Devices and methods for drug delivery

Abstract

A drug delivery device includes a mechanical drive assembly and a flexible drug reservoir coupled to a housing. The mechanical drive assembly is configured to move a first needle from a first configuration to a second configuration. The flexible drug reservoir includes an external surface and an internal chamber containing a drug. A pneumatic pressure source coupled to the housing is operable to apply pneumatic pressure to the external surface of the flexible drug reservoir to compress the flexible drug reservoir. A compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the first needle when the first needle is in the second configuration.

Description

DEVICES AND METHODS FOR DRUG DELIVERYFIELD OF THE DISCLOSURE

[0001] The present disclosure relates to processes and devices for parenteral delivery of therapeutic agents or drugs. More particularly, the present disclosure relates to processes and devices for parenteral delivery of relatively large volumes of drugs (for example, volumes greater than 2m L).BACKGROUND OF THE DISCLOSURE

[0002] Various injection devices have been developed to advantageously administer therapeutic agents or drugs to patients without the presence of medical professionals. Such devices are often capable of maintaining needles in sterile environments prior to injection. Some such devices are also capable of obscuring their needles, which may be beneficial for patients that are uncomfortable with seeing or directly handling needles. However, improved devices for efficient parenteral delivery of drugs would be beneficial, particularly improved devices for delivering relatively higher volumes of drugs (for example, volumes greater than 2mL).SUMMARY

[0003] According to an exemplary embodiment of the present disclosure, a drug delivery device includes a housing and a mechanical drive assembly coupled to the housing. The mechanical drive assembly includes a first needle and is configured to move the first needle from a first configuration to a second configuration. The device further includes a flexible drug reservoir coupled to the housing and a pneumatic pressure source coupled to the housing. The flexible drug reservoir includes an external surface and an internal chamber containing a drug. The pneumatic pressure source is operable to apply pneumatic pressure to the external surface of the flexibledrug reservoir to compress the flexible drug reservoir. Compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the first needle when the first needle is in the second configuration.

[0004] According to another exemplary embodiment of the present disclosure, a method of operating a drug delivery device includes actuating a mechanical drive assembly of the drug delivery device, wherein the mechanical drive assembly moves a first needle from a first configuration to a second configuration. The method further includes activating a pneumatic pressure source of the drug delivery device when the first needle is in the second configuration. The pneumatic pressure source applies pneumatic pressure to an external surface of a flexible drug reservoir of the drug delivery device and thereby compresses the flexible drug reservoir and causes a drug to flow from an internal chamber of the flexible drug reservoir to the first needle.

[0005] According to yet another exemplary embodiment of the present disclosure, a drug delivery device includes a housing, a needle coupled to the housing, a flexible drug reservoir coupled to the housing, and a pneumatic pressure source coupled to the housing. The flexible drug reservoir includes an external surface and an internal chamber containing a drug. The pneumatic pressure source is operable to apply pneumatic pressure to the external surface of the flexible drug reservoir to compress the flexible drug reservoir. The device further includes an electronic controller coupled to the housing and a pressure sensor coupled to the housing and operably coupled to the electronic controller. A compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle. The electronic controller is configured to determine an end-of-dose state upon determining a change to a pressure decay model of the pneumatic pressure applied to the external surface of the flexible drug reservoir and sensed by the pressure sensor.

[0006] According to still exemplary embodiment of the present disclosure, a method of operating a drug delivery device includes activating a pneumatic pressure source of the drug delivery device. The pneumatic pressure source applies pneumaticpressure to an external surface of a flexible drug reservoir of the drug delivery device to compress the flexible drug reservoir and causes a drug to flow from an internal chamber of the flexible drug reservoir to a needle of the drug delivery device. The method further includes sensing, via a pressure sensor of the drug delivery device, the pneumatic pressure applied to the external surface of the flexible drug reservoir. The method further includes determining an end-of-dose state, via an electronic controller of the drug delivery device, in response to the electronic controller determining a change to a pressure decay model of the pneumatic pressure applied to the external surface of the flexible drug reservoir and sensed by the pressure sensor.

[0007] According to another exemplary embodiment of the present disclosure, a drug delivery device includes a housing, a needle coupled to the housing, and a flexible drug reservoir coupled to the housing. The flexible drug reservoir includes an internal chamber containing a drug. The device further includes a pressure source coupled to the housing, an electronic controller coupled to the housing, and an optical sensor coupled to the housing and operably coupled to the electronic controller. The pressure source is operable to apply pressure to the flexible drug reservoir. The optical sensor is configured to emit light toward the flexible drug reservoir and sense light reflected by the flexible drug reservoir. An application of pressure to the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle. The electronic controller is configured to determine an end-of-dose state in response to the optical sensor sensing an increase in light reflected by the flexible drug reservoir.

[0008] According to yet another exemplary embodiment of the present disclosure, a method of operating a drug delivery device includes activating a pressure source of the drug delivery device. The pressure source applies pressure to a flexible drug reservoir of the drug delivery device and thereby causes a drug to flow from an internal chamber of the flexible drug reservoir to a needle of the drug delivery device. The method includes emitting, via an optical sensor of the drug delivery device, light toward the flexible drug reservoir and sensing, via the optical sensor of the drug delivery device, light reflected by the flexible drug reservoir. The method further includesdetermining an end-of-dose state, via an electronic controller of the drug delivery device, in response to the optical sensor of the drug delivery device sensing an increase in light reflected by the flexible drug reservoir.

[0009] According to still another exemplary embodiment of the present disclosure, a drug delivery device includes a housing, a needle coupled to the housing, and a flexible drug reservoir coupled to the housing. The flexible drug reservoir includes an external surface and an internal chamber containing a drug. The device further includes a pneumatic pump coupled to the housing. The pneumatic pump is operable to apply pneumatic pressure to the external surface of the flexible drug reservoir and thereby compress the flexible drug reservoir. The device further includes an electronic controller coupled to the housing and an optical sensor coupled to the housing and operably coupled to the electronic controller. The optical sensor is configured to sense a configuration of the flexible drug reservoir. A compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle. The electronic controller is configured to determine an end-of-dose state in response to determining a configuration change of the flexible drug reservoir via the optical sensor.

[0010] According to another exemplary embodiment of the present disclosure, a method of operating a drug delivery device includes activating a pneumatic pump of the drug delivery device. The pneumatic pump applies pneumatic pressure to an external surface of a flexible drug reservoir of the drug delivery device and thereby causes a drug to flow from an internal chamber of the flexible drug reservoir to a needle of the drug delivery device. The method further includes sensing, via an optical sensor of the drug delivery device, a configuration of the flexible drug reservoir. The method further includes determining, via an electronic controller of the drug delivery device, an end-of- dose state in response to determining a configuration change of the flexible drug reservoir via the optical sensor.

[0011] According to yet another exemplary embodiment of the present disclosure, a drug delivery device includes a housing, a needle coupled to the housing, and a flexible drug reservoir coupled to the housing. The flexible drug reservoir includes an external surface and an internal chamber containing a drug. The device further includes a pneumatic pressure source coupled to the housing. The pneumatic pressure source is operable to apply pneumatic pressure to the external surface of the flexible drug reservoir and thereby compress the flexible drug reservoir. The device further includes an electronic controller coupled to the housing, a pressure sensor coupled to the housing and operably coupled to the electronic controller, and an optical sensor coupled to the housing and operably coupled to the electronic controller. A compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle. The electronic controller is configured to determine an end-of-dose state in response to (1 ) determining a change to a pressure decay model of the pneumatic pressure applied to the flexible drug reservoir and sensed by the pressure sensor, and (2) determining a configuration change of the flexible drug reservoir via the optical sensor.

[0012] According to still another exemplary embodiment of the present disclosure, a method of operating a drug delivery device includes activating a pneumatic pressure source of the drug delivery device. The pneumatic pressure source applies pneumatic pressure to an external surface of a flexible drug reservoir of the drug delivery device to cause a drug to flow from an internal chamber of the flexible drug reservoir to the needle of the drug delivery device. The method further includes sensing, via a pressure sensor of the drug delivery device, the pneumatic pressure applied to the external surface of the flexible drug reservoir and sensing, via an optical sensor of the drug delivery device, a configuration of the flexible drug reservoir. The method further includes determining an end-of-dose state, via an electronic controller of the drug delivery device, in response to (1) determining a change to a pressure decay model of the pneumatic pressure applied to the external surface of the flexible drugreservoir and sensed by the pressure sensor, and (2) determining a configuration change of the flexible drug reservoir via the optical sensor.

[0013] According to another exemplary embodiment of the present disclosure, a drug delivery device includes a housing, a needle coupled to the housing, and a flexible drug reservoir coupled to the housing. The flexible drug reservoir includes a transverse mid-plane, a first sheet disposed on a first side of the transverse mid-plane, a second sheet disposed on a second, opposite side of the transverse mid-plane, and an internal chamber disposed between the first sheet and the second sheet. The internal chamber contains a drug. The device further includes an electronic controller coupled to the housing and an optical sensor coupled to the housing and operably coupled to the electronic controller. The optical sensor includes a plurality of light emitters configured to emit light toward the flexible drug reservoir. The plurality of light emitters are disposed in the transverse mid-plane, and the optical sensor is configured to sense light reflected by the flexible drug reservoir. A compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle. The electronic controller is configured to determine an end-of-dose state in response to the optical sensor sensing an increase in light reflected by the flexible drug reservoir.BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The above-mentioned and other features and advantages of this disclosure, and the manner of attaining them, will become more apparent and the invention itself will be better understood by reference to the following description of embodiments of the invention taken in conjunction with the accompanying drawings, wherein:

[0015] FIG. 1 is a perspective view of a drug delivery device according to an embodiment of the present disclosure;

[0016] FIG. 2 is a schematic view of the drug delivery device of FIG. 1 .

[0017] FIG. 3 is a side sectional view of the drug delivery device of FIG. 1 .

[0018] FIG. 4 is a detail side sectional view of the drug delivery device within line4-4 of FIG. 3.

[0019] FIG. 5 is a perspective view of a reservoir housing and a flexible drug reservoir of the drug delivery device of FIG. 1 .

[0020] FIG. 6 is an exploded perspective view of the reservoir housing and the flexible drug reservoir of FIG. 5.

[0021] FIG. 7 is a top view of a flexible bag of the flexible drug reservoir of FIG. 5.

[0022] FIG. 8 is a detail top view of an outlet of the flexible drug reservoir ofFIG. 5.

[0023] FIG. 9 is a partial perspective view of the flexible drug reservoir and a reservoir sensor of the drug delivery device of FIG. 1 .

