DRUG DELIVERY DEVICE WITH INCREASED SAFETY

Abstract

A disposable, single-dose delivery device for self-administration by a patient of a predefined amount or dose of drug from a reservoir through an outlet of the reservoir includes a device operation lock to prevent a delivery operation of the delivery device as shipped to the patient, an embedded electronic control unit with a wireless receiver for receiving an unlock command or message, and an electromechanical actuator for mechanically unlocking the device operation lock and enabling delivery device operation by the patient. The control unit is configured to activate the actuator instantaneously and unconditionally upon receipt of the unlock command. The unlocking mechanism of the delivery device is adapted to be activated from remote in response to a confirmative message indicative of additional double check by a Health Care Professional HCP or expert system.

Claims

1. A delivery device for self-administration of a predefined amount of drug from an outlet of a reservoir, comprising: a device operation lock preventing a delivery operation of the delivery device as shipped; a wireless receiver for receiving an unlock command; and an actuator for unlocking the device operation lock and configured to be activated instantaneously upon receipt of the unlock command.

2. The delivery device of claim 1, wherein the delivery device is an auto-injector or a patch-injector.

3. The delivery device of claim 2, wherein the device operation lock comprises an outlet cover lock for preventing removal of an outlet cover sealing the outlet of the reservoir.

4. The delivery device of claim 3, wherein the outlet cover lock is adapted to be re-locked by the actuator before the delivery operation has occurred.

5. The delivery device of claim 3, wherein the outlet cover lock is a device cap lock comprising a flexible ledge engaging a counter-ledge and is prevented from disengaging by a locking slider.

6. The delivery device of claim 1, further comprising a wireless transmitter adapted to send an unlock request message.

7. The delivery device of claim 6, further comprising a device-activation sensor to detect a user-initiated preparation of the delivery device.

8. The delivery device of claim 1, further comprising drug delivery sensor means configured to monitor and report the delivery operation of the delivery device.

9. The delivery device of claim 1, further comprising an actuator comprising a shape-memory-alloy element.

10. The delivery device of claim 1, wherein the device operation lock comprises a thermo-sensitive element configured to melt, evaporate, soften and/or otherwise become structurally weakened when subjected to an elevated temperature.

11. The delivery device of claim 10, wherein the actuator comprises heating means for heating the device operation lock and/or the thermo-sensitive element to the elevated temperature conditionally upon the receipt of the unlock command.

12. The delivery device of claim 11, wherein the device operation lock is adapted to engage a proximal end of a plunger rod of an auto-injector prior to the receipt of the unlock command, and wherein a syringe of the auto-injector is adapted to be moved in a distal direction by the plunger rod in an unlocked state.

13. A method of unlocking a delivery device comprising a device operation lock for preventing a delivery operation of the delivery device as shipped, the delivery device for self-administration by a patient of a predetermined quantity of drug from a reservoir through an outlet of the delivery device, the method comprising: establishing an electronic communication between the patient and a Health Care Professional (HCP) or a Health Care Expert System (HCES), and inquiring about an intended self-administration; confirming, by the HCP or the HCES, suitability of the intended self-administration by transmitting an unlock command; receiving, by a wireless receiver of the delivery device, the unlock command; and activating, instantaneously upon receipt of the unlock command, an actuator of the delivery device to unlock the device operation lock.

14. The method of claim 13, further comprising: assigning, at a therapy management system, the delivery device to the patient; and transmitting, by the therapy management system, the unlock command following a confirmation by the HCP and based on the assignment.

15. The method of claim 13, further comprising: detecting, by a device-activation sensor of the delivery device, a user-initiated preparation of the delivery device; sending, by a wireless transmitter of the delivery device, an unlock request message to the HCP or HCES; and contacting, by the HCP or HCES, the patient.

16. The method of claim 13, wherein the delivery device is an auto-injector or a patch-injector, the method further comprising: activating, instantaneously upon the receipt of the unlock command, the actuator of the delivery device to unlock an outlet cover sealing the outlet.

17. The method of claim 16, further comprising: re-locking the outlet cover by the actuator before the delivery operation has occurred.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0050] The subject-matter of the invention will be explained in more detail in the following text with reference to preferred exemplary embodiments as illustrated in the attached drawings, of which

[0051] FIG. 1 depicts a medical injection monitoring and patient support system;

[0052] FIG. 2 is a flow chart of an exemplary method of safely unlocking a delivery device;

[0053] FIGS. 3a to 3d depict an auto-injector, a locking slider, and an unlocking actuator of a first embodiment;

[0054] FIGS. 4a to 4h illustrate three variants of the locking slider—device cap interaction;

[0055] FIGS. 5a and 5b depict an auto-injector and a plunger rod of a second embodiment; and

[0056] FIGS. 6a and 6b depict a trigger component and a cross-section view of the second embodiment.

