Drug delivery systems and methods of use

Abstract

Systems and methods for use with drug delivery devices relating to controlling the drug delivery device and communicating information obtained from the drug delivery device are provided. A drug delivery system is disclosed that includes a drug delivery device having a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient. The drug delivery system may further include one or more sensors coupled to the drug delivery device, a wireless transmitter, and a controller coupled to the one or more sensors and the wireless transmitter. The controller may be configured to determine a condition or operating state of the drug delivery device using the one or more sensors and to control the wireless transmitter to wirelessly transmit one or more reports representing the condition or operating state of the drug delivery device.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS The benefit of priority is claimed from U.S. Provisional Patent Application No. 62 / 007,007, filed June 3, 2014, the entire contents of which are expressly incorporated herein by reference.

[0002] This patent relates to systems and methods for use with drug delivery devices relating to the control of the drug delivery device and the communication of information obtained from the drug delivery device. [Background technology]

[0003] Drugs can be administered through the use of drug delivery devices, such as autoinjectors or on-body injectors or syringes. These devices can replace older delivery systems that use syringe / drug or medication vial combinations or pre-filled syringes. Autoinjectors and on-body injectors can be used to automate the injection and delivery or administration process, thereby simplifying the process for certain patient populations or subgroups who, for physiological or psychological reasons, would be disadvantaged by the use of syringe / vial combinations or pre-filled syringe systems.

[0004] Even when using a drug delivery device such as an autoinjector, patients may experience difficulties during the initial use of the drug delivery device after being prescribed a drug to be delivered or administered using the drug delivery device. For example, a user may be unsure whether the drug in the drug delivery device is the drug prescribed for them. Furthermore, a user may be unsure whether the drug has expired. Furthermore, a user may be unsure whether an injection should be delayed after the drug delivery device is removed from refrigeration, such as in a refrigerator, and if so, how long. A user may also be unsure whether the actions and their sequence are correct to operate the drug delivery device. Even if the correct actions are performed in the correct order, a user may be unsure whether the drug has been fully delivered to complete the injection.

[0005] Other patients may experience difficulties in adhering to or complying with a treatment regimen. For example, certain patients may completely forget to inject and not inject according to the treatment regimen. Other patients may inject but then be distracted before being able to record that they inject and cannot remember whether they did so. Some patients may choose not to inject due to misunderstandings or miscommunication about when or how the drug acts on the patient's disease or symptoms, especially if the effect is not felt by the patient until a significant portion of the treatment regimen has been administered. Some patients may need support and / or encouragement from others (such as healthcare providers, caregivers, family members, etc.), and are unable to provide this support and / or encouragement because the people providing the support and / or encouragement do not know whether the patient has administered the treatment or is correctly following the treatment regimen.

[0006] Additionally, the status and use of drug delivery devices is important to other parties, such as drug device manufacturers, pharmacies, healthcare providers, and insurers. For example, information about the status of drug delivery devices along the supply chain may be relevant to whether the drug delivery device is in working order for use with patients when it arrives. Information about the location of drug delivery devices along the supply chain may be relevant to manufacturers and pharmacies to ensure pharmacies have sufficient inventory to deliver to users. The adherence information mentioned above may be important to healthcare providers and insurers, as well as to patients, because adherence to a treatment regimen can directly impact the success of treatment.

[0007] As described in further detail below, the present disclosure describes a drug delivery system that embodies a beneficial alternative to existing drug delivery devices and may address one or more of the difficulties or needs referenced above. Summary of the Invention

[0008] According to certain aspects of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end received within a patient. The drug delivery system also includes one or more sensors coupled to the drug delivery device, a wireless transmitter, and a controller coupled to the one or more sensors and the wireless transmitter. The controller can be configured to determine a condition or operating state of the drug delivery device using the one or more sensors and control the wireless transmitter to wirelessly transmit one or more reports representative of the condition or operating state of the drug delivery device.

[0009] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient, and a removable sterile barrier disposed around the distal end of the delivery cannula. The drug delivery system also includes a first sensor configured to detect movement of the removable sterile barrier, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to use the first sensor to determine whether the removable sterile barrier has been removed from the distal end of the delivery cannula, and, if the removable sterile barrier has been removed from the distal end of the delivery cannula, control the wireless transmitter to wirelessly transmit a report indicating the removal of the removable sterile barrier.

[0010] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient, and an actuator configured to actuate the drug delivery device. The drug delivery system also includes a first sensor configured to detect movement of the actuator, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to use the first sensor to determine whether the actuator has been used to actuate the drug delivery device, and, if the actuator has been used, control the wireless transmitter to wirelessly transmit a report indicating the actuation of the drug delivery device.

[0011] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end received within a patient, and a needle shield movable relative to the distal end of the delivery cannula. The drug delivery system also includes a first sensor configured to detect movement of the needle shield, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to use the first sensor to determine whether the needle shield has been moved relative to the distal end of the delivery cannula, and, if the needle shield has been moved relative to the distal end of the delivery cannula, control the wireless transmitter to wirelessly transmit a report indicating insertion of the distal end of the delivery cannula into the patient.

[0012] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end received within a patient, and a needle shield movable relative to the distal end of the delivery cannula. The drug delivery system also includes a first sensor configured to detect movement of the needle shield, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to use the first sensor to determine whether the needle shield is disposed around the distal end of the delivery cannula, and, when the needle shield is disposed around the distal end of the delivery cannula, control the wireless transmitter to wirelessly transmit a report indicating completion of delivery of the drug from the reservoir to the patient.

[0013] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end received within a patient, and a plunger movable through the reservoir to release a medication from the reservoir. The drug delivery system also includes a first sensor configured to detect movement of the plunger, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to use the first sensor to determine whether the plunger has completed a delivery stroke, and, when a needle shield is disposed around the distal end of the delivery cannula, control the wireless transmitter to wirelessly transmit a report indicating completion of delivery of the medication from the reservoir to the patient.

[0014] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for receipt within a patient, and a plunger movable through the reservoir to release a medication from the reservoir. The drug delivery system also includes a first sensor configured to detect movement of the plunger, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to determine a distance traveled by the plunger using the first sensor and to control the wireless transmitter to wirelessly transmit a report indicating an amount of medication delivered from the reservoir to the patient based on the distance traveled by the plunger.

[0015] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for receipt within a patient. The drug delivery system also includes a first sensor configured to detect the presence or absence of fluid in the reservoir, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to determine an amount of drug remaining in the reservoir using the first sensor and control the wireless transmitter to wirelessly transmit a report indicating an amount of drug delivered from the reservoir to the patient based on the amount of drug remaining in the reservoir.

[0016] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end received within a patient, and a housing having an opening for the distal end of the delivery cannula. The drug delivery system also includes a first sensor configured to detect contact between the housing and an object, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to use the first sensor to determine whether the housing is in contact with the patient and to control the wireless transmitter to wirelessly transmit a report indicative of contact between the housing and the patient.

[0017] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient. The drug delivery system also includes a first sensor configured to detect a temperature of the drug in the reservoir, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to use the first sensor to determine whether the temperature of the drug is above or below a threshold temperature and to control the wireless transmitter to wirelessly transmit a report indicating the suitability of the drug for delivery to the patient.

[0018] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device comprising a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient. The drug delivery system also includes a first sensor configured to detect a geographic location of the drug delivery device, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to determine the geographic location of the drug delivery device using the first sensor and control the wireless transmitter to wirelessly transmit a report representing the geographic location of the drug delivery device.

[0019] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for receipt within a patient. The drug delivery system also includes a first sensor configured to detect an orientation of the delivery cannula, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to use the first sensor to determine whether the delivery cannula is oriented to deliver a drug in the reservoir to the patient and to control the wireless transmitter to wirelessly transmit a report indicating proper or improper orientation of the delivery cannula to deliver the drug to the patient.

[0020] According to another aspect of the present disclosure, a drug delivery system includes a drug delivery device including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for reception within a patient, and a battery. The drug delivery system also includes a first sensor configured to detect a charge level of the battery, a wireless transmitter, and a controller coupled to the first sensor and the wireless transmitter. The controller may be configured to determine a charge level of the battery using the first sensor and control the wireless transmitter to wirelessly transmit a report representing the charge level of the battery.

[0021] According to a further aspect of the present disclosure, there is provided a method of using a drug delivery system including a reservoir, a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end for receipt within a patient, and a removable sterile barrier disposed around a second end of the delivery cannula, the method including determining whether the removable sterile barrier has been removed from the distal end of the delivery cannula, and if the removable sterile barrier has been removed from the distal end of the delivery cannula, transmitting a report indicating the removal of the removable sterile barrier. [Brief explanation of the drawings]

[0022] It is believed that the present disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the figures may be simplified by the omission of selected elements for the purpose of more clearly showing other elements. Such omission of elements in some figures does not necessarily indicate the presence or absence of the particular element in any of the example embodiments, except as may be explicitly depicted in the corresponding written description. None of the drawings are necessarily to scale.

[0023] [Figure 1] 1 is a schematic diagram of a drug delivery system in communication with one or more computing devices and one or more networks, according to an embodiment of the present disclosure. [Figure 2] 2 is a block diagram of a method of operating the drug delivery system shown in FIG. 1 according to an embodiment of the present disclosure. [Figure 3A] FIG. 2 is a block diagram of a method of operating the drug delivery system shown in FIG. 1 according to another embodiment of the present disclosure. [Figure 3B] FIG. 2 is a block diagram of a method of operating the drug delivery system shown in FIG. 1 according to another embodiment of the present disclosure. [Figure 3C] FIG. 2 is a block diagram of a method of operating the drug delivery system shown in FIG. 1 according to another embodiment of the present disclosure. [Figure 4] FIG. 2 is a block diagram of a method of operating a computing device such as that shown in FIG. 1 according to an embodiment of the present disclosure, the computing device being in communication with, for example, a drug delivery system operating according to one of the methods disclosed herein. [Figure 5] FIG. 10 is a block diagram of a method of operating a drug delivery system according to another embodiment of the present disclosure. [Figure 6] FIG. 10 is a block diagram of a method of operating a drug delivery system according to a further embodiment of the present disclosure. [Figure 7]7 is a block diagram of a method of operating a computing device according to an embodiment of the present disclosure, the computing device being in communication with a drug delivery system operating according to the method of FIG. 6, for example. [Figure 8] FIG. 10 is a block diagram of a method performed by a drug delivery system according to another embodiment of the present disclosure. [Figure 9] 9 is a partial cross-sectional view illustrating an embodiment of a system used to implement the method of FIG. 8. [Figure 10] FIG. 10 is a block diagram of a method performed by a drug delivery system according to yet another embodiment of the present disclosure. [Figure 11] FIG. 10 is a block diagram of a method performed by a drug delivery system according to a further embodiment of the present disclosure. [Figure 12A] FIG. 12 is a schematic diagram of an embodiment of a system used to implement the method of FIG. 11. [Figure 12B] FIG. 12 is a schematic diagram of an embodiment of a system used to implement the method of FIG. 11. [Figure 13] 1 is a cross-sectional view of an embodiment of a drug delivery system including an automatic injection device. [Figure 13A] FIG. 14 is a cross-sectional view of an alternative cannula subassembly for the drug delivery system of FIG. 13. [Figure 14] 1 is a perspective view of an embodiment of a drug delivery system including an on-body infusion device. [Figure 15] 15 is a cross-sectional view of the drug delivery device of FIG. 14 taken along section line 15-15. [Figure 16] 16 is a cross-sectional view of the drug delivery device of FIG. 14 taken along section line 16-16. [Figure 17] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device. [Figure 18A] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device. [Figure 18B] FIG. 18b is a top view of the needle shield of the autoinjector of FIG. 18a positioned in a distal position. [Figure 18C]FIG. 18b is a top view of the needle shield of the autoinjector of FIG. 18a in the proximal position. [Figure 19] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device. [Figure 20] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device. [Figure 21A] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device with incomplete drug delivery. [Figure 21B] FIG. 21b is a cross-sectional view of the drug delivery system of FIG. 21a with drug delivery partially completed. [Figure 21C] FIG. 21b is a cross-sectional view of the drug delivery system of FIG. 21a after drug delivery has been completed. [Figure 22A] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device with incomplete drug delivery. [Figure 22B] FIG. 22b is a cross-sectional view of the drug delivery system of FIG. 22a after drug delivery has been completed. [Figure 22C] FIG. 22c is a close-up view of a sensor used in the drug delivery system of FIGS. 22a and 22b. [Figure 23A] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device. [Figure 23B] FIG. 23b is a circuit diagram depicting the controller and sensors used by the drug delivery system of FIG. 23a. [Figure 24A] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device with incomplete drug delivery. [Figure 24B] FIG. 24b is a cross-sectional view of the drug delivery system of FIG. 24a after drug delivery is complete. [Figure 25A] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device with incomplete drug delivery. [Figure 25B] FIG. 25b is a cross-sectional view of the drug delivery system of FIG. 25a after drug delivery is complete. [Figure 26] [Figure 26A]1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device with incomplete drug delivery. [Figure 26B] 26b is a cross-sectional view of the autoinjector of FIG. 26a taken along line BB. [Figure 27C] FIG. 26b is a cross-sectional view of the drug delivery system of FIG. 26a with drug delivery partially completed. [Figure 27D] FIG. 26b is a cross-sectional view of the drug delivery system of FIG. 26a after drug delivery is complete. [Figure 27E] FIG. 27 is a circuit diagram depicting the controller and sensors used by the drug delivery system of FIGS. 27a-d. [Figure 28] 1 is a cross-sectional view of another embodiment of a drug delivery system including an automatic injection device. [Figure 29A] 1 is a cross-sectional view of another embodiment of a drug delivery system including an autoinjector prior to contact with a patient. [Figure 29B] FIG. 29b is a cross-sectional view of the drug delivery system of FIG. 29a during contact with a patient. [Figure 30A] FIG. 1 is a perspective view of another embodiment of a drug delivery system including an on-body infusion device. [Figure 30B] FIG. 30a is another perspective view of the drug delivery system. [Figure 31] FIG. 10 is a perspective view of a drug delivery system according to a further embodiment of the present disclosure including a removable anti-rotational sterility barrier. [Figure 32] FIG. 32 is an assembly view of the anti-rotation removable sterility barrier of FIG. 31. [Figure 33] 1 is a cross-sectional view of an embodiment of a removable sterility barrier attached to a housing of a drug delivery device. [Figure 34] FIG. 33 is a cross-sectional view of the removable sterility barrier of FIG. 32 after removal from the housing of the drug delivery device. DETAILED DESCRIPTION OF THE INVENTION

[0024] The present disclosure is directed to systems including drug delivery devices and methods for using drug delivery systems. Specifically, the systems and methods involve determining one or more conditions, which may be determined using one or more sensors in combination with one or more controllers. The sensors may rely on mechanical, electrical, or chemical sensing methods, and the controllers may be mechanical, electrical, or electromechanical. By way of example and not limitation, the conditions may relate to the operation of the drug delivery device or a condition of the drug delivery device. The systems and methods may use the condition determination to control the operation of the drug delivery device and / or communicate the condition determination to another device, such as a third-party server, which may collect, process, and / or further disseminate the condition determination received from a system including the drug delivery device, one or more sensors, and one or more controllers. Additionally or alternatively, the systems and methods may communicate the condition determination to a local device, such as a mobile computing device (e.g., a mobile phone).

[0025] A drug delivery system according to the present disclosure may include a drug delivery device having a reservoir (which may also be referred to as a primary container, e.g., a syringe, vial, or cartridge). The reservoir may contain a drug, which may also be referred to as a medicine or agent. The drug may be, but is not limited to, various biologics, such as peptides, peptibodies, or antibodies. The drug may be in fluid or liquid form, although the present disclosure is not limited to a particular state (e.g., it does not intend to distinguish between solutions, gels, or lyophilized formulations). The drug delivery device also includes a delivery cannula having a first end connected to or connectable in fluid communication with the reservoir and a second end inserted into the patient. As used herein, the term "delivery cannula" or "cannula" is defined herein to mean a tube that can be inserted into the body for delivery of a fluid. The cannula may include, by way of example and not limitation, a rigid or semi-rigid needle or a blunt cannula, or may be flexible. The cannula may be integrated with other elements of the drug delivery device, or the cannula may be separate from other elements of the drug delivery device until immediately prior to use. According to certain embodiments, the drug delivery device may further include an inserter for introducing the second end into the patient, although this is not required according to each embodiment of the present disclosure. The inserter may or may not be retracted within the device, thereby leaving the cannula in the patient.

[0026] In view of the foregoing description of drug delivery devices, the devices may be considered autoinjectors or on-body injectors, or injectors (reference to an injector is intended to also include reference to an injector to the extent a distinction is suggested). Autoinjectors may be single-use devices that administer a single dose during a single application of the device to the user's skin, but autoinjectors are not limited to single-use devices; they may also be multi-use devices. On-body injectors may be multi-use devices that administer multiple doses during one or more applications of the device to the user's skin, but on-body devices may also be used as single-use devices. Either autoinjectors or on-body injectors may have assemblies or subassemblies that are reusable, where the assembly can be used and reused, for example, by refilling the reservoir, removing an empty reservoir and replacing it with a filled reservoir, or by changing the cannula.

[0027] As noted above, a system or method according to the present disclosure determines one or more conditions associated with a drug delivery device.

[0028] For example, the system or method may determine whether the drug delivery device is in one or more operational states (i.e., states associated with the operation of the drug delivery device to deliver a drug to a patient). A non-exhaustive list of general operational states may include: (i) a packaged / ready for distribution operational state; (ii) a packaged / distributed operational state; (iii) an unpackaged / ready for administration operational state; (iv) a sterility barrier removed operational state; (v) a device applied operational state; (vi) a cannula injected (or inserted) operational state; (vii) a drug delivery initiated operational state; (viii) a drug delivery completed operational state; and (ix) a device removed operational state. The system or method may determine a specific operational state within each general operational state; for example, the system or method may determine whether the plunger has moved from a first end of the bore (defining the drug reservoir) to a second end of the bore to determine whether the drug delivery device is in a “drug delivery completed” state.

[0029] Additionally, the system or method may determine whether the drug delivery device is in one or more condition states (i.e., states related to the condition of the drug delivery device that are not necessarily related to the operation of the drug delivery device to deliver a drug to a patient). A non-exhaustive list of condition states may include: (i) product age (e.g., relative to date of manufacture or expiration date), (ii) sterilization / contamination, (iii) temperature (or temperature history), and (iv) orientation. Determining a condition state may be considered part of determining an operational state; for example, determining a temperature state may be considered part of a "ready to administer" state. Alternatively, the operational conditions and condition states may be determined separately.

[0030] These states may be determined through the use of one or more sensors. The sensor may be specific to the condition state being determined; for example, a thermocouple disposed adjacent to the reservoir may be used to determine the temperature state of the drug delivery device. The sensor may also be specific to the operating state being determined; for example, to determine the "sterility barrier removed" operating state, a switch may be coupled to the needle protection device to determine when the needle cap is removed, the switch opening when the needle cap is disposed on the second end of the cannula, and the switch closing when the needle protection device is not disposed on the second end of the cannula. Sensors may be used to determine both the condition state and the operating state; for example, a thermocouple may be used to determine the temperature condition state of the device (or more specifically, the drug) and / or a thermocouple may be used to determine the "ready to administer" operating state.

[0031] The system or method may use the determined condition to control operation of the drug delivery device. For example, the system may include a controller coupled to the sensor and may be coupled to one or more of the above-mentioned drug delivery device assemblies or subassemblies, or to one or more additional assemblies or subassemblies of the drug delivery device. The controller may be structurally adapted, or (if electrical or electromechanical) programmed, to activate or inhibit these assemblies or subassemblies according to the determined condition. For example, the drug delivery device may include a lockout that limits or completely inhibits operation of the injection device, and the controller may activate the lockout in a reversible manner when the temperature condition of the drug delivery device (and particularly the drug in the reservoir) is below a threshold condition.

[0032] The system or method may communicate the determined status(ies) to another device or system, and this communication may be in conjunction with using the determined status(ies) to control the operation of the drug delivery device. For example, the system or method may communicate the determined status(ies) to a networked device using a communication link. In this sense, a networked device is intended to include any device that communicates with at least one other device over a communication link, and may include communication with devices such as a mobile device (e.g., a mobile phone or mobile computing device) using a Bluetooth® connection or a computing device using a Wi-Fi connection. The networked device may communicate the determined status to another computing device remote from the drug delivery system via a network that includes a networked device such as a server. According to certain embodiments of the present disclosure, the system communicates directly with the network (i.e., without an intermediate networked device; the system is a networked device) or directly with a remote computing device such as a server (e.g., using a 3G antenna). The status information communicated over the network may then be used, for example, to determine whether a patient is compliant or whether a class of drug delivery devices is exhibiting a system anomaly. The state information may also be used in other ways.

[0033] The systems and methods may also include information related to the identification of the drug, the drug delivery device, or the user, and / or control of the drug delivery device pursuant to communication of this identification information. Identification information related to the drug may include the drug name, drug concentration, dosage information, lot or serial number, and manufacturing and / or expiration date. Identification information related to the drug delivery device may include the device type (e.g., autoinjector, on-body injector), lot or serial number, and manufacturing date. Information related to the user may include the patient name, demographic information, and patient subgroup information. This information may be referred to as "static" information, as opposed to the status information discussed above.

[0034] With regard to the communication of information, and particularly with regard to the identifying information discussed immediately above, it is understood that not all information will be useful, desirable, or even accessible to all different parties due to convenience, patient privacy, or data security concerns.

[0035] FIG. 1 illustrates a drug delivery system 100 according to an embodiment of the present disclosure. The drug delivery system 100 may be associated with a patient 102 who may use the drug delivery system 100 to inject a drug as part of a treatment plan. The drug delivery system 100 may communicate with a computing device (e.g., a server) 104 via one or more intermediate computing devices and / or one or more networks. The server 104 may then communicate with the drug delivery system 100, the patient 102, and one or more computing devices (along with their associated parties) via one or more intermediate computing devices and / or one or more networks. As also shown in FIG. 1, the server 104 may communicate directly with the drug delivery system 100 using, for example, a 3G antenna.

[0036] For example, the drug delivery system 100 is shown communicating with a mobile computing device 110 (e.g., a smartphone) via a first communication link 112 and with a computing device (e.g., a personal computer or dedicated hub) 114 via a second communication link 116. Both links 112, 116 may operate according to a short-range communication protocol, such as Bluetooth. The mobile computing device 110 may communicate with a cellular network 118 via a communication link 120, while the other computing device 114 may communicate with a hard-wired network (e.g., a local area network or a wide area network) 122 via a communication link 124. These networks 118, 122 may also communicate with the server 104.

[0037] The networks 118, 122 may facilitate communication between the server 104 and one or more parties associated with the patient 102, such as the patient's caregiver 130, support person 132, and healthcare provider 134, via their mobile computing devices (e.g., smartphones). The server 104 may also be in communication with one or more computing devices (e.g., servers) associated with one or more additional parties associated with the patient 102. For example, a health management system server 140, a payment server 142, a pharmacy server 144, a logistics provider server 146, and a government agency server 148 are shown in communication with the server 104 via the network 122. It will be understood that the networks 118, 122 may also be in communication with each other.

[0038] 2 illustrates a method 200 of operating a drug delivery system, such as the drug delivery system 100 of FIG. 1, for determining various states of the drug delivery system, controlling the drug delivery system according to these states, and communicating the determined state information to a computing device, such as the mobile device 110 and / or the server 104. From a brief review of the flowchart of FIG. 1, it will be understood that the method 200 according to FIG. 2 illustrates determining various operational states of a drug delivery device that is part of the drug delivery system, and actions taken and communications made in connection with or regarding these operational states. It should also be understood that while the method 200 includes the actions described herein, other embodiments of a method of operating a drug delivery system according to the present disclosure may include only some of the actions described herein, as specifically shown, for example, in FIG. 3. Those actions outlined in FIG. 2 that are not included in other embodiments of a method of operating a drug delivery device according to the present disclosure may be omitted or excluded.

[0039] The actions and communications from the drug delivery system may change with the operational state of the drug delivery device as the device goes through a usable product lifecycle from manufacture to disposal, as shown in FIG. 2. Indeed, determinations made based on a single sensor may change according to the operational state of the drug delivery device. As an example, for those drug delivery devices that utilize a needle cap disposed on the second end of the cannula to maintain sterility, a determination made using the needle cap sensor that the needle cap has been removed from on or around the second end of the cannula prior to packaging or packaging removal may indicate that the integrity of the primary container has been compromised, whereas separation or removal of the needle cap from on or around the second end of the cannula after packaging or packaging removal may indicate that the device is ready to administer a drug.

[0040] Method 200 begins at block 202 and, when it is determined that the drug delivery system is packaged, continues from block 204 to blocks 206 and 208. Specifically, once the device is determined to be packaged in block 204, communication occurs in block 206 to report changes in the operational state of the device, and the method continues to block 208 where a determination is made whether the device has been distributed.