[0024] FIG. 10 is a side schematic view of the flexible drug reservoir and the reservoir sensor of the drug delivery device of FIG. 1 .

[0025] FIG. 11 is a perspective view of the reservoir sensor of FIG. 9.

[0026] FIG. 12 is another side schematic view of the flexible drug reservoir and the reservoir sensor of FIG. 9.

[0027] FIG. 13 is a perspective view of a reservoir sensor for a drug delivery device according to another embodiment of the present disclosure.

[0028] FIG. 14 is a side schematic view of the flexible drug reservoir of FIG. 5 and the reservoir sensor of FIG. 13.

[0029] FIG. 15 is a perspective view of a mechanical drive assembly of the drug delivery device of FIG. 1 .

[0030] FIG. 16 is another perspective view of the mechanical drive assembly ofFIG. 15.

[0031] FIG. 17 is an exploded view of the mechanical drive assembly of FIG. 15.

[0032] FIG. 18 is a perspective view illustrating internal components of the mechanical drive assembly of FIG. 15.

[0033] FIGS. 19-21 are a block diagram of a method of operating a drug delivery device according to an embodiment of the present disclosure.

[0034] FIG. 22 is a plot of sensed pressures, sensed optical parameters, and a calculated pressure decay constant versus time during operation of a drug delivery device according to an embodiment of the present disclosure.

[0035] Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary embodiments of the invention and such exemplifications are not to be construed as limiting the scope of the invention in any manner.DETAILED DESCRIPTION

[0036] The present disclosure relates to devices and methods for parenteral delivery of therapeutic agents or drugs. In some embodiments, such devices and methods are for parenteral delivery of relatively high volumes of drugs (for example, volumes greater than 2mL, or any other suitable volume).1 . Drugs / Therapeutic Agents

[0037] Devices according to the present disclosure may carry and facilitate delivery of a drug to a subject. The term “drug” or “medication” refers to one or more therapeutic agents including but not limited to therapeutic antibodies, inhibitors, gastric inhibitory polypeptide (GIP), GIP analogs, GIP derivatives, combined GIP / GLP-1 agonists such as tirzepatide, oxyntomodulin analogs, oxyntomodulin derivatives, insulins, insulin analogs and derivatives, GLP-1 receptor agonists such as dulaglutide or liraglutide, glucagon, glucagon analogs, glucagon derivatives, and any other therapeutic agent that is capable of delivery by devices according to the present disclosure. Thedrug may be formulated with one or more excipients. Devices according to the present disclosure are operated in a manner generally as described herein by a patient, caregiver or healthcare professional to deliver a drug to a subject.

[0038] In certain embodiments, the drug is protein, such as a monoclonal antibody or some other protein which is therapeutically useful. In some embodiments, the protein may have a concentration of from about 75 mg / mL to about 500 mg / mL in a fluid. In certain embodiments, the protein may have a concentration of about 150 mg / mL, 200 mg / mL, 250 mg / mL, or more. A drug may further contain a solvent or nonsolvent, such as water, perfluoroalkane solvent, safflower oil, or benzyl benzoate for example.2. Drug delivery devices and MethodsA. Overall Device Structure

[0039] FIGS. 1 -3 illustrate a drug delivery device 100 according to an embodiment of the present disclosure. Illustratively, the drug delivery device 100 generally includes a relatively compact and elongated profile, although any suitable profile may be provided. In operation, the device 100 is positioned on a subject’s skin and actuated to deliver a medication to the subject. Referring specifically to FIG. 1 , the drug delivery device 100 generally includes a device housing 102 that carries a user input 104 accessible by a user to actuate the device 100. More specifically, the user input 104 is coupled to housing 102 and is actuatable to cause the device 100 to deliver a drug to a subject via a first, or “drug delivery”, needle 120 (FIG. 2) that extends from the bottom of the housing 102. The user input 104 is illustratively a depressible button, although other suitable actuator mechanisms may be used such as, for example, a rotary knob, a sliding button, etc. The device housing 102 also illustratively includes a transparent or translucent window 106 that facilitates visualization of one or more internal components of the device 100, such as the drug container for example. In one embodiment, the device housing 102 is attachable to a subject’s skin with a multilayer adhesive patch (not shown) positioned on the underside of the housing 102. Asillustrated in FIG. 1 , device housing 102 includes an upper housing portion 103 and a lower housing portion 105 that are coupled together to house and support internal components.

[0040] Referring now to FIGS. 2-4, the device housing 102 carries various internal components of device 100 that facilitate delivering the drug to a subject, including a reservoir housing 110, a pressure source 108, a drive assembly 118, an electronic controller 124, and sensors 126, 128, 130. In the illustrative embodiment, the reservoir housing 110 comprises a rigid shell forming an internal pressure chamber 111 , and a flexible drug reservoir 114 is disposed within the pressure chamber 111. The housing 110 and drug reservoir 114 are coupled to a port component 138 (FIG. 3) at an end of the housing 110. The reservoir housing 110 and drug reservoir 114 cooperate to form a drug reservoir assembly. The pneumatic pressure source 108, such as a pneumatic pump for example, is operably coupled to the reservoir housing 110 and is operable to provide pneumatic pressure to the pressure chamber 111 and apply the pressure to an external surface 112 (FIG. 3) of a flexible drug reservoir 114 disposed within the pressure chamber 111. Alternatively, the device 100 may include a different type of pressure source, such as a mechanical pressure source or an electrolytic gas generator, for compressing the flexible drug reservoir 114. In any case, the flexible drug reservoir 114 initially carries the drug 117 within an internal chamber 116 (FIG. 6), and compression of the flexible drug reservoir 114 by the pressure source 108 causes the drug 117 to flow from the internal chamber 116. Additional details of the reservoir housing 110 and the flexible drug reservoir 114 are provided herein.

[0041] The flexible drug reservoir 114 delivers the drug to a flow path of the mechanical drive assembly 118. The mechanical drive assembly 118 includes a first needle 120 in fluid communication with a second needle 122 and is movable between first and second configurations. In particular, the second, or “coupling”, needle 122 is movable from a first, or “fluid isolation”, configuration to a second, or “fluid communication”, configuration. In the first configuration, the retracted position of the second needle 122 inhibits fluid communication between the flexible drug reservoir 114and the drive assembly 118. In the second configuration, the second needle 122 permits fluid communication between the flexible drug reservoir 114 and the drive assembly 118.

[0042] The first needle 120 of the mechanical drive assembly 118 is movable from a first, or stowed, configuration to a second, or deployed, configuration. In the first configuration, the first needle 120 may be completely positioned or retracted within the external profile of the device housing 102. In the second configuration, the first needle 120 at least partially extends outwardly from the device housing 102 and is configured to pierce the skin of the subject. As such, the first needle 120 is configured to deliver the drug to the subject in the second configuration. Additional details of the drive assembly 118 are provided herein.

[0043] With continued reference to FIGS. 2-4, the device 100 includes the electronic controller 124 (FIG. 2) that operably couples to various device components to control delivery of the drug to the subject. The electronic controller 124 may be or include, for example, one or more dedicated processors (e.g., microprocessors), one or more Field Programmable Gate Arrays (FPGAs), one or more Programmable Logic Devices (PLDs), one or more Complex PLDs (CPLDs), one or more custom Application Specific Integrated Circuits (ASICs), or the like. In the exemplary embodiment, the controller 124 includes at least one processor (e.g., microprocessor) that executes software and / or firmware stored in memory of the controller 124. The software / firmware code contains executable instructions (e.g., computer code, machine-useable instructions, and the like) that, when executed by the controller 124, cause the controller 124 to perform the functions, operations, and methods described herein. The memory may include, for example, read-only memory (ROM), random access memory (RAM), and non-volatile storage. Other hardware, conventional and / or custom, may also be included.

[0044] The controller 124 operably couples to the user input 104, the pressure source 108, and the mechanical drive assembly 118. The controller 124 also operablycouples to a power source (not shown - such as one or more batteries). In addition, the controller 124 operably couples to one or more sensors and, based on inputs received from the sensors, causes, modifies, and / or inhibits delivery of the drug to the subject. Illustratively, the sensors include at least a skin sensor 126 (FIGS. 2 and 3), a pressure sensor 128 (FIGS. 2-4), and a reservoir sensor 130 (FIG. 2). In some embodiments, the device 100 further includes a temperature sensor 135 operative to detect a temperature within the pressure chamber 111 (or within housing 102 external to the chamber 111 ) and provide a signal representative of the temperature to the controller 124.

[0045] The controller 124 communicates with the skin sensor 126 to determine whether the device 100 is properly positioned against the subject’s skin prior to and during delivery. The controller 124 initiates drug delivery at least partially in response to an output signal from sensor 126 indicating the device 100 is positioned properly against the body of the subject. In the illustrated embodiment, controller 124 does not actuate the pressure source 108 and / or the drive assembly 118 if the skin sensor 126 indicates that the device 100 is not properly positioned against the skin of the subject. Skin sensor 126 may also be used to indicate to the controller 124 that delivery has ended prematurely, such as when the device 100 is removed from the skin before detection of complete dose delivery, and controller 124 in response is operative to halt continued delivery by disabling or depressurizing pressure source 108 and / or retracting drive assembly 118. The skin sensor 126 may take various forms, such as a contactbased sensor (for example, a mechanical switch or spring-biased plunger that is depressed when pushed against the skin, as illustrated in FIGS. 3 and 4), a non-contact sensor (for example, an optical sensor or a capacitive sensor that detects skin adjacent to the housing), or the like. In one embodiment, the housing 102 includes an opening positioned below the skin sensor 126 and sized to allow a contact-based sensor to extend / retract or an optical sensor to transmit an optical signal through the opening and detect the user’s skin surface. In an embodiment with a capacitive-based sensor, anopening is optionally not provided in the housing 102 below the sensor 126 with the capacitance detectable through the housing wall.

[0046] The pressure sensor 128 operably couples to the controller 124 and the reservoir housing 110 and provides a signal representative of a pneumatic pressure in the chamber 111. In particular, the controller 124 communicates with the pressure sensor 128 to determine the pneumatic pressure applied to the external surface 112 of the drug reservoir 114 within the chamber 111. Based on the sensed pneumatic pressure and other sensed or stored parameter(s) (e.g., elapsed time of delivery, temperature, properties of the drug such as viscosity, physical dimensions of the reservoir, etc.), the controller 124 is configured to determine an end-of-dose state of the device (that is, when the drug has been completely delivered, or a therapeutically effective of amount of the drug has been delivered, to the subject). The pressure sensor 128 may take various forms, such as a PCB-mounted piezoelectric sensor (e.g., Micro Electro Mechanical Systems or MEMS sensor), for example. Other suitable sensors may be used such as metal thin-film or ceramic thick-film pressure sensors, for example. Additional details of operation of the device 100 in response to parameters sensed by the pressure sensor 128 are provided herein.