[0057] For consistency, the same reference numerals are used to denote similar elements illustrated throughout the drawings.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0058] FIG. 1 depicts a medical drug delivery monitoring and patient support system including a delivery device 1 for self-administration of a dose of drug to a patient 0. A smartphone of the patient serves as a user and/or device gateway 2 to a therapy management system 3. A pharmacy 4 is adapted to sell and supply the delivery device 1 to the patient and to provide an association or link between delivery device 1 and patient 0 to the therapy management system 3. A Health Care Professional (HCP) 5 such as a physician is enabled to interact with the patient 0 and the therapy management system 3, optionally via a dedicated tele-health portal or interface 6. An electronic patient file 7 comprising therapy relevant information and/or specific recipes of the patient 0 may be available for reading and writing by the pharmacy 4 and the HCP 5.

[0059] The delivery device 1 is a disposable auto-injector with an elongate, pen-shaped device housing essentially symmetric around a main device axis, and a patient-operable trigger element for triggering automated delivery of the dose of drug. The delivery device may also be a disposable patch injector, or wearable bolus injector, with an essentially flat shape factor and with a skin adhesive layer for injection of the dose over prolonged periods of up to 15 minutes. The delivery device may also be a manual device with a delivery lever or button for drug delivery through a force provided by the user.

[0060] The delivery device integrates an electronic unit with a short-range communication facility such as Bluetooth Low Energy (BLE) or equivalent short or near range wireless communication technology, such as NFC, WiFi, or IR, to communicate with a nearby gateway device 2 such as a mobile device of the user, including a smartphone or tablet device running a dedicated application program, or a laptop computer configured accordingly. The gateway device 2 in turn communicates with a therapy management system 3 on a cloud-based, distributed data server or computing facility, by way of a 4G/LTE cellular mobile and/or wire-based communication network, and is adapted to relay data between the delivery device 1 or the patient and the therapy management system. Alternatively, the communication facility of the delivery device 1 may communicate directly with the therapy management system 3 via wireless long-range communication networks such as 5G cellular mobile networks, nb-IoT, LTE-m, LoRa, Sigfox, and the patient 0 may interface the data servers of the therapy management system 3 via other communication means. All communication is state-of-the-art encrypted, authenticated and/or otherwise secured in order to comply with relevant regulations applicable to protected health information.

[0061] The therapy management system 3 is configured to handle device unlocking requests from the delivery device 1 and unlocking approvals from the HCP 5. To that end, the system receives and registers, in a user account of the patient 0, an assignment or association between the patient 0 and the delivery device 1, either from the pharmacy 2 supplying the device, or from the patient, e.g. by recording and transmitting a Unique Device Identification UDI of the device in the form of printed text, an optical code, or an RFID tag. The UDI includes more generic information about the package in which the specific device was supplied, the production batch, and the drug type, quantity, concentration, and expiry date. The therapy management system may be adapted to store delivery data, drug information, patient adherence data, or any further monitoring data accumulated by adequate sensors of the electronic unit of the delivery device 1 and uploaded to the data server of the therapy management server 3.

[0062] The HCP and pharmacy have access to the electronic file of the patient, which comprises at least the prescription for the current therapy, and which may be stored in or next to the user account of the patient on the data server of the therapy management system. The HCP has access to the therapy management system and the registered assignments, or is otherwise given the authority, to have the system dispatch unlock commands based on unlocking approvals from the HCP. The unlock approval of the HCP may be indicating i) any delivery device with the correct drug type, quantity, and concentration as specified, ii) any one device of a production batch as specified, iii) any one device of a package or box of plural devices as specified, or iv) a specific delivery device. The therapy management system is configured to identify, in cases i) to iii), a specific delivery device available to the patient for the intended administration, and to send an unlock command for or to precisely this device.

[0063] FIG. 2 is a flow chart of a method 200 summarizing essential steps of an exemplary method of safely unlocking a delivery device with a device operation lock. Method 200 may involve establishing a communication between the patient 0 and the HCP 5 in operation 210; inquiring about intended self-administration in operation 220; confirming suitability of intended self-administration in operation 230; dispatching or transmitting an unlock command in operation 240; receiving an unlock command in operation 250; and unlocking the device operation lock of the delivery device 1 in operation 260.