[0041] Between the determination that the drug delivery system is packaged and the determination that the drug delivery system is distributed to a user, the drug delivery device may pass through different portions of the supply chain. The portions of the supply chain that the drug delivery system may pass through may depend on the drug in the drug delivery device, the intended use of the drug delivery device by the user, who may be a patient or a medical professional, or other factors (e.g., the structure and characteristics of the drug delivery device itself).

[0042] As packaged devices emerge from manufacturing, there is an interest in maintaining up-to-date knowledge of information about authenticity, environmental history, and current or past location throughout distribution. Therefore, while the method and system await a decision to transition to the next operational state in block 208, the system may monitor and communicate this information in block 210. By automating the collection and reporting of information in this state, supply chain partners can leverage improved information and supply chain management systems. Information such as product identification, expiration date, and anti-counterfeiting measures can be useful to logistics, warehousing, and customs inspectors. This information, when added to what is known about combination products (i.e., therapeutic and diagnostic agents combining drugs, devices, and / or biologics) during manufacturing, can be useful in alerting interested and authorized parties regarding product location during product shipments or field events such as exchanges due to returns and recalls.

[0043] Depending on the path the drug delivery system takes between the manufacturer and distribution of the drug delivery system to the patient or healthcare provider, the drug delivery system may also pass through a pharmacy, where the system may also monitor and communicate information in block 210. If the drug delivery system passes through a pharmacy, information such as drug / dosage / device, environmental history, expiration date, anti-counterfeiting, and location data can provide useful information to those responsible for inventory control and ensuring product quality when delivered to the end user. Incorporating signals that trigger access to label and instruction manual information can provide value in training end users on the delivery device or drug product, can provide access to user communities, and can provide information flow to users or user networks regarding the availability of product training or related materials. These signals, when added to what is known about the combination product during manufacturing, can be useful for noting product location during product shipments or field events such as exchanges due to returns and recalls.

[0044] If a determination is made at block 208 that the packaged product has been distributed to a user (e.g., a patient or a healthcare provider), the method 200 may continue at block 212 where a change in operational state is communicated. The method 200 may continue with a determination as to whether the drug delivery device has been unpacked at block 214. If a determination is not made that the drug delivery device has been unpacked, the method 200 may monitor the drug delivery system and report information at block 216. If a determination is made that the drug delivery device has been unpacked, the method may continue at block 218 where the operational state change is communicated.

[0045] During this operational state, information such as environmental history, usage instructions, storage instructions, product authenticity, or the lot of material produced, expiration date, medication reminders, and any related on-site alerts for current location or expected arrival throughout delivery provide information of interest to the user. The use of sensors to provide signals regarding environmental conditions such as temperature can help the user understand whether the product is currently suitable for use, i.e., the method may proceed from block 214 to block 220 (with a report generated at block 218). One broad example of this is the “wake-up” of the electronic device to a high-activity state for delivery and reporting when the temperature exceeds a certain threshold, such as 15°C. This may result in a message to the user (e.g., via the user's networked device) to return the device to refrigeration or to administer within 24 hours. Similarly, the sensed temperature may cause the electronic device to return to a low-energy “sleep” state if the drug product drops below a preset threshold, such as 15°C.

[0046] If a determination is made at block 214 that the device has been unpacked (perhaps by a user), method 200 may report the operational state change at block 218 and proceed to the determination at block 220. As noted above, before method 200 can proceed to block 220, the method may perform determinations other than those shown in block 214.

[0047] In determining whether the system is ready for use at block 220, it is common for the system to verify the quality of the presented product. While the user may perform this action, the system may also include sensors to perform this action. For example, verification may include verifying label information to confirm authenticity, visually inspecting the device for signs of damage or whether the needle cap has been dislodged during shipping, and visually inspecting the drug product container for color and clarity. Validation may also include determining whether the environmental history of the device is such that it is safe to use. Such a determination may take into account environmental conditions during storage and distribution that may have damaged the drug product or delivery device. Including sensors within the device (e.g., needle cap position or proximity sensors or temperature sensors) can automate many of these inspection steps, providing greater ease of use for the user and more information for the user and their network.

[0048] Depending on the determination made in block 220, method 200 may proceed to block 222 where the user discards the device rather than using it. For example, it may be determined in block 220 that the environmental history of the device is such that the device cannot be safely used. In such a case, the device may indicate to the user that the device is being discarded in block 222 and may communicate this information to a remote server that tracks such device determinations, or it may communicate with a local device (such as a mobile, cell phone or other mobile device, or a handheld computing device) that is networkable or networked and communicates the information to a remote server.

[0049] On the other hand, if a determination is made at block 220 that the system is ready to administer, method 200 may proceed to block 224 with a report of the change in operational status. Method 200 may then continue to block 226, where a determination is made that the barrier is no longer sterile and has been prematurely deployed, or that the barrier has been prematurely removed or separated from the drug delivery device such that the sterility of the device is no longer maintained or can no longer be guaranteed. In this case, the barrier may be a sterility barrier such as a needle cap (i.e., minimal packaging that prevents microbial ingress and allows the product to present as sterile at the point of use). If a determination is made at block 226 that the barrier is still sterile, method 220 may remain at block 228, where the operational and condition status of the system is monitored and the information is communicated to a local or remote device. If a determination is made that the barrier is no longer sterile, method 200 may continue to block 230, where the change in operation is reported, and method 200 may continue to block 232.

[0050] Regarding the decision made in block 226, it is common for autoinjectors and on-body devices to have components or packaging products that maintain the sterility of the needle or injection head that are removed immediately prior to administration. While occasionally the outer protective packaging is improperly removed and discarded days before drug administration, typically the patient may be minutes or less away from insertion and / or injection when the sterile barrier is removed from the device. This decision also provides an important opportunity to ensure that the drug delivery device electronics are "awake" during the injection process without requiring the extra cost and bulk of ensuring adequate power throughout manufacturing, storage, and distribution before critical functions are performed.

[0051] By triggering the electronics to "wake up" to a high-activity state upon removal of the sterile barrier, the built-in electronics of a smart drug delivery device can offer significantly improved power consumption during manufacturing, storage, and distribution. According to certain embodiments, for example, the startup sequence, including activation, completion of pre-tests, and patient / user interaction before attempting administration, can take 10 to 200 seconds (this interaction may include waiting for the device / drug to warm to room temperature, which may further increase the total time required). Conversely, the user may wait for physical contact or delivery activation to wake up the built-in electronics, but this likely does not provide an opportunity for all desired "smart" features. Similarly, if something such as the removal of the initial packaging were used to wake up the electronics, there is a risk that a significant amount of power would be utilized prior to delivery, which could make optimizing the device and drug delivery system difficult.

[0052] It is possible to design a component that is removed along with the sterile barrier, which has generally offered opportunities to increase ease of removal, ergonomics, or clarity. By designing a tab or other electrically insulating feature into this component, the component can be inserted into the power circuit of the on-board electronics such that removal of the sterile barrier connects a battery or other power source and wakes the electronics to perform a necessary function. Alternatively, removal of the barrier may result in the closure of a switch, completing a circuit with the power source and thus powering on the system.

[0053] At block 232, a determination is made whether the drug delivery system has been applied to the patient. For an autoinjector, this determination may involve determining whether the autoinjector is held in place against the patient's skin. For an on-body injector, this determination may involve determining whether adhesive is exposed on the surface of the on-body injector and the injector is placed on the patient's skin. According to certain embodiments of method 200, if a determination is made at block 232 that the drug delivery system has not been applied within a specified time after the barrier is no longer sterile, the user may be instructed to discard the device at block 234, and this event may be communicated to a local and / or remote device. Alternatively, if a determination is made at block 232 that the device has been provided to the patient, an operational state change is reported at block 236, and method 200 proceeds to block 238.

[0054] In some embodiments, the determination made regarding skin application in block 232 may be repeated at predetermined intervals (e.g., every 5 milliseconds) throughout the remainder of method 200. By doing so, it may be possible to determine whether the drug delivery device was prematurely removed from the patient's skin before drug delivery to the patient was complete. Also, if premature removal occurred, it may be possible to determine when it occurred relative to the start of drug delivery. The timing of the premature removal may be used to calculate the actual amount of drug actually delivered to the patient before removal of the drug delivery device from the patient's skin.

[0055] As in the above case, it may also be useful to know when intentional contact has occurred, as this may be a useful opportunity to "wake up" the on-board electronics from a low-power state, for example, depending on what "smart" functionality is desired by the circuitry. Alternatively, some tests to ensure the device is ready to administer may be performed to provide the user with greater confidence in the usefulness of the injection.

[0056] Additionally, there is a risk of intentional non-compliance, as many commercially available injection devices can be tricked into dispensing medication by depressing the needle protection device and activating the product to dispense into the air instead of the patient. There is incremental value in knowing that the device was in contact with the body throughout the delivery period, especially when additional information exists that matches the expected characteristics of human tissue and the appropriate injection site. The overlap of known body contact and completion with the duration of drug delivery can be used to estimate the missed dose in the event of negligence, as further described in the analogy to the "needle inserted" condition.

[0057] The method 200 determines whether the second end of the cannula has been injected or inserted into the patient at block 238. In many drug delivery devices, application of the drug delivery device to the patient's skin and injection of the cannula into the patient are not simultaneous. For example, there may be a delay between application and injection due to the time required for various assemblies or subassemblies of the drug delivery device to recognize that the drug delivery device has been applied and activate the injection device. Alternatively, there may be a planned delay in injection of the cannula because administration of the drug is planned to occur after a time delay has elapsed after application of the drug delivery device to prevent damage to the cannula or patient discomfort due to a planned delay between application and injection. In yet another alternative, in an on-body drug delivery device, a needle, referred to as an introducer needle, may be activated to insert a cannula that may remain inserted into the patient. The needle then retracts again into the delivery device, leaving the cannula behind. The actual injection or introduction of the medication can occur immediately thereafter or at a desired later time. Thus, if it is determined at block 238 that the cannula was not inserted, the method 200 may proceed to block 240, where the system may monitor the operating state and one or more condition states and communicate that information.

[0058] Like body contact information, infusion information may be used in combination with other processes to achieve greater confidence in the collected information. In contrast to body contact information, precise measurement of needle insertion into a target route of administration, e.g., intradermal, subcutaneous, intramuscular, intravenous, intraocular, or other route, can provide direct confirmation that the drug product has been delivered to the correct anatomical depth and location.

[0059] One use of the needle insertion signal could be the release of a delivery lockout once the needle is inserted into the patient. Alternatively, if complete drug delivery occurs and the needle is inserted for the entire period between "delivery initiated" and "delivery completed," a very high degree of certainty of successful dosing is achieved. Conversely, if the timing of events does not overlap appropriately, it may be possible to predict a successfully delivered dose based on system delivery characteristics. When an incomplete or unsuccessful dose is detected and reported, there is significant incremental value if the dose discrepancy is also reported. "Smart drug delivery devices" can be used for many different types of medications with different therapeutic effects and toxicity risk profiles. For example, some medications have a low risk of toxicity, but if there is a high risk of complications with a missed or incomplete dose, urgent completion of the medication, such as by a second injection for any incomplete dose, may be required. Alternatively, if the risk of complications is low, a healthcare provider may want to know the missed or incomplete dose but prefer to wait for the next dose instead of scheduling an alternative. Importantly, if missed doses are properly recorded and reported, there may be an opportunity to mitigate problems associated with incomplete dosing by administering the correct missed dose, which may provide an opportunity to minimize the overall cost of care while maximizing benefits.

[0060] If a determination is made at block 238 that the needle has been inserted, the method 200 may communicate the operational state change at block 242 and determine whether drug administration has begun or been initiated at block 244. If the cannula has been inserted but administration has not yet begun, the method 200 may remain at block 246 to monitor the status of the drug delivery device and communicate that information. A delay between the insertion of the cannula and the administration of the drug product may occur due to sequential operation of an assembly or subassembly of the drug delivery device, i.e., the delay may be designed so that the cannula is inserted into the patient simultaneously or nearly simultaneously with application of the device to the patient's skin, but administration occurs at least a time delay thereafter.

[0061] Successful triggering of delivery is generally considered to result in successful dosing, except when the device may be programmed to insert a cannula and then initiate medication infusion at a later time. Once triggered, the patient typically performs the action intended to produce a therapeutic result. Triggering of delivery, according to certain embodiments, may be viewed as evidence of a higher level of commitment compared to physical contact or needle insertion alone. It is believed that some patients "feel" committed before triggering delivery by placing the device on their body, trying different sites. Many devices include features to ensure that such attempts do not trigger delivery. Thus, triggering of delivery is generally seen as an indication that the patient has mentally committed to administering the prescribed therapy. Enabling a "smart drug delivery device" to sense when delivery has been triggered provides value to many stakeholders as an indication of adherence. While not a metric for measuring successful delivery compared to other methods, detection of the triggering signal can be achieved through relatively simple means, offering greater value for money and reliability.

[0062] Once a determination is made at block 244 that dispensing of the drug product has begun, the method may proceed to block 248 where the change in operating state of the device is communicated to local and / or remote devices. Method 200 then proceeds to block 250 where a determination is made that dispensing of the drug product is complete. The system continues to monitor the device and communicate information at block 252 until a determination is made that dispensing of the drug product is complete. Once a determination is made at block 250 that dispensing is complete, the change in operating state is communicated at block 254 and method 200 proceeds to block 256.

[0063] Capturing administration or delivery completion is a useful indicator, especially in combination with other device status information. If the device does not have a means for capturing other device status, its value exists in itself, and indeed, if it is unable to report other status, it provides sufficient value to many stakeholders. However, compared to other device status, capturing the time and date of administration delivery completion can provide a very high level of confidence (or disproof) that the drug was successfully delivered. For example, if dose completion occurs while the needle is still inserted, this confirms that the patient or caregiver administering the medication did not remove the device from the body while or after the device was initiated, thus compromising the accuracy of the administration. While commonly available drug delivery devices may lock out to prevent drug delivery before application to the body, once the device is applied to the body, there is no means to keep the device secured to the body for the entire duration of delivery. In most cases, if the needle is removed after delivery has been initiated, the drug will continue to be delivered and will spill into the air as waste. Sometimes, medications can be painful or cause certain sensations due to certain ingredients or the rate of delivery, thus causing a reflex action that impairs the dosage even after needle insertion. At other times, the operation of the delivery device itself can startle the user and cause the same reflex action. It is known that it is important for users or user networks to understand the difference between a slow response and non-compliance with treatment in order to provide patients with the evidence needed to encourage compliance with prescribed treatment or to change treatment strategies. Therefore, there is tremendous value for patients in comprehensive measurement and reporting of drug delivery device performance.

[0064] Some of the embodiments disclosed below may be extended in scope to monitor the overall progress of delivery. For example, if an optical sensor is optimized to detect stopper material and disposed at the end of the delivery stroke where it can be used to relay completion information, similarly, a series of optical sensors placed parallel to the movement of the plunger through the drug reservoir may be used to monitor progress throughout the movement.

[0065] At block 256, the method 200 determines whether the device has been removed from the patient. The determination at block 256 may be based on a skin sensor determining whether the device is no longer in contact with the patient's skin. According to other embodiments, the determination may be made on a needle shield or other structure positioned to prevent contact with the second end of the cannula of the drug delivery device after removal from the skin. According to yet other embodiments, removal of the drug delivery device may be based on a change in the orientation of the drug delivery device. In either case, the method and system may monitor the device and communicate information with local and / or remote devices at block 258 until it is determined that the drug delivery device has been removed. When it is determined that the drug delivery device has been removed, the method communicates this change in operating state at block 260 and ends at block 262.

[0066] Disposal of the device, and alternatively, receipt of the used device by a collection center, provides a final opportunity to query any stored information and / or utilize the receipt itself to serve as evidence of a previous state change. Any previously collected data may be stored for download at the collection point. Additionally, for situations where a return warrants replacement or other on-site compensation, awareness of the location of the drug delivery device throughout distribution and return delivery is beneficial. The same signal, combined with remote approval of the return, can allow return delivery to be electronically approved and paid for by the user or an appropriate partner in the distribution network, with minimal impact to the user.

[0067] It will be understood that, according to other embodiments of the present disclosure, the various operational states described with respect to FIG. 2 may be considered optional. For example, making decisions related to cannulation and initiating drug product administration at blocks 238 and 244 may not be necessary if, for example, a device has been applied and a decision that drug product administration is complete has been made at blocks 232 and 250. Furthermore, while method 200 includes communication of operational state changes after each operational state change, none of the operational state changes may be stored within the system, and communication of each operational state change may not occur until block 260. Furthermore, while monitoring of the drug delivery device is shown to occur while method 200 waits for certain decisions to be made (e.g., blocks 208 and 210), this monitoring need not occur in all instances shown.

[0068] 2 may include more than just monitoring the various operational state changes discussed. Monitoring may also include monitoring condition state changes. In fact, methods and systems may monitor one or more sensors for these operational and / or condition state changes, where information or signals from one or more sensors may be used in decisions made at various points along method 200.

[0069] 3A-3C illustrate a method 300 that may be considered to illustrate some of the operational and condition state monitoring of a mixture that may occur in methods and systems according to the present disclosure. Method 300 may be considered to illustrate how one or more sensors may be used to determine the above-mentioned state changes. Additionally, method 300 may be considered to provide a disclosure of operational and condition state monitoring and communication of that information not shown in FIG.

[0070] Referring first to FIG. 3A , method 300 may start with a drug delivery device in a package, and the method waits at block 302 until it is determined that the package has been opened. At this point, the device may optionally be locked until the system performs one or more verifications, checks, or tests to ensure the device is ready for administration, the sterility barrier has been removed, and / or the device has been (correctly) applied (see blocks 220, 226, 232 of method 220 in FIG. 2 ). Before performing each of the one or more verifications, checks, or tests, method 300 may determine whether the drug delivery device is adapted or programmed to perform the verification, check, or test. For example, a determination may be made at block 304 that the drug delivery device is adapted or programmed to check the sterility of the drug delivery device; in particular, the verification or check may relate to a sterility barrier disposed at the second end of the cannula. If the drug delivery device is adapted or programmed to perform a sterility test, the method 300 may proceed to block 306 where it is determined whether a sterility barrier has been disposed, for example, on or around the second end of the cannula.

[0071] If the barrier is determined to be in place at block 306, the method may proceed to block 308 where the user is instructed to remove the barrier. The method 300 may then determine whether the barrier has been removed at block 310. When the barrier is determined to be removed, a sterilization timer may be started, and expiration of the sterilization timer may cause the drug delivery device to be placed or remain in a locked state, preventing use of the drug delivery device.

[0072] If it is determined in block 306 that the barrier is not in place (i.e., the barrier was prematurely removed), the method 300 may proceed to block 312, where the delivery device is locked (e.g., a lock or lockout device is activated) or, if the device was already locked, the delivery device remains locked. According to certain embodiments, the locking of the delivery device in block 312 may be irreversible. According to other embodiments, including the embodiment shown in FIGS. 3A-3C, the lock may be reverted once it is determined in block 314 that the drug product (e.g., the drug product reservoir) has been replaced. If the drug product is not replaced or cannot be replaced (i.e., the lock is irreversible), information regarding the failed sterilization test may be communicated by the system.

[0073] If (i) a determination is made at block 304 that the system is adapted to verify, confirm, or check sterility of the device, (ii) a determination is made at block 306 that the barrier is in place and then a determination is made at block 310 that the barrier has been removed, or (iii) a determination is made at block 306 that the barrier is not in place, but a determination is made at block 314 that the drug product has been replaced, method 300 continues at block 316. At block 316, a determination is made whether the drug delivery device is capable of performing a visual and / or environmental inspection. If the device is so adapted, the method proceeds to block 318, where a determination is made whether the visual inspection and / or environmental conditions are within desired thresholds. If a determination is made that the visual inspection and / or environmental conditions are outside the desired thresholds, the method may proceed to blocks 312, 314. If a determination is made that the visual inspection and / or environmental conditions are within the desired thresholds, method 300 may proceed to block 320.

[0074] At block 320, a determination is made whether the drug delivery system is able to verify the user identification. If the drug delivery system is so adapted, method 300 continues to block 322, where a determination is made whether the user identification matches the authorization for use of the drug delivery device. If the user is not identified as an authorized user at block 322, method 300 continues to block 324, where the drug delivery device is locked or remains locked, and block 326, where information regarding the attempted unauthorized use is communicated to local and / or remote devices. If the user is identified as an authorized user, method 300 proceeds to FIG. 3B and block 328.

[0075] At block 328, a further determination is made as to whether the drug delivery system is enabled to check the temperature of the drug product. If the system is so adapted, method 300 continues to block 330. At block 330, a determination is made as to whether the drug product temperature is within a range for predictable delivery (neither too high nor too low). If a determination is made at block 330 that the temperature is not within a range for predictable delivery, method 300 continues to block 332, where a determination is made as to whether the device can heat or cool the drug product to bring the product temperature within range. If the system is not so adapted, the method proceeds to block 334, where the device may be locked or remain locked, allow passive heating or cooling to occur, and the user may be notified. Optionally, the system may also communicate this information to local and / or remote devices. If the system is enabled to allow heating or cooling, the method proceeds to block 336, where the device may be locked or remain locked, heating or cooling may be initiated, and the user may be notified. Regardless of passive or active heating or cooling (blocks 334, 336), method 300 may continue to block 338 where delivery is delayed to allow time for the heating or cooling to occur before the method returns to block 330. According to certain embodiments, method 300 may end after block 330 (e.g., in the case of an excessive temperature) and may communicate that information to local and / or remote devices.

[0076] In some embodiments, the temperature check performed in block 330 may involve evaluating the drug product's temperature history to determine the range and duration of temperatures the drug product has experienced in the past (e.g., during storage, distribution, delivery, etc.). If the drug product's temperature history is unacceptable, for example, because the drug product was exposed to high temperatures for several days or hours during delivery, the controller 350 may lock out the drug delivery device 302 so that it cannot be used to deliver the drug product to a patient and may further control the communications module 352 to send a report to the local computing device 304 or the remote computing device 306 indicating the unacceptability of the drug product's temperature history. In some embodiments, once it is determined that the drug product's temperature has exceeded a threshold temperature, the controller may start a timer that runs until the temperature returns below the threshold temperature. If the duration of the timer exceeds a predetermined time limit, the controller 350 may control the communications module 352 to lock out the drug delivery device 302 and send a report indicating the unacceptability of the drug product's temperature history.

[0077] 3B , if the device is not adapted to perform temperature checking at block 328 or a determination is made at block 330 that the drug product temperature is within a desired range, the method may continue to block 340, where a determination is made whether the device has been enabled to determine whether it is properly positioned on or oriented relative to the patient. If the device is so adapted, the method proceeds to block 342, where a determination is made whether the device is properly positioned or oriented. Depending on the preferred insertion site, knowledge of the device's orientation may then be useful in providing a successful injection. For example, self-administration into the abdomen will likely result in an orientation of the autoinjector axis that is approximately horizontal.

[0078] If the device is not properly positioned, the method proceeds to block 344, where the device may be locked and the user is instructed to reposition or reorient the device. Method 300 may then proceed to block 346, where a time delay is provided for the user to reposition the device before method 300 returns to block 342 for further determinations regarding the device's position. Alternatively, if the device is properly positioned, the method may proceed to block 348, where any locks or lockouts that may have been activated are removed (or the device is unlocked).

[0079] Method 300 continues at block 350 where a determination is made whether the system has been enabled to determine whether delivery has been initiated. If a determination is made that the system has been so adapted, the method proceeds to block 352 where a determination is made whether the device has been activated or started. If a determination is made at block 352 that the device has not been started, method 300 may proceed to block 354 where the system may prompt the user to start the device. According to other embodiments, the drug delivery device may wait for a predetermined and / or pre-programmed time delay to occur before automatically starting the device once the time delay is complete. According to yet other embodiments, method 300 may optionally determine whether a timer has elapsed at block 355, for example, to reduce the risk of contamination and infection. According to such an embodiment, a timer may be started based on a determination that the barrier was properly removed at block 310 (or may be started based on a determination that the barrier was removed according to further embodiments), and if method 300 does not determine that the device was triggered within a certain time from that event, method 300 may return to block 312, for example, as shown in FIGS. 3B and 3A. If triggering is determined to have occurred at block 350, the method proceeds to block 356, where the user may be notified of the device triggering and / or the date, time, and location of delivery may be saved or recorded. Optionally, this information may also be communicated to local and / or remote devices in communication with the system. Method 300 then continues to FIG. 3C.

