement of the elastomeric member, when the expandable assembly transitions from the first configuration to the second configuration, the movable seal member 7480 (i.e., the valve member) moves from the second seal position to a third seal position. Movement of the movable seal member 7480 to the third seal position releases pressurized gas from the gas chamber 7460 to the external volume, as described herein.

[0182] In other words, prior to actuation, the movable seal member 7480 is in the first seal position SP1, and the gas chamber 7460 is in fluid communication with the external volume via the balance bypass 7470 and the vent opening 7112. When device 7000 is actuated, pressurized gas is released from gas container 7410. An initial portion of the pressurized gas enters the gas chamber 7460 and exerts a force on the movable seal member 7480, causing the movable seal member 7480 to move to the second seal position. In the second seal position, the movable seal member 7480 fluidly isolates the gas chamber 7460 from the external volume. The pressurized gas also exerts a force on the elastomeric member, causing the elastomeric member to move to dispense a portion of the drug contained within the drug container assembly 7200. After the elastomeric member has moved a sufficient amount, the movable seal member 7480 moves from the second seal position to the third seal position to release the pressurized gas from the gas chamber 7460 to the external volume, and the third seal position may be the same as the first seal position SP1.

[0183] In some embodiments, the movable seal member 7480 is the first movable seal member. In such embodiments, the device 7000 may include a second movable seal member that is coupled to a release member of the system actuator assembly (e.g., the seal member 4574 is coupled to the release member 4550). Additionally, the device 7000 may further include a third movable seal member that is coupled to the carrier (e.g., the outer O-ring 4370 is coupled to the carrier 4360).

[0184] Although 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. In cases where the above methods indicate that certain events occur in a certain order, the order of certain events may be modified. Additionally, if possible, some of the events may be performed simultaneously in parallel processes as well as sequentially as described above.

[0185] For example, in some embodiments, a drug delivery device may include two or more drug containers, each drug container having a delivery member through which the drug may be delivered. Such embodiments may accommodate the delivery of viscous drugs and / or large volume drugs (e.g., >1 mL dose) by delivering portions of the total dose in parallel. In particular, as discussed above with respect to Equation 1, the needle length (L) and needle gauge (identified as the radius R of the needle lumen) may have a profound impact on the pressure required to deliver a desired volume of drug. Thus, by using a "parallel delivery" device of the type shown and described herein, the delivery of viscous drugs, such as certain larger or macromolecular injectables, which include carbohydrate-derived formulations, lipids, nucleic acids, hyaluronidase, proteins / peptides (e.g., monoclonal antibodies), and other biotech-derived drugs, may be facilitated. Any of the venting mechanisms, electronic circuitry, or other components described herein may be included in the dual-container device of the type shown and described in the '4345 PCT or '0040 PCT.

[0186] For example, any of the elastomeric members described herein may be composed 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 may be coated. Such a coating may include, for example, polydimethylsiloxane. In some embodiments, at least a portion of any of the elastomeric members described herein may be coated with an amount of polydimethylsiloxane between about 0.02 mg / cm 2 and about 0.80 mg / cm 2 2.

[0187] Any one of the drug container assemblies described herein can have any suitable dimensions (e.g., length and / or diameter) and can accommodate any suitable volume of drug. In some embodiments, any one of the drug container assemblies described herein can be a pre-filled (or pre-fillable) syringe, e.g., those manufactured by Becton Dickinson, Gerresheimer, Ompi Pharma, or other companies. For example, in some embodiments, the drug container assembly 4200 (and any one of the drug container assemblies described herein) can be a Becton Dickinson "BD Hypak Physiolis" pre-fillable syringe that accommodates any one of the drugs described herein. Additionally, any one of the drug delivery devices and / or medical syringes described herein can be configured to inject any suitable dose of any one of the drugs described herein, e.g., a dose up to 1 mL. In other embodiments, any one of the drug delivery devices and / or medical syringes described herein can be configured to inject a dose up to 2 mL, 3 mL, 4 mL, 5 mL, or higher of any one of the drugs described herein.

[0188] Any one of the container bodies described herein can be constructed of glass and can be assembled and / or coupled to any suitable needle. For example, in some embodiments, any one of the container bodies described herein (including container body 4210) can be coupled to a needle having any suitable dimensions. Any one of the drug container assemblies and / or pre-fillable syringes described herein can be coupled to a needle having a gauge size of 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31. Any one of the drug container assemblies and / or pre-fillable syringes described herein can be coupled to a needle having any suitable length, e.g., a length of 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 greater. In some embodiments, any one of the drug containers and / or pre-fillable syringes described herein can be connected to a 29-gauge needle having a length of about 0.5 inches. Moreover, any one of the drug containers and / or pre-fillable syringes described herein can include a stub needle at its distal end.