[0047] The reservoir sensor 130 is operably coupled to the flexible drug reservoir 114 and communicates with the controller 124 to provide a signal representative of a configuration or state of the flexible drug reservoir 114. In particular, based on a configuration change (for example, a shape change) of the flexible drug reservoir 114 sensed by the reservoir sensor 130, the controller 124 is operative to determine an end- of-dose state of the device 100. The reservoir sensor 130 may take various forms, such as an optical sensor including one or more light emitters and one or more light receivers. Other suitable types of reservoir sensors include, for example, small charge- coupled device (CCD) sensors or infrared (IR) dot projector-receiver sensors. Additional details of the reservoir sensor 130 of the illustrated embodiment, and operation of the device 100 in response to parameters sensed by the reservoir sensor 130, are provided herein.

[0048] With specific reference to FIG. 2, the controller 124 may include multiple control units, such as multiple separate printed circuit board assemblies (PCBAs), that are communicatively coupled to each other. In some embodiments, each control unit operably couples to a subset of the electronic components described herein, and the control units operably couple to each other to exchange sensor data, control signals, etc. For example, the controller 124 may include a first control unit 132A that operably couples to the mechanical drive assembly 118 and a second control unit 132B that operably couples to the user input 104, the pressure source 108, and the sensors 126, 128, 130, and 135. The control units 132A, 132B cooperate to control the operation of the device 100. Other suitable hardware arrangements of the controller 124 may be provided, including a single control unit provided on a single PCBA.

[0049] FIGS. 3 and 4 illustrate an exemplary embodiment of controller 124 having first and second control units 132A, 132B each comprising a printed circuit board assembly (PCBA). Illustratively, the control unit 132A is coupled to the mechanical drive assembly 118 (see also FIG. 16). The control unit 132B is illustratively coupled to the lower housing portion 105 and in some embodiments may provide structural support to certain components. The pressure source 108 (e.g., air pump) is illustratively positioned below the control unit 132B while the reservoir housing 110 and reservoir 114 are positioned above the control unit 132B. A manifold 109 routes the pressurized air from the pressure source 108 to an inlet 113 of the reservoir housing 110 that extends through an opening in the control unit 132B. The pressure sensor 128 is coupled to the underside of the control unit 132B and sealingly coupled to the manifold 109 to detect pressure in the air chamber formed by the manifold 109 and housing 110, although other suitable locations of sensor 128 in the sealed air pathway may be provided to detect pressure in housing 110. The skin sensor 126 is illustratively positioned below the control unit 132B and between the drive assembly 118 and the pressure source 108. The drive assembly 118 is also coupled to lower housing 105 and positioned at the end of control unit 132B opposite the pressure source 108 andhousing 110 and illustratively extends through a slot or opening in the control unit 132B.Other suitable arrangements of device components in housing may be provided.B. Drug Reservoir and Pressurization Assembly

[0050] Referring to FIGS. 5-8, the drug reservoir assembly including the reservoir housing 110 (FIGS. 5 and 6) and the flexible drug reservoir 114 are further illustrated. The flexible reservoir 114 includes a rigid port component or bulkhead 138 and a flexible bag or container 140 sealingly coupled to a flange of the port 138. The reservoir housing 110 includes a wall 134 having an open end 136 and a closed end 137 and forming a pocket for receiving the reservoir 114. The closed end 137 of the wall 134 is illustratively rounded in shape and sized to extend to at least the length of the flexible bag 140. The open end 136 of the wall 134 is sized to receive and couple to the port 138 of the reservoir 114, illustratively with an interference fit and UV-cured glue joint between the port 138 and open end 136. The wall 134 is illustratively made of a rigid material, such as a plastic or other polymer. The wall 134 of the reservoir housing 110 sealingly couples to the port component 138 at the open end 136 to form a sealed interior space between the wall 134 and the flexible bag 140. The inlet 113 formed on the underside of the wall 134 sealingly couples to the pressure manifold 109 (FIG. 3). The port 138 serves as a rigid component supporting the end of the flexible bag 140, and the flexible bag 140 forms the internal chamber 116 that initially carries the drug. A pneumatic pressure is generated in the sealed space between the wall 134 and the flexible bag 140 and is applied to the external surface 112 of the bag 140 to cause the drug to flow from the internal chamber 116.

[0051] The flexible bag 140 may be constructed of one or more sheets (illustratively, two sheets, or an upper sheet 142 and a lower sheet 144 bonded together at the perimeter) of a flexible polymer, more specifically a thermoplastic copolymer, and more specifically ethylene-vinyl alcohol copolymer (“EVOH”), for example. Appropriate materials may have a Young’s modulus in a range of 3000 to 4000 MPa, more specifically 3250 to 3750 MPa, and more specifically about 3500 MPa. Appropriatematerials may have a flexural modulus in a range of 2800 to 3800 MPa, more specifically 3050 to 3550 MPa, and more specifically about 3300 MPa.

[0052] Referring to FIGS. 5, 6, and 8, the port 138 of the flexible drug reservoir 114 includes an outlet 146 in fluid communication with the internal chamber 116 of the bag 140. The outlet 146 includes a reservoir septum 148 that is pierceable by the second needle 122 (FIG. 3) in its second configuration (described herein) to permit fluid communication between the internal chamber 116 of the flexible drug reservoir 114 and the flow path of the drive assembly 118. The outlet 146 further includes an annular cap 150, such as a laser welded cap, a snap-on cap, or a crimped cap, that secures the reservoir septum 148 to the port 138.C. Reservoir / Optical Sensing Assembly

[0053] Referring now to FIGS. 9 and 10, an exemplary embodiment of the reservoir sensor 130 of FIG. 2 is illustrated. The reservoir sensor 130 is used to detect a configuration change (for example, a shape change) of the flexible drug reservoir 114 (FIG. 10). In response, the controller 124 (FIG. 2) determines an end-of-dose state of the device 100 based on the detected optical refraction indicating a collapsed state of the flexible bag 140. Illustratively and referring specifically to FIG. 9, the reservoir sensor 130 includes an optical sensor that is coupled to a fitting 152, and that assembly is received in a blind aperture 154 formed in the wall of the port 138 of the flexible reservoir 114. In one embodiment, the sensor 130 includes a small printed circuit board (PCB) with an optical sensor and connector that is communicatively coupled to the controller 124 (e.g., to control unit 132B of FIG. 2).

[0054] With reference again to FIGS. 9 and 10, the port 138, or at least one or more wall portions 155 of the port 138 adjacent to the field of view of the optical sensor 130, may be transparent, and the optical sensor 130 emits light though the portion(s) 155 of the port 138 and into the internal chamber 116 (FIG. 10) of the flexible drug reservoir 114. Generally, relatively low amounts of light reflect off the flexible drug reservoir 114 (e.g., sheets 142, 144) and return to the optical sensor 130 when theflexible drug reservoir 114 carries relatively high volumes of the drug (that is, prior to delivery of the drug to a patient). In contrast, relatively high amounts of light reflect off the flexible drug reservoir 114 and return to the optical sensor 130 when the flexible drug reservoir 114 carries relatively low volumes of the drug (that is, when a significant amount of the drug has been delivered to the patient, or in an end-of-dose state when the upper sheet 142 and the lower sheet 144 of the flexible bag 140 (each shown in FIG. 10) have collapsed toward each other). Generally, the controller 124 is configured to determine the end-of-dose state when the reflected light sensed by the optical sensor 130 exceeds a threshold. In one embodiment, the end-of-dose state is detected when the upper and lower sheets 144 of the flexible bag 140 have collapsed over the wall portion 155 of the port 138 such that the space in the internal chamber 116 between the wall portion 155 and the sheets 142, 144 is substantially eliminated or reduced.

[0055] The exemplary optical sensor 130 is further illustrated in FIGS. 11 and 12, and the port 138 and the flexible bag 140 of the flexible drug reservoir 114 are further illustrated in FIG. 12. As illustrated, the optical sensor 130 includes a plurality of light emitters, more specifically two left light emitters 156 and two right light emitters 158, and a receiver 160 is disposed between the left light emitters 156 and the right light emitters 158. The light emitters 156, 158 and the receiver 160 are each disposed in the transverse mid-plane 162 (FIG. 12) of the flexible drug reservoir 114, or the plane on which the upper sheet 142 and the lower sheet 144 are disposed on opposite sides - stated another way, the plane of the page as shown in FIG. 7. In this configuration, light emitted by the light emitters 156, 158 is typically not reflected by any air bubbles (e.g., air bubble 145) positioned in the internal chamber 116 and near the optical sensor 130, including relatively large air bubbles (for example, one or more air bubbles having a total volume of less than 150 microliters (pL)) which could be within the sensor’s field of view. In some embodiments, avoiding or limiting detection of air bubbles in chamber 116 may reduce the likelihood that the controller 124 falsely determines an end-of-dose state.

[0056] Alternatively, optical sensors of devices according to the present disclosure may take other forms. For example, optical sensors may include different arrangements and / or combinations of one or more light emitters and one or more light receivers. As one specific example, FIGS. 13 and 14 illustrate an optical sensor 200 having a left light emitter 202, a right light emitter 204, an upper light emitter 206, and a lower light emitter 208, and a light receiver 210 is disposed centrally between the light emitters 202, 204, 206, and 208. The left light emitter 202, the receiver 210, and the right light emitter 204 are disposed in the transverse mid-plane 212 of the flexible drug reservoir 214, and the upper light emitter 206 and the lower light emitter 208 are disposed above and below the transverse mid-plane 212, respectively, in vertical alignment with the receiver 210. In one embodiment, light emitted by the light emitters 202, 204, 206, and 208, particularly the upper light emitter 206 and the lower light emitter 208, may be reflected by air bubbles (e.g., air bubble 145) that are present within the internal chamber 216 and near the optical sensor 200, even relatively small air bubbles. In this embodiment, controller 124 is programmed to check for and detect these air bubbles in the reflected light calculations and to negate their effect on the end- of-dose state determination in order to reduce the likelihood of an erroneous or premature detection of the end-of-dose state.