[0080] A further determination may be made at block 358 whether the system is enabled to determine whether the device remains properly positioned on or properly oriented relative to the body. If the system is so adapted, method 300 continues to block 360, where a determination is made whether the device is properly positioned on or properly oriented relative to the body. If the device is not properly positioned or oriented, method 300 may continue to block 362, where the user is notified to reposition or reorient the device, and block 364, where a time delay is provided to the user to reposition or reorient the device, before returning to block 360, where the position or orientation of the device on the patient's body is determined. If the device is properly positioned or oriented, method 300 may proceed to block 366. Optionally, method 300 may periodically repeat block 360 to ensure that the device remains correctly positioned throughout the time that the device is administering the drug product.

[0081] At block 366, a determination is made whether the system is enabled to determine whether administration is complete. If the system is so adapted, method 300 continues at block 368, where a determination is made whether delivery is complete. If a determination is made at block 368 that delivery is not complete, a further determination is made at block 370 whether delivery can be completed. If delivery is not complete but can be completed, method 300 returns to block 368 via block 372, where the device is allowed to continue administering the drug product. If delivery is not complete and cannot be completed (e.g., the device has been removed from the patient's skin), method 300 continues at block 374, where information regarding the drug and drug delivery may be communicated to local and / or remote devices. For example, information regarding whether certain operational states occurred (cannula inserted, delivery initiated, delivery partially completed), the timing of the operational states, and the amount of drug product administered may be communicated.

[0082] If a determination is made at block 368 that delivery is complete, the method proceeds to block 376 where the system indicates to the user that delivery is complete. Further, method 300 communicates information regarding the drug delivery, the drug delivery device, and the drug product to local and / or remote devices at block 378. For example, the information may include that certain operational states occurred and the timing of the operational states. Method 300 may also verify, if the system is enabled to make a determination that the device was properly positioned throughout. Method 300 may also proceed to block 378 if the system is not enabled to determine whether administration of the drug product is complete, and an assumption is made that the drug delivery device has been determined to have passed through one or more of the preceding operational states that necessarily lead to the conclusion that delivery is complete.

[0083] Again, while the above description relates to a method including a series of states of a device and alternative actions that may depend on those states, it should be noted that a device need not determine each and every state or perform each and every action shown in Figures 3A-3C. Rather, those skilled in the art will understand that determining certain states or performing certain actions may be omitted or omitted to result in a system that can control or communicate with a device based on a subset of the described states.

[0084] Having discussed possible methods of operating a drug delivery system in the context of the methods shown in Figures 2 and 3A-3C, a possible method of operating one or more computing devices in communication with the drug delivery system will now be discussed in the context of method 400 shown in Figure 4. It will be understood that method 400 may be performed by a single computing device, such as server 104 shown in Figure 1. Alternatively, the operations discussed with respect to Figure 4 may be performed by multiple computing devices, such as mobile device 110 or computing device 114 in combination with server 104.

[0085] Method 400 begins with a determination as to whether a report has been received from the drug delivery system at block 402. If a report has not been received, method 400 waits at block 402, and once it is determined at block 402 that a report has been received, method 400 proceeds to block 404.

[0086] At block 404, the reports received from the drug delivery system are used to update one or more records. In doing so, one or more computing devices adapted or programmed to perform method 400 may retrieve one or more records from storage in one or more memory storage devices, write the information received from the drug delivery device to the one or more records, and then store the one or more records in one or more memory storage devices. The one or more memory storage devices may be part of the one or more computing devices, may be separate from the one or more computing devices, or may include one or more of a memory storage device that is part of one or more computing devices and one or more memory storage devices that are separate from the one or more computing devices (i.e., the records are stored on the computing device, in a backup storage device, separate and possibly remotely from the computing device).

[0087] As mentioned above, reports may be used to update one or more records. For example, there may be one record per individual patient stored in a patient record database. The patient record may be used, for example, to track an individual patient's (e.g., patient 102) compliance with their plan(s). There may also be records related to the drug delivery systems used by individual patients stored in a drug delivery system database. The drug delivery system records may be used to store information about the drug delivery systems throughout their use. The drug delivery system records may be accessed by drug delivery system manufacturers or drug suppliers for quality control purposes (e.g., to monitor individual instances of drug delivery systems for failures or malfunctions caused by the drug delivery system, or to track the environmental condition history of one or more drug delivery systems for patterns that may assist in determining improvements in the design, packaging, shipping, or handling of the drug delivery systems). There may also be records related to drugs used in drug delivery systems stored in a drug database. This record may be used for quality control purposes in a manner similar to the drug delivery system records.

[0088] In addition to updating the record at block 404, a computing device adapted or programmed to perform method 400 may also be adapted or programmed to perform one or more actions based on information in the report received from the drug delivery system. For example, a computing device may be adapted or programmed to perform an action at block 406. This action may require not only the information received in the report and / or information previously stored in the record updated at block 404, but may also require additional information, such as from other patient records, drug system delivery records, and / or drug records. In this case, a determination may be made at block 408 that these other records need to be accessed, and a determination may be made at block 410 that the information has been obtained (e.g., by retrieving these other records from patient, drug delivery system, and drug databases and retrieving information from these records once obtained). The action may then be performed at block 412.

[0089] As one example, one or more computing devices adapted or programmed to perform method 400 may be adapted or programmed to use information received in the report to create a patient adherence history, which tracks instance use of a drug delivery system by an individual patient for that patient's treatment plan to determine how well the patient has followed the treatment plan, and which may be stored in the patient record. Additionally, the one or more computing devices may determine whether a pharmacy should be contacted to order the shipment of additional drug delivery devices for the individual patient and may generate a communication to be sent to the pharmacy to order the shipment of additional drug delivery systems. Additionally, the one or more computing devices may determine whether a reminder should be sent to the patient via the mobile device 110, for example, to improve or assist the individual patient's adherence to the treatment plan, in which case the one or more computing devices may generate a communication to be sent to the patient or device user. Additionally, the one or more computing devices may determine that the operation of the drug delivery device should be modified, for example, due to a condition state received from the drug delivery device. For example, the one or more computing devices may determine that the drug delivery system should be locked to prevent its use, for example, due to the temperature history of the drug within the drug delivery system. In this case, the one or more computing devices may generate a communication in the form of, for example, a signal that is sent to the drug delivery system to lock a drug delivery device that is part of the drug delivery system. Other possible actions are discussed in detail below, but this discussion is for illustrative purposes only and is not intended to be limiting.

[0090] Depending on the actions taken in block 412, or even if it was determined in block 406 that no actions need to be taken, method 400 may proceed to blocks 414, 416, and 418, where a determination is made as to whether the computing device should contact other parties (block 414), interact with the patient (or user, if not the same as the patient) (block 416), or control a drug delivery device that is part of the drug delivery system (block 418). For example, as discussed above, the actions taken in block 412 may involve communication or generation of a signal that is sent to a third party, such as a pharmacy, the patient, or the drug delivery device. In such cases, one or more computing devices may perform the actions of blocks 420, 422, and 424 as required by the determinations made in blocks 414, 416, and 418. Alternatively, one or more computing devices may perform the actions of blocks 420, 422, and 424 even if it was determined in block 406 that no actions need to be taken. For example, one or more computing devices may forward certain information to a third party 420 based solely on receipt of the information in a report from the drug delivery device, such that the one or more computing devices do not have to separately determine that an action should be taken with respect to the received information (i.e., the one or more computing devices act as a relay station for such information, and a communication is automatically sent based on the fact that the information was received). Receipt of information from the drug delivery device may also prompt a communication to be sent to the patient / user or control a signal sent to the drug delivery system without a separate determination that such action needs to be taken; a communication or control signal is sent simply because certain information and / or report was received from the drug delivery system.

[0091] Once the determinations at blocks 414, 416, and 418 have been made and the operations of blocks 420, 422, and 424 have been performed, method 400 may return to block 402 to await the next report. It will be appreciated that one or more computing devices may perform the operations of method 400 in parallel for each report received from different instances of the drug delivery system, or may perform the steps sequentially for each report. When performed in parallel, one or more computing devices may determine whether to perform an operation with respect to one report while one or more computing devices are interacting with another patient regarding information contained in the report received from that patient. Furthermore, the one or more computing devices performing method 400 need not be adapted or programmed to perform each of the operations described above in accordance with all embodiments of the one or more computing devices. For example, one of the one or more computing devices may be adapted or programmed to update each patient's record and determine whether patient interaction is necessary, while another of the one or more computing devices may be adapted or programmed to update each drug delivery device's record and determine that a control signal should be sent to the drug delivery device, while another of the one or more computing devices does not update any records but is adapted or programmed to, for example, access the patient record to determine whether a pharmacy needs to be contacted to order additional instances of the drug delivery system for the patient associated with the accessed patient record and generate a communication if ordering additional instances of the system is necessary.

[0092] It will be understood that the above methods 200, 300, and 400 only scratch the surface of the possible status and identification information that may be used to control and / or monitor a drug delivery system and that may be communicated between the drug delivery system and one or more computing devices, and how the information may be used by the drug delivery system and one or more computing devices. Additional embodiments are possible in accordance with the present disclosure.

[0093] For example, a non-limiting matrix of status and identity information may include:

[0094] Condition Status Information: temperature Shock or vibration exposure light exposure Color and / or turbidity (associated with the drug) Orientation geographical location temporal information

[0095] Working status information: The device was removed from the packaging The device is removed from refrigeration (e.g., a refrigerator) Device / drug temperature is ready for administration Delivery started The device was applied to the patient The device was applied in the correct position / orientation on the patient The cannula is inserted into the patient and / or into the correct tissue Delivery is in progress Delivery completed An error occurred

[0096] Device Identification Information: Drug name or identity, concentration, and / or amount Confidentiality and / or anti-counterfeiting information Patient prescription / treatment plan

[0097] Patient Identification Information: Point-of-care diagnosis for patients Self-analysis and measurement of progress Fingerprint, PIN, or other secure identification

[0098] This information may be communicated to other computing devices or otherwise used to control the drug delivery system or device being used, and an exemplary list of certain additional uses is included below: The following list and additional comments are intended to augment, not replace, the above discussion and are intended to be non-limiting.

[0099] As one example, the drug delivery system or one or more computing devices may make a determination regarding the authenticity of the drug and its compliance with manufacturing standards. Such a determination may be made by the drug delivery device at block 220 of method 200 or block 318 of method 300, or by one or more computing devices at block 406 of method 400, for example. The determination may be made based on the drug delivery device / drug's temperature, shock or vibration exposure, and / or light exposure (or the history of one or more of these conditions), as well as the color and / or turbidity of the drug (as determined by optical inspection). This determination may result in control of the drug delivery device to either lock or unlock the device according to the determination made. See blocks 220, 222, and 224 of method 220, blocks 318, 312, and 314 of method 300, and blocks 406-412 and 418 and 424 of method 400.

[0100] As another example, the drug delivery system or one or more computing devices may make a determination as to whether a drug is appropriate for a patient. See block 220 of method 200, block 322 of method 300, and blocks 406-412 of method 400. The determination may be made based on one or more of the device's items of patient identification information listed above, and may also result in control of the drug delivery device to either lock or unlock the device according to the determination made. See blocks 220, 222, and 224 of method 220, blocks 322, 324, and 326 of method 300, and blocks 406-412 and 418 and 424 of method 400.

[0101] As a further example, the drug delivery system or one or more computing devices may make a determination as to whether the dose was correctly administered. This determination may be made after determining that the drug is appropriate for the patient and / or that the drug is authentic (e.g., not counterfeit) and complies with manufacturing standards. See the previous paragraph. The determination of whether the dose was correctly administered may depend on one or more of the types of operational status information listed above. See blocks 220-260 of method 200 and blocks 328-378 of method 300. This information may be used to update patient records, determine patient compliance or treatment progress, and may facilitate communication with a pharmacy regarding refills or communication with a payer (e.g., an insurance company) to approve payment for the drug delivery device. See blocks 404-414 of method 400 and servers 142, 144 of FIG. 1.

[0102] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a decision regarding the operational status of the drug delivery device and generate instructional messages to guide the user through the actions necessary for proper use of the drug delivery device. The decision may be based on any of the operational status information listed above, and the generated instructions may be directed by the action that needs to be taken immediately after the operational status occurs. Implementing interactive instructions following changes in the status of the drug delivery device may help the user feel confident in administering the drug. See also Figures 6 and 7 below.

[0103] As a further alternative, the drug delivery system or one or more computing devices may use the information to determine that other people nearby are taking the same medication. See blocks 406-412 of method 400. This determination may be made based on the drug-identifying information and the patient-identifying information in combination with the geographic location information of the drug delivery system. This determination may facilitate communication with the patient regarding a local support network of people who have a similar condition and / or are taking a similar drug or medication (see method 400 blocks 416 and 422), allowing the patient to receive support and encouragement from such a network. Alternatively, the determination may facilitate communication with a local support network(s) to provide support and encouragement to the patient (see blocks 414 and 420 of method 400). As a further alternative, the determination may facilitate a personalized intervention communication sent to the patient (see again blocks 416 and 422 of method 400).

[0104] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination whether the patient is not adhering to their treatment plan. See blocks 406-412 of method 400. The determination may be based in part on drug identification information, such as the prescribed treatment plan, in part on condition status information, such as the passage of time, and in part on operational status information, such as the drug delivery device being removed from the packaging but no additional operational status information being determined, reported, or received during the passage of time since the removal-from-package operational state. Based on this information, the drug delivery system and / or one or more computing devices may determine that an interaction with the patient should be generated, such as a notification being displayed or sent to the patient. See blocks 416 and 422 of method 400. Additionally, the drug delivery system and / or one or more computing devices may determine that a communication should be generated to be displayed or sent to a healthcare provider, caregiver, support person, and / or payer to encourage adherence to the plan. See blocks 414 and 420 of method 400.

[0105] As a further alternative, the drug delivery system or one or more computing devices may use the information to determine that the patient needs more medication (a refill). See blocks 406-412 of method 400. The determination may be based in part on drug identification information, such as a prescribed treatment regimen, and in part on operational status information, such as whether drug delivery has been completed. Based on this information, the one or more computing devices may generate a communication to be sent to a payer and / or pharmacy to request a prescription refill. See blocks 414, 420 of method 400.

[0106] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination that an injection was not performed correctly. See blocks 406-412 of method 400. The determination may be based, in part, on operational status information compared to information that may be collected and stored regarding conventional general levels of operation. Alternatively or additionally, a comparison between determined, reported, or received operational status information allows a determination that an injection was not performed correctly to be made. For example, determining, reporting, or receiving operational status information indicating drug delivery was completed without operational status information indicating that the device was initiated, that the device was applied to the patient, and / or that the cannula was inserted may indicate that the drug delivery device failed to perform correctly, was incomplete, or performed incorrectly.

[0107] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination that the patient's condition is improving. The determination may be based, in part, on patient-identifying information, such as point-of-care diagnostics (e.g., blood glucose tests or other tests) or self-analysis reports administered to the patient, and in part on determining, reporting, or receiving operational status information, such as that drug delivery has been completed. The determination may rely on overall trends as opposed to individual determinations or reports, as trends in data or reports are typically more indicative of an improvement in the patient's condition than individual case-by-case determinations of severe illness. Thus, information collected regarding the patient and the operational status of the drug delivery system / device may be combined in conjunction with treatment adherence history. This determination may result in personalized interventions being generated, which (e.g., encouraging messages and other forms of positive reinforcement) may increase persistence in treatment.

[0108] As a further alternative, the drug delivery system or one or more computing devices may use the information to determine the time of day (or week, month, etc.) when the patient typically takes their medication. This determination may be based, in part, on patient records in which time information is associated with operational status information related, for example, to the initiation of the drug delivery device or the completion of drug delivery. This determination may also depend on device identification information, such as a prescribed treatment plan. Based on this determination, the one or more computing devices may generate a reminder communication, for example, sent to the mobile device 110, to notify the patient that it is nearly time to administer the patient's next dose. It may be beneficial to facilitate the patient's decision to take their medication at a specific time of day, week, month, etc., because the usefulness of reminders is enhanced when there is adequate access to and opportunity for use of the drug delivery device. Based on this determination, the one or more computing devices may also generate personalized interventions, such as encouraging messages used as positive reinforcement.

[0109] As a further alternative, the drug delivery system or one or more computing devices may use the information to determine where the patient typically takes their medication. This determination may be based, in part, on patient records in which geographic location information is associated with operational status information related, for example, to the initiation of the drug delivery device or the completion of drug delivery. This determination may also depend on device identification information, such as a prescribed treatment plan. Based on this determination, the one or more computing devices may generate a reminder communication, for example, sent to the mobile device 110, to notify the patient that it is nearly time to administer their next dose when the patient is at or near a geographic location where the drug delivery system is typically used. It is beneficial to encourage the patient's decision to take their medication when they are in their usual location to take their medication, because the usefulness of the reminder is enhanced when there is reasonable access to and opportunity for use of the drug delivery device. Based on this determination, the one or more computing devices may also generate personalized interventions, such as encouraging messages used as positive reinforcement.

[0110] Of course, determinations regarding the usual time and location of use of the drug delivery device may be combined, and the one or more computing devices may generate a message only when the patient or user is at or near their usual location of use at or around the time they normally use the drug delivery device.

[0111] While the foregoing has focused primarily on decisions made by the drug delivery system and / or one or more computing devices regarding a patient or the patient's use of the drug delivery device, decisions may be made regarding the drug delivery device or drug before the drug delivery device is made available to the patient or user.

[0112] For example, the drug delivery system or one or more computing devices may use the information to make a determination as to whether delivery of a certain number of doses of a particular drug (e.g., in the case of a drug delivery device containing a particular drug) has arrived, for example, at a particular logistics or pharmacy location. This determination may be made based in part on the geographic location information and in part on the drug identification information. Based on this information, the one or more computing devices may generate a communication that is sent to a pharmacy or logistics provider (e.g., via a pharmacy or logistics provider server) to inform the pharmacy or logistics provider of the delivery of the drug delivery device. A pharmacy or logistics provider may use such smart drug delivery devices to simplify, for example, their logistics and inventory systems.

[0113] Along similar lines, the drug delivery system or one or more computing devices may use the information to determine that one or more of the drug delivery devices were damaged en route to a particular logistics or pharmacy location. The determination may be based in part on geographic location information and in part on drug identification information. The determination may also be based in part on condition state information, such as temperature, shock / vibration exposure, light exposure, or drug color and / or turbidity (i.e., history established in the drug delivery device record or drug record), whether determined at a particular time or over a period of time. The determination may also or instead be based in part on product age related to the product's manufacturing date or expiration date. The determination may also or instead be based in part on operational state information, such as removal of a sterility barrier from the second end of the cannula of the drug delivery device. Based on this information, the one or more computing devices may generate a communication to be sent to a pharmacy or distributor (e.g., via a pharmacy or distributor server) to inform the pharmacy or distributor that the drug delivery device has been damaged or expired. The pharmacy or distributor may use such a smart drug delivery device to, for example, facilitate replacement of damaged or expired product at the distributor or pharmacy, preventing delays in patient treatment.

[0114] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination that the product is as described and not counterfeit. Such a determination may be based on drug identification information, such as the product's name, strength, and amount, as well as security and anti-counterfeiting measures associated with the drug. The determination made by the one or more computing devices may result in the generation of a communication, which may be sent to a government agency (e.g., customs / immigration officials) via a government agency server, to a logistics provider and / or pharmacy via their respective servers, and / or to the patient and caregiver via their personal mobile devices.

[0115] As a further alternative, certain decisions made by a drug delivery system and / or one or more computing devices operating in accordance with embodiments of the present disclosure may be used to operate a drug delivery device remotely (i.e., without a control device present in the same geographic location (e.g., room, building, or city) as the drug delivery device).

[0116] For example, the drug delivery system or one or more computing devices may use the information to make a determination that the device needs to be controlled to prevent inadvertent operation. The determination may be based, in part, on the drug identification information in combination with certain patient identification information, such as biometric information in the form of a fingerprint. If it is determined that an unauthorized party is attempting to use the drug delivery device, the one or more computing devices may generate a signal that is sent to the drug delivery system to lock the drug delivery device or to keep it locked until the drug delivery system is accessed by the patient or user for whom it is intended.

[0117] As a further alternative, the drug delivery system or one or more computing devices may use information to determine that a patient associated with the drug delivery device falls into a particular group or subgroup of patients or users who require or prefer a particular mode of drug delivery device operation. This determination may be made, in part, using information related to patient and drug identity. Based on this determination, the drug delivery system and / or one or more computing devices may generate a signal that personalizes the operation of the drug delivery device. For example, the drug delivery device may be personalized with respect to the sounds and / or lights used to notify the patient of various conditions or operating states according to a particular market segment or patient population associated with that patient. As one example, different sounds may be used for pediatric patients than for adult patients, louder sounds may be used for patients with hearing loss, and different lights or light sequences may be used for patients with color blindness. Such control of the drug delivery device through the drug delivery system and / or one or more computing devices may reduce costs for drug delivery by allowing a single drug delivery device to be used that is tailored to the patient via software, rather than using multiple different drug delivery device types, each with different hardware than other types of drug delivery devices.

[0118] As a further alternative, the drug delivery system or one or more computing devices may use the information to make a determination that the drug delivery device did not perform properly and generate a communication regarding that point in the manufacture of the drug delivery device. The manufacturer may then determine changes and / or improvements to enable proper administration of the drug, and if that is not followed or successful, can perform a check on the sensed information and relay the error.

[0119] As noted above, the drug delivery system and / or one or more computing devices in communication with the drug delivery system need not be adapted or programmed to perform all of the operations listed in Figures 2, 3A-C, and 4. Several views of embodiments of a drug delivery system or computing device according to the present disclosure will now be discussed in connection with Figures 5-12B. Figures 5-12B illustrate methods for operating a drug delivery system or computing device that represent a subset of the operations discussed above with respect to Figures 2, 3A-C, and 4 and related systems. Figures 5-9 relate to methods relating to the sterility barrier, while Figure 10 relates to activation of the device and Figures 11 and 12A-12B relate to the needle shield.

[0120] 5, a method 500 is illustrated in which a drug delivery system is adapted or programmed to provide instructions to a patient or user through the use of an output device, such as a light-emitting diode, display, speaker, or other device, and to communicate with a computing device (e.g., mobile device 110 or computing device 114) over a communications link (e.g., 112 or 116) to send a report to the computing device. Method 500 focuses on a single problem: whether the sterility of the device has been compromised. Method 500 determines whether the sterility of the device has been maintained based on whether a barrier in the form of a needle cap is disposed on the second end of the cannula, which is intended to be inserted into the patient.

[0121] Method 500 begins at block 502 by making a determination as to whether the needle cap is in place. This determination may be made as to whether a signal is received by a controller adapted or programmed to perform method 500 from a switch or other proximity sensor adjacent structure of the automatic injection device when the needle cap is properly disposed on the end of the needle. If a determination is made at block 502 that the needle cap is in place, method 500 continues at block 504, where the user may be instructed to remove the needle cap, for example, by illuminating one or more light-emitting diodes visible to the patient or the user of the drug delivery device. The controller may also cause a transmitter (capable of at least one-way communication and which may be capable of two-way communication (i.e., a transceiver)) at block 504 to transmit a report indicating the fact that the sterility of the device has not been compromised to one or more computing devices in communication with the transmitter. For example, the transmitter may be a short-range transmitter that may use, for example, Bluetooth or a similar protocol.

[0122] The method 500 may continue at block 506, where the controller determines whether the needle cap has been removed after the patient or user is instructed to remove it. For example, the controller may determine that the needle cap has been removed when it receives a different signal (or no signal) from a switch or other proximity sensor. When the controller determines that the needle cap has been removed, the method continues at block 508, where the controller causes the transmitter to transmit a report indicating the fact that the needle cap has been removed after the sterility of the device has been confirmed.

[0123] As shown in FIG. 5 , if the controller determines in block 502 that the barrier is not in place—for example, the needle cap was not disposed around the end of the needle at the beginning of the process—method 500 includes a different set of actions. If such a determination is made in block 502, method 500 remains at block 510, where the controller locks the drug delivery device, instructs the patient or user to replace the product container, and causes the transmitter to transmit a report indicating the fact that the sterility of the device has been compromised. Similar to the actions performed in block 504, the controller may instruct the patient or user to replace the product by illuminating a light-emitting diode. The controller may also lock the product by preventing the operation of one or more other assemblies necessary to administer the medication to the patient; for example, the controller may prevent the needle from being inserted into the patient. The controller then waits until a determination is made in block 512 that the product has been replaced. The controller may determine that the product has been replaced depending on whether a switch proximate the container has changed state only if the container has been replaced. When the controller determines that the product has been replaced, method 500 continues to block 514, where the controller causes the transmitter to transmit a report to one or more computing devices in communication with the drug delivery system indicating the fact that the sterility of the device was initially compromised but that the product has been replaced.

[0124] 5, which is performed by a drug delivery system having a controller adapted or programmed to perform method 500, methods 520, 540 of Figures 6 and 7 are performed by a drug delivery system and associated computing device, where the drug delivery system is adapted or programmed to perform method 520 and the computing device is adapted or programmed to perform method 540. It will be appreciated that methods 520, 540 may limit the amount of hardware required by the drug delivery system by shifting patient or user interaction events to the computing device, which may be in the form of a mobile device 110, to take advantage of output devices or peripherals already associated with the computing device.