[0189] For example, any one of the medical syringes shown and described herein can include a base (or distal actuator) having a mechanism for cooling the target injection site. By cooling the target injection site, patient comfort during the injection procedure can be improved. Such a cooling mechanism can include, for example, an electronic cooler (e.g., a thermoelectric cooler) that is triggered upon removal of a safety guard, a chemical substance or spray emitted by the base upon removal of the safety guard, or any other suitable mechanism.

[0190] Any of the medical syringes shown and described herein may include a base (or distal actuator) having means for expanding, stretching, or otherwise tensioning the patient's skin at or near the injection site. In other embodiments, the base (or distal actuator) of any of the syringes described herein may include means for increasing the surface area of the base (or distal actuator) against the injection site. For example, in some embodiments, the base may include a series of gripping portions, protrusions, microneedles, or the like, which may grip the skin and expand to stretch the surface prior to actuation and / or injection, or allow a larger contact surface area against the skin for increased stability of injectate administration. In other embodiments, the base may include a series of gripping portions, protrusions, microneedles, or the like, which may grip the skin and clamp the surface together prior to actuation and / or injection. Such a base may include a dome or other structure to clamp certain portions of an anatomical structure such as the abdomen.

[0191] While the drug syringes shown and described above include a delivery mechanism involving pressurized gas release (e.g., 4300), in other embodiments, the drug delivery device may include any suitable method for delivering the drug disposed therein. For example, in some embodiments, any of the devices described herein may include a mechanical energy storage (e.g., spring, gear, rack, pinion, pulley, or the like) member instead of a compressed gas container. In other embodiments, any of the devices described herein may include any other suitable energy storage member (e.g., magnetic, electrical, propellant-based, chemically-based, or the like).

[0192] While the medical syringes herein are described as gas-powered "pistonless" autoinjectors, in other embodiments, any of the medical syringes may include any suitable energy storage member configured to directly generate a force on the drug container and / or carrier (e.g., as described in the '849 patent). For example, in some embodiments, the medical syringe may include one or more biasing members, springs, and / or any other suitable mechanical driver (as described above) configured to apply a force on one or more drug containers. As an example, the medical syringe 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 that is substantially equal to the force generated by the first spring. Additionally, the first spring and the second spring may be actuated substantially simultaneously and / or via the same actuation event such that the first spring and the second spring cause the first drug container and the second drug container to move substantially simultaneously.

[0193] Although specific injection events, mechanisms, devices, and / or components have been described herein, it should be understood that they have been presented by way of example and not limitation. In other words, an autoinjector can include more than one drug container and can be configured to deliver at least one dose of a drug in response to any suitable actuation event and / or similar event to a patient.

[0194] Any of the devices and / or drug containers shown and described herein can be constructed of any suitable material. Such materials include glass, plastics (including thermoplastics such as cycloolefin copolymers), or any other material used to manufacture a prefilled syringe containing a drug.

[0195] Any of the devices and / or drug containers shown and described herein can accommodate and / or deliver a wide range of larger or macromolecular injectables, which include carbohydrate-derived formulations, lipids, nucleic acids, hyaluronidase, proteins / peptides (e.g., monoclonal antibodies), and other biotech-derived drugs. For example, an anti-tumor necrosis factor agent, such as infliximab, etanercept, adalimumab, golimumab, natalizumab, vedolizumab, and certolizumab, can be administered using the autoinjector described herein. Other macromolecular injectable drugs that can be administered using the devices and / or drug containers shown and described herein include viscous drugs targeting pro-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 related receptors), including dupilumab, sarilumab, mepolizumab, benralizumab, reslizumab, lebrikizumab, ustekinumab, anrukinzumab, bertilimumab, tralokinumab, and risankizumab. Larger anti-adhesion molecules can be administered using the devices and / or drug containers shown and described herein to treat various diseases, including etrolizumab and vatelizumab. Yet some other larger 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).