[0057] In an exemplary embodiment, the light emitters contemplated herein, including the light emitters 156, 158 and the light emitters 202, 204, 206, and 208, may emit green light, and the receivers contemplated herein, including the receivers 160 and 210, may be most sensitive to green light. In this embodiment, such light emitters and receivers may provide an advantageous signal-to-noise ratio. Alternatively, any of the light emitters contemplated herein may emit other wavelengths of light and / or any of the receivers contemplated herein may be most sensitive to other wavelengths of light.D. Mechanical Drive Assembly

[0058] FIGS. 15-17 further illustrate the mechanical drive assembly 118, and FIG. 18 illustrates components thereof. The mechanical drive assembly 118 includesthe selectively movable first needle 120 (FIGS. 17 and 18), which is configured to pierce the skin and deliver the drug to a subject. The mechanical drive assembly 118 further includes the selectively movable second needle 122 (FIGS. 17 and 18), which is configured to selectively facilitate fluid communication with the flexible drug reservoir 114 (shown elsewhere). The second needle 122 and the first needle 120 are in fluid communication via a flexible conduit 164 that is sized to allow translational movement of each needle 120, 122. In the illustrated embodiment, the first needle 120 is configured to translate in a direction perpendicular to the direction that the second needle 122 translates following actuation.

[0059] Referring to FIGS. 15-17, the mechanical drive assembly 118 includes a drive housing 165 that carries and supports the drive components. Illustratively, the first control unit 132A of the controller 124 (FIG. 2) is coupled externally to a side wall of the drive housing 165. In the exemplary embodiment, the drive housing 165 includes a pair of externally extending posts 169 (FIG. 17) that are configured to engage corresponding slots 171 formed in first control unit 132A. The drive housing 165 also carries a first drive septum 166 (FIGS. 17 and 18) that is pierceable by the first needle 120 in its second configuration and, similarly, a second drive septum 168 that is pierceable by the second needle 122 in its second configuration. Openings are provided in corresponding walls of the drive housing 165 to receive the respective extended needles 120, 122 therethrough, and the septa 166, 168 are attached to the drive housing 165 over the respective two wall openings. Septa 166, 168 may each comprise a foil seal that is adhered (e.g., heat sealed) to the drive housing 165 over each corresponding wall opening. Septa 166, 168 alternatively may comprise rubber septa positioned in the wall openings. In an exemplary embodiment, the drive housing 165 and the septa 166, 168 cooperate to provide a sterile internal environment for the parts contained therein, including for the fluid path provided with the first and second needles 120, 122 and the conduit 164.

[0060] The drive housing 165 further carries a motor 170 via an external clamp 173 that fastens externally to the housing 165, and the attached motor 170 is operablycoupled to and controlled by the first control unit 132A. The motor 170 is operable to drive a transmission 172 (FIGS. 17 and 18), and the transmission 172 in turn drives the first needle 120 and the second needle 122 from their first (retracted) configurations to their second (extended) configurations and vice versa. Illustratively, the transmission 172 includes a first intermediate gear 174 that is driven by the motor 170, a second intermediate gear or wheel 176 that is driven by the first intermediate gear 174, and a first pinion gear 178 and a second pinion gear 180 that are rotatably fixed to the second intermediate gear 176. The first pinion gear 178 forms part of a first rack and pinion assembly 182, together with a first rack 184 that carries the first needle 120. The second pinion gear 180 forms part of a second rack and pinion assembly 186, together with a second rack 188 that carries the second needle 122.

[0061] Mechanical end-of-travel stops are fixed to or formed in the drive housing 165 to limit the travel of the rack and pinion assemblies 182, 186. For example, the stops may be arranged to engage racks 184, 188. The electric motor 170 may also use electric braking to reduce motor speed prior to the racks 184, 188 hitting the end-of- travel stops. Illustratively, the rack and pinion assemblies 182, 186 are arranged substantially perpendicularly relative to each other. Stated another way, the rack and pinion assemblies 182, 186 may be arranged such that the first needle 120 and the second needle 122 (and corresponding racks 184, 188) move substantially perpendicularly relative to each other from their first configurations to their second configurations and vice versa. In other embodiments, the transmission 172 may take different forms. For example, the transmission 172 may include a different number of gears and / or different components for driving the first needle 120 and the second needle 122. Additionally, needles 120, 122 may be arranged to move at a different angle relative to each other depending on the layout and orientation of the device.

[0062] The drive housing 165 illustratively includes an upper or lid portion and a lower portion that are coupled together to form an interior space to house the rack and pinion assemblies 182, 186, the needles 120, 122, and the flexible conduit 164. The first and second intermediate gears 174, 176 are positioned external to the drivehousing 165, illustratively in the space between the first control unit 132A and the drive housing 165. In an exemplary embodiment, at least a portion of the second intermediate gear 176 is positioned external to the drive housing 165 to facilitate sensing of the rotational position of the transmission 172 by the control unit 132A, as described herein. The second intermediate gear 176 includes a shaft 194 that extends through an opening 195 (FIG. 17) formed in the drive housing 165 and that couples to the second pinion gear 180 positioned in the housing 165. A seal 196 (e.g., o-ring) may provide a sealing interface between the shaft 194 and the drive housing 165. Illustratively, an opposite end of the shaft 194 extends into an opening 197 (FIG. 17) formed in the circuit board of first control unit 132A such that the shaft 194 is freely rotatable relative to the control unit 132A.

[0063] In the illustrated embodiment of FIGS. 15-17, a lock arm 175 is pivotably coupled externally to the drive housing 165 above the second intermediate gear 176. A slot or notch 177 (FIG. 17) formed in the top center of the second intermediate gear 176 is configured to receive a tab 179 of the lock arm 175. The lock arm 175 serves as a needle lockout feature during device assembly. For example, after initial assembly of the mechanical drive assembly 118 (as shown in FIGS. 15 and 16) but prior to final device assembly (as shown in FIG. 3), the lock arm tab 179 is engaged in the notch 177 of intermediate gear 176 to prevent or block accidental needle motion. The lock arm 175 keeps the drive assembly 118 locked through all assembly phases until the final device assembly. During final device assembly when the upper housing portion 103 (FIG. 3) is placed onto the lower housing portion 105 (FIG. 3), a rib or other protrusion (not shown) formed in and extending downwardly from the upper housing portion 103 contacts and pushes the end of the lock arm 175 to force the lock arm 175 to pivot relative to the drive assembly 118 and lift the tab 179 from the notch 177, thereby unlocking the drive assembly 118 for future device operation.

[0064] With specific reference to FIG. 16, the drive assembly 118 further includes a needle configuration sensor 190 operably coupled to the first control unit 132A. The needle configuration sensor 190 senses the configuration or position of the transmission172 and provides a signal(s) representative of the configuration to the controller 124 (e.g., first control unit 132A), thereby permitting the controller 124 to determine the configuration of the first needle 120 and the second needle 122. More specifically, the first control unit 132A determines whether the first needle 120 and the second needle 122 are disposed in their first configurations, their second configurations, or an intermediate configuration based on the signal(s) from the sensor 190. The needle configuration sensor 190 may be, for example, an optical sensor that emits light toward and receives reflected light from the second intermediate gear 176. In the illustrative embodiment, the optical sensor senses the presence and absence of a partial circumferential wall 192 of the second intermediate gear 176 (see also FIG. 18) as the gear 176 rotates during extension and retraction, and the first control unit 132A thereby determines the angular configuration of the second intermediate gear 176. Based on the angular configuration of the second intermediate gear 176, the first control unit 132A determines the configurations of the first needle 120 and the second needle 122.

[0065] In the illustrative embodiment, the needle configuration sensor 190 includes a pair of optical gate sensors 190 (FIG. 16) arranged circumferentially on the circuit board in the rotational path of the second intermediate gear 176 and operating as first and second photo-interrupt gates to optically detect the angular position of the partial circumferential wall 192. This sensing arrangement is configured to detect four states or configurations of the mechanical drive assembly 118 as follows:Table 1 : States of Drive Assembly 118When the first sensor and second sensor both detect “open”, i.e., the partial circumferential wall 192 is absent from the view of each optical sensor, the control unit 132A determines the needles 120, 122 are retracted. When the first sensor detects “blocked” and the second sensor detects “open”, i.e., the partial circumferential wall 192 is present in the view of the first sensor but absent from the view of the second sensor, the control unit 132A determines the needles 120, 122 are in motion (intermediate state) but closer to the retracted position. When the first sensor and second sensor both detect “blocked”, i.e., the partial circumferential wall 192 is present in the view of each optical sensor, the control unit 132A determines the needles 120, 122 are in motion (intermediate state) but closer to the extended position. When the first sensor detects “open” and the second sensor detects “blocked”, i.e., the partial circumferential wall 192 is absent from the view of the first sensor but present in the view of the second sensor, the control unit 132A determines the needles 120, 122 are in the extended position. In this arrangement, the control unit 132A is configured to determine which direction the needles 120, 122 are moving (i.e., in the direction of retraction or extension) based on the progression of the detected states with the sensors 190. Other suitable sensor arrangements may be provided to detect various states of the drive assembly 118.E. Overall Device Operation

[0066] FIG. 19 illustrates a method of operating a drug delivery device according to an embodiment of the present disclosure. The following description of the method illustratively refers to the drug delivery device 100, components thereof, and the corresponding figures, although it is understood that the method may be used to operate any device contemplated by the present disclosure. The method begins at block 302 upon the controller 124 (FIG. 2) determining that the user input 104 (FIGS. 1 and 2) has been actuated and that the device 100 is properly positioned against the skin of the subject based on output from the skin sensor 126. In the illustrated embodiment, the controller 124 does not proceed to block 304 upon actuation of the user input 104 unless the device is positioned properly against the skin as determined via skin sensor 126. In one embodiment, the controller 124 may also be configured to require thetemperature detected with sensor 135 (FIG. 2) to reach a threshold prior to proceeding to block 304.

[0067] Next and at block 304, the controller 124 initiates a device check or initialization test by activating the pneumatic pressure source 108 (FIGS. 2-4), and the pneumatic pressure source 108 delivers pneumatic pressure to the sealed reservoir housing 110 (FIGS. 2-4) while the drive assembly 118 remains unactuated. With the drug reservoir 114 still fluidly isolated from the needle flow path of the drive assembly 118, the controller 124 monitors the pneumatic pressure, via the pressure sensor 128 (FIGS. 2-4), over a preset time window to detect a potential pneumatic leak in the reservoir housing 110. More specifically, the controller 124 may detect a pneumatic leak upon sensing a pressure decrease that exceeds a first threshold (or threshold rate) during the initialization procedure. In response to detecting a leak, the controller 124 recalibrates the device 100 (for example, by adjusting pressure cycles or parameter(s) of the end-of-dose calculation) before moving to block 306. Additional details of leak detection and device recalibration are provided below. Once the device recalibration is complete, or if no pneumatic leak is detected and thus no recalibration occurs, the method proceeds to block 306. In an exemplary embodiment, if the pressure leak detected at block 304 exceeds a higher second threshold, the controller 124 enters an error state and does not proceed with drug delivery, as described herein.