[0125] 6 begins at block 522 where a controller that is part of the drug delivery system determines whether the barrier is still sterile, i.e., whether a needle cap is disposed on the end of the needle. If a determination is made that the needle cap is initially in place, then at block 524 the controller causes a transmitter to send a report to a computing device indicating the fact that a needle cap is disposed on the end of the needle.

[0126] 7 begins at block 542 with the receipt of a report from the drug delivery device. If the computing device determines that a report has been received and that the received report represents the fact that the needle cap is initially in place, method 540 proceeds to block 544, where the computing device controls an associated display device to display a message to the user or patient that the needle cap should be removed. According to one embodiment of the present disclosure, if the computing device is a handheld mobile device such as a smartphone, the message may be displayed on a display device associated with the mobile device in the form of an image that may include text, a picture, or a combination thereof, representing instructions for removing the needle cap. Method 540 then proceeds to block 546, where the computing device awaits the receipt of a report representing the fact that the needle cap has been removed from the drug delivery system.

[0127] 6 , after an initial determination is made that the needle cap has not initially been removed, method 520 remains at block 526 where a controller associated with the drug delivery device determines whether the needle cap has been removed. The controller begins this determination with the completion sending of the report at block 524, and thus the determination is not dependent on the patient or user receiving an instruction to remove the needle cap via the computing device, although, according to certain embodiments, the controller's determination of whether the needle cap has been removed at block 526 may be made in response to the user first receiving a message from the computing device that the needle cap should be removed. When the controller determines that the needle cap has been removed, method 520 remains at block 528 where a report is sent to the computing device indicating the fact that the needle cap has been removed.

[0128] Returning to Figure 7, once it is determined at block 546 that a report that the needle cap has been removed has been received by the computing device, the method 540 may continue at block 548 where a report indicating the fact that the drug delivery system is ready for use is sent to the server 104 of Figure 1 by the mobile device 110 of Figure 1, for example, via the network 118. According to other embodiments, the report may be more specific, for example, indicating the fact that the barrier was still sterile initially and that the needle cap was subsequently removed.

[0129] In an alternative example, the controller of the drug delivery system may determine that the barrier was not initially in place at block 522. If so, the controller may lock the drug delivery device and cause the transmitter to send a report to the computing device indicating the fact that the barrier was not initially in place at block 530. The controller of the drug delivery system may then determine whether the product has been replaced at block 532.

[0130] Meanwhile, if the computing device receives a report at block 542 indicating the fact that the barrier was not originally in place, method 540 continues at block 550, where the device controls an associated display device to display a message to the user or patient that the product has been replaced. According to the embodiments of the present disclosure discussed above, if the computing device is a handheld mobile device, the message may be displayed on a display device associated with the mobile device in the form of an image that may include text, pictures, or a combination thereof, indicating replacement product instructions. Method 540 then remains at block 552, where the computing device determines whether a report has been received from the drug delivery system indicating the fact that the drug product has been replaced.

[0131] 6 , if a determination is made at block 532 that the product has been replaced, the controller may cause the transmitter to transmit a report indicating the fact that the product has been replaced at block 534. When the computing device determines at block 552 of FIG. 7 that a report has been received, the method 540 continues to block 548 where a report indicating the fact that the drug delivery device is ready for use is transmitted to the server 104, for example.

[0132] For that matter, it is not a requirement of the present disclosure that decisions regarding condition state information, operational state information, or other information be made by a controller or computing device contained in the same housing as the drug delivery device. In fact, a controller that makes decisions regarding a particular state of the drug delivery device may be disposed in a housing that is removable from the drug delivery device. For example, again with reference to an embodiment that determines whether a sterility barrier is still sterile based on whether a needle cap is disposed on the end of a needle, a method 560 is provided in FIG. 8 involving a controller disposed in the needle cap and coupled to a sensor, such as a switch or other proximity sensor, that determines when the needle cap has been removed from the end of the needle.

[0133] Before discussing method 500, it may be helpful to discuss the diagram of FIG. 9, which includes a needle cap 600 and portions of an embodiment of an autoinjector 602 with which the needle cap 600 is used. It will be understood that much of the structure of the autoinjector 602 has been omitted to facilitate discussion of the structure and operation of the needle cap 600. The autoinjector 602 may include other structures, subassemblies, and / or assemblies that may be inserted into a patient's cannula and force a drug or medication from a reservoir through the cannula and into the patient. In this regard, reference is made to the embodiment of the autoinjector shown in FIG. 13 below.

[0134] According to the simplified illustration of an autoinjector 602 shown in FIG. 9 , the autoinjector includes a syringe-shaped reservoir 604. Thus, the reservoir 604 is defined by a substantially cylindrical wall 606 having a hub 608 on which a cannula 610 is disposed and secured (or supported by a stake). The cannula 610 has a first end 612 in fluid communication with an interior 614 of the reservoir 604 and a second end 616 intended for insertion into a patient. The reservoir 604 may also include a plunger 618 that moves along the reservoir 604 to force fluid from the reservoir 604, through the cannula 610, and into the patient. The autoinjector 602 may also include a structure 620 that cooperates with structure of the needle cap 600, and the structure 620 is disposed about the cannula 610. The structure 620 may be, for example, a needle shield (described in more detail in connection with the embodiment of FIG. 13) or part of the housing of the autoinjector 602 .

[0135] The needle cap 600 includes an annular collar (or hub) 622 within which the hub 608 of the reservoir 604 is received. The collar 622 fits closely around the hub 608 at one end and receives the second end 616 of the cannula 610 within an interior space 624 of the collar 622. The collar 622 may also be described as being disposed around the second end 616 of the cannula 610. The collar 622 is attached to a body 626 (which may be in the form of a housing) within which a power source 628 and a controller / communications module assembly 630 are disposed. The power source 628 and module assembly 630 may be coupled through the use of a switch 632 including first and second contacts 634, 636 as shown. When the contacts 634, 636 are adjacent to one another, the module assembly 630 is coupled to the power source 6268.

[0136] 9, first contact 634 is adjacent needle shield 620 having needle cap 600 disposed about second end 616 of cannula 610 and therefore, in this first state, is not adjacent end 638 of second contact 636. When needle cap 600 is removed (second state), first contact 634 is free to move toward second contact 636 and adjacent end 638 of second contact 636. With contacts 634, 636 adjacent to one another, a circuit is closed and module 630 is coupled to power source 628.

[0137] According to method 560 of FIG. 8 , the controller of module 630 may determine, at block 562, that the needle cap 602 is disposed on the end 616 of the needle 610 based on a signal received (or not received) from a switch or sensor 632. The sensor may be quite simple for this embodiment, and may include a pair of contacts 634, 636 that are typically disposed on opposite sides of or otherwise spaced apart by the needle shield or housing 620 (see FIG. 9 ), but that are connected or coupled when the needle cap 602 is removed (such that the needle shield or housing 620 is no longer disposed between or prevents the contacts 634, 636 from contacting each other). In fact, according to such an embodiment, the sensor 632 and the controller of module assembly 630 may be of the same structure. When the module 630 determines that the needle cap 602 has been removed, the module assembly 630 controls the associated transmitter to transmit a report indicating the fact that the needle cap 602 has been removed at block 564. Again, according to embodiments in which the contacts 634, 636 are sensors 632, the connection or coupling of the contacts 634, 636 may close a circuit including the transmitter 630 and the power source 628 (e.g., a battery), which causes the transmitter 630 to transmit the necessary report.

[0138] 10 and 11 illustrate methods similar to that of FIG. 8, in which each method focuses on determining a single condition or operating state of the drug delivery device and transmits a report when the condition or operating state occurs. In this regard, method 570 focuses on determining whether the drug delivery device has been activated by determining whether an actuator (e.g., a button) has been depressed, and method 580 focuses on determining whether a needle shield, which is part of the drug delivery device, has been deployed (which typically occurs after drug delivery is completed and the drug delivery device has been removed from the patient's skin). Also, like the embodiment of FIG. 9, the embodiment of FIGS. 10 and 11 may be implemented through the use of a sensor in the form of a switch or pair of contacts that closes a circuit including a transmitter and a power source once an operating state has been determined.

[0139] Thus, according to FIG. 10 , method 570 begins at block 572, where the controller / switch determines whether the actuator has been depressed according to whether the switch state has changed according to a switch contacting a portion of the drug delivery device that normally does not contact the switch unless the button is depressed (see, e.g., switch 766 in FIG. 13 ). For example, a switch may be attached to the actuator (e.g., a button) and take over the actuator such that when the actuator moves relative to the housing of the drug delivery device, the switch contacts a structure on the drug delivery device that changes the state of the drug delivery device. When this occurs, method 570 remains at block 574, where the controller / switch causes the transmitter to transmit a report indicating the fact that the drug delivery device has been activated by closing a circuit between the transmitter and a power source (e.g., a battery, capacitor, or inductive power source). Activation of the drug delivery device may coincide with activation of a driver associated with the reservoir to cause the expulsion of medicament from the reservoir, but activation of the driver need not coincide with activation of the drug delivery device.

[0140] 11 , method 580 begins at block 582 where the controller / pair of contacts determines whether the needle shield 656 is deployed according to whether the pair of contacts are connected or coupled together. As shown in Figures 12A and 12B, an embodiment of a drug delivery device system for performing method 580 may include a reservoir 650 in the form of a syringe (see Figure 12A) having a cannula 652 in the form of a needle having an end 654 to be inserted into a patient, and a needle shield 656 including a conductive pad 658 that connects to the pair of contacts 660, 662 when the needle shield 656 is deployed in a distal position; alternatively, one of the pair of contacts 660, 662 may be disposed on the housing of the drug delivery device and the other of the pair of contacts 660, 662 may be disposed on the needle shield 656 such that the contacts 660, 662 are connected or coupled when the needle shield 656 moves relative to the housing of the drug delivery device. More specifically, after the needle shield 656 is moved distally from a proximal position (where the needle shield 656 does not surround the distal end 654 of the delivery cannula 652) to a distal position (where the needle shield 656 surrounds the distal end 654 of the delivery cannula 652), the conductive pad 658 may contact each of the pair of contacts 660, 662, thereby forming a closed electrical circuit. When this occurs, the method 580 remains at block 584, and the circuit including the power supply 664 and the controller and transmitter module assembly 668 closes, causing the transmitter of module 668 to transmit a report indicating the fact that drug delivery is complete (under most circumstances). Thus, a report indicating completion of drug delivery is transmitted in response to the needle shield 656 being disposed around the distal end 654 of the delivery cannula 652 after the needle shield 656 is moved from its proximal position to its distal position.

[0141] In some embodiments, the pair of contacts 660, 662 may be part of a latch circuit. The latch circuit may be configured so that initial contact between the conductive pad 658 and the pair of contacts 660, 662 powers the transmitter module assembly 668. Then, after a period of time, the latch circuit powers the transmitter module assembly 668 independently of contact between the conductive pad 658 and the pair of contacts 660, 662. Thus, the latch circuit helps ensure that power is supplied to the transmitter module assembly 668 even if the conductive pad 658 inadvertently moves out of contact with the pair of contacts 660, 662 after its initial contact with the pair of contacts 660, 662.

[0142] 12A and 12B, repositioning of contacts 660, 662 relative to conductive pad 658 allows the system of FIGURES 12A and 12B to determine whether needle shield 656 has been moved relative to end 654 of cannula 652 to determine that cannula 652 has been inserted into a patient. Rather than movement of needle shield 656 toward the bottom of the page, which causes conductive pad 658 to close the circuit between contacts 660, 662, movement of needle shield 656 toward the top of the page causes conductive pad 658 to close the circuit between contacts 660, 662, which causes module assembly 668 to send a report indicating the fact that a needle has been inserted. As a further alternative embodiment, two sets of contacts may be included, spaced apart from one another in the direction of movement of the needle shield 656, with the set of contacts closest to the top of the page being used to determine whether the needle shield 656 has been moved relative to the end 654 of the cannula 652, indicating insertion of the end 654 into the patient, and the set of contacts closest to the bottom of the page being used to determine whether the needle shield has been disposed around the end 654 of the cannula 652, indicating completion of delivery to the patient.

[0143] The methods discussed above may be implemented with a variety of different drug delivery systems. Figures 13 and 14-16 illustrate two examples of such systems, with the embodiment of Figure 13 including a drug delivery system that includes a drug delivery device in the form of an autoinjector, and the embodiment of Figures 14-16 including a drug delivery system that includes a drug delivery device in the form of an on-body injection device or injector.

[0144] Referring first to the drug delivery device of FIG. 13 , the autoinjector 700 includes a housing 710 in which assemblies or structures may be disposed that insert or allow insertion of a cannula into a patient and inject a drug or medicament from a reservoir through the cannula and into the patient. According to certain embodiments, the same assembly or structure that inserts the cannula into the patient may also allow the drug or medicament to flow from the reservoir through the cannula and into the patient. The autoinjector 700 may also include assemblies or structures that connect the cannula to the reservoir, retract the cannula into the housing 710, or position other structures that prevent contact with the cannula once the cannula is removed from the patient. Further and additional assemblies and structures are also possible. Accordingly, the specific embodiments of the autoinjector 700 discussed below are by way of example and not limitation. For example, the automatic injection device 700 may lack an assembly or structure for inserting a cannula (e.g., a needle) into a patient, and insertion of the cannula into the patient may occur by the cannula being substantially fixed relative to the housing of the automatic injection device 700 and the automatic injection device 700 being moved toward the patient.

[0145] The drug delivery system 700 includes a reservoir 712 and a cannula 714 having a first end 716 that may be connected to or fluidly connectable to the reservoir 712, and a second end 718 that may be inserted into a patient. The cannula 714 may be, for example, a rigid needle with a beveled edge that may be sized so that the second end 718 of the cannula 714 is received under the skin to deliver a subcutaneous infusion of the drug in the reservoir 712. The first end 716 of the cannula 714 may be disposed through a wall 720 of the reservoir 712 and thus may be fluidly connected to the reservoir 712. As shown, the first end 716 of the cannula 714 may be disposed partially through the wall 720 (which may be, for example, a resealable septum or stopper) such that the first end of the cannula 714 cannot be fluidly connected until the second end 718 of the cannula 714 is inserted into the patient. In such circumstances, the first end 716 of the cannula 714 may be described as being fluidly connectable to the reservoir 712 in this manner, although it will be understood that there are other mechanisms by which the first end 716 of the cannula 714 may be fluidly connectable to the reservoir 712 but is not connected.

[0146] The drug delivery device 700 includes a shield 722 that may be positioned to restrict access to the second end 718 of the cannula 714, at least after an injection is completed. According to certain embodiments, the shield 722 may have a biasing element 724 (such as a spring) that stretches the shield 722 from the housing 710 such that the distal end 726 of the shield 722 extends beyond the second end 718 of the cannula 714 except when the shield 722 is positioned against the skin and an injection of the cannula 714 is activated. Indeed, according to certain embodiments of the autoinjector 700, an injection of the cannula 714 may be activated by placing the distal end 726 of the shield on or against the patient's skin. The automatic injection device 700 may also include a lock 728 associated with the shield 722 and limiting movement of the shield 722 relative to the housing 710 of the automatic injection device 700 so that, after delivery of the drug, the distal end 726 of the shield 722 extends a sufficient distance from the housing 710 to limit or prevent contact with the second end 718 of the cannula 714 after the cannula 714 is removed from the patient's skin.

[0147] The drug delivery device 700 also includes at least one driver 730, which may be used to insert the second end 718 of the cannula 714 into the patient's skin and inject the drug or agent from the reservoir 712 through the cannula 714 and into the patient. According to certain embodiments, the driver 730 may include one or more springs. According to other embodiments, the driver 730 may include a source of pressurized gas or material in which a phase change occurs, such that the effused gas or phase-change material provides a motive force capable of pushing the drug into and out of the reservoir 712. According to still other embodiments, the driver 730 may include an electromechanical system, for example, a prime mover, although such an electromechanical system may be more suitable for an on-body autoinjector or injector, as described in further detail below. Other embodiments of the driver 730 will be understood.

[0148] Driver 730 may cooperate with wall 732 of reservoir 722 to move wall 732 toward the patient's skin. According to such embodiments, wall 732 may be a stopper that is received within bore 734 and can move along bore 734 from a first end to a second end to inject the drug from reservoir 712. Driver 730 may also cooperate with stopper 732 and / or bore 734 to move reservoir 712 relative to housing 710 to move second end 718 of cannula 714 relative to housing 710 and into the patient. According to embodiments in which driver 730 cooperates with stopper 732, this may occur before first end 716 of cannula 714 is in fluid communication with reservoir 712. According to an embodiment in which the driver cooperates with hole 734, the driver may include one component (e.g., a first spring) that cooperates with hole 734 to move reservoir 712 and cannula 714 relative to housing 710, and a second component (e.g., a second spring) that cooperates with stopper 732 to move stopper 732 relative to hole 734.

[0149] The driver 730 is associated with an actuator 740. The actuator 740 activates the driver, causing the driver 730 to insert the cannula 714 and inject the drug from the reservoir 712 through the cannula 714 and into the patient. According to certain embodiments, the actuator 740 may be the shield 722. According to other embodiments, such as the illustrated embodiment, the actuator 740 may be a button that can be depressed by the user once the autoinjector 700 is placed on or against the patient's skin. While the embodiment shown in FIG. 13 has the actuator 740 disposed on one end of the device, the actuator 740 may also be disposed on the side of the device.

[0150] As shown, reservoir 712, biasing element 724, lock 728, and driver 730 are disposed within housing 710, along with at least a portion of cannula 714. Also disposed within housing 710 are controller 750, communications module 752, and at least one sensor or switch. According to the illustrated embodiment, four sensors are included: a temperature sensor 760, a proximity sensor 762 (for determining the presence of a needle cap (not shown) or the position of needle shield 722), and two orientation sensors 764. Additionally, switch 766 is also provided to determine whether button 740 is depressed. Controller 750 is coupled to communications module 752, sensors 760, 762, 764, and switch 766. One or more of the controller 750, communication module 752, sensors 760, 762, 764, and switch 766 may be packaged together as a single module, or each component may be manufactured separately and combined once the components are disposed within the housing 710. According to certain embodiments, each component may be integrated with the structure of the device 702 with which it is associated (e.g., sensors 762, 764 may be integrated with the shield 722), and the locations of the sensors in FIG. 12 are merely exemplary.

[0151] Controller 750 may include at least one processor and memory. Controller 750 may also include or be coupled to a power source, such as a battery. The processor may be programmed to perform the operations that the controller is adapted to perform, and the memory may include one or more readable, non-transitory, tangible memories having executable instructions stored thereon that, when executed by the at least one processor, cause the at least one processor to perform the operations that the controller 750 is adapted to perform. Alternatively, the controller may include other circuitry that performs the operations that the controller is adapted to perform.

[0152] The communications module 752 may be any of several different communications modules used to communicate with the mobile device 110 and / or computing device 114 (see FIG. 1 ). According to one embodiment, the communications module 752 may be a Bluetooth / Bluetooth Low Energy module mounted with the controller 750. The communications module 752 is used to transmit information from the autoinjector 700 to the mobile device 110 or computing device 114. Alternatively, other protocols may be used by the communications module 752, such as radio frequency identification, Zigbee, Wi-Fi, near field communication, etc.

[0153] Given the presence of temperature sensor 760, proximity sensor 762, orientation sensor 764, and switch 766, controller 750 may be adapted or programmed to implement most of the method 300 shown in Figures 3A-3C, as well as the methods shown in Figures 5-7, 10, and 11, along with the provision of suitable output devices as needed.

[0154] While the cannula 714 of the drug delivery system 300 shown in FIG. 13 is fixed relative to the reservoir 712 and therefore in constant fluid communication with the reservoir 712, other embodiments may be arranged differently, for example, with the cannula 714 being movable relative to the reservoir 712. FIG. 13A illustrates a cannula subassembly 780 that can be implemented within the drug delivery system 700 of FIG. 13 and that allows the first end 716 of the cannula 714 to move into fluid communication with the reservoir 712 when the second end 718 of the cannula 714 is inserted into a patient and to lose fluid communication with the reservoir 712 when the second end 718 of the cannula 714 is removed from the patient. To achieve this functionality, the cannula subassembly 780 includes a spring seat 782 fixed to the cannula 714 and a spring 784 positioned between the spring seat 782 and the distal end of the reservoir 714. The spring seat 782 may have a distal end surface 786 configured to press against the patient's skin and a proximal end surface 788 in contact with the spring 784. As shown in FIG. 13A , the proximal end surface 788 may include a guide channel or groove 790 to receive the distal end of the spring 784 and prevent the spring 784 from disengaging from the spring seat 782. Prior to delivery of the agent to the patient, the spring 784 may be in its natural, uncompressed state, as seen in FIG. 13A , and may bias the spring seat 782 away from the reservoir 712. Thus, the first end 716 of the cannula 714 is spaced from the reservoir 712 and is not in fluid communication with the reservoir 712 when the spring 784 is uncompressed. When drug delivery system 700 is used to deliver a medication to a patient, the patient's skin presses against distal end surface 786 of spring seat 782, thereby compressing spring 784 and moving cannula 714 distally until first end 716 of cannula 714 penetrates septum 720 and enters the interior of reservoir 712. In this configuration, fluid communication is established between cannula 714 and reservoir 712 such that cannula 714 can deliver the medication within reservoir 712 to the patient. When drug delivery system 700 is removed from the patient's body, spring 784 expands and returns to its natural, uncompressed state shown in FIG. 13A .As a result, spring 784 moves away from spring seat 786 and first end 716 of cannula 714 is removed from reservoir 712. Thus, first end 716 of cannula 714 is no longer in fluid communication with reservoir 712. One advantage of cannula subassembly 780 depicted in FIG. 13A is that premature removal of drug delivery device 700 from the patient's skin during drug delivery is less likely to result in wasteful release of the drug. This is because premature removal of drug delivery system 700 from the patient's skin automatically causes cannula 714 in cannula subassembly 700 to become out of fluid communication with reservoir 712.

[0155] FIG. 14 illustrates a drug delivery system 800. System 800 may be a wearable disposable system. System 800 may include a disposable housing 802 that can be attached to a patient or wearer, for example, with an adhesive.

[0156] Disposable housing 802 may be made of a plastic material. As seen in FIG. 15, housing 802 may be defined by two regions: a plate 804 that is applied in contact with the wearer's skin and a dome 806 that is preferably attached to plate 804 by a sealant at a contact surface between outer peripheral edge 808 of plate 804 and outer peripheral edge 810 of dome 806.

[0157] As shown in FIG. 15, housing 802 has an inner surface 812 and an outer surface 816 that define an internal space 814. Specifically, plate 804 has an inner surface 818 and an outer surface 820, and dome 806 has an inner surface 822 and an outer surface 824. According to the illustrated embodiment, inner surface 812 of housing 802 is defined by inner surfaces 818, 822 of plate 804 and dome 806, while outer surface 816 of housing 802 is defined by outer surfaces 820, 824 of plate 804 and dome 806.

[0158] As noted above, the housing 802 may be attached to the wearer's skin. Specifically, an adhesive may be used. The adhesive may be adapted to releasably secure the housing to the skin during a single application. As shown in FIG. 15 , the adhesive is disposed on a portion 828 of the exterior surface 816 of the housing 802, specifically in a layer 826 on the exterior surface 820 of the plate 804. The adhesive is covered with a removable, disposable sheet 830 prior to application of the housing 802 to the wearer's skin.

[0159] 15 and 16 , reservoir 840, driver 842, cannula (or structure, see below) 844, and inserter 846 are disposed within housing 802. According to the illustrated embodiment, reservoir 840 may be defined, at least in part, by the combination of a rigid-walled cylinder or bore 860 having a port 862 at a first end 864, and a plunger 866 fitted for movement along a longitudinal axis 868 of cylinder 860 between a second end 870 and first end 864 to force the medication from reservoir 840 through port 862 ( FIG. 14 ). Movement of plunger 866 may be effected by operation of driver 842.

[0160] The driver 842 may be similar in structure and operation to mechanisms for moving a plunger along a cylinder, as can be found in U.S. Patent Nos. 6,656,158, 6,656,159, 7,128,727, and 7,144,384, which are incorporated by reference herein for all purposes. The driver 842 may include a plunger arm, a prime mover, a transmission, and a power source (e.g., a battery). The plunger arm may contact the plunger 866 at at least a first end to urge the plunger 866 along the cylinder 860, and the transmission may be coupled to the plunger arm and the prime mover and move the plunger arm according to the operation of the prime mover. The power source provides a power source for the prime mover. The combination of the prime mover, transmission, and power source may also be referred to as an example of an actuator. Other mechanisms, such as a spring, pressurized gas, or phase-change material, may also be used to apply force to the plunger to move it along the cylinder.