[0196] Any of the devices and / or pharmaceutical containers shown and described herein may include any suitable drug or therapeutic agent. In some embodiments, the drug contained within any of the pharmaceutical containers shown herein may be a vaccine, for example, an influenza vaccine, a hepatitis vaccine, a Haemophilus influenzae type B (HiB) vaccine, a measles vaccine, a mumps vaccine, a rubella vaccine, or a combination vaccine (e.g., measles, mumps, and rubella, quadrivalent or hexavalent vaccine), a polio vaccine, a human papillomavirus (HPV) vaccine, a tetanus vaccine, a diphtheria vaccine, a pertussis vaccine, a plague vaccine, a yellow fever vaccine, a cholera vaccine, a malaria vaccine, a smallpox vaccine, a pneumococcal vaccine, a rotavirus vaccine, a varicella vaccine, a dengue vaccine, a rabies vaccine, and / or a meningococcal vaccine. In other embodiments, the drug contained within any of the pharmaceutical containers shown herein may be a catecholamine, for example, epinephrine. In other embodiments, the drug contained within any of the pharmaceutical containers shown herein may be an opioid receptor antagonist, for example, naloxone, including any of the naloxone formulations described in U.S. Patent No. 8,627,816, titled "Medicament Delivery Device for Administration of Opioid Antagonists Including Formulation for Naloxone," filed on February 28, 2011. In still some other embodiments, the drug contained within any of the pharmaceutical containers shown herein may include peptide hormones, for example, insulin and glucagon; human growth hormone (HGH); sumatriptan; corticosteroids, for example, dexamethasone; ondansetron; opioid agonist receptor modulators, for example, fentanyl; partial agonist opioid receptor modulators, for example, buprenorphine; mixed agonist / antagonist opioid receptor modulators, for example, nalbuphine; benzodiazepines, for example, diazepam, midazolam, or lorazepam; erythropoiesis-stimulating agents (ESAs), for example, darbepoetin alfa; immunoglobulins, including bispecific variable domain immunoglobulins; interferons; anti-tumor; recombinant human granulocyte colony-stimulating factor (GCSF), for example, pegfilgrastim; icatibant; and other therapeutic agents suitable for injection into mammals. In still some other embodiments, the drug contained within any of the pharmaceutical containers shown herein may be a placebo substance (i.e., a substance without active ingredients), for example, water.

[0197] The drug containers and / or drug delivery devices disclosed herein can accommodate any suitable amount of any drug. For example, in some embodiments, a drug delivery device as shown herein can be a single-dose device that accommodates a drug amount of about 0.4 mg, 0.8 mg, 1 mg, 1.6 mg, or 2 mg to be delivered. As described above, the fill volume can be such that the ratio of the delivery volume to the fill volume is any suitable value (e.g., 0.4, 0.6, or a similar value). In some embodiments, the electronic circuitry can include a "configuration switch" that can select an electronic output corresponding to the dose contained within the drug container when actuated during the assembly of the delivery device.

[0198] In some embodiments, a medical syringe can include two pre-filled syringes, each pre-filled syringe containing up to 1 mL (or more) of a drug, and each pre-filled syringe having a needle. Such a device (e.g., a "dual-container device") is shown and described in '4345 PCT, which is incorporated herein by reference. When the device is actuated (as described above), a single energy storage member (e.g., a compressed gas container) can release energy to move the two containers within the housing in substantially the same operation to inject the two needles. The force generated by the energy storage member can also inject the drug from each container. In such embodiments, the two containers can include the same drug or two different drugs. For example, a dual-container device can be filled and / or used to inject methotrexate (from one container) and tocilizumab (in the other container) to treat rheumatoid arthritis. In some embodiments, a dual-container device can be filled and / or used to inject: tocilizumab and methotrexate to treat rheumatoid arthritis; adalimumab and methotrexate to treat psoriasis or rheumatoid arthritis; etanercept and methotrexate to treat psoriatic arthritis; belimumab and rituximab to treat primary Sjogren's syndrome; lanreotide autogel and pegvisomant to treat acromegaly; narlaprevir and ritonavir to treat chronic hepatitis C; alemtuzumab and rituximab to treat chronic lymphocytic leukemia; pertuzumab and trastuzumab to treat HER2-positive early breast cancer; long-acting insulin glargine and rapid-acting insulin lispro to treat type 2 diabetes; pramlintide and insulin to treat type 1 diabetes; insulin glargine and insulin lispro to treat type 1 diabetes; mosunetuzumab and atezolizumab to treat neoplasms; nivolumab and tumor-infiltrating lymphocytes with interleukin-2 to treat metastatic melanoma; pertuzumab and trastuzumab to treat HER2-positive early breast cancer; ocrelizumab and recombinant human hyaluronidase to treat multiple sclerosis; daratumumab and recombinant human hyaluronidase to treat multiple myeloma; nivolumab and recombinant human hyaluronidase to treat metastatic tumors; and insulin lispro and recombinant human hyaluronidase to treat diabetes.