[0068] At block 306, the controller 124 activates the mechanical drive assembly 118 (FIGS. 2 and 15-18) to deploy the first needle 120 and the second needle 122. That is, the mechanical drive assembly 118 moves the second needle 122 from its first configuration (that is, being disposed apart from the second drive septum 168 and the reservoir septum 148) to its second configuration (that is, piercing the second drive septum 168 and the reservoir septum 148). The mechanical drive assembly 118 simultaneously moves the first needle 120 from its first configuration (that is, being completely positioned within the drive housing 165 and the device housing 102) to its second configuration (that is, piercing the first drive septum 166 and extending outwardly from the device housing 102 to pierce the skin of the subject). The drugreservoir 114 is thereby in fluid communication with the percutaneous space of the subject.

[0069] At block 308, the controller 124 again activates the pneumatic pressure source 108, and the pneumatic pressure source 108 applies pneumatic pressure to the external surface 112 of the flexible drug reservoir 114 (FIGS. 2-4). The pneumatic pressure compresses the flexible drug reservoir 114 and causes the drug to flow from the internal chamber 116 of the flexible drug reservoir 114, through the flow path of the drive assembly 118 (i.e., through the second needle 122, through the flexible conduit 164 (FIGS. 17-18), through the first needle 120), and into the percutaneous space of the subject. As discussed herein, controller 125 illustratively cycles the applied pressure with pressure source 108, for example by applying pressure pulses at intervals, to hold the air pressure level in the chamber 111 within a preset pressure range as the volume of drug exits the container 114 until dose completion.

[0070] At block 310 and while the device 100 delivers the drug to the subject, the controller 124 monitors parameters sensed by the pressure sensor 128 and the reservoir sensor 130 (FIG. 2) to determine when the device 100 has reached an end-of- dose state (that is, when the drug has been completely delivered, or a therapeutically effective of amount of the drug has been delivered, to the subject). Additional details of end-of-dose determination are provided below. Additionally, the controller 124 is configured to use the parameters sensed by the pressure sensor 128 and the reservoir sensor 130 to estimate the flow rate of the drug through the delivery path and to monitor for an occlusion in the delivery path (i.e., limited or no flow but the reservoir 114 is not near empty). In one embodiment, the flow rate estimation is further used by the controller 124 to adjust the applied pressure in the pressure chamber 111 to control / adjust the flow rate during delivery and also estimate the delivered drug volume, thereby providing a feedback loop in the delivery control program of the controller 124.

[0071] At block 312 and after determining that the device 100 has reached an end-of-dose state at block 310, the controller 124 causes the pneumatic pressuresource 108 to apply an increased pneumatic pressure pulse to the external surface 112 of the flexible drug reservoir 114. The increased pneumatic pressure facilitates additional delivery of any last amount of drug remaining in the reservoir 114.

[0072] At block 314, the controller 124 then activates the mechanical drive assembly 118 to retract the first needle 120 and the second needle 122. That is, the mechanical drive assembly 118 moves the second needle 122 from its second configuration (that is, piercing the reservoir septum 148 and the second drive septum 168) to its first configuration (that is, being disposed within the drive housing 165 apart from the reservoir septum 148 and the second drive septum 168). The mechanical drive assembly 118 simultaneously moves the first needle 120 from its second configuration (that is, extending outwardly from the device housing 102 and piercing the skin of the subject) to its first configuration (that is, being completely positioned within the device housing 102 and the drive housing 165).

[0073] The controller 124 may provide feedback to the user of the status of drug delivery such as with visual (e.g., illuminate a light-emitting diode (LED)), audible, or vibratory feedback, for example. In one embodiment, the controller 124 controls one or more LEDs that illuminate in various colors and / or audible / vibratory devices to indicate a device wake-up or “on” state, a ready-for-delivery state, a dose start state, a dosing active state, an end-of-dose state, and an error state, for example.

[0074] Retraction of the needles 120, 122 following end-of-dose detection provides “sharps protection” to shield the tip of the needle from the user following removal of the device 100 from the skin. Additionally, retraction of the needles 120, 122 may substantially reduce or stop fluid flow. If there is any liquid remaining in the flexible container 114 following end-of-dose detection, residual pressure may tend to push that liquid out the needle 120 once the backpressure of the subcutaneous space is removed (i.e., when the device 100 is removed from the body). While there should be minimal (if any) amount of drug remaining at the end of a completed delivery, there may be a significant amount of remaining drug in the container 114 if there is accidental ordeliberate removal of the device 100 prior to dose completion. Breaking the fluid path to the container 114 upon detection of end-of-dose or detection of device removal (via skin sensor 126) reduces the likelihood that any remaining drug contents are pushed out when the device 100 is removed from the user’s skin.F. End-of-Dose Detection

[0075] As described herein, the controller 124 monitors output from the pressure sensor 128 and / or the reservoir sensor 130 during drug delivery to determine when the device 100 has reached an end-of-dose state. Referring to FIG. 20, at block 316 the controller 124 monitors, via the pressure sensor 128, the pressure in the chamber 111 applied to the drug reservoir 114. At block 318, the controller 124 determines that the device 100 has reached the end-of-dose upon determining a specific change to the pressure applied to the drug reservoir 114 (or to a parameter derived from the pressure). Examples of such a pressure change are provided in detail herein.

[0076] Referring to FIG. 21 , at block 320, the controller 124 monitors, via the reservoir sensor 130, the configuration (for example, a shape) of the drug reservoir 114 during drug delivery. At block 322, the controller 124 determines that the device 100 has reached the end-of-dose upon determining a specific change to the configuration (for example, the shape) of the drug reservoir 114. Examples of such a configuration change are provided in detail herein.

[0077] In the illustrative embodiment, the controller 124 monitors parameter(s) based on the output signal from the pressure sensor 128 as a primary method of determining when the device 100 has reached an end-of-dose state, and the controller 124 monitors parameter(s) based on the output signal from the reservoir sensor 130 as an auxiliary or secondary method of determining when the device 100 has reached the end-of-dose state. The controller 124 may determine the end-of-dose state upon detecting specific changes to both the chamber pressure and the configuration / shape of the reservoir 114. The use of both primary and secondary technologies to detect end- of-dose may also enable differentiation by the controller 124 between end-of-dose andocclusion detection, thereby allowing the controller 124 to detect potential under-dose conditions.

[0078] For example, if the monitored pressure parameter via sensor 128 indicates end-of-dose, but the monitored optical parameter via sensor 130 does not indicate end-of-dose, the controller 124 may determine an occlusion in the flow path has occurred. If the pressure parameter and the optical parameter both indicate end-of- dose, the controller 124 may determine the end-of-dose state has been achieved. Other suitable arrangements may be provided. For example, in an alternative embodiment, the controller 124 determines that the device 100 has reached the end-of- dose state in response to determining the first of a specific parameter change to the pressure applied to the drug reservoir 114 and a specific parameter change to the configuration / shape of the drug reservoir 114.

[0079] FIG. 22 illustrates a plot of operating parameters versus time during operation of a drug delivery device 100 according to one exemplary embodiment of the present disclosure. The following description of the plot illustratively refers to the drug delivery device 100, components thereof, and the corresponding figures, although it is understood that the plot may be associated with any device contemplated by the present disclosure. Generally, the operating parameters include pressure parameters sensed by the pressure sensor 128 and optical parameters sensed by the reservoir sensor 130 (see, for example, FIG. 2). The operating parameters also include a pressure decay constant calculated with a pressure decay model using the sensed pressure over elapsed time. As described herein, these operating parameters are used by the controller 124 to determine the end-of-dose state of the device 100. Additional parameters or inputs that may be used by the controller 124 in conjunction with one or more of these operating parameters to determine end-of-dose include elapsed time of delivery, estimated flow rate or delivered volume, the detection of a pneumatic leak, temperature, and properties of the drug such as viscosity, for example.

[0080] During a start-up period 400 initiated by user input 104 (FIG. 1 ), the controller 124 executes the initialization and recalibration procedure. As described briefly above, the controller 124 may monitor pneumatic pressure via the sensor 128 during the start-up period 400 to detect a potential pneumatic leak. More specifically, during the start-up period 400 the controller 124 actuates the pressure source 108, and the pressure source 108 provides a specific pneumatic pressure to the pressure chamber 111. If the pneumatic pressure in the pressure chamber 111 subsequently decreases at a rate that exceeds a threshold rate, the controller 124 detects a pneumatic leak. In such cases, for example, the controller 124 may adjust the pressure decay model (e.g., the threshold decay constant) used to determine that the device 100 has reached an end-of-dose state. The controller 124 may also be configured to execute a larger number of pressure cycles (and / or shorter periods between cycles) to complete delivery when a leak is detected. In some embodiments, if the leak is determined to be substantial (i.e. , exceeds a higher second threshold), the controller 124 may indicate an error state and disable further operation of the device 100. The second threshold rate may be preset to correspond to a detected leak that is large enough that the pressure source 108 is likely unable to generate sufficient pressure in the chamber 111 to deliver the drug into a reasonable subcutaneous backpressure.

[0081] Following the start-up period 400, the controller 124 during a main operating period 402 cyclically actuates the pressure source 108, and the pressure source 108 thereby cyclically provides pneumatic pressure to the pressure chamber 111 to maintain the pressure in the chamber 111 with a target pressure range. As a result, during the main operating period 402 the pressure sensor 128 senses a pressure increase and a pressure decrease (i.e., due to drug outflow) each cycle, as illustrated with the sawtooth pattern of exemplary plot 410. The period between each pressure cycle may increase over time to maintain the pressure within the target range.

[0082] The pressure in the chamber 111 at a time t may be calculated based on the following exponential decay function:P = Poe~ct(1 ) wherein P is the instantaneous detected pressure, Po is the initial detected pressure for a cycle (for example, the maximum pressure following a pressurization cycle), t is the elapsed time of the cycle, and C is the decay constant. Based on the decay model of equation (1 ), the following equation for the decay constant may be obtained:

[0083] An exemplary decay constant is illustrated with plot 412 in FIG. 22. A lower decay constant C may indicate a slower pressure decay rate, and a higher decay constant may indicate a faster pressure decay rate. The controller 124 may estimate a drug delivery flow rate, or detect a decreasing flow rate, based on a decreasing decay constant C over the course of drug delivery. A particular value of the decay constant C may indicate to the controller 124 either an end-of-dose state or an occlusion state. In one embodiment, the controller 124 determines the end-of-dose or occlusion state when the calculated decay constant C (i.e. , the slope of the natural logarithm of (P / Po)) approaches zero, as this may indicate the flow has substantially stopped. Exemplary threshold values of the decay constant C may include about 0, 0.1 , 0.2, 0.3, 0.4, and 0.5 depending on device configuration, although any suitable threshold values of C may be used in the end-of-dose determination based on configuration. In some embodiments, the controller 124 detects air bubbles exiting the drug container 140 based on deviations or momentary spikes in the cyclical pattern of the decay constant.