[0161] According to another variant, a non-rigid collapsible pouch may be used in place of the rigid-walled cylinder 860 and plunger 866 shown in FIG. 15 . It will be appreciated that if the reservoir 860 is in the form of a non-rigid collapsible pouch, a spring-based mechanical system may be used to compress and pressurize the reservoir. According to a further variant, a non-mechanical system may be used to move the plunger 866 or compress the bag. For example, a gas-generating system may be used, including a two-component system that keeps the components separate when combined until gas is generated. As a further alternative, a swellable gel may be used, where the introduction of water from a water source internal to the device causes the gel to expand in size, moving the plunger or compressing the pouch. As a further example, the propellant reservoir may be opened, releasing the propellant to move the plunger 866 or compress the bag. Examples of such alternative mechanisms can be found in US Pat. Nos. 5,957,895, 5,858,001, and 5,814,020, which are incorporated herein by reference for all purposes.

[0162] According to certain embodiments, reservoir 840 may be a pre-filled container, such as a pre-filled cartridge or a pre-filled syringe. Alternatively, delivery system 800 may include an inlet 880 adapted to receive the luer tip of a syringe (e.g., the syringe shown in FIG. 14 ) in fluid communication with reservoir 840, although a rubber septum, for example, may be used instead. In use, a healthcare provider may inject medication from a syringe through inlet 880 into reservoir 840, which may be provided to a healthcare provider in a kit with delivery system 800 as a pre-filled syringe (filled with any of the substances described above).

[0163] Cannula 844 may have a retracted state in which tip 890 (effectively the entire cannula 844) may be retracted into housing 802, and a deployed state in which tip 890 protrudes from housing 802, with inserter 846 moving needle 844 from the retracted state to the deployed state. Example inserter examples can be found in U.S. Patent Nos. 7,128,727 and 7,144,384, which are incorporated by reference herein for all purposes.

[0164] Cannula 844 may be hollow and may be used to administer a drug directly to a patient. Alternatively, structure 844 may be used in conjunction with cannula 892, where structure 844 is used to insert cannula 892 into a patient through an infusion site, with the drug passing through catheter 892 into the patient during administration. Stated slightly differently, according to certain example embodiments, system 800 may automatically insert a soft cannula into subcutaneous tissue.

[0165] 15, housing 802 (specifically plate 804) may have an aperture or opening 894 formed therein that allows cannula (or structure) 844 (and optionally cannula 892) to pass therethrough. According to certain embodiments, aperture 894 may be unobstructed, such that there is no impediment or hindrance to movement of cannula 844 (and catheter 892) through aperture 894. However, a septum may be disposed in or over aperture 894 to better preserve the sterility of cannula 844 and the container occlusion integrity (CCI) of the device.

[0166] A septum, which may be made of rubber, may be disposed between cannula 844 (and space 814) and the patient's skin when needle 844 is in the retracted state. When deployed, at least a portion of needle 844 (i.e., tip 890) hangs down from space 814 through the septum. As such, the septum always exists as a barrier between interior space 814 and the outside environment.

[0167] System 800 may also include a controller 900, which may include at least one processor and memory, where the processor is programmed to perform the operations the controller is adapted to perform, and the memory includes one or more readable non-transitory tangible memories having executable instructions stored thereon that, when executed by the at least one processor, may cause the at least one processor to perform the operations the controller is adapted to perform. Alternatively, the controller may include other circuitry that performs the operations the controller is adapted to perform. By way of example and not limitation, controller 900 may be adapted to perform any one of the methods described above for a drug delivery system.

[0168] In addition to the controller 900, the system 800 may include a communications module 902 and at least one sensor or switch. The communications module 902 may be any of several different communications modules used to communicate with the mobile device 110 and / or the computing device 114 (see FIG. 1 ). According to one embodiment, the communications module 902 may be a Bluetooth / Bluetooth Low Energy module coupled to the controller 900. The communications module 902 is used to communicate information from the system 800 to the mobile device 110 or the computing device 114. Alternatively, other protocols may be used by the communications module 752, such as Radio Frequency Identification, Zigbee, Wi-Fi, Near Field Communication, etc. According to the illustrated embodiment, the system 800 also includes a temperature sensor 904 mounted on the base of the controller 900, and thus may be capable of implementing at least some of the methods described in FIGS. 2 and 3A-3C.

[0169] While only a few possible sensors or sensing systems are mentioned above, further examples are provided below categorized based on the conditions or operating states that can be determined using these sensors or sensing systems.

[0170] Condition state information, generally

[0171] Temperature may be determined using thermal paper that changes color when exposed to thermal energy, used in combination with an optical sensor capable of detecting color or color change. Temperature may also be determined using a thermocouple external to the device, for example, with contact with the drug reservoir, and the voltage across a series resistor is used to determine whether and by how much the reservoir temperature or ambient temperature is lower than that of the device. A reversible circuit featuring a material such as nitinol that changes shape with temperature may be used; each time a temperature threshold is exceeded, the shape change closes the circuit, thereby starting a cumulative timer, which is used to ensure that the total time the temperature has exceeded the threshold temperature is less than a predetermined threshold period. Shape-changing materials may also be used to activate flags or shields to display readiness indicators that can be read, for example, using optical devices.

[0172] Light exposure may also be determined using photosensitive paper that changes color upon exposure to light used in combination with an optical device capable of sensing color or color change. Alternatively, a photoresistor in conjunction with a voltage divider circuit may be used to sense the presence of light.

[0173] The orientation of the drug delivery system (and device) may be determined by using an accelerometer or magnetometer. Additionally, the drug delivery system may use two-way communication with a computing device, such as the mobile device 110, to obtain orientation information from the mobile device 110 and thereby infer the orientation of the drug delivery device. Indeed, the drug delivery system may be connected to the mobile device 110 to improve the strength of the inference that the orientation of the mobile device 110 corresponds to the orientation of the drug delivery device.

[0174] The color and / or turbidity of the product may be measured using an optical device, such as a pair of optical transmitters / receivers, which may be disposed on the same side of the reservoir or on opposite sides of the reservoir. Measurements obtained using the optical device for the drug reservoir may be compared to a reference measurement. In fact, a reference may be provided in the drug device adjacent to the drug reservoir so that the optical device can be used to optically inspect the drug in the reservoir and the reference, thereby enabling a comparison to be made, for example, between measurements obtained for the drug product in the reservoir and measurements obtained for the reference. Alternatively, any gaps in reception of light transmitted through the reservoir may indicate a cloudy product or a product that has undergone a color change, as this may be reception (or failure to receive) light deflected at a particular angle due to the presence of particulate matter in the product. Alternatively, a CCD array may be used to take a photograph of the product in the reservoir, which is analyzed to determine color and / or turbidity, which analysis may be performed by the system or by a local or remote device (in which case the photograph may be transmitted to a local or remote device for analysis).

[0175] The geographic location may be determined using a global positioning satellite transceiver. Additionally, the drug delivery system may use two-way communication with a computing device, such as the mobile device 110, to obtain geographic location information from the mobile device 110 and infer the location of the drug delivery device. Indeed, the drug delivery system may be connected to the mobile device 110 to improve the strength of the inference that the location of the mobile device 110 corresponds to the location of the drug delivery device.

[0176] The temporal information may be obtained using a timer that is started at the time of manufacture and may have a calibrated expiration date. Alternatively, a radio frequency identification device tag encoded with the date of manufacture may be included in the packaging or with the device and may be interrogated by the system prior to administration.

[0177] Operating status information, generally

[0178] The packaging may be used as a Faraday cage, and the drug delivery system may include circuitry to detect interference with the signal or increased received signal as a result of removal of the packaging to determine the operational state that the device has been unpackaged.

[0179] Various sensors may be used to determine the operating status of patient application. For example, back electromotive force from a moving magnet on the needle shield passing through a coil may indicate that the device has been applied to a patient. Alternatively, displacement of a component or assembly (e.g., the needle shield) resulting from application of the drug delivery device to a patient may open or close a switch / circuit to signal this operating status. Along similar lines, movement of a component or assembly may be detected using an optical sensor, whereby a light beam between a transmitter and a receiver is interrupted by a change in the position of a component, such as the needle shield or reservoir (e.g., a syringe or cartridge), upon application of the drug delivery device to a patient. As a further alternative, capacitive or resistive sensors may be used, or pressure sensors may be used. Indeed, information regarding cannula (or needle) insertion may be determined by measuring the resistance through the needle and / or skin to external contact. Changes in temperature of the end of the drug delivery device intended to be adjacent to the patient's skin may also be used to determine the operating status of patient application.

[0180] A similar set of sensors associated with the needle shield may be used to determine when the needle shield is deployed and locked into place when drug delivery is complete.

[0181] A similar set of sensors associated with the actuator or button (instead of the needle shield) may be used to determine when the actuator or button is depressed to initiate delivery of the drug.

[0182] An accelerometer may be used to sense the impact impulse of the actuator being manipulated or the needle shield being moved to determine one of the operating states: triggering the device, initiating drug delivery, and completing drug delivery. A pressure sensor may be mounted within the reservoir to detect the increase in pressure in the reservoir that occurs when drug delivery is initiated, thereby used to determine the initiation of drug delivery operating state. As a further alternative, a microphone or audio sensor may be used to determine whether mechanical noise from a component indicates activation of the device. As a further alternative, a strain sensor may be mounted on a thin column that bends under force between the drive mechanism and the plunger to sense the initiation of drug device operating state. In fact, according to certain embodiments, the strain sensor may be limited to single use (i.e., the sensor bends and fails or permanently deforms) to "leave" the fact that delivery has been initiated, thus eliminating the need for frequent signal monitoring.

[0183] Described below in connection with Figures 17-30 are additional embodiments of sensors and sensing systems for detecting condition and / or operational status information associated with a drug delivery device. While the sensors and sensing systems described below are configured for use with an automatic injection device, one or more of these sensors and sensing systems may also be configured for use with an on-body injection device. Furthermore, any combination of the following sensors or sensing systems may be implemented within a single automatic injection device or a single on-body injection device, or any other drug delivery device. Furthermore, one or more of the following sensors or sensing systems may be used in combination with one or more of the sensors or sensor systems described in connection with Figures 1-16.

[0184] 17, an embodiment is illustrated in which an autoinjector 1700 is configured to detect and report whether it has been primed to deliver its medication. The autoinjector 1700 includes a reservoir 1710 configured to contain a medication and a delivery cannula 1712 having a proximal end 1714 and a distal end 1716. The proximal end 1714 of the delivery cannula 1712 is in fluid communication with the reservoir 1710, and the distal end 1716 of the delivery cannula 1712 is configured to be received within a patient. The autoinjector 1700 may also include a plunger 1720 movable distally through the reservoir 1710 to expel (e.g., push) the medication from the reservoir 1710 through the delivery cannula 1712 and into the patient. In some embodiments, the plunger 1720 may move linearly along a longitudinal axis A of the autoinjector 1700. Longitudinal axis A may coincide with the longitudinal axis of reservoir 1710. Plunger 1720 may have a proximal end 1722 and a distal end 1724 including a stopper 1726. Stopper 1726 may be configured to sealingly and slidably engage an inner wall of reservoir 1710 such that stopper 1726 can force the medicament through reservoir 1710 and into delivery cannula 1712. Movement of plunger 1720 may be achieved via a drive mechanism 1730, such as a spring, an electric motor, or any other element capable of providing motive force for movement of plunger 1720 through reservoir 1710. In some embodiments, plunger 1720 may be omitted and the medicament may be expelled from reservoir 1710 by pressurized air.

[0185] The autoinjector 1700 may further include an actuator 1740 configured to initiate delivery of the medication to the patient. As shown in FIG. 17 , the actuator 1740 may be a button that can be manually depressed by the patient or healthcare provider. In some embodiments, the actuator 1740 may be configured to activate the drive mechanism 1730 to move the plunger 1720 distally to release the medication from the reservoir 1710. In embodiments in which the drive mechanism 1730 includes a spring, depression of the actuator 1740 may release the spring, causing it to lengthen, thereby moving the plunger 1720 along the longitudinal axis A toward the distal end of the autoinjector 1700. In other embodiments, the actuator 1740 may be a switch that activates a prime mover to move the plunger 1720.

[0186] The autoinjector 1700 may also include a removable sterility barrier 1750 disposed about the distal end 1716 of the delivery cannula 1712 and a needle shield 1760 movable relative to the distal end 1716 of the delivery cannula 1712. The removable sterility barrier 1750 may be removably attached to the distal end of the reservoir 1710. In some embodiments, the removable sterility barrier 1750 may form an interference or snap fit with the distal end of the reservoir 1710. Frictional forces associated with the interference or snap fit can be overcome by manually pulling the removable sterility barrier 1750 away from the housing 1762 of the autoinjector 1700. The needle shield 1760 may be biased in the distal direction by a biasing member 1764 (e.g., a spring).

[0187] In use, the patient or healthcare provider may first remove the removable sterility barrier 1750 from the autoinjector 1700 and press the needle shield 1760 against the patient's skin. The recoil force from the patient's skin may be countered by a biasing force from the biasing member 1764, which may push the needle shield 1760 proximally until it reaches a proximal position within the housing 1762. This action exposes the distal end 1716 of the delivery cannula 1712, causing it to pierce the patient's skin. The patient or healthcare provider may then depress the actuator 1740 to activate the drive mechanism 1730 and move the plunger 1720 distally. As a result, the plunger 1720 expels the medication from the reservoir 1710 through the delivery cannula 1712 and into the patient. When delivery of the medication is complete and / or the plunger 1720 has completed its delivery stroke, the patient or healthcare provider may remove the automatic injection device 1700 from the skin, which may allow the biasing member 1764 to move the needle shield 1760 distally back to its distal position where it is disposed around (i.e., surrounds) the distal end 1716 of the delivery cannula 1712.

[0188] 17, the autoinjector 1700 may additionally include a controller 1770 and a communications module 1772 coupled to the controller 1770. The controller 1770 and / or the communications module 1772 may be disposed within the housing 1762 of the autoinjector 1700. The controller 1770 may include at least one processor (e.g., a microprocessor) and at least one memory (e.g., non-volatile memory such as random access memory (RAM), a hard disk, flash memory, removable memory, non-removable memory, etc.). The controller 1770 may also include or be coupled to a power source (e.g., a battery). At least the processor may be programmed to perform the operations that the controller 1700 is configured to perform, and the memory may include one or more readable, non-transitory, tangible memories having executable instructions stored thereon in the form of software that, when executed by the at least one processor, cause the at least one processor to perform the operations that the controller 1770 is configured to perform. Alternatively, controller 1700 may include other circuitry that performs the operations assigned to controller 1700. In some embodiments, controller 1770 may use only hardware to perform its tasks, thus avoiding the use of software.

[0189] The communications module 1772 may be coupled to the controller 1770 and may be configured to transmit and / or receive information via wireless and / or wired communications. The communications module 1772 may be any of several different communications modules used to communicate with the mobile device 110 and / or computing device 114 (see FIG. 1 ). According to one embodiment, the communications module 1772 may be a wireless transmitter mounted with the controller 1770, such as a Bluetooth module or a Bluetooth low energy module. The communications module 1770 may be used to transmit information from the autoinjector 1700 to the mobile device 110 or computing device 114. Alternatively, other protocols may be used by the communications module 1772, such as radio frequency identification, Zigbee, Wi-Fi, near field communication, etc.

[0190] 17, the autoinjector 1700 may include a sensor 1780 configured to detect movement of the actuator 1740. The sensor 1780 may be coupled to the controller 1770 and configured to output a signal to the controller 1770 indicating that the actuator 1740 has been moved. According to one embodiment, the sensor 1780 may be an electrical switch (e.g., a latching normally-open electrical switch) positioned so that when the actuator 1740 is depressed by a patient or healthcare provider, the actuator 1740 contacts and closes the electrical switch. Closing this electrical switch may create a closed electrical circuit, which in turn outputs an electrical signal to the controller 1770. In response to the electrical signal, the controller 1770 may determine that the actuator 1770 has been used to initiate delivery of the medication to the patient. The sensor 1780 is not limited to a latching normally-open electrical switch, but may be any sensor suitable for detecting movement of the actuator 1740, including a pogo pin, an optical sensor, a ferromagnetic proximity sensor, a pressure sensor, etc.

[0191] If the controller 1700 determines that the actuator 1740 has been used to activate delivery of the medication to the patient, the controller 1700 may generate a report indicating the activation of the autoinjector 1700 and control the communications module 1772 to transmit the report. In embodiments in which the communications module 1772 includes a wireless transmitter, the controller 1770 may control the communications module 1772 to transmit the report wirelessly. In some embodiments, the report may be transmitted by the communications module 1772 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0192] 18a-18c, an embodiment of an autoinjector 1800 configured to detect and report delivery of a drug from a reservoir to a patient is illustrated. The autoinjector 1800 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 1810, a delivery cannula 1812 having a proximal end 1814 and a distal end 1816, a plunger 1820 having a proximal end 1822 and a distal end 1824 including a stopper 1826, a longitudinal axis A, an actuator 1840, a drive mechanism 1830, a removable sterility barrier 1850, a needle shield 1860, a housing 1862, a biasing member 1864, a controller 1870, and a communications module 1872.

[0193] The autoinjector 1800 may further include a sensor 1880 configured to detect movement of the needle shield 1860. The sensor 1880 may be coupled to the controller 1870 and configured to output a signal to the controller 1870 that the needle shield 1860 has been moved. According to one embodiment, the sensor 1880 may include an annular spring 1882 coupled to an outer circumferential surface of the needle shield 1860. Alternatively, the annular spring 1882 may be integrally configured with the needle shield 1860 such that the annular spring 1882 and the needle shield 1860 are a single component. The annular spring 1882 may include radially protruding tabs 1884, 1886 configured to be received in respective apertures 1888, 1890 formed in the housing 1862 of the autoinjector 1800. The radially protruding tabs 1884, 1886 may be located at diametrically opposed positions on the annular spring 1882, as shown in FIGS. 18b and 18c. In an alternative embodiment, the housing 1862 may include recesses rather than apertures to receive the radially protruding tabs 1884, 1886. In terms of materials, the annular spring 1882 may be made of a conductive and resilient material such as a metal.

[0194] 18a and 18b, when the needle shield 1860 is positioned in its distal position (i.e., when the needle shield 1860 is disposed around the distal end 1816 of the delivery cannula 1812), the radially protruding tabs 1884, 1886 of the annular spring 1882 may be received within their respective apertures 1880, 1890 in the housing 1862. When the needle shield 1860 is pressed against the patient's skin and moved proximally to its proximal position (see FIG. 18c), the radially protruding tabs 1884, 1886 of the annular spring 1882 may slide out of their respective apertures 1888, 1890 and may be pushed radially inward by the inner wall of the housing 1862. Thus, a gap may be formed between the annular spring 1882 and the inner wall of the housing 1862. After completion of delivery of the medication to the patient and removal of the autoinjector 1800 from the patient's skin, the biasing member 1864 may push the needle shield 1860 back to its distal position, causing the radially protruding tabs 1884, 1886 to slide along the inner surface of the housing 1862 until aligned with their respective apertures 1888, 1890. The annular spring 1882 may expand radially outward such that the radially protruding tabs 1884, 1886 are forced into their respective apertures 1888, 1890 (see FIG. 18b). Thus, the gap between the annular spring 1882 and the inner wall of the housing 1862 may be eliminated.

[0195] 18b, when the radially protruding tabs 1884, 1886 are received within their respective apertures 1888, 1890, an outer portion of the annular spring 1882 may be configured to contact the first electrical contact 1892 and the second electrical contact 1894. As a result, a closed electrical circuit may be formed between the first electrical contact and the second electrical contact 1892, 1894. This closed electrical circuit may output an electrical signal to the controller 1870 via a conductive wire (not shown). In response to the electrical signal, the controller 1870 may determine that the needle shield 1860 has been disposed around the distal end 1816 of the delivery cannula 1862. The controller 1870 may then generate a report indicating completion of delivery of the drug from the reservoir 1810 to the patient and control transmission of the report to the communications module 1872. In embodiments in which communication module 1872 includes a wireless transmitter, controller 1870 may control communication module 1872 to wirelessly transmit the report. In some embodiments, the report may be transmitted by communication module 1872 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0196] 19 illustrates an embodiment of an autoinjector 1900 configured to detect and report whether the distal end of a delivery cannula has been inserted into a patient. The autoinjector 1900 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 1910, a delivery cannula 1912 having a proximal end 1914 and a distal end 1916, a plunger 1920 having a proximal end 1922 and a distal end 1924 including a stopper 1926, a longitudinal axis A, an actuator 1940, a drive mechanism 1930, a removable sterility barrier 1950, a needle shield 1960, a housing 1962, a biasing member 1964, a controller 1970, and a communications module 1972.

[0197] The autoinjector 1900 may further include a sensor 1980 configured to detect movement of the needle shield 1960. The sensor 1980 may be coupled to the controller 1970 and configured to output a signal to the controller 1970 that the needle shield 1960 has been moved. According to one embodiment, the sensor 1980 may include a washer 1982 made of a conductive material, such as a metal. The washer 1982 may be coupled to a proximal axial end surface of the needle shield 1960, as shown in FIG. 19 . The washer 1982 may have an annular shape with a central aperture to allow the reservoir 1910 to pass through the washer 1982.

[0198] When the needle shield 1960 is pressed against the patient's skin and moved proximally to its proximal position, the washer 1982 may contact the first electrical contact 1992 and the second electrical contact 1994, thereby forming a closed electrical circuit between the first electrical contact 1992, 1994. This closed electrical circuit may output an electrical signal to the controller 1970 via the conductive wire. In response to the electrical signal, the controller 1970 may determine that the needle shield 1960 has been moved relative to the distal end 1916 of the delivery cannula 1912. The controller 1970 may then generate a report indicating that insertion of the distal end 1916 of the delivery cannula 1912 into the patient is complete and control the report to be transmitted to the communications module 1972. In embodiments in which the communications module 1972 includes a wireless transmitter, the controller 1970 may control the communications module 1972 to transmit the report wirelessly. In some embodiments, the report may be transmitted by the communications module 1972 to an external mobile device (eg, mobile device 110) and / or an external computing device (eg, computing device 114).

[0199] 20 illustrates another embodiment of an autoinjector 2000 configured to detect and report whether the distal end of a delivery cannula has been inserted into a patient. The autoinjector 2000 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2010, a delivery cannula 2012 having a proximal end 2014 and a distal end 2016, a plunger 2020 having a proximal end 2022 and a distal end 2024 including a stopper 2026, a longitudinal axis A, an actuator 2040, a drive mechanism 2030, a removable sterility barrier 2050, a needle shield 2060, a housing 2062, a biasing member 2064, a controller 2070, and a communications module 2072.

[0200] The autoinjector 2000 may further include a sensor 2080 configured to detect movement of the needle shield 2060. The sensor 2080 may be coupled to the controller 2070 and configured to output a signal to the controller 2070 that the needle shield 2060 has been moved. According to one embodiment, the sensor 2080 may include a pogo pin 2082 fixed to an inner wall of the housing 2062.

[0201] When the needle shield 2060 is pressed against the patient's skin and moved proximally to its proximal position, the pogo pins 2082 may contact and / or be depressed by the proximal axial end surface of the needle shield 2060, thereby creating a closed electrical circuit. This closed electrical circuit may output an electrical signal to the controller 2070. Conductive wires (not shown) may couple the pogo pins 2082 to the controller 2070. In response to the electrical signal, the controller 2070 may determine that the needle shield 2060 has been moved relative to the distal end 2016 of the delivery cannula 2012. The controller 2070 may then generate a report indicating that insertion of the distal end 2016 of the delivery cannula 2012 into the patient is complete and control the report to be transmitted to the communications module 2072. In embodiments in which the communications module 2072 includes a wireless transmitter, the controller 2070 may control the communications module 2072 to transmit the report wirelessly. In some embodiments, the report may be transmitted by the communications module 2072 to an external mobile device (eg, mobile device 110) and / or an external computing device (eg, computing device 114).

[0202] 21a and 21b, another embodiment of an autoinjector 2100 configured to detect and report delivery of a drug from a reservoir to a patient is illustrated. The autoinjector 2100 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2110, a delivery cannula 2112 having a proximal end 2114 and a distal end 2116, a plunger 2120 having a proximal end 2122 and a distal end 2124 including a stopper 2126, a longitudinal axis A, an actuator 2140, a drive mechanism 2130, a removable sterility barrier 2150, a needle shield 2160, a housing 2162, a biasing member 2164, a controller 2170, and a communications module 2172.

[0203] The autoinjector 2100 may further include a sensor 2180 configured to detect movement of the plunger 2120. The sensor 2180 may be coupled to the controller 2170 and configured to output a signal to the controller 2170 indicating that the plunger 2120 has been moved. According to one embodiment, the sensor 2180 may include an optical sensor 2182 affixed to an inner wall of the needle shield 2160, as shown in FIGS. 21a and 21b. The optical sensor 2182 may be configured to detect infrared light emitted from one or more objects, such as the stopper 2126. The optical sensor 2182 may have a field of view 2184 capable of detecting the presence of one or more objects. The optical sensor 2182 may also be configured to output a signal to the controller 2170 representing the distance between the optical sensor 2182 and an object within its field of view 2184.