[0199] Any of the drug containers described herein may include any suitable elastomeric member and / or plunger. For example, the elastomeric member may be formulated to be compatible with the drug contained within the drug container. Additionally, the drug container may include any number of elastomeric members. For example, in some embodiments, the drug container may include a dry portion of the drug and a fluid portion of the drug, which are configured to be mixed prior to injection. The piston portion of the drug delivery mechanism may be configured to engage a plurality of elastomeric members associated with these portions of the drug. In this way, the plurality of elastomeric members may be engaged prior to completion of the injection event to mix the dry portion of the drug with the fluid portion. In some embodiments, for example, any of the devices shown and described herein may include a mixing actuator similar to the mixing actuator shown and described in U.S. Patent No. 9,173,999, titled "Devices and Methods for Delivering Medicaments from a Multi-Chamber Container," filed on January 25, 2012, which is incorporated herein by reference in its entirety.

[0200] Although the syringes described herein have been shown and described as including a mechanism for needle retraction, in other embodiments, any of the syringes shown and described herein may include a needle guard that extends distally after injection to cover the exposed needle. Such a design may be used, for example, in the "pistonless" design described above. For example, in some embodiments, the base (e.g., base 4510) of a medical syringe may be (or include) an extension portion that extends distally to cover the needle upon completion of the injection. In some such embodiments, a venting assembly may transfer all or a portion of a pressurized gas into the volume within the housing such that the transferred gas applies a force on the base (or a portion of the base) to cause the base (or a portion of the base) to extend distally to cover the needle. In other such embodiments, a spring, biasing member, or retracting member may push the base (or a portion of the base) distally.

[0201] Although the venting assembly 4310 is shown and described herein as moving a valve portion relative to a seal to selectively fluidly couple an internal gas chamber to an external volume, in other embodiments, any of the venting assemblies disclosed herein can be operable to vent all or a portion of a pressurized gas into a second region within the housing. Additionally, any of the venting assemblies disclosed herein can include any suitable valve arrangement. For example, in some embodiments, a portion of the housing and / or the venting assembly can include a tear seal that is pierced or torn when a portion of the drug carrier or a portion of the elastomeric member moves past a particular point during a delivery event. In other embodiments, a portion of the housing and / or the venting assembly can include a movable valve member (e.g., a lift valve, a ball, or the like) that moves to release pressure when a portion of the drug carrier or a portion of the elastomeric member moves past a particular point during a delivery event.

[0202] Although the various embodiments have been described as having a particular combination of features and / or components, other embodiments having any combination of any features and / or components from any of the embodiments are also possible where appropriate. For example, any of the devices shown and described herein can include electronic circuitry as described herein.

Claims

1. An apparatus, comprising: a housing that defines a gas chamber and a balance bypass, the housing being surrounded by an external volume; a gas container disposed within the housing, the gas container configured to generate pressurized gas within the gas chamber when the apparatus is actuated; a drug container assembly disposed within the housing, the drug 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 in response to a force applied by the pressurized gas within the gas chamber to deliver the drug contained therein; and a movable seal member disposed within the housing, the movable seal member configured to move from a first seal position to a second seal position, wherein: when the movable seal member is in the first seal position, the gas chamber is in fluid communication with the external volume via the balance bypass, and when the movable seal member is in the second seal position, the gas chamber is fluidly isolated from the external volume by the movable seal member.

2. The apparatus according to claim 1, further comprising: a system actuator assembly including a release member and a piercer coupled to the release member, wherein: the release member is movable within the housing between a first release member position and a second release member position, when the release member is in the first release member position, the piercer is spaced from the gas container, and when the release member is in the second release member position, the piercer pierces a portion of the gas container, and the movable seal member is coupled to the release member, and when the release member is in the first release member position, the movable seal member is in the first seal position, and when the release member is in the second release member position, the movable seal member is in the second seal position.

3. The apparatus according to claim 1, further comprising: a system actuator assembly including a release member, a piercer, and an actuation spring disposed within the housing, wherein: the release member is movable within the housing, prior to actuation of the apparatus, the release member is in a locked configuration and the actuation spring has an energy storage configuration, and when the apparatus is actuated, the release member is in a released configuration in response to an actuation force applied by the actuation spring to the release member, the piercer is coupled to the release member and positioned to pierce the gas container in response to a transition of the release member from the locked configuration to the released configuration, the movable seal member is coupled to the release member and positioned between the release member and an inner wall of the housing, when the release member is in the locked configuration, the movable seal member is in the first seal position, and the movable seal member is configured to move to the second seal position in response to a transition of the release member from the locked configuration to the released configuration.