[0084] With continued reference to FIG. 22, during the main operating period 402 the controller 124 via the reservoir sensor 130 also monitors a configuration (for example, a shape) of the flexible drug reservoir 114. The reservoir sensor 130 emits light into the reservoir 114 and senses light reflected by the reservoir 114, as discussed above with FIGS. 9-14. In one embodiment, the optical emitter(s) of sensor 130 are cycled to emit light pulses at intervals, and the optical receiver(s) of sensor 130 remain on throughout the cycle to read ambient light levels during the periods that the emitters are off. The controller 124 thereby is operative to separate the reflected light from theambient or background light in the signal to compensate for the ambient light. The controller 124 may recalibrate determination of the end-of-dose state to compensate for ambient light sensed by the reservoir sensor 130.

[0085] FIG. 22 shows an exemplary plot 414 illustrating the reflected light intensity (“lux”) detected with sensor 130 during drug delivery. In the illustrative embodiment, in response to determining a threshold increase in the reflected light intensity, the controller 124 determines that the flexible bag 140 has collapsed and thus the device 100 has reached an end-of-dose state (e.g., at 210 seconds in the examplary plot 414 of FIG. 22). More specifically, the controller 124 may determine that the device 100 has reached an end-of-dose state if the increase in lux exceeds a threshold. The threshold may be a target value of lux, a target percent increase, or a target rate of increase, for example. Such a threshold may be an absolute value or a value relative to a baseline. The baseline may be predetermined or calculated during operation. For example, the controller 124 may determine that the device 100 has reached an end-of- dose state if, following a decrease in reflected light intensity to a baseline value during delivery (for example, a minimum amount of reflected light during the main operating period 402), the reflected light intensity subsequently increases by a threshold amount relative to the baseline value. In an exemplary embodiment, the threshold amount is measured as a threshold percent increase, such as at least a 40 percent increase, at least a 50 percent increase, or at least a 60 percent increase for example, relative to the baseline value. Other suitable thresholds may be provided depending on device configuration.

[0086] After determining the device 100 has reached the end-of-dose state, the controller 124 increases the pressure in the chamber 111 for a predetermined duration to empty remaining fluid from the reservoir 114, as described above.

[0087] As discussed briefly above, the controller 124 is configured to estimate a drug flow rate during delivery based on the calculated decay constant C. The estimated flow rate and the time elapsed may be used by the controller 124 to estimate a totaldelivered drug volume as another data point to determine the present dose progress as well as that the end-of-dose state has been reached. In one embodiment, the controller 124 is programmed to determine the end-of-dose state in response to a detection that the pressure decay constant has reached a target value, the container 114 is in a collapsed state based on the detected light intensity reaching a target value, and the estimated delivered drug volume has reached a target delivery volume.G. Summary