[0204] 21a, prior to actuation of plunger 2120, stopper 2126 may be outside the field of view 2184 of optical sensor 2182. Thus, optical sensor 2182 may or may not output a signal to controller 2170 and may determine that delivery of medication from the reservoir to the patient is not complete. Controller 2170 may control communications module 2172 to send (e.g., wirelessly) a report to an external computer system representing the determination that delivery of medication is not complete.

[0205] FIG. 21b shows the plunger 2120 moving through the reservoir 2110 to deliver medication to the patient, but not yet completing its delivery stroke. At this stage, the stopper 2126 may be within the field of view 2184 of the optical sensor 2182. Accordingly, the optical sensor 2182 may output a signal to the controller 2170 indicating the distance between the optical sensor 2182 and the stopper 2126. The controller 2170 may compare the measured distance to a threshold distance to determine whether the measured distance is less than or equal to the threshold distance. In the configuration shown in FIG. 21b, the measured distance is greater than or equal to the threshold distance. Therefore, the controller 2170 determines that the plunger 2120 has not completed its delivery stroke and generates a report indicating the fact that delivery of the medication to the patient has not been completed. The controller 2170 may control the communications module 2172 to transmit (e.g., wirelessly) this report to an external computer system.

[0206] FIG. 21c depicts the plunger 2120 having completed its delivery stroke, resulting in the completion of delivery of the medication to the patient. Here, the stopper 2126 may be within the field of view 2184 of the optical sensor 2182, which may therefore output a signal to the controller 2170 indicating the distance between the optical sensor 2182 and the stopper 2126. The controller 2170 may compare the measured distance to a threshold distance to determine whether the measured distance is less than or equal to the threshold distance. In the configuration shown in FIG. 21c, the measured distance is less than or equal to the threshold distance. Thus, the controller 2170 determines that the plunger has completed its delivery stroke and generates a report indicating the completion of delivery of the medication to the patient. The controller 2170 may control the communications module 2172 to transmit (e.g., wirelessly) this report to an external computer system.

[0207] In an alternative embodiment, the optical sensor 2182 may be fixed to an interior wall of the housing 2162 proximal to the needle shield 2160. In such an embodiment, the controller 2170 may evaluate whether the measured distance is greater than or equal to a threshold distance to determine whether the plunger has or has not completed its delivery stroke.

[0208] 22a-22c illustrate another embodiment of an autoinjector 2200 configured to detect and report delivery of a drug from a reservoir to a patient. The autoinjector 2200 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2210, a delivery cannula 2212 having a proximal end 2214 and a distal end 2216, a plunger 2220 having a proximal end 2222 and a distal end 2224 including a stopper 2226, a longitudinal axis A, an actuator 2240, a drive mechanism 2230, a removable sterility barrier 2250, a needle shield 2260, a housing 2262, a biasing member 2264, a controller 2270, and a communications module 2272.

[0209] The autoinjector 2200 may further include a sensor 2280 configured to detect movement of the plunger 2220. The sensor 2280 may be coupled to the controller 2270 and configured to output a signal to the controller 2270 indicating that the plunger 2220 has been moved. According to one embodiment, the sensor 2280 may include a first conductive member 2282 spaced apart from the plunger 2220 and a second conductive member 2284 coupled to the plunger 2220 such that the second conductive member 2284 moves with the plunger 2220. The second conductive member 2284 may be configured to slidably engage the first conductive member 2282 during movement of the plunger 2220 prior to completion of the delivery stroke by the plunger 2220 (see FIG. 22a). While the first and second conductive members 2282, 2284 are engaged, the first and second conductive members 2282, 2284 may form a closed electrical circuit that outputs a signal to the controller 2270. Upon completion of the delivery stroke by the plunger 2220 (see FIG. 22b), the second conductive member 2284 may disengage from the first conductive member 2282 such that the first and second conductive members 2282, 2284 no longer contact one another. As a result, an open electrical circuit may be formed and, as a result, no signal may be output from the sensor 2280 to the controller 2270.

[0210] In response to the absence of a signal from sensor 2280, controller 2270 may determine that plunger 2220 has completed its delivery stroke and may generate a report indicating the completion of delivery of the medication to the patient. Controller 2270 may control communications module 2272 to transmit (e.g., wirelessly) the report to an external computer system. In embodiments in which communications module 2272 includes a wireless transmitter, controller 2270 may control communications module 2272 to transmit the report wirelessly. In some embodiments, the report may be transmitted by communications module 2272 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0211] 22c, the first conductive member 2282 may include a spring-biased clip 2290 secured to the housing 2262 of the autoinjector 2200, and the second conductive member 2284 may include a wire 2292 secured to and movable with the plunger 2220. The wire 2292 may be retracted behind the plunger 2220 as the plunger 2220 is moved distally to expel the medication from the reservoir 2210. The spring-biased clip 2290 may be configured to slidably grasp the wire 2292 as it translates. The length of the wire 2292 may be such that when the plunger 2220 reaches its distal-most position, thus completing its delivery stroke, the wire 2292 is not long enough to reach the spring-based clip 2290. As a result, the wire 2292 may disengage from the spring-biased clip 2290, thereby creating an open electrical circuit.

[0212] 23a and 23b, an embodiment of an autoinjector 2300 configured to detect and report the amount of medication delivered to a patient is illustrated. The autoinjector 2300 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2310, a delivery cannula 2312 having a proximal end 2314 and a distal end 2316, a plunger 2320 having a proximal end 2322 and a distal end 2324 including a stopper 2326, a longitudinal axis A, an actuator 2340, a drive mechanism 2330, a removable sterility barrier 2350, a needle shield 2360, a housing 2362, a biasing member 2364, a controller 2370, and a communications module 2372.

[0213] The autoinjector 2200 may further include a sensor 2380 configured to detect movement of the plunger 2320. The sensor 2380 may be coupled to the controller 2370 and configured to output a signal to the controller 2370 indicative of the movement of the plunger 2320 and / or the distance traveled by the plunger 2320. According to one embodiment, the sensor 2380 has an adjustable electrical resistance R x The variable resistor 2382 may include a variable resistor 2382 having an electrical resistance R x may be proportional to the length of variable resistor 2382 through which the current must travel before reaching controller 2370. In some embodiments, the electrical resistance R of variable resistor 2382 x may increase as the length of the current path through variable resistor 2382 increases, and the electrical resistance R x may decrease as the length of the current path through variable resistor 2382 decreases.

[0214] To vary the length of the current path through the variable resistor 2382, a conductive member 2384 may be slidably engaged with the variable resistor 2382, as shown in FIG. 23 a. The conductive member 2384 may be coupled to the plunger 2320 such that the conductive member 2384 moves with the plunger 2320. Thus, movement of the plunger 2320 may cause the conductive member 2384 to slide along the variable resistor 2382. This may vary the length of the current path through the variable resistor 2382. Thus, movement of the plunger 2320 may cause the electrical resistance R of the variable resistor 2382 to change. x may result in changes in

[0215] In the configuration shown in FIG. 23a, movement of plunger 2320 in the distal direction toward the distal end of autoinjector 2300 increases the length of the electrical path through variable resistor 2382, thereby increasing electrical resistance R x The control device 2370 increases the electrical resistance R xmay be configured to correlate the electrical resistance R with the distance traveled by the plunger 2320 and / or the amount of drug delivered to the patient. x The controller 2370 may be configured to measure the period over which the change in the drug changes and correlate this period with the rate at which the drug is delivered to the patient. The controller 2370 may then generate a report indicating the amount of drug delivered to the patient and / or the rate of delivery and control the communications module 2372 to transmit (e.g., wirelessly) this report to an external computer system. In embodiments where the communications module 2372 includes a wireless transmitter, the controller 2370 may control the communications module 2372 to transmit the report wirelessly. In some embodiments, the report may be transmitted by the communications module 2372 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0216] Figure 23b is a circuit diagram illustrating an example where an electrical circuit includes the controller 2370 and variable resistor 2382 depicted in Figure 23a. As shown in Figure 23b, the controller 2370 may be placed in parallel with resistor R1. In this circuit, V 入 is V 出 *((R x / (R x +R1). Therefore, the electrical resistance R of the variable resistor 2382 x As increases, V 入 The controller 2370 may increase V 入 may be correlated to the distance traveled by the plunger 2320 and / or the amount of drug delivered to the patient.

[0217] 24a and 24b depict yet another embodiment of an autoinjector 2400 configured to detect and report delivery of a drug from a reservoir to a patient. The autoinjector 2400 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2410, a delivery cannula 2412 having a proximal end 2414 and a distal end 2416, a plunger 2420 having a proximal end 2422 and a distal end 2424 including a stopper 2426, a longitudinal axis A, an actuator 2440, a drive mechanism 2430, a removable sterility barrier 2450, a needle shield 2460, a housing 2462, a biasing member 2464, a controller 2470, and a communications module 2472.

[0218] The autoinjector 2400 may further include a sensor 2480 configured to detect movement of the plunger 2420. The sensor 2480 may be coupled to the controller 2470 and configured to output a signal to the controller 2470 indicating that the plunger 2420 has been moved. According to one embodiment, the sensor 2480 may include a first conductive member 2482 spaced from the plunger 2420 and a second conductive member 2484 coupled to the plunger 2420 such that the second conductive member 2484 moves with the plunger 2420. The first conductive member 2482 may be a deflectable electrical contact secured to an inner wall of the housing 2462 and extending inwardly therefrom. The conductive member 2484 may be a spring retainer lip secured to the plunger 2420.

[0219] 24b, the second conductive member 2484 may be configured to engage with the first conductive member 2482 to form a closed electrical circuit when the plunger 2420 completes its delivery stroke. This closed electrical circuit may output a signal to the controller 2470. Prior to completion of the delivery stroke, the second conductive member 2484 may be disengaged (e.g., moved away) from the first conductive member 2482, such that an open electrical circuit is formed and therefore no signal is output to the controller 2470.

[0220] In response to an electrical signal created by the engagement of the first and second conductive members 2482, 2484, the controller 2470 may determine that the plunger 2420 has completed its delivery stroke and may generate a report indicating the completion of delivery of the medication to the patient. The controller 2470 may control the communications module 2472 to transmit (e.g., wirelessly) the report to an external computer system. In embodiments in which the communications module 2472 includes a wireless transmitter, the controller 2470 may control the communications module 2472 to transmit the report wirelessly. In some embodiments, the report may be transmitted by the communications module 2472 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0221] 25a and 25b illustrate another embodiment of an autoinjector 2500 configured to detect and report delivery of a drug from a reservoir to a patient. The autoinjector 2500 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2510, a delivery cannula 2512 having a proximal end 2514 and a distal end 2516, a plunger 2520 having a proximal end 2525 and a distal end 2525 including a stopper 2526, a longitudinal axis A, an actuator 2540, a drive mechanism 2530, a removable sterility barrier 2550, a needle shield 2560, a housing 2562, a biasing member 2564, a controller 2570, and a communications module 2572.

[0222] The autoinjector 2500 may further include a sensor 2580 configured to detect movement of the plunger 2520. The sensor 2580 may be coupled to the controller 2570 and configured to output a signal to the controller 2570 indicating that the plunger 2520 has been moved. According to one embodiment, the sensor 2580 is coupled to a spring 2584 and a voltage source V s Resistor R electrically connected in series with s 25a and 25b show a resistor R in schematic form. s and voltage source V sand therefore the resistor R s and voltage source V s It does not represent the actual location or physical configuration of the resistor R s and voltage source V s may be stored together with the housing 2562 of the autoinjector 2500.

[0223] The spring 2584 may correspond to the drive mechanism 2530 and thus may be responsible for moving the plunger 2520 distally to complete its delivery stroke. When released (e.g., by depressing the actuator 2540), the spring 2530 may increase in length from length L1 (see FIG. 25a) to length L2 (see FIG. 25b), thereby pushing the plunger 2520 distally and expelling the medication from the reservoir 2510. The spring 2584 may have multiple helically wound coils, with adjacent pairs of coils separated by a distance. The spring 2584 may function like an inductor by virtue of its multiple coils. The inductance of the spring 2584 may vary according to the distance between adjacent pairs of coils. In some embodiments, increasing the length of spring 2584 from length L1 to length L2 may increase the distance between each adjacent pair of coils, thereby decreasing the inductance associated with spring 2584. In such embodiments, the inductance of spring 2584 may be inversely proportional to the length of spring 2584. Further, in such embodiments, the inductance of spring 2584 may be inversely proportional to the distance between adjacent pairs of coils. As a result of the change in inductance of spring 2584, resistor R s The current through resistor R can change. s The change in current through the resistor R s The voltage drop across the resistor may be measured (by measuring the voltage drop across the resistor).

[0224] resistor R sIn response to a change in the current flowing through the plunger 2520, the controller 2570 may determine that the plunger 2520 has completed its delivery stroke and may generate a report indicating the completion of delivery of the medication to the patient. The controller 2570 may control the communications module 2572 to transmit (e.g., wirelessly) the report to an external computer system. In embodiments in which the communications module 2572 includes a wireless transmitter, the controller 2570 may control the communications module 2572 to transmit the report wirelessly. In some embodiments, the report may be transmitted by the communications module 2572 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0225] 26 illustrates another embodiment of an autoinjector 2600 configured to detect and report delivery of a drug from a reservoir to a patient. The autoinjector 2600 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2610, a delivery cannula 2612 having a proximal end 2614 and a distal end 2616, a plunger 2620 having a proximal end 2626 and a distal end 2626 including a stopper 2626, a longitudinal axis A, an actuator 2640, a drive mechanism 2630, a removable sterility barrier 2650, a needle shield 2660, a housing 2662, a biasing member 2664, a controller 2670, and a communications module 2672.

[0226] The autoinjector 2600 may further include a sensor 2680 configured to detect movement of the plunger 2620. The sensor 2680 may be coupled to the controller 2670 and configured to output a signal to the controller 2670 indicating that the plunger 2620 has been moved. According to one embodiment, the sensor 2680 may be a ferromagnetic proximity sensor 2682 configured to output a signal indicative of the presence or absence of a metal plunger rod 2584 in a predetermined position within the autoinjector 2600.

[0227] 26 , the ferromagnetic proximity sensor 2682 may be fixed to an inner wall of the housing 2662. The ferromagnetic proximity sensor 2682 may be positioned such that the metallic plunger rod 2684 advances past the ferromagnetic proximity sensor 2682 when the plunger 2620 completes its delivery stroke, as seen in FIG. 26 . As a result, the ferromagnetic proximity sensor 2682 may detect the absence of the metallic plunger rod 2684. Meanwhile, prior to the completion of the delivery stroke, the metallic plunger rod 2684 may align with the ferromagnetic proximity sensor 2682 such that the ferromagnetic proximity sensor 2682 detects the presence of the metallic plunger rod 2684.

[0228] In response to a signal from the ferromagnetic proximity sensor 2682 indicating the absence of the metallic plunger rod 2684, or in response to the absence of a signal from the ferromagnetic proximity sensor 2682 indicating the presence of the metallic plunger rod 2684, the controller 2670 may determine that the plunger 2620 has completed its delivery stroke and generate a report indicating the completion of delivery of the medication to the patient. The controller 2670 may control the communications module 2672 to transmit (e.g., wirelessly) the report to an external computer system. In embodiments in which the communications module 2672 includes a wireless transmitter, the controller 2670 may control the communications module 2672 to transmit the report wirelessly. In some embodiments, the report may be transmitted by the communications module 2672 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0229] 27a-e illustrate another embodiment of an autoinjector 2700 configured to detect and report the amount of medication delivered to a patient. The autoinjector 2700 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2710, a delivery cannula 2712 having a proximal end 2714 and a distal end 2716, a plunger 2720 having a proximal end 2722 and a distal end 2724 including a stopper 2726, a longitudinal axis A, an actuator 2740, a drive mechanism 2730, a removable sterility barrier 2750, a needle shield 2760, a housing 2762, a biasing member 2764, a controller 2770, and a communications module 2772.

[0230] The autoinjector 2700 may further include a sensor 2780 configured to detect movement of the plunger 2720. The sensor 2780 may be coupled to the controller 2770 and configured to output a signal to the controller 2770 indicating that the plunger 2720 has been moved and / or the distance the plunger 2720 has traveled. According to one embodiment, the sensor 2780 may comprise a plurality of photoresistors 2782a-d. The electrical resistance of each of the photoresistors 2782a-d may decrease as the incident light intensity increases. As depicted in FIG. 27a, the photoresistors 2782a-d may be positioned adjacent to one another and parallel to the longitudinal axis A of the autoinjector 2700. The photoresistors 2782a-d may be fixed to the exterior of the reservoir 2710.

[0231] To allow ambient light to enter the photoresistors 2782a-d, the housing 2762 of the autoinjector 2700 may include one or more windows 2784a and 2784b, as shown in FIG. 27b. The plunger 2720, including the stopper 2726, may be made of an opaque material so that the plunger 2720 blocks ambient light from shining through the windows 2784a and 2784b as the plunger 2720 advances distally through the reservoir 2710 along the longitudinal axis A. The plunger 2720 may be provided with an opaque sleeve 2786 for this purpose, as shown in FIG. 27a. The farther the plunger 2720 advances distally, the more of the windows 2784a and 2784b that are covered. Thus, advancement of plunger 2720 distally along longitudinal axis A may reduce the ambient light incident on each of multiple photoresistors 2782a-d in turn. For example, as shown in FIG. 27c, when plunger 2720 has completed approximately halfway through its delivery stroke, ambient light may be prevented from reaching photoresistors 2782a and 2782b, but ambient light may still be incident on each of photoresistors 2782c and 2782d. The lack of ambient light incident on photoresistors 2782a and 2782b may result in an increase in the electrical resistance of each of these photoresistors, and may even cause each of photoresistors 2782a and 2782b to stop conducting current. Meanwhile, photoresistors 2782c and 2782d, which are still exposed to ambient light, may exhibit a low electrical resistance and continue to conduct current. When plunger 2720 completes its delivery stroke as shown in FIG. 27d, all ambient light through windows 2784a and 2784b may be blocked, which may result in a substantial increase in the electrical resistance of all of photoresistors 2782a-d.

[0232] FIG. 27e is a circuit diagram illustrating an example of an electrical circuit including controller 2770 and photoresistors 2782a-d. The electrical circuit may include resistor R2 having a known, constant electrical resistance. Photoresistors 2782a-d may be placed in parallel with controller 2770. Controller 2770 may be able to measure the voltage drop across all of photoresistors 2782a-d and therefore calculate their total effective electrical resistance. In some embodiments, controller 2770 may be configured to individually determine the electrical resistance of each of photoresistors 2782a-d. Also, in some embodiments, autoinjector 2700 may include a reference photoresistor 2790 located on the outside of autoinjector housing 2762 to calibrate controller 2770 to the natural intensity of ambient light.

[0233] The controller 2770 may correlate the electrical resistance of one or more of the photoresistors 2782a-d with the distance traveled by the plunger 2720 and / or the amount of medication delivered to the patient. In some embodiments, the controller 2770 may be configured to measure the time period over which the electrical resistance of one or more of the photoresistors 2782a-d changes and correlate this time period with the rate at which the medication is delivered to the patient. The controller 2770 may then generate a report indicating the amount of medication delivered to the patient and / or the rate of delivery and control the communications module 2772 to transmit (e.g., wirelessly) this report to an external computer system. In embodiments in which the communications module 2772 includes a wireless transmitter, the controller 2770 may control the communications module 2772 to wirelessly transmit the report. In some embodiments, the report may be transmitted by the communications module 2772 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0234] 28 depicts yet another embodiment of an autoinjector 2800 configured to detect and report the amount of medication delivered to a patient. The autoinjector 2800 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2810, a delivery cannula 2812 having a proximal end 2814 and a distal end 2816, a plunger 2820 having a proximal end 2822 and a distal end 2824 including a stopper 2826, a longitudinal axis A, an actuator 2840, a drive mechanism 2830, a removable sterility barrier 2850, a needle shield 2860, a housing 2862, a biasing member 2864, a controller 2870, and a communications module 2872.

[0235] The autoinjector 2800 may further include a sensor 2880 configured to detect movement of the plunger 2820. The sensor 2880 may be coupled to the controller 2870 and configured to output signals to the controller 2870 indicative of the presence or absence of various levels of fluid in the reservoir 2810. According to one embodiment, the sensor 2880 may include a capacitive fluid level sensor 2882 coupled to the exterior of the reservoir 2810. In some embodiments, the capacitive fluid level sensor 2882 may be oriented such that its longitudinal axis is parallel to the longitudinal axis of the reservoir. Thus, as the fluid level in the reservoir 2810 decreases, the capacitive fluid level sensor 2882 may be gradually exposed.

[0236] In response to the signal from sensor 2880, controller 2870 may determine the amount of drug remaining in reservoir 2810 and / or may generate a report indicating the amount of drug delivered to the patient from the reservoir based on the amount of drug remaining in the reservoir. Controller 2870 may control communications module 2872 to transmit (e.g., wirelessly) the report to an external computer system. In embodiments in which communications module 2872 includes a wireless transmitter, controller 2870 may control communications module 2872 to transmit the report wirelessly. In some embodiments, the report may be transmitted by communications module 2872 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0237] 29a and 29b depict an embodiment of an autoinjector 2900 configured to detect and report contact between a patient and the housing of the autoinjector 200. The autoinjector 2900 may include some or all of the same components as the autoinjector 1700 described above, including, for example, a reservoir 2910, a delivery cannula 2912 having a proximal end 2914 and a distal end 2916, a plunger 2920 having a proximal end 2922 and a distal end 2924 including a stopper 2926, a longitudinal axis A, an actuator 2940, a drive mechanism 2930, a removable sterility barrier 2950, ​​a needle shield 2960, a housing 2962, a biasing member 2964, a controller 2970, and a communications module 2972.

[0238] The autoinjector 2900 may further include a sensor 2980 configured to detect contact between the housing 2962 and an object (e.g., a patient's skin or a patient's clothing). The sensor 2980 may be coupled to the controller 2970 and configured to output a signal to the controller 2970 indicative of contact with the object. According to one embodiment, the sensor 2980 may include a first conductive member 2982 coupled to an axial end surface of the distal end of the housing 2962 and a second conductive member 2984 coupled to an axial end surface of the distal end of the needle shield 2960. In some embodiments, the first and second conductive members 2982, 2984 may each comprise a conductive adhesive. The first conductive member 2982 may be spaced apart from the second conductive member 2984 such that the first and second conductive members 2982, 2984 are not in physical contact with each other, at least when the needle shield 2960 is biased to its distal position by the biasing member 2964 as shown in FIG. 29a.

[0239] 29b, when the needle shield 2960 is pressed against the skin 2990 of the patient 2992, the needle shield 2960 may be pushed into the housing 2962 toward its proximal position and the first conductive member 2982 may move into contact with the skin 2990 of the patient 2992. In this manner, both the first and second conductive members 2982, 2984 may contact the skin 2990 of the patient 2992 when the needle shield 2960 is pressed against the skin 2990 of the patient 2990.

[0240] The skin 2990 of the patient 2992 may conduct electricity between the first and second conductive members 2982, 2984. As a result, a closed electrical circuit may be formed between the first and second conductive members 2982, 2984 when both are in contact with the skin 2990 of the patient 2992. This closed electrical circuit may output a signal to the controller 2970.

[0241] In response to a signal from sensor 2280, controller 2970 may determine that housing 2962 is in contact with the patient and may generate a report indicating contact between housing 2962 and patient 2992 and / or insertion of the delivery cannula into patient 2992. Controller 2970 may control communications module 2972 ​​to transmit (e.g., wirelessly) the report to an external computer system. In embodiments in which communications module 2972 ​​includes a wireless transmitter, controller 2970 may control communications module 2972 ​​to transmit the report wirelessly. In some embodiments, the report may be transmitted by communications module 2972 ​​to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0242] 30a and 30b illustrate an embodiment of an on-corporeal infusion device 3000 configured to detect and report contact between the housing of the on-corporeal infusion device 3000 and a patient. The on-corporeal infusion device 3000 may include some or all of the same components as the drug delivery system 800 shown in FIGS. 14-16, including, for example, a housing 802 having an exterior surface 816, a portion 828 of the exterior surface 816 configured to face and / or contact the patient's skin during use of the on-corporeal infusion device 3000, a controller 900, and a communications module 902. The portion 828 of the exterior surface 816 may have an opening 3004 sized to receive the distal end 844 of a delivery cannula.