4. The apparatus according to claim 3, wherein: The system actuator assembly includes a positioning member coupled to the release member; When the release member is in the locked configuration, the positioning member has a first shape, and when the release member is in the release configuration, the positioning member has a second shape. The positioning member engages a receiving portion of the housing when in the second shape; When the positioning member engages the receiving portion of the housing, the movable seal member is held in a third seal position; And When the movable seal member is in the third seal position, the gas chamber is fluidly isolated from the external volume through the movable seal member.

5. The device according to claim 4, wherein, The third seal position is located between the first seal position and the second seal position along a movement path.

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

7. The apparatus according to claim 6, wherein: The movable seal member is coupled to the carrier and positioned between the carrier and an inner wall of the housing; and Movement of the carrier in response to a force applied by a pressurized gas causes the movable seal member to move relative to the housing from the first seal position to the second seal position to isolate the gas chamber from the external volume.

8. The apparatus according to claim 1, further comprising: A venting assembly configured to selectively fluidly communicate the gas chamber with the external volume. The venting assembly includes a valve member configured to seal a vent opening defined by the housing, wherein: Before the apparatus is actuated, the valve member blocks the vent opening when in a first valve position, 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, and When the valve member is in the second valve position, the gas chamber is fluidly communicated with the external volume via the vent opening.

9. The apparatus according to claim 8, further comprising: 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 convert from a first configuration to a second configuration when the elastomeric member moves within the container body; and When the expandable assembly converts from the first configuration to the second configuration, the valve member moves from the first valve position to the second valve position to release pressurized gas from the gas chamber to the external volume.

10. The apparatus according to claim 8, wherein, The size of the ventilation opening is designed to maintain the force of the pressurized gas in the gas chamber at a magnitude greater than the force exerted by the retracting spring during the time of drug dispensing, and the force of the pressurized gas decreases to a magnitude less than the force exerted by the retracting spring upon completion of drug dispensing.

11. The device according to claim 10, wherein, The size of the ventilation opening is designed such that the pressurized gas causes the first 20% of the drug to be dispensed within a first duration and causes the last 20% of the drug to be dispensed within a second duration, and the second duration is less than twice the first duration.

12. The apparatus according to claim 8, wherein, The movable sealing member is a first movable sealing member, and the device further comprises: a carrier, the carrier being 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 first portion of the boundary of the gas chamber; and a second movable sealing member, the second movable sealing member being coupled to the carrier and positioned between the carrier and the inner wall of the housing, the second movable sealing member defining a second portion of the boundary of the gas chamber.

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

14. The device according to claim 13, further comprising: a ventilation assembly configured to selectively place the gas chamber in fluid communication with the external volume, the ventilation assembly including a valve member configured as the movable sealing member and a ventilation opening defined by the housing, the valve member being configured to seal the ventilation opening, wherein when the valve member is in the first seal position, the gas chamber is in fluid communication with the ventilation opening via the balance bypass.

15. The device according to claim 14, further comprising: an expandable assembly having a first member, a second member, and a third member, the first member being coupled to the elastomeric member, the second member being coupled between the first member and the third member, the third member being coupled to the valve member, the expandable assembly being configured to convert from a first configuration to a second configuration when the elastomeric member moves within the container body; and when the expandable assembly converts from the first configuration to the second configuration, the valve member moves from the second seal position to the third seal position to release the pressurized gas from the gas chamber to the external volume.

16. The device according to claim 1, wherein: the container body moves 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 sealing member is coupled to the container body and positioned between the container body and the inner wall of the housing; and Movement of the container body in response to a force applied by pressurized gas causes the movable sealing member to move relative to the housing from the first seal position to the second seal position to isolate the gas chamber from the external volume.

17. The apparatus according to claim 1, further comprising: A delivery control mechanism coupled to the drug container assembly, the delivery control mechanism including a flow restriction member configured to regulate the flow of pressurized gas into the container body acting on an elastomeric member, wherein: The drug container assembly is configured to move from a first container position to a second container position in response to a force applied by pressurized gas, and The flow restriction member is configured to limit movement of the elastomeric member until the drug container assembly is in the second container position.

18. The apparatus according to claim 17, wherein: The gas chamber is a first gas chamber; The flow restriction member is configured to permit pressurized gas to be transferred from the first gas chamber to a second gas chamber in fluid communication with the elastomeric member; A first portion of the pressurized gas in the first gas chamber has a first pressure magnitude; A second portion of the pressurized gas in the second gas chamber has a second pressure magnitude; and The first pressure magnitude is greater than the second pressure magnitude.

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

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