[0088] Exemplary aspects of the present disclosure include the following:1 . A drug delivery device comprising: a housing; a mechanical drive assembly coupled to the housing, the mechanical drive assembly comprising a first needle, and the mechanical drive assembly configured to move the first needle from a first configuration to a second configuration; a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising an external surface and an internal chamber containing a drug; and a pneumatic pressure source coupled to the housing, the pneumatic pressure source being operable to apply pneumatic pressure to the external surface of the flexible drug reservoir to compress the flexible drug reservoir, wherein compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the first needle when the first needle is in the second configuration.2. The drug delivery device of aspect 1 , wherein the pneumatic pressure source comprises a pump.The drug delivery device of any of aspects 1 -2, wherein the first needle is positioned completely within the housing in the first configuration, and the first needle extends outwardly from the housing in the second configuration. The drug delivery device of any of aspects 1 -3, wherein the flexible drug reservoir comprises a septum, and the mechanical drive assembly further comprises a second needle in fluid communication with the first needle, wherein the second needle is disposed apart from the septum in the first configuration, and the second needle pierces the septum in the second configuration to allow the drug to flow from the flexible drug reservoir, through the second needle, and to the first needle. The drug delivery device of aspect 4, wherein the mechanical drive assembly further comprises: a first rack and pinion assembly operable to move the first needle from the first configuration to the second configuration; and a second rack and pinion assembly operable to move the second needle from the first configuration to the second configuration. The drug delivery device of aspect 5, wherein the mechanical drive assembly further comprises a motor operable to operate both the first rack and pinion assembly and the second rack and pinion assembly and thereby move both the first needle and the second needle from the first configuration to the second configuration. The drug delivery device of any of aspects 5-6, wherein the first needle and the second needle move substantially perpendicularly relative to each other from the first configuration to the second configuration.The drug delivery device of any of aspects 1-7, further comprising an electronic controller operably coupled to the mechanical drive assembly and the pneumatic pressure source. The drug delivery device of aspect 8, further comprising a pressure sensor coupled to the housing and operably coupled to the electronic controller, wherein the electronic controller is configured to determine an end-of-dose state upon determining a change to a pressure decay model of the pneumatic pressure applied to the external surface of the flexible drug reservoir and sensed by the pressure sensor. The drug delivery device of aspect 9, wherein the electronic controller is configured to calculate the natural logarithm of (P / Po), where Po is an initial pressure sensed by the pressure sensor and P is an instantaneous pressure sensed by the pressure sensor, and the electronic controller is configured to determine the end-of-dose state when the slope of the natural logarithm of (P / Po) approaches zero. The drug delivery device of any of aspects 9-10, wherein the electronic controller is configured, prior to determining the end-of-dose state, to determine the presence of a pneumatic leak in the drug delivery device. The drug delivery device of aspect 11 , wherein, upon determining the presence of the pneumatic leak in the drug delivery device, the electronic controller is configured to recalibrate determination of the end-of-dose state. The drug delivery device of any of aspects 9-12, wherein the pneumatic pressure source is operably coupled to the electronic controller, and the electronic controller is configured, upon determining the end-of-dose state, to cause thepneumatic pressure source to apply an increased pneumatic pressure to the external surface of the flexible drug reservoir. The drug delivery device of aspect 8, further comprising an optical sensor coupled to the housing and operably coupled to the electronic controller, wherein the electronic controller is configured to determine an end-of-dose state upon determining a configuration change of the flexible drug reservoir via the optical sensor. The drug delivery device of aspect 14, wherein the optical sensor is configured to emit light towards the flexible drug reservoir and sense light reflected by the flexible drug reservoir, and the electronic controller is configured to determine the end-of-dose state upon the optical sensor sensing an increase in light reflected by the flexible drug reservoir. The drug delivery device of any of aspects 14-15, wherein the flexible drug reservoir comprises: a port component coupled to the housing, and the optical sensor being coupled to the port component; and a flexible bag coupled to the port component, the flexible bag comprising the internal chamber of the flexible drug reservoir. The drug delivery device of any of aspects 1 -16, further comprising a pressure chamber coupled to the housing, the flexible drug reservoir disposed within the pressure chamber, and the pressure chamber being in fluid communication with the pneumatic pressure source and configured to receive pneumatic pressure.A method of operating a drug delivery device, the method comprising: actuating a mechanical drive assembly of the drug delivery device, wherein the mechanical drive assembly moves a first needle from a first configuration to a second configuration; and activating a pneumatic pressure source of the drug delivery device when the first needle is in the second configuration, wherein the pneumatic pressure source applies pneumatic pressure to an external surface of a flexible drug reservoir of the drug delivery device and thereby compresses the flexible drug reservoir and causes a drug to flow from an internal chamber of the flexible drug reservoir to the first needle. The method of aspect 18, wherein the pneumatic pressure source comprises a pump, and the pneumatic pump applies the pneumatic pressure to the external surface of the flexible drug reservoir of the drug delivery device and thereby compresses the flexible drug reservoir and causes the drug to flow from the internal chamber of the flexible drug reservoir to the first needle. The method of any of aspects 18-19, wherein the first needle is positioned completely within a housing of the drug delivery device in the first configuration, and the first needle extends outwardly from the housing in the second configuration. The method of any of aspects 18-20, wherein the flexible drug reservoir comprises a septum, and the mechanical drive assembly further comprises a second needle in fluid communication with the first needle, wherein actuating the mechanical drive assembly further comprises moving the second needle from the first configuration to the second configuration, the second needle being disposed apart from the septum in the first configuration, and the second needle piercingthe septum in the second configuration and causing the drug to flow from the flexible drug reservoir, through the second needle, and to the first needle. The method of aspect 21 , wherein the mechanical drive assembly further comprises a first rack and pinion assembly and a second rack and pinion assembly, and actuating the mechanical drive assembly further comprises moving the first needle from the first configuration to the second configuration via the first rack and pinion assembly and moving the second needle from the first configuration to the second configuration via the second rack and pinion assembly. The method of aspect 22, wherein the mechanical drive assembly further comprises a motor, and actuating the mechanical drive assembly further comprises moving both the first rack and pinion assembly and the second rack and pinion assembly via the motor and thereby moving both the first needle and the second needle from the first configuration to the second configuration. The method of any of aspects 22-23, wherein moving the first needle from the first configuration to the second configuration and moving the second needle from the first configuration to the second configuration comprises moving the first needle and the second needle substantially perpendicularly relative to each other. The method of any of aspects 18-24, wherein the drug delivery device further comprises an electronic controller operably coupled to the mechanical drive assembly and the pneumatic pressure source. The method of aspect 25, wherein the drug delivery device further comprises a pressure sensor operably coupled to the electronic controller, and the methodfurther comprises determining, via the electronic controller, an end-of-dose state upon determining a change to a pressure decay model of the pneumatic pressure applied to the external surface of the flexible drug reservoir and sensed by the pressure sensor. The method of aspect 26, further comprising calculating, via the electronic controller, the natural logarithm of (P / Po), where Po is an initial pressure sensed by the pressure sensor and P is an instantaneous pressure sensed by the pressure sensor, and determining, via the electronic controller, the end-of-dose state when the slope of the natural logarithm of (P / Po) approaches zero. The method of any of aspects 26-27, further comprising, prior to determining the end-of-dose state, determining the presence of a pneumatic leak in the drug delivery device, via the electronic controller, based upon the pressure sensor sensing an initial pressure decrease. The method of aspect 28, further comprising, upon determining the presence of the pneumatic leak in the drug delivery device, recalibrating, via the electronic controller, determination of the end-of-dose state. The method of any of aspects 26-29, wherein the pneumatic pressure source is operably coupled to the electronic controller, and further comprising applying an increased pneumatic pressure, via the electronic controller and the pneumatic pressure source, to the external surface of the flexible drug reservoir upon the electronic controller determining the end-of-dose state. The method of aspect 25, further comprising an optical sensor operably coupled to the electronic controller, and the method further comprises determining, via theelectronic controller, an end-of-dose state upon determining a configuration change of the flexible drug reservoir via the optical sensor. The method of aspect 31 , further comprising: emitting, via the optical sensor of the drug delivery device, light toward the flexible drug reservoir; and sensing, via the optical sensor of the drug delivery device, light reflected by the flexible drug reservoir; wherein determining the end-of-dose state further comprises determining, via the electronic controller, the end-of-dose state upon the optical sensor sensing an increase in light reflected by the flexible drug reservoir. The method of any of aspects 31 -32, wherein the flexible drug reservoir comprises: a port component, the optical sensor being coupled to the port component; and a flexible bag coupled to the port component, the flexible bag comprising the internal chamber of the flexible drug reservoir. A drug delivery device comprising: a housing; a needle coupled to the housing; a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising an external surface and an internal chamber containing a drug; a pneumatic pressure source coupled to the housing, the pneumatic pressure source being operable to apply pneumatic pressure to the external surface of the flexible drug reservoir to compress the flexible drug reservoir; an electronic controller coupled to the housing; and a pressure sensor coupled to the housing and operably coupled to the electronic controller;wherein compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle, and the electronic controller is configured to determine an end-of-dose state upon determining a change to a pressure decay model of the pneumatic pressure applied to the external surface of the flexible drug reservoir and sensed by the pressure sensor. The drug delivery device of aspect 34, wherein the electronic controller is configured to calculate the natural logarithm of (P / Po), where Po is an initial pressure sensed by the pressure sensor and P is an instantaneous pressure sensed by the pressure sensor, and the electronic controller is configured to determine the end-of-dose state when the slope of the natural logarithm of (P / Po) approaches a threshold value. The drug delivery device of any of aspects 34-35, wherein the electronic controller is configured, prior to determining the end-of-dose state, to determine the presence of a pneumatic leak in the drug delivery device. The drug delivery device of aspect 36, wherein, upon determining the presence of the pneumatic leak in the drug delivery device, the electronic controller is configured to recalibrate determination of the end-of-dose state. The drug delivery device of any of aspects 34-36, wherein the pneumatic pressure source includes a pneumatic pump operably coupled to the electronic controller, and the electronic controller is configured, upon determining the end- of-dose state, to cause the pneumatic pump to apply an increased pneumatic pressure to the external surface of the flexible drug reservoir.A method of operating a drug delivery device, the method comprising: activating a pneumatic pressure source of the drug delivery device, wherein the pneumatic pressure source applies pneumatic pressure to an external surface of a flexible drug reservoir of the drug delivery device to compress the flexible drug reservoir and causes a drug to flow from an internal chamber of the flexible drug reservoir to a needle of the drug delivery device; sensing, via a pressure sensor of the drug delivery device, the pneumatic pressure applied to the external surface of the flexible drug reservoir; and determining an end-of-dose state, via an electronic controller of the drug delivery device, in response to the electronic controller determining a change to a pressure decay model of the pneumatic pressure applied to the external surface of the flexible drug reservoir and sensed by the pressure sensor. The method of aspect 39, further comprising calculating, via the electronic controller, the natural logarithm of (P / Po), where Po is an initial pressure sensed by the pressure sensor and P is an instantaneous pressure sensed by the pressure sensor, and determining, via the electronic controller, the end-of-dose state when the slope of the natural logarithm of (P / Po) approaches a threshold value. The method of any of aspects 39-40, further comprising, prior to determining the end-of-dose state, determining the presence of a pneumatic leak in the drug delivery device, via the electronic controller, based upon the pressure sensor sensing an initial pressure decrease. The method of aspect 41 , further comprising, upon determining the presence of the pneumatic leak in the drug delivery device, recalibrating, via the electronic controller, determination of the end-of-dose state.The method of any of aspects 39-42, wherein the pneumatic pump is operably coupled to the electronic controller, and further comprising applying an increased pneumatic pressure, via the electronic controller and the pneumatic pump, to the external surface of the flexible drug reservoir upon the electronic controller determining the end-of-dose state. A drug delivery device comprising: a housing; a needle coupled to the housing; a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising an internal chamber containing a drug; a pressure source coupled to the housing, the pressure source being operable to apply pressure to the flexible drug reservoir; an electronic controller coupled to the housing; and an optical sensor coupled to the housing and operably coupled to the electronic controller, the optical sensor being configured to emit light toward the flexible drug reservoir and sense light reflected by the flexible drug reservoir; wherein an application of pressure to the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle, and the electronic controller is configured to determine an end-of- dose state in response to the optical sensor sensing an increase in light reflected by the flexible drug reservoir. The drug delivery device of aspect 44, wherein the electronic controller is configured to determine the end-of-dose state in response to determining that the increase in light reflected by the flexible drug reservoir and sensed by the optical sensor exceeds a threshold.The drug delivery device of aspect 44, wherein the electronic controller is configured to determine the end-of-dose state upon the optical sensor sensing at least a 50 percent increase in light reflected by the flexible drug reservoir compared to a baseline value. The drug delivery device of aspect 44, wherein the electronic controller is configured to determine the end-of-dose state following a decrease in light reflected by the flexible drug reservoir to a baseline value and a subsequent increase in light reflected by the flexible drug reservoir by a threshold amount greater than the baseline value. The drug delivery device of any of aspects 44-47, wherein the flexible drug reservoir comprises: a port component coupled to the housing, and the optical sensor being coupled to the port component; and a flexible bag coupled to the port component, the flexible bag comprising the internal chamber of the flexible drug reservoir. The drug delivery device of any of aspects 44-48, wherein the flexible drug reservoir comprises a transverse mid-plane, the optical sensor comprises a plurality of light emitters configured to emit light toward the flexible drug reservoir, and the plurality of light emitters are disposed in the transverse mid-plane. The drug delivery device of aspect 49, wherein the optical sensor further comprises a light receiver configured to sense light reflected by the flexible drug reservoir, the light receiver being disposed in transverse mid-plane.The drug delivery device of any of aspects 44-47, wherein the flexible drug reservoir comprises: a port component coupled to the housing, and the optical sensor being coupled to the port component; and a flexible bag coupled to the port component, the flexible bag comprising: a transverse mid-plane; a first sheet disposed on a first side of the transverse mid-plane; and a second sheet disposed on a second, opposite side of the transverse mid-plane; wherein the internal chamber of the flexible drug reservoir is disposed between the first sheet and the second sheet; wherein the optical sensor comprises a plurality of light emitters configured to emit light toward the flexible drug reservoir, and the plurality of light emitters are disposed in the transverse mid-plane. The drug delivery device of aspect 51 , wherein the optical sensor further comprises a light receiver configured to sense light reflected by the flexible drug reservoir, the light receiver being disposed in transverse mid-plane. The drug delivery device of any of aspects 44-48, wherein the optical sensor comprises a plurality of light emitters configured to emit green light toward the flexible drug reservoir. The drug delivery device of any of aspects 44-53, wherein the electronic controller is configured to detect one or more air bubbles in the internal chamber based on a change in the signal provided with the optical sensor and to ignore the one or more air bubbles in determining the end-of-dose state.A method of operating a drug delivery device, the method comprising: activating a pressure source of the drug delivery device, wherein the pressure source applies pressure to a flexible drug reservoir of the drug delivery device and thereby causes a drug to flow from an internal chamber of the flexible drug reservoir to a needle of the drug delivery device; emitting, via an optical sensor of the drug delivery device, light toward the flexible drug reservoir; sensing, via the optical sensor of the drug delivery device, light reflected by the flexible drug reservoir; and determining an end-of-dose state, via an electronic controller of the drug delivery device, in response to the optical sensor of the drug delivery device sensing an increase in light reflected by the flexible drug reservoir. The method of aspect 55, wherein determining the end-of-dose state, via the electronic controller of the drug delivery device, comprises determining that the increase in light reflected by the flexible drug reservoir and sensed by the optical sensor exceeds a threshold. The method of aspect 56, wherein determining that the increase in light reflected by the flexible drug reservoir and sensed by the optical sensor exceeds the threshold comprises determining an increase of at least 50 percent in light reflected by the flexible drug reservoir. The method of aspect 55, wherein determining the end-of-dose state, via the electronic controller of the drug delivery device, comprises detecting an initial decrease in light reflected by the flexible drug reservoir to a baseline value and a subsequent increase in light reflected by the flexible drug reservoir by a threshold amount greater than the baseline value.The method of any of aspects 55-57, wherein determining the end-of-dose state, via the electronic controller of the drug delivery device, comprises compensating for ambient light detected with the optical sensor. A drug delivery device comprising: a housing; a needle coupled to the housing; a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising an external surface and an internal chamber containing a drug; a pneumatic pump coupled to the housing, the pneumatic pump being operable to apply pneumatic pressure to the external surface of the flexible drug reservoir and thereby compress the flexible drug reservoir; an electronic controller coupled to the housing; and an optical sensor coupled to the housing and operably coupled to the electronic controller, the optical sensor being configured to sense a configuration of the flexible drug reservoir; wherein compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle, and the electronic controller is configured to determine an end-of-dose state in response to determining a configuration change of the flexible drug reservoir via the optical sensor. The drug delivery device of aspect 60, wherein the flexible drug reservoir comprises: a port component coupled to the housing, and the optical sensor being coupled to the port component; and a flexible bag coupled to the port component, the flexible bag comprising the internal chamber of the flexible drug reservoir.A method of operating a drug delivery device, the method comprising: activating a pneumatic pump of the drug delivery device, wherein the pneumatic pump applies pneumatic pressure to an external surface of a flexible drug reservoir of the drug delivery device and thereby causes a drug to flow from an internal chamber of the flexible drug reservoir to a needle of the drug delivery device; sensing, via an optical sensor of the drug delivery device, a configuration of the flexible drug reservoir; and determining an end-of-dose state, via an electronic controller of the drug delivery device, in response to determining a configuration change of the flexible drug reservoir via the optical sensor. A drug delivery device comprising: a housing; a needle coupled to the housing; a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising an external surface and an internal chamber containing a drug; a pneumatic pressure source coupled to the housing, the pneumatic pressure source being operable to apply pneumatic pressure to the external surface of the flexible drug reservoir and thereby compress the flexible drug reservoir; an electronic controller coupled to the housing; a pressure sensor coupled to the housing and operably coupled to the electronic controller; and an optical sensor coupled to the housing and operably coupled to the electronic controller; wherein compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle, and wherein the electronic controller is configured to determine an end-of-dosestate in response to (1 ) determining a change to a pressure decay model of the pneumatic pressure applied to the flexible drug reservoir and sensed by the pressure sensor, and (2) determining a configuration change of the flexible drug reservoir via the optical sensor. The drug delivery device of aspect 63, wherein the electronic controller is configured to calculate a decay constant of the pressure decay model based on an initial pressure sensed by the pressure sensor and an instantaneous pressure sensed by the pressure sensor, and wherein the electronic controller is configured to determine the end-of-dose state in response to the decay constant approaching a threshold value. The drug delivery device of any of aspects 63 and 64, wherein, prior to initiating drug delivery from the flexible drug reservoir, the electronic controller is configured to detect a decrease in the pressure applied to the external surface of the flexible drug reservoir to determine the presence of a pneumatic leak in the drug delivery device. The drug delivery device of aspect 65, wherein, upon determining the presence of the pneumatic leak in the drug delivery device, the electronic controller is configured to recalibrate determination of the end-of-dose state. The drug delivery device of any of aspects 63-66, wherein the pneumatic pressure source is operably coupled to the electronic controller, and the electronic controller is configured, upon determining the end-of-dose state, to cause the pneumatic pressure source to apply an increased pneumatic pressure to the external surface of the flexible drug reservoir.The drug delivery device of any of aspects 63-67, wherein the optical sensor is configured to emit light toward the flexible drug reservoir and sense light reflected by the flexible drug reservoir, and wherein the electronic controller is configured to determine the end-of-dose state in response to the optical sensor sensing an increase in light reflected by the flexible drug reservoir. The drug delivery device of any of aspects 63-68, wherein the pneumatic pressure source is a pump. A method of operating a drug delivery device, the method comprising: activating a pneumatic pressure source of the drug delivery device, wherein the pneumatic pressure source applies pneumatic pressure to an external surface of a flexible drug reservoir of the drug delivery device to cause a drug to flow from an internal chamber of the flexible drug reservoir to the needle of the drug delivery device; sensing, via a pressure sensor of the drug delivery device, the pneumatic pressure applied to the external surface of the flexible drug reservoir; sensing, via an optical sensor of the drug delivery device, a configuration of the flexible drug reservoir; and determining an end-of-dose state, via an electronic controller of the drug delivery device, in response to (1 ) determining a change to a pressure decay model of the pneumatic pressure applied to the external surface of the flexible drug reservoir and sensed by the pressure sensor, and (2) determining a configuration change of the flexible drug reservoir via the optical sensor. The method of aspect 70, further comprising calculating, via the electronic controller, a decay constant of the pressure decay model based on an initial pressure sensed by the pressure sensor and an instantaneous pressure sensedby the pressure sensor, wherein determining the change to the pressure decay model comprises determining the decay constant approaches a threshold value. The method of any of aspects 70-71 , further comprising, prior to causing the drug to flow from the internal chamber, determining the presence of a pneumatic leak in the drug delivery device, via the electronic controller, based upon the pressure sensor sensing an initial pressure decrease. The method of any of aspects 70-72, further comprising, upon determining the presence of the pneumatic leak in the drug delivery device, recalibrating, via the electronic controller, determination of the end-of-dose state. The method of any of aspects 70-73, wherein the pneumatic pressure source is operably coupled to the electronic controller, and further comprising applying an increased pneumatic pressure, via the electronic controller and the pneumatic pressure source, to the external surface of the flexible drug reservoir upon the electronic controller determining the end-of-dose state. The method of any of aspects 70-74, further comprising: emitting, via the optical sensor of the drug delivery device, light toward the flexible drug reservoir; and sensing, via the optical sensor of the drug delivery device, light reflected by the flexible drug reservoir; wherein determining the end-of-dose state further comprises determining, via the electronic controller, the end-of-dose state upon the optical sensor sensing an increase in light reflected by the flexible drug reservoir. The method of any of aspects 70-75, wherein the pneumatic pressure source is a pump.A drug delivery device comprising: a housing; a needle coupled to the housing; a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising: a transverse mid-plane; a first sheet disposed on a first side of the transverse mid-plane; a second sheet disposed on a second, opposite side of the transverse mid-plane; and an internal chamber disposed between the first sheet and the second sheet, the internal chamber containing a drug; an electronic controller coupled to the housing; and an optical sensor coupled to the housing and operably coupled to the electronic controller, the optical sensor comprising a plurality of light emitters configured to emit light toward the flexible drug reservoir, the plurality of light emitters being disposed in the transverse mid-plane, and the optical sensor being configured to sense light reflected by the flexible drug reservoir; wherein compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle, and the electronic controller is configured to determine an end-of-dose state in response to the optical sensor sensing an increase in light reflected by the flexible drug reservoir. A drug delivery device comprising: a housing; a needle coupled to the housing;a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising an external surface and an internal chamber containing a drug; a pneumatic pressure source coupled to the housing, the pneumatic pressure source being operable to apply pneumatic pressure to the external surface of the flexible drug reservoir and thereby compress the flexible drug reservoir; an electronic controller coupled to the housing and operably coupled to the pneumatic pressure source; and a pressure sensor coupled to the housing and operably coupled to the electronic controller, wherein compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle, and wherein the electronic controller is configured to determine the presence of a pneumatic leak in the drug delivery device based on a pressure decrease sensed by the pressure sensor. A drug delivery device comprising: a housing; a needle coupled to the housing; a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising an external surface and an internal chamber containing a drug; a pneumatic pressure source coupled to the housing, the pneumatic pressure source being operable to apply pneumatic pressure to the external surface of the flexible drug reservoir and thereby compress the flexible drug reservoir; and an electronic controller coupled to the housing and operably coupled to the pneumatic pressure source; wherein compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the needle, andwherein the electronic controller is configured to determine an end-of-dose state and, upon determining the end-of-dose state, cause the pneumatic pressure source to apply an increased pneumatic pressure to the external surface of the flexible drug reservoir.