[0243] The on-body infusion device 3000 may further include a sensor 3010 configured to detect contact between the housing 802 and an object (e.g., the patient's skin or the patient's clothing). The sensor 3010 may be coupled to the controller 900 and configured to output a signal to the controller 900 indicative of contact with the object. According to one embodiment, the sensor 3010 may include a first conductive member 3012 and a second conductive member 3014 coupled to different locations on the portion 828 of the exterior surface 816 of the housing 802. In some embodiments, the first conductive member and the second conductive member 3012, 3014 may each include a conductive adhesive (e.g., a conductive gel adhesive pad). The first conductive member 3012 may be spaced from the second conductive member 3014 so that the first conductive member and the second conductive member 3012, 3014 do not physically contact each other.

[0244] When the portion 828 of the exterior surface 816 of the housing 802 is pressed against the patient's skin, both the first and second conductive members 3012, 3014 may contact the patient's skin. The patient's skin may conduct electricity between the first and second conductive members 3012, 3014. As a result, a closed electrical circuit may be formed between the first and second conductive members 3012, 3014 when both are pressed into contact with the patient's skin. This closed electrical circuit may output a signal to the controller 900.

[0245] In response to a signal from sensor 3010, controller 900 may determine that housing 802 is in contact with the patient and may generate a report indicating contact between housing 802 and the patient and / or insertion of the delivery cannula into the patient. Controller 900 may control communications module 902 to transmit (e.g., wirelessly) the report to an external computer system. In embodiments in which communications module 902 includes a wireless transmitter, controller 900 may control communications module 902 to transmit the report wirelessly. In some embodiments, the report may be transmitted by communications module 902 to an external mobile device (e.g., mobile device 110) and / or an external computing device (e.g., computing device 114).

[0246] The above-described methods and drug delivery systems describe locking out of a drug delivery device in response to various determinations regarding the condition, operating state, and / or identity of the drug delivery device, the medicament contained within the drug delivery device, and / or the user of the drug delivery device. A lock to achieve this functionality may be coupled to the plunger assembly, the needle shield, and / or the actuator. In some embodiments, the lock may include a wall that can be controlled to selectively abut a gap or notch in the plunger, needle shield, or actuator to limit movement of the plunger, needle shield, or actuator, respectively. In some embodiments, the lock may be coupled to and selectively actuated by a controller of the drug delivery device.

[0247] In addition to monitoring and reporting the condition and / or operational status of the drug delivery device, the drug delivery systems and methods of the present disclosure may include features that improve the usability of the drug delivery system by patients, particularly those who have difficulty grasping or handling drug delivery devices, such as elderly and physically disabled patients. In addition to inhibiting contamination of the interior of the drug delivery device, the removable sterile barrier provides anti-rotation functionality and aids the patient in grasping and removing the drug delivery device from the removable sterile barrier, optionally housing various electronic components including, for example, a controller, memory, one or more sensors, and / or a communications module, as described below with reference to Figures 31 and 32.

[0248] Specifically, as shown in FIG. 31 , a drug delivery system 3100 is provided that includes a drug delivery device 3102. The drug delivery device 3102 may be in the form of an autoinjector and, as such, may be configured for handheld use and application against a patient's skin. The drug delivery device 3102 may include some or all of the same components as the drug delivery devices described above in connection with FIGS. 9, 12A, 12B, 13, and 17-29. The drug delivery device 3102 may include a housing 3110 in which an assembly or structure is disposed that introduces a delivery cannula into a patient and forces a drug or agent from a reservoir, through the delivery cannula, and into the patient. The drug delivery device 3102 may also include an actuator 3112 disposed at a proximal end of the housing 3110 and configured to be depressed by the patient to activate a drive that causes a plunger to expel the drug from the reservoir, through the delivery cannula, and into the patient.

[0249] The drug delivery device 3102 may further include a removable sterility barrier 3120 removably attached to the distal end of the housing 3110. The removable sterility barrier 3120 reduces the risk of contamination of the delivery cannula and other elements within the housing 3110 prior to use of the drug delivery device 3102. The removable sterility barrier 3120 may be formed by a tubular member 3122 and a covering member 3124 that covers the open end of the tubular member 3122. The tubular member 3122 and the covering member 3124 may be integrally formed as a single, unitary structure, or alternatively, may be formed as separate components that are bonded or mechanically interconnected to one another.

[0250] The tubular member 3122 may be disposed around (e.g., surround) the distal end of the housing 3110 and / or the distal end of the delivery cannula (not shown), and may removably attach the removable sterility barrier 3120 to the housing 3110. As shown in FIG. 32 , the tubular member 3122 may be assembled by engaging two mating, generally C-shaped members 3128, 3130 on the distal end of the housing 3110. In some embodiments, the removable sterility barrier 3120 may form an interference or snap fit with the distal end of the housing 3110. Frictional forces associated with an interference or snap fit can be overcome by manually pulling the removable sterility barrier 3120 in a distal direction, away from the housing 3110. The interference or snap fit may be formed by configuring the inner diameter of the tubular member 3122 to be slightly smaller than the outer diameter of the distal end of the housing 3110. Alternatively, or in addition, the tubular member 3122 may have a frangible or weakened member (not shown) connecting the tubular member 3122 to the distal end of the housing 3110 and that can be broken or torn by the patient when the removable sterility barrier 3120 is pulled away from the housing 3110. The tubular member 3122 may further include a plurality of outwardly protruding ribs 3126 designed to assist the patient in grasping the tubular member 3122 and removing it from the housing 3110. The ribs 3126 may be particularly useful for elderly and physically disabled patients who have less than average grip strength.

[0251] The covering member 3124 may be secured to the distal end of the tubular member 3122 and may completely cover the opening formed in the distal end of the tubular member 3122. The distal end surface 3132 of the covering member 3124 may be flat so that the drug delivery device 3102 can be disposed on a flat surface in an upright configuration without tipping over. In an alternative embodiment, the distal end surface 3132 of the covering member 3124 may have a slight curve to prevent a user from standing the drug delivery device 3102 on a flat surface. Additionally, the outer periphery of the covering member 3124 may be wider than the outer periphery of the tubular member 3122 so that a ledge or overhang 3134 is formed at the interface between the covering member 3124 and the tubular member 3122. This ledge 3134 may help prevent a patient's fingers from slipping on the covering member 3124 when attempting to pull the removable sterility barrier 3120 away from the housing 3110.

[0252] Because the housing 3110 may have a round cross-section resulting in a circular exterior side, the drug delivery device 3102 may be prone to unintentionally rolling across a surface when placed on its side. To impede or prevent the drug delivery device 3102 from rolling across a surface when placed on its side, the tubular member 3122 and / or the covering member 3124 may be formed with at least one rotationally inhibiting exterior side. The at least one rotationally inhibiting exterior side may extend between the proximal and distal ends of the tubular member 3122 and / or the proximal and distal ends of the covering member 3124. The at least one rotationally inhibiting exterior side of the tubular member 3122 and / or the covering member 3124 may be parallel to the longitudinal axis A of the drug delivery device 3102 and / or perpendicular to the distal end surface 3132 of the covering member 3124.

[0253] 31 and 32, the tubular member 3122 has a triangular cross-section formed by three flat outer sides 3140, 3142, and 3144, and the cover member 3124 has a triangular cross-section formed by three flat outer sides 3150, 3152, and 3154. The unresolved cross-sections are perpendicular to the longitudinal axis A of the drug delivery device 3102. Each of the flat outer sides 3140, 3142, 3144, 3150, 3152, and 3154 is an example of a rotation-constraining outer side because each of the flat outer sides 3140, 3142, 3144, 3150, 3152, and 3154 is configured to impede (e.g., prevent) the removable sterility barrier 3120 and / or drug delivery device 3102 from rolling across a support surface when the respective flat outer side rests against the support surface.

[0254] As used herein, the term "flat" is defined herein to mean flat or substantially flat. As shown in Figures 31 and 32, each of the flat exterior sides 3140, 3142, 3144, 3150, 3152, and 3154 bulges outward and thus exhibits only a slight curvature. While the flat exterior sides 3140, 3142, 3144, 3150, 3152, and 3154 are not completely flat, they are nonetheless substantially flat and are therefore considered "flat" in accordance with the principles of the present disclosure. In alternative embodiments, one or more of the flat exterior sides 3140, 3142, 3144, 3150, 3152, and 3154 may be completely flat, such that they exhibit no curvature. Regardless of whether the flat outer sides 3140, 3142, 3144, 3150, 3152, and 3154 have a flat or substantially flat configuration, the flat outer sides 3140, 3142, 3144, 3150, 3152, and 3154 may have the ability to impede (e.g., prevent) the removable sterility barrier 3120 and / or the drug delivery device 3102 from rolling.

[0255] The anti-rotation functionality of the removable sterility barrier 3120 can be achieved through a variety of different shapes and sizes of the tubular member 3122 and / or covering member 3124. In some embodiments, only the tubular member 3122 or only the covering member 3124 may have a triangular cross-section. Other cross-sectional shapes of the tubular member 3122 and / or covering member 3124 may prevent or impede rolling, including, but not limited to, a hemispherical, square, rectangular, pentagonal, hexagonal, or any other polygonal shape. Additionally, vertices or corners formed by one or more flat exterior sides of the tubular member 3122 and / or covering member 3124 may be rounded to reduce the likelihood of the vertices or corners causing injury or pain to a patient when gripping the removable sterility barrier 3120.

[0256] It should be noted that the particular shape of the removable sterility barrier 3120 shown in Figures 31 and 32 is an aesthetic feature not dictated by function.

[0257] In an alternative embodiment, the drug delivery device 3102 may include a second removable sterile barrier attached directly to the reservoir and separate from the removable sterile barrier 3120 surrounding the delivery cannula, similar to the removable sterile barrier 1750 shown in Figure 17. In such an embodiment, the removable sterile barrier 3120 may cover and / or surround the second removable sterile barrier.

[0258] Additionally, various electronic components of the drug delivery device 3102 may be housed (e.g., embedded) within the removable sterile barrier 3120. For example, a controller, memory, processor (e.g., microprocessor), communication module (e.g., Bluetooth module, Bluetooth low energy module, etc.), skin sensor, orientation sensor, fingerprint sensor, and / or temperature sensor configured in a manner similar to one of the embodiments discussed above in connection with Figures 9, 12A, 12B, 13, and 17-29 may be housed (e.g., embedded) within the removable sterile barrier 3120. In some embodiments, the removable sterile barrier 3120 may be configured to include one or more of the electronic elements 630-638 shown in Figure 9.

[0259] The removable sterility barrier 3120 can be designed for a single, one-time use or for multiple uses. The embodiment of the removable sterility barrier 3120 shown in FIG. 32 may be assembled by separately fitting each of the C-shaped members 3128, 3130 around the distal end of the housing 3110 and then securing the C-shaped members 3128, 3130 together with an adhesive. After a user removes the removable sterility barrier 3120 from the housing 3110, it can be difficult, if not impossible, to reattach the removable sterility barrier 3120 to the housing 3110 (or the housing of another drug delivery device), at least without separating the C-shaped members 3128, 3130 and then refitting and re-adhering them around the housing 3110. As a result, the removable sterility barrier 3120 shown in FIG. 32 may be disposable and for only one use. In an alternative embodiment (not shown), the C-shaped members 3128, 3130 may be hinged in a clamshell configuration. In such an alternative embodiment, after removing the removable sterility barrier 3120 from the housing 3110, it may be possible to reattach the removable sterility barrier 3120 to the housing 3110 (or the housing of another drug delivery device) by opening the C-shaped members 3128, 3130 like a clamshell and then fitting them around the distal end of the housing 3110. The non-hinged ends of the C-shaped members 3128, 3130 may include a locking mechanism (e.g., mating locking tabs and / or slots) so that the C-shaped members 3128, 3130 may be secured to one another after being secured around the housing 3110. Substantial cost savings may be realized by the reusable configuration of the removable sterility barrier 3120, as the electronics mounted on the removable sterility barrier 3120 may be used more than once. In a further embodiment, the removable sterility barrier 3120 may be manufactured in one piece and then axially attached onto the housing 3110 of the drug delivery device 3102.

[0260] Removal of the removable sterility barrier 3120 from the housing 3110 may initiate a mechanism that automatically activates a communications module (e.g., a Bluetooth module, a Bluetooth low energy module, etc.), controller, and / or other electronic components embedded within the removable sterility barrier 3120. In some embodiments, the mechanism may be similar in structure and / or operation to the switch 632 shown in FIG. 9. In other embodiments, such as those shown in FIGS. 33 and 34, the removable sterility barrier 3120 may include a spring arm 3160 and a normally open momentary switch 3162 to achieve this functionality. The normally open momentary switch 3162 may selectively provide an electrical connection between a battery and the controller, communications module, and / or other electronic components embedded within the removable sterility barrier 3120.

[0261] 33 illustrates a cross-sectional view of the removable sterility barrier 3120 prior to removal of the removable sterility barrier 3120 from the housing 3110 of the drug delivery device 3102. The spring arm 3160 may have a first end 3164 fixed on an inner wall 3166 of the removable sterility barrier 3120, a second end 3168 movable relative to the inner wall 3166 of the removable sterility barrier 3120, and a deflectable body portion 3170 connecting the first and second ends 3164, 3168. The deflectable body portion 3170 may protrude inward from the inner wall 3166. As shown in FIG. 33 , the deflectable body portion 3170 may have a triangular shape with its apex pointing inward, away from the inner wall 3166. When the removable sterility barrier 3120 is disposed around the housing 3110, it may press against and deflect the deflectable body portion 3170 of the spring arm 3160, causing the housing 3110 to move such that the deflectable body portion 3170 moves distally axially downward toward the inner wall 3166. As a result, the second end 3168 of the spring arm 3160 may also move distally axially downward such that it no longer contacts and depresses the normally open momentary switch 3162. Thus, in this configuration, the normally open momentary switch 3162 assumes an off position. When the normally open momentary switch 3162 is in its off position as shown in FIG. 33 , the controller, communication module, and / or other electronic components may not be powered by the battery.

[0262] 34 illustrates the removable sterility barrier 3120 after it has been removed from the housing 3110 of the drug delivery device 3102. The absence of the housing 3110 allows the deflectable body portion 3170 of the spring arm 3160 to resiliently return to its natural, uncompressed shape. This causes the second end 3168 of the spring arm 3160 to move upward in the proximal axial direction until it contacts and depresses the normally open momentary switch 3162. By depressing the normally open momentary switch 3162, the second end 3168 of the spring arm 3160 causes the normally open momentary switch 3162 to assume its on position. As a result, the controller, communication module, and / or other electronic components embedded within the removable sterility barrier 3120 may be electrically connected to and powered by a battery embedded within the removable sterility barrier 3120. In some embodiments, powering the control device may cause the control device to control a communications module to send a signal representing the removal of the detachable sterility barrier 3120 from the drug delivery device 3102 to an external computing device (e.g., a smartphone) via Bluetooth or Bluetooth low energy communications.

[0263] During manufacturing, a delay may occur between assembly of the removable sterility barrier 3120 and its attachment onto the housing 3110 of the drug delivery device 3102. During this delay, it may be desirable to prevent the second end 3168 of the spring arm 3160 from depressing the normally open momentary switch 3162 and turning on any electronic devices mounted on the removable sterility barrier 3120. To address this concern, the deflectable body portion 3170 of the spring arm 3160 may be twisted so that the second end 3168 of the spring arm 3160 is not aligned with the normally open momentary switch 3162. A pin (not shown) may hold the second end 3168 of the spring arm 3160 in this misaligned configuration. Later, when the removable sterility barrier 3120 is fitted onto the housing 3110, the housing 3110 may deflect the deflectable body portion 3170 of the spring arm 3160, thereby moving the second end 3168 distally and axially downward in the manner discussed above. Alternatively, the second end 3168 may slide over the pin and the deflectable body portion 3170 will naturally untwist due to its resiliency. This movement may realign the second end 3168 of the spring arm 3160 with the normally open momentary switch 3162, so that when the removable sterility barrier 3120 is later removed from the housing 3110 (as seen in FIG. 34 ), the second end 3168 of the spring arm 3160 will depress the normally open momentary switch 3162.

[0264] The above description describes various systems and methods for use with a drug delivery device. The system, drug delivery device, or method may further include the use of the agents listed below, although it should be clear that none of the following lists should be considered all-inclusive or limiting. The agent is stored in a reservoir. In some cases, the reservoir is a primary container that is either filled or pre-filled with the agent for treatment. The primary container may be a cartridge or a pre-filled syringe.

[0265] For example, the drug delivery device, or more specifically the reservoir of the device, may be loaded with a colony-stimulating factor, such as granulocyte colony-stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neupogen® (filgrastim) and Neulasta® (pegfilgrastim). In various other embodiments, the drug delivery device may be used in conjunction with various pharmaceutical products, such as erythropoiesis-stimulating agents (ESAs), which may be in liquid or lyophilized form. ESAs are any molecules that promote erythropoiesis, such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, epoetin beta, epoetin alpha ... and epoetin zeta, epoetin theta, and epoetin delta, as well as molecules or variants or analogs thereof disclosed in the following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Pat. Nos. 4,703,008, 5,441,868, 5,547,933, 5,618,698, 5,621,080, 5,756,349, 5,756,349, and 5,762,112. Nos. 6,778, 5,773,569, 5,955,422, 5,986,047, 6,583,272, 7,084,245, and 7,271,689, and PCT Publication Nos. WO91 / 05867, WO95 / 05465, WO96 / 40772, WO00 / 24893, WO01 / 81405, and WO2007 / 136752.

[0266] The ESA may also be an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" refers to any protein that directly or indirectly activates the erythropoietin receptor, for example, by binding to the erythropoietin receptor and inducing its dimerization. Erythropoiesis-stimulating proteins include erythropoietin and its variants, analogs, or derivatives that bind to and activate the erythropoietin receptor, antibodies that bind to and activate the erythropoietin receptor, or peptides that bind to and activate the erythropoietin receptor. Erythropoiesis-stimulating proteins include, but are not limited to, epoetin alpha, epoetin beta, epoetin delta, epoetin omega, epoetin iota, epoetin zeta, and analogs thereof, pegylated erythropoietin, carbamylated erythropoietin, mimetic peptides (including EMP1 / hematide), and mimetic antibodies. Exemplary erythropoiesis-stimulating proteins include erythropoietin, darbepoietin, erythropoietin agonist variants, and peptides or antibodies that bind to and activate the erythropoietin receptor (as well as compounds reported in U.S. Patent Publication Nos. 2003 / 0215444 and 2006 / 0040858, the disclosures of each of which are incorporated herein by reference in their entireties), and erythropoietin molecules or variants or analogs thereof disclosed in the following patents or patent applications, each of which is incorporated herein by reference in its entirety: U.S. Patent Nos. 4,703,008; 5,441,868; 5,547,933; No. 3, No. 5,618,698, No. 5,621,080, No. 5,756,349, No. 5,767,078, No. 5,773,569, No. 5, No. 955,422, No. 5,830,851, No. 5,856,298, No. 5,986,047, No. 6,030,086, No. 6,310,078 Nos. 6,391,633, 6,583,272, 6,586,398, 6,900,292, 6,750,369, 7,030,226, 7,084,245, and 7,217,689; U.S. Patent Publication Nos. 2002 / 0155998 and 2003 / 0077753;Same No. 2003 / 0082749, Same No. 2003 / 0143202, Same No. 2004 / 0009902, Same No. 2004 / 0071694 No. 2004 / 0091961, No. 2004 / 0143857, No. 2004 / 0157293, No. 2004 / 01753 No. 79, No. 2004 / 0175824, No. 2004 / 0229318, No. 2004 / 0248815, No. 2004 / 026 No. 6690, No. 2005 / 0019914, No. 2005 / 0026834, No. 2005 / 0096461, No. 2005 / 0 No. 107297, No. 2005 / 0107591, No. 2005 / 0124045, No. 2005 / 0124564, No. 2005 / 0137329, 2005 / 0142642, 2005 / 0143292, 2005 / 0153879, 2005 / 0142642 05 / 0158822, 2005 / 0158832, 2005 / 0170457, 2005 / 0181359, 2005 / 0181482, 2005 / 0192211, 2005 / 0202538, 2005 / 0227289, See PCT Publication Nos. 2005 / 0244409, 2006 / 0088906, and 2006 / 0111279, and PCT Publication Nos. WO91 / 05867, WO95 / 05465, WO99 / 66054, WO00 / 24893, WO01 / 81405, WO00 / 61637, WO01 / 36489, WO02 / 014356, WO02 / 19963, WO02 / 20034, WO02 / 49673, WO02 / 085940, WO03 / 029291, WO20 03 / 055526, WO2003 / 084477, WO2003 / 094858, WO2004 / 002417, WO2004 / 002424, WO2004 / 009627, WO2004 / 024761, WO2004 / 03 3651, WO2004 / 035603, WO2004 / 043382, WO2004 / 101600, WO2004 / 101606, WO2004 / 101611, WO2004 / 106373, WO2004 / 018667,The same No. WO2005 / 001025, The same No. WO2005 / 001136, The same No. WO2005 / 021579, The same No. WO2005 / 025606, The same No. WO 2005 / 032460, WO2005 / 051327, WO2005 / 063808, WO2005 / 063809, WO2005 / 070451, WO2005 / 081687, WO2005 / 084711, WO2005 / 103076, WO2005 / 100403, WO2005 / 092369, WO2006 / 50959, WO2006 / 02646, and WO2006 / 29094.

[0267] Examples of other pharmaceutical products for use with the device include, but are not limited to, antibodies such as Vectibix® (panitumumab), Xgeva™ (denosumab), and Prolia™ (denosumab); other biologics such as Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF inhibitor), Neulasta® (pegfilgrastim, pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-Met-G-CSF), and Nplate® (romiplostim); and small molecule drugs such as Sensipar® (cinacalcet). The device may also be used with therapeutic antibodies, polypeptides, proteins, or other chemicals such as iron, e.g., ferumoxytol, iron dextran, ferric gluconate, and iron sucrose. The pharmaceutical product may be reconstituted from a liquid form or a lyophilized form.

[0268] Among examples of particular proteins are the specific proteins described below, including fusions, fragments, analogs, variants, or derivatives thereof.