[0089] While this invention has been described as having exemplary designs, the present invention can be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the invention using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims.

Claims

WHAT IS CLAIMED IS:1 . A drug delivery device comprising: a housing; a mechanical drive assembly coupled to the housing, the mechanical drive assembly comprising a first needle, and the mechanical drive assembly configured to move the first needle from a first configuration to a second configuration; a flexible drug reservoir coupled to the housing, the flexible drug reservoir comprising an external surface and an internal chamber containing a drug; and a pneumatic pressure source coupled to the housing, the pneumatic pressure source being operable to apply pneumatic pressure to the external surface of the flexible drug reservoir to compress the flexible drug reservoir, wherein compression of the flexible drug reservoir causes the drug to flow from the internal chamber of the flexible drug reservoir to the first needle when the first needle is in the second configuration.

2. The drug delivery device of claim 1 , wherein the pneumatic pressure source comprises a pump.

3. The drug delivery device of any of claims 1-2, wherein the first needle is positioned completely within the housing in the first configuration, and the first needle extends outwardly from the housing in the second configuration.

4. The drug delivery device of any of claims 1 -3, wherein the flexible drug reservoir comprises a septum, and the mechanical drive assembly further comprises a second needle in fluid communication with the first needle, wherein the second needle is disposed apart from the septum in the first configuration, and the second needle pierces the septum in the second configuration to allow the drugto flow from the flexible drug reservoir, through the second needle, and to the first needle.

5. The drug delivery device of claim 4, wherein the mechanical drive assembly further comprises: a first rack and pinion assembly operable to move the first needle from the first configuration to the second configuration; and a second rack and pinion assembly operable to move the second needle from the first configuration to the second configuration.

6. The drug delivery device of claim 5, wherein the mechanical drive assembly further comprises a motor operable to operate both the first rack and pinion assembly and the second rack and pinion assembly and thereby move both the first needle and the second needle from the first configuration to the second configuration.

7. The drug delivery device of any of claims 5-6, wherein the first needle and the second needle move substantially perpendicularly relative to each other from the first configuration to the second configuration.

8. The drug delivery device of any of claims 1-7, further comprising an electronic controller operably coupled to the mechanical drive assembly and the pneumatic pressure source.

9. The drug delivery device of claim 8, further comprising a pressure sensor coupled to the housing and operably coupled to the electronic controller, wherein the electronic controller is configured to determine an end-of-dose state upon determining a change to a pressure decay model of the pneumatic pressureapplied to the external surface of the flexible drug reservoir and sensed by the pressure sensor.

10. The drug delivery device of claim 9, wherein the electronic controller is configured to calculate the natural logarithm of (P / Po), where Po is an initial pressure sensed by the pressure sensor and P is an instantaneous pressure sensed by the pressure sensor, and the electronic controller is configured to determine the end-of-dose state when the slope of the natural logarithm of (P / Po) approaches zero.11 . The drug delivery device of any of claims 9-10, wherein the electronic controller is configured, prior to determining the end-of-dose state, to determine the presence of a pneumatic leak in the drug delivery device.

12. The drug delivery device of claim 11 , wherein, upon determining the presence of the pneumatic leak in the drug delivery device, the electronic controller is configured to recalibrate determination of the end-of-dose state.

13. The drug delivery device of any of claims 9-12, wherein the pneumatic pressure source is operably coupled to the electronic controller, and the electronic controller is configured, upon determining the end-of-dose state, to cause the pneumatic pressure source to apply an increased pneumatic pressure to the external surface of the flexible drug reservoir.

14. The drug delivery device of claim 8, further comprising an optical sensor coupled to the housing and operably coupled to the electronic controller, wherein the electronic controller is configured to determine an end-of-dose state upon determining a configuration change of the flexible drug reservoir via the optical sensor.

15. The drug delivery device of claim 14, wherein the optical sensor is configured to emit light towards the flexible drug reservoir and sense light reflected by the flexible drug reservoir, and the electronic controller is configured to determine the end-of-dose state upon the optical sensor sensing an increase in light reflected by the flexible drug reservoir.

16. The drug delivery device of any of claims 14-15, wherein the flexible drug reservoir comprises: a port component coupled to the housing, and the optical sensor being coupled to the port component; and a flexible bag coupled to the port component, the flexible bag comprising the internal chamber of the flexible drug reservoir.

17. The drug delivery device of any of claims 1-16, further comprising a pressure chamber coupled to the housing, the flexible drug reservoir disposed within the pressure chamber, and the pressure chamber being in fluid communication with the pneumatic pressure source and configured to receive pneumatic pressure.

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