[0269] , OPGL-specific antibodies having either a light chain of SEQ ID NO:2 set forth in Figure 2 of the following publications and / or a heavy chain of SEQ ID NO:4 set forth in Figure 4 of the following publications, each of which is individually and specifically incorporated by reference in its entirety as disclosed in the following publications:

[0270] , each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the following publications, particularly with reference in part to myostatin-specific peptibodies, including but not limited to the mTN8-19 family of peptibodies, including those in SEQ ID NOS: 305-351, TN8-19-1 to TN8-19-40, TN8-19 con1, and TN8-19 con2, i.e., peptibodies of the mL2 family of SEQ ID NOS: 357-383, the mL15 family of SEQ ID NOS: 384-409, the mL17 family of SEQ ID NOS: 410-438, the mL20 family of SEQ ID NOS: 439-446, the mL21 family of SEQ ID NOS: 447-452, the mL24 family of SEQ ID NOS: 453-454, and myostatin-binding proteins, peptibodies, and related proteins, including those of SEQ ID NOS: 615-631, in particular the myostatin-specific peptibodies described in U.S. Patent Publication No. 2004 / 0181033 and PCT Publication No. WO2004 / 058988, which are incorporated by reference in their entireties;

[0271] Each of the following publications is individually and specifically incorporated herein by reference in its entirety as if fully disclosed in the following, particularly in relation to IL-4 receptor-specific antibodies, particularly such antibodies as described therein, specifically those set forth therein, i.e., L1H1, L1H2, L1H3, L1H4, L1H5, L1H6, L1H7, L1H8, L1H9, L1H10, L1H11, L2H1, L2H2, L2H3, L2H4, L2H5, L2H6, L2H7, L2H8, L2H9, L2H10, L2H11: , L2H12, L2H13, L2H14, L3H1, L4H1, L5H1, L6H1, but are not limited to those described in PCT Publication No. WO2005 / 047331 or PCT Application No. PCT / US2004 / 37242 and U.S. Patent Publication No. 2005 / 112694, which are incorporated herein by reference in their entireties, and which specifically inhibit activities mediated by binding to the IL-4 and / or IL-13 receptors, such as IL-4 receptor-specific antibodies, peptibodies, and related proteins;

[0272] Interleukin 1-receptor 1 ("IL1-R1")-specific antibodies, peptibodies, and related proteins, including, but not limited to, those described in U.S. Patent Publication No. 2004 / 097712, which is incorporated herein by reference in its entirety, particularly with respect to IL1-R1-specific binding proteins, monoclonal antibodies, specifically, but not limited to, those set forth therein, i.e., 15CA, 26F5, 27F2, 24E12, and 10H7, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the aforementioned publication;

[0273] Each of the sequences is specifically incorporated herein by reference in its entirety as if it were disclosed in the aforementioned publication, particularly in relation to Ang2-specific antibodies and peptibodies, etc., and in particular those of the sequences described in the following publications: L1(N), L1(N)WT, L1(N)1KWT, 2xL1(N), 2xL1(N)WT, Con4(N), Con4(N)1KWT, 2xCon4(N)1K, L1C, L1C 1K, 2xL1C, Con4C, Con4C 1K, 2xCon4C 1K, Con4-L1(N), Con4-L1C, TN-12-9(N), C17(N), TN8-8(N), TN8-14(N), Con1(N), including but not limited to those described in PCT Publication No. WO03 / 057134 and U.S. Patent Publication No. 2003 / 0229023, which are incorporated by reference in their entireties, and with respect to anti-Ang2 antibodies and formulations, in particular Ab526, Ab528, Ab531, Ab533, Ab535, Ab536, and various permutations thereof, as described in the following publications: Ang2-specific antibodies, peptibodies, and related proteins, including anti-Ang2 antibodies and formulations such as those described in PCT Publication No. WO 2003 / 030833, which is incorporated by reference in its entirety, including Ab537, Ab540, Ab543, Ab544, Ab545, Ab546, A551, Ab553, Ab555, Ab558, Ab559, Ab565, AbF1AbFD, AbFE, AbFJ, AbFK, AbG1D4, AbGC1E8, AbH1C12, AblA1, AblF, AblK, AblP, and those described in PCT Publication No. WO 2003 / 030833, which is incorporated by reference in its entirety,

[0274] With respect to NGF-specific antibodies and related proteins related thereto, specifically including but not limited to the NGF-specific antibodies set forth in the following publications, 4D4, 4G6, 6H9, 7H2, 14D10, and 14D11, NGF-specific antibodies, peptibodies, and related proteins, including but not limited to those described in U.S. Patent Publication No. 2005 / 0074821 and U.S. Patent No. 6,919,426, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the following publications:

[0275] Humanized and fully human antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, particularly human CD22-specific IgG antibodies, such as, for example, a dimer of human-mouse monoclonal hLL2 gamma chain disulfide linked to a human-mouse monoclonal hLL2 kappa chain, including, but not limited to, the human CD22-specific fully humanized antibody of epratuzumab (CAS Registry Number 501423-23-0), including, but not limited to, human CD22-specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 5,789,554, which is incorporated herein by reference in its entirety with respect to CD22-specific antibodies and related proteins;

[0276] and IGF-1 specific antibodies set forth in the following publications, each of which is disclosed in the aforementioned publications and is individually and specifically incorporated herein by reference in its entirety: L1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30, L31H31, L32H32, and L33H 33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1 receptor-specific antibodies, peptibodies, and related proteins, such as those described in PCT Publication No. WO 06 / 069202, which is incorporated by reference in its entirety with respect to IGF-1 receptor-specific antibodies and related proteins, including, but not limited to, IGF-1R-binding fragments and derivatives thereof;

[0277] Also among the non-limiting examples of anti-IGF-1R antibodies for use in the methods and compositions of the present invention are each and every one of those described below. (i) U.S. Patent Publication Nos. 2006 / 0040358 (published February 23, 2006), 2005 / 0008642 (published January 13, 2005), and 2004 / 0228859 (published November 18, 2004), including, but not limited to, Antibody 1A (DSMZ Accession No. DSM ACC 2586), Antibody 8 (DSMZ Accession No. DSM ACC 2589), Antibody 23 (DSMZ Accession No. DSM ACC 2588), and Antibody 18, as described in the following patent publications: (ii) antibodies, including but not limited to, antibodies 2F8, A12, and IMC-A12, described in PCT Publication Nos. WO 06 / 138729 (published December 28, 2006) and WO 05 / 016970 (published February 24, 2005), and Lu et al. (2004), J. Biol. Chem. 279:2856-2865; (iii) PCT Publication Nos. WO07 / 012614 (published February 1, 2007), WO07 / 000328 (published January 4, 2007), WO06 / 013472 (published February 9, 2006), WO05 / 058967 (published June 30, 2005), and WO03 / 059951 (published July 24, 2003); (iv) antibodies described in the following patent publications, including, but not limited to, antibody 7C10, chimeric antibody C7C10, antibody h7C10, antibody 7H2M, chimeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version 2, humanized antibody 7C10 version 3, and antibody 7H2HM: U.S. Patent Publication No. 2005 / 0084906 (published April 21, 2005); (v) antibodies described in U.S. Patent Publication Nos. 2005 / 0249728 (published November 10, 2005), 2005 / 0186203 (published August 25, 2005), 2004 / 0265307 (published December 30, 2004), and 2003 / 0235582 (published December 25, 2003), including, but not limited to, EM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, and huEM164 v1.3; and Maloney et al. (2003), Cancer Res. 63:5073-5083; (vi) U.S. Patent No. 7,037,498 (issued May 2, 2006); U.S. Patent Publication Nos. 2005 / 0244408 (published November 30, 2005) and 2004 / 0086503 (published May 6, 2004); and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073, (vii) U.S. Patent Publication Nos. 2005 / 0136063 (published June 23, 2005) and 2004 / 0018191 (published January 29, 2004), including, but not limited to, antibody 19D12, described in the following patent publications: U.S. Patent Publication Nos. 2005 / 0136063 (published June 23, 2005) and 2004 / 0018191 (published January 29, 2004); and antibodies comprising a heavy chain encoded by the polynucleotide of plasmid 15H12 / 19D12 HCA(γ4), deposited with the ATCC under accession number PTA-5214, and a light chain encoded by the polynucleotide of plasmid 15H12 / 19D12 LCF(κ), deposited with the ATCC under accession number PTA-5220; (viii) U.S. Patent Publication No. 2004 / 0202655 (published October 14, 2004), including, but not limited to, the antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3, PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2, PINT-12A3, PINT-12A4, and PINT-12A5, which are each and every incorporated by reference herein in their entireties with respect to the foregoing antibodies, peptibodies, and related proteins that specifically target the IGF-1 receptor;

[0278] B-7 related protein 1-specific antibodies, peptibodies, related proteins, and the like ("B7RP-1," also referred to in the literature as B7H2, ICOSL, B7h, and CD275), particularly B7RP-specific fully human monoclonal IgG2 antibodies, particularly fully human IgG2 monoclonal antibodies that bind to an epitope in the first immunoglobulin-like domain of B7RP-1, particularly those that inhibit the interaction of B7RP-1 with ICOS, the natural receptor for B7RP-1, particularly on activated T cells, and particularly antibodies set forth in the following patent publications, each of which is individually and specifically incorporated herein by reference in its entirety as disclosed in the aforementioned publications: 16H (in which the light chain variable region sequence and heavy chain variable region sequence are SEQ ID NO: 1 and SEQ ID NO: 7, respectively), 5D (in which the light chain variable region sequence and heavy chain variable region sequence are SEQ ID NO: 1 and SEQ ID NO: 7, respectively), and and 15H (having light chain variable region sequences SEQ ID NO:4 and SEQ ID NO:12, respectively). In all of the foregoing respects, those disclosed in U.S. Patent Publication No. 2008 / 0166352 and PCT Publication No. WO07 / 011941, which are incorporated by reference herein in their entireties, with respect to such antibodies and related proteins, including, but not limited to, 2H (having light chain variable region sequences SEQ ID NO:5 and SEQ ID NO:13, respectively), 2H (having light chain variable region sequences SEQ ID NO:6 and SEQ ID NO:14, respectively), 2H (having light chain variable region sequences SEQ ID NO:7 and SEQ ID NO:10, respectively), 43H (having light chain variable region sequences SEQ ID NO:8 and SEQ ID NO:11, respectively), 41H (having light chain variable region sequences SEQ ID NO:9 and SEQ ID NO:11, respectively), and 15H (having light chain variable region sequences SEQ ID NO:12 and SEQ ID NO:13, respectively).

[0279] IL-15 specific antibodies, peptibodies, and related proteins, particularly antibodies, particularly humanized monoclonal antibodies, such as those disclosed in U.S. Patent Publication Nos. 2003 / 0138421, 2003 / 023586, and 2004 / 0071702, and U.S. Patent No. 7,153,507, each of which is incorporated herein by reference in its entirety, for IL-15 specific antibodies and related proteins, including, specifically, peptibodies, including, but not limited to, HuMax IL-15 antibodies and related proteins, such as 146B7;

[0280] IFNγ-specific antibodies, peptibodies, and related proteins, etc., particularly human IFNγ-specific antibodies, particularly fully human anti-IFNγ antibodies, such as, for example, IFNγ-specific antibodies, particularly fully human anti-IFNγ antibodies, such as those described in the following patent publications: U.S. Patent Publication No. 2005 / 0004353, which is incorporated herein by reference in its entirety with respect to the antibodies designated 1118, 1118*, 1119, 1121, and 1121*: The entire sequences of the heavy and light chains of each of these antibodies, as well as the sequences of their heavy and light chain variable regions and complementarity-determining regions, are each individually and specifically incorporated herein by reference in their entirety as disclosed in the aforementioned publications and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. Additionally, the descriptions of the properties of these antibodies provided in the aforementioned publications are also incorporated herein by reference in their entirety. Specific antibodies include those having a heavy chain of SEQ ID NO: 17 and a light chain of SEQ ID NO: 18, those having a heavy chain variable region of SEQ ID NO: 6 and a light chain variable region of SEQ ID NO: 8, those having a heavy chain of SEQ ID NO: 19 and a light chain of SEQ ID NO: 20, those having a heavy chain variable region of SEQ ID NO: 10 and a light chain variable region of SEQ ID NO: 12, those having a heavy chain of SEQ ID NO: 32 and a light chain of SEQ ID NO: 20, those having a heavy chain variable region of SEQ ID NO: 30 and a light chain variable region of SEQ ID NO: 12, those having a heavy chain sequence of SEQ ID NO: 21 and a light chain sequence of SEQ ID NO: 22, those having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 16, those having a heavy chain of SEQ ID NO: 21 and a light chain of SEQ ID NO: 33, and those having a heavy chain variable region of SEQ ID NO: 14 and a light chain variable region of SEQ ID NO: 31, as disclosed in the aforementioned publications. Specific antibodies contemplated include antibody 1119, as disclosed in the aforementioned U.S. publication, having the complete heavy chain of SEQ ID NO: 17 as disclosed in the aforementioned U.S. publication and the complete light chain of SEQ ID NO: 18 as disclosed in the aforementioned U.S. publication;

[0281] TALL-1 specific antibodies, peptibodies, and related proteins, such as those described in U.S. Patent Publication Nos. 2003 / 0195156 and 2006 / 0135431, each of which is incorporated herein by reference in its entirety as if fully disclosed in the aforementioned publications, and other TALL specific binding proteins, particularly with respect to the molecules in Tables 4 and 5B,

[0282] Parathyroid hormone ("PTH")-specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 6,756,480, which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind PTH;

[0283] thrombopoietin receptor ("TPO-R")-specific antibodies, peptibodies, and related proteins, such as those described in U.S. Pat. No. 6,835,809, which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind to TPO-R;

[0284] Hepatocyte growth factor ("HGF")-specific antibodies, peptibodies, and related proteins, including those that target the HGF / SF:c-Met axis (HGF / SF:c-Met), such as fully human monoclonal antibodies that neutralize hepatocyte growth factor / scatter (HGF / SF), described in U.S. Patent Publication No. 2005 / 0118643 and PCT Publication No. WO2005 / 017107, huL2G7, described in U.S. Patent No. 7,220,410, and OA-5d5, described in U.S. Patent Nos. 5,686,292 and 6,468,529 and PCT Publication No. WO96 / 38557, each of which is incorporated by reference in its entirety, particularly with respect to proteins that partially bind HGF;

[0285] TRAIL-R2 specific antibodies, peptibodies, related proteins, etc., such as those described in U.S. Pat. No. 7,521,048, which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind TRAIL-R2;

[0286] Activin A-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Publication No. 2009 / 0234106, which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind activin A;

[0287] TGF-β specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent No. 6,803,453 and U.S. Patent Publication No. 2007 / 0110747, each of which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind TGF-β;

[0288] Amyloid β protein-specific antibodies, peptibodies, related proteins, and the like, including, but not limited to, those described in PCT Publication No. WO2006 / 081171, which is incorporated herein by reference in its entirety, particularly with respect to proteins that partially bind to amyloid β protein. One contemplated antibody is an antibody having a heavy chain variable region comprising SEQ ID NO:8 and a light chain variable region having SEQ ID NO:6, as disclosed in the aforementioned publication;

[0289] c-Kit-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Publication No. 2007 / 0253951, which is incorporated herein by reference in its entirety, particularly with respect to proteins that bind, in part, to c-Kit and / or other stem cell factor receptors;

[0290] OX40L-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, those described in U.S. Patent Publication No. 2006 / 0002929, which is incorporated herein by reference in its entirety, particularly with respect to proteins that bind, in part, to OX40L and / or other ligands of the OX40 receptor;

[0291] Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), Epogen® (epoetin alfa, or erythropoietin), GLP-1, Avonex® (interferon beta-1a), Bexxar® (tositumomab, an anti-CD22 monoclonal antibody), Betaseron® (interferon beta), Campath® (alemtuzumab, an anti-CD52 monoclonal antibody), Dynepo® (epoetin delta), Velcade® (bortezomib), MLN0002 (anti-alpha4beta7 mAb), MLN1202 (anti-CCR2 chemokine receptor mAb), Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF inhibitor), Eprex® (epoetin alfa), Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1), Genotropin® (somatropin, human growth hormone), Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb), Humatopeptide® (anti-HER2 / neu(erbB2) receptor mAb), Rope® (somatropin, human growth hormone), Humira® (adalimumab), insulin in solution, Infergen® (interferon alfacon-1), Natrecor® (nesiritide, recombinant human B-type natriuretic peptide (hBNP), Kineret® (anakinra), Leukine® (sargamostim, rhuGM-CSF), LymphoCide® (epratuzumab, anti-CD22 mAb), Benlysta™ (lymphostat B, belimumab, anti-BlyS)mAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-complement C5), Numax® (MEDI-524), Lucentis® (ranibizumab), Panorex® (17-1A, edrecolomab), Trabio® (lerdelimumab), TheraCim hR3 (nimotuzumab), Omnitarg (pertuzumab, 2C4), Osidem® (IDM-1), OvaRex® (B43.13), Nuvion® (vigilizumab), cantuzumab mertansine (huC242-DM1), NeoRecormon® (epoetin beta), Neumega® (oprelvekin, human interleukin-11), Neulasta® (pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF, hu-Met-G-CSF), Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody), Procrit® (epoetin alfa), Remicade® (infliximab, anti-TNFα monoclonal antibody), Reopro® (abciximab, anti-GP 1Ib / Ilia receptor monoclonal antibody), Actemra® (anti-IL6 receptor mAb), Avastin® (bevacizumab), HuMax-CD4 (zanolimumab), Rituxan® (rituximab, anti-CD20mAb), Tarceva® (erlotinib), Roferon-A® (interferon alpha-2a), Simulect® (basiliximab), Prexige® (lumiracoxib), Synagis® (palivizumab), 146B7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, anti-alpha4 integrin mAb), Valortim® (MDX-1303, anti-anthrax protective antigen mAb), ABthrax™, Vectibix® (panitumumab), Xolair® (omalizumab), ETI211 (anti-MRSA mAb), IL-1 trap (the Fc portion of human IgG1 and the extracellular domain of both IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF trap (the domain of VEGFR1 fused to IgG1 Fc), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2Rα mAb), Zevalin® (ibritumomab tiuxetan), Zetia® (ezetimibe), Orencia® (atacicept, TACI-Ig), anti-CD80 monoclonal antibody (galiximab), anti-CD23 mAb (lumiliximab), BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist), CNTO148 (golimumab, anti-TNFα mAb), HGS-ETR1 (mapatuzumab, human anti-TRAIL receptor-1 mAb), HuMax-CD20 (ocrelizumab, anti-CD20 human mAb), HuMax-EGFR (zalutumumab), M200 (volociximab, anti-α5β1 integrin mAb), MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1), anti-BR3 mAb, anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388), anti-CD22 dsFv-PE38 conjugate (CAT-3888 and CAT-8015), anti-CD25 mAb (HuMax-TAC), anti-CD3 mAb (NI-0401), adecatumumab, anti-CD30mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38 mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019), anti-CTLA4 mAb, anti-eotaxin-1 mAb (CAT-213), anti-FGF8 mAb, anti-ganglioside GD2 mAb, anti-ganglioside GM2 mAb, anti-GDF-8 human mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFNα mAb (MEDI-545, MDX-1103), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-integrin receptor mAb (MDX-018, CNTO95), anti-IP10 ulcerative colitis mAb (MDX-1100), anti-LLY antibody, BMS-66513, anti-mannose receptor / hCGβ mAb (MDX-1307), anti-mesothelin dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106(ONO-4538)), anti-PDGFRα antibody (IMC-3G3), anti-TGFβ Other exemplary proteins include mAb (GC-1008), anti-TRAIL receptor-2 human mAb (HGS-ETR2), anti-TWEAK mAb, anti-VEGFR / Flt-1 mAb, anti-ZP3 mAb (HuMax-ZP3), NVS antibody no. 1, and NVS antibody no. 2.

[0292] Sclerostin antibodies may also be included, such as, but not limited to, romosozumab, brosozumab, or BPS804 (Novartis). Further therapeutic agents may be included, such as rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX, or XGEVA. Further, see, for example, U.S. Patent No. 8,030,547, U.S. Patent Publication No. 2013 / 0064825, WO 2008 / 057457, WO 2008 / 057458, WO 2008 / 057459, WO 2008 / 063382, WO 2008 / 133647, WO 2009 / 100297, WO 2009 / 100318, WO 2011 / 037791, WO 2011 / 053759, WO 2011 / 053783, WO 2008 / 125623, WO 2011 / 072263, WO 2009 Monoclonal antibodies (IgG) that bind to human proprotein convertase subtilisin / kexin type 9 (PCSK9) may also be included in the device, as described in US Pat. Nos. 2012 / 055783, 2012 / 0544438, 2010 / 029513, 2011 / 111007, 2010 / 077854, 2012 / 088313, 2012 / 101251, 2012 / 101252, 2012 / 101253, 2012 / 109530, and 2001 / 031007.

[0293] Talimogene laherparepvec or other oncolytic HSVs for the treatment of melanoma or other cancers can also be included. Examples of oncolytic HSVs include, but are not limited to, talimogene laherparepvec (U.S. Patent Nos. 7,223,593 and 7,537,924), OncoVEXGALV / CD (U.S. Patent No. 7,981,669), OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143), G207, 1716, NV1020, NV12023, NV1034, and NV1042 (Vargehes et al. (2002), Cancer Gene Ther., 9(12):967-978).

[0294] TIMPs are also included. TIMPs are endogenous tissue inhibitors of metalloproteinases (TIMPs) and are important in many natural processes. TIMP-3 is expressed by various cells or / and present in the extracellular matrix, inhibits all major cartilage-degrading metalloproteinases, and may play a role in many connective tissue degrading diseases, including rheumatoid arthritis and osteoarthritis, as well as in cancer and cardiovascular conditions. The amino acid sequence of TIMP-3 and the nucleic acid sequence of DNA encoding TIMP-3 are disclosed in U.S. Patent No. 6,562,596, issued May 13, 2003, the disclosure of which is incorporated herein by reference. Descriptions of TIMP mutations can be found in U.S. Patent Publication No. 2014 / 0274874 and PCT Publication No. WO2014 / 152012.

[0295] Also included are antagonistic antibodies of the human calcitonin gene-related peptide (CGRP) receptor, and bispecific antibody molecules that target the CGRP receptor and other headache targets. Further information regarding these molecules can be found in PCT Application No. WO2010 / 075238.

[0296] Additionally, bispecific T cell-inducing antibodies (BiTe), such as brinotumomab, can be used in the device. Alternatively, APJ macromolecular agonists, such as apelin or analogs thereof, can be included in the device. Information related to such molecules can be found in PCT Publication No. WO2014 / 099984.

[0297] In certain embodiments, the agent comprises a therapeutically effective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLP receptor antibody. Examples of anti-TSLP antibodies that may be used in such embodiments include, but are not limited to, those described in U.S. Patent Nos. 7,982,016 and 8,232,372, and U.S. Patent Publication No. 2009 / 0186022. Examples of anti-TSLP receptor antibodies include, but are not limited to, those described in U.S. Patent No. 8,101,182. In a particularly preferred embodiment, the agent comprises a therapeutically effective amount of the anti-TSLP antibody designated A5 in U.S. Patent No. 7,982,016.

[0298] It should be noted that the configurations of the various embodiments of the drug delivery devices and drug delivery systems described herein are exemplary only. While only a few embodiments of the drug delivery devices and drug delivery systems are detailed in this disclosure, those skilled in the art who review this disclosure will readily understand that many modifications (e.g., changes in the size, dimensions, structure, shape, and proportions of various elements, parameter values, installation arrangements, material use, orientation, etc.) are possible without significantly departing from the novel teachings and advantages of the subject matter of the present disclosure. For example, any combination of one or more of the sensors and sensor systems described herein may be incorporated into one or more of the drug delivery systems and drug delivery devices described herein. Also, the order or sequence of any process or method steps described herein may be changed or rearranged in any combination according to alternative embodiments. Furthermore, any combination of one or more of the elements of one or more of the claims set forth at the end of this disclosure is possible.

[0299] While the preceding text sets forth detailed descriptions of different embodiments of the present invention, it should be understood that the legal scope of the present invention is defined by the terms of the claims set forth at the end of this patent. The detailed description is intended to be merely exemplary and does not describe every possible embodiment of the present invention, as describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent that remains within the scope of the claims defining the invention.

[0300] It should be understood that unless a term is expressly defined in this patent using the sentence "As used herein, the term '______' is herein defined to mean ..." or similar language, no term is intended to limit the meaning of the term, either explicitly or by implication, beyond its plain or conventional meaning, and such term should not be construed as limiting in scope based on any statement made in any part of this patent (other than the terminology in the claims). To the extent that any term recited in a claim at the end of this patent is referenced herein in a manner consistent with a single meaning, that is done for purposes of clarity so as not to confuse the reader, and such claim terminology is not intended, by implication or otherwise, to be limited to a single meaning. Finally, unless a claim element is defined by reciting the word "means" and a function without any recitation of structure, the scope of any claim element is not intended to be construed based on application of 35 U.S.C. §112, paragraph 6.

Claims

1. 1. A drug delivery device comprising: a housing having an exterior surface; a reservoir disposed at least partially within the housing; an opening formed in the exterior surface of the housing; an adhesive disposed on the exterior surface of the housing for releasably attaching the drug delivery device to the patient's skin; a delivery member having a proximal end and a distal end, the proximal end connected or configured to be connected in fluid communication with the reservoir, the distal end of the delivery member being disposed within the housing in an initial state and configured to extend through the opening in an operative state; a removable cover coupled to the housing, the removable cover comprising a sheet covering the adhesive and configured to be removable by the patient or user to expose the adhesive; a sensor configured to detect contact with the patient's skin; Equipped with the drug delivery device comprising: (a) determining whether the removable cover has been removed from the housing to expose the adhesive; (b) determining whether the medication delivery device is in contact with the patient's skin, and if contact does not occur within a predetermined time period after (a), outputting a control signal to a controllable element; (c) a drug delivery device configured or programmed to notify the patient or user if or when the drug delivery device has been activated to deliver a drug to the patient.

2. The drug delivery device of claim 1 , comprising a controller coupled to the sensor.

3. 3. The drug delivery device of claim 2, comprising a wireless transmitter coupled to the controller.

4. 4. The drug delivery device of claim 3, wherein the control device is configured to determine whether the drug delivery device is in contact with the patient's skin based on output from the sensor and to control the wireless transmitter to wirelessly transmit a report indicating contact between the drug delivery device and the patient's skin.

5. 3. The drug delivery device of claim 2, wherein the control device is programmed to repeatedly determine at predetermined intervals whether the drug delivery device is in contact with the patient.

6. The drug delivery device of claim 1 , wherein the sensor comprises a first conductive member.

7. The drug delivery device of claim 6 , wherein the sensor comprises a second conductive member.

8. The drug delivery device of claim 7 , wherein when the housing is in contact with the patient's skin, the first conductive member, the second conductive member, and the patient's skin form a closed electrical circuit.

9. The drug delivery device of claim 7 , wherein the opening is disposed between the first conductive member and the second conductive member.

10. The drug delivery device of claim 1 , wherein the adhesive and the sensor are integrally configured.

11. The drug delivery device of claim 1 , comprising a drug disposed within a reservoir.

12. 12. The drug delivery device of claim 11, wherein the drug is selected from the group consisting of a TNF inhibitor, an antibody against the calcitonin gene-related peptide receptor, a granulocyte colony-stimulating factor (G-CSF), an erythropoiesis-stimulating agent, an apelin receptor agonist, an antibody against proprotein convertase subtilisin / kexin type 9 (PCSK9), and a tissue inhibitor of metalloproteinase.

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