[0064] FIG. 3a depicts a perspective view of an auto-injector device 1 according to a first embodiment, in an initial or storage state with a device cap 11 for removing a needle shield of a prefilled syringe 12 being mounted to the device. The housing of the auto-injector has been omitted in order to reveal the axially movable cover sleeve 13 as the trigger element and a drive unit at a proximal end of the device. The latter includes an electronic unit 14 with a Printed Circuit Board PCB mounted immovably in the device and oriented parallel to the main axis of the device. The PCB accommodates sensors for sensing a status of the device and communication means for transmitting and receiving device and/or operation data to or from a nearby mobile device of the patient or a remote expert. The electronic unit 14 also includes an actuator for a cap unlocking mechanism with a shape memory alloy wire arranged on the outer side of the PCB. The actuator is connected to a locking slider 15 that essentially extends from the electronic unit 14 to the device cap 11 and may be shifted axially back and forth a distance corresponding to an actuating hub. A proximal end of the locking slider 15 is axially fixed to a bracket 16 of the actuator and a distal end is adapted and/or arranged to interact with the cap unlocking mechanism. A major part of the locking slider 15 is radially arranged between the cover sleeve 13 and a syringe holder, a proximal flange of which acts as a guiding means for the locking slider 15. The permanent connection between the actuator and the locking slider is established at final assembly, when a syringe unit including the prefilled syringe and the locking slider is coupled to the drive unit including the drive spring and the actuator. The actuator and the locking slider are temporarily axially secured and/or suitably guided by dedicated gripping means in order to enable the connection.

[0065] FIG. 3b depicts the locking slider 15 of FIG. 10a in an isolated view. The locking slider comprises a part-cylindrical base 15a at a proximal end and two arms 15b extending therefrom in distal direction. The two arms 15b are radially closer to the center of the device axis and obscured by the cover sleeve 13 in the view of FIG. 3a. A radial blocking surface at the tip or distal end 15c of the arms interacts with the cap unlocking mechanism as detailed below.

[0066] FIG. 3c and FIG. 3d depict a top view of the unlocking actuator in the locked state, FIG. 3c, and in the unlocked state, FIG. 3d. A first or unlocking shape memory alloy wire 17a is arranged parallel to the main axis, with a proximal end thereof fixed to a first electrical contact on the PCB, and with a distal end thereof fixed to the metallic actuator bracket 16 as a second electrical contact. Specifically, the distal end is connected to an axially flexible actuator arm 16a of the bracket, which is biased and in turn biases the locking slider 15 in the distal direction by virtue of the elastic properties of the metallic bracket 16. For actuating the cap unlocking mechanism, a current is passed through the first wire 17a, which causes the wire to heat up to a critical temperature at which phase change sets in, and to correspondingly reduce its length by 2-5%. By way of example, a commercial shape memory alloy wire with a diameter of 0.05-0.1 mm and a length of 50-70 mm may develop a hub of 1.5-3 mm within 1-2 seconds when heated to a temperature of 70° or higher by a current of 100-200 mA This contraction in turn pulls the actuator arm 16a and the locking slider 15 in a proximal direction against the bias mentioned. A transverse ledge 16b of the actuator arm 16a engages a proximally oriented blocking surface 18a or edge of a transversally movable anchor 18. Such engagement prevents the locking slider 15 in the unlocked state from shifting distally under the bias of the flexible bracket arm. The actuator includes a second, or locking, shape memory alloy wire 17b connected at both ends to corresponding contacts and forming a kink or deviation angle at an intermediate pulley 18b of the anchor 18. For actuating a cap locking mechanism, or for de-actuating the cap unlocking mechanism, a current is passed through the second wire 17b, which in turn contracts and pulls the intermediate pulley 18b and the anchor 18 in a transverse direction in an attempt to decrease the deviation angle. The transverse ledge 16b passes out of engagement with the blocking surface 18a of the anchor 18, and the actuator arm 16a and locking slider 15 move distally under the distal bias of the elastic bracket 16. Alternatively, the second wire may be arranged to urge the transverse ledge 16b out of engagement with a stationary blocking surface. The blocking surface 18a and the transverse ledge 16b, or at least a counterpart surface thereof, may be made of electrically conductive material and build a contact switch of which the closed state signals the device cap unlocking state.

[0067] FIG. 4a and FIG. 4b depict a longitudinal section along the main axis of the auto-injector with a first variant of the locking slider—device cap interaction in the locked state (FIG. 4a) and in the unlocked state (FIG. 4b). An inner sleeve 11a of the device cap 11 comprises a recess 11b engaged in the locked state by a locking ledge 10a at a distal end of a flexible locking arm 10b integral with the housing 10. A distal tip 15c of the locking slider 15 prevents the locking ledge 10a from radial movement and from disengaging the recess 11b. In the unlocked state the locking slider 15 has moved proximally by an unlocking hub allowing the locking ledge 10a to flex radially, by virtue of an inclined contact surface at the locking ledge 10a and/or the recess 11b, when the device cap 11 is pulled distally.

[0068] FIG. 4c and FIG. 4d depict a longitudinal section along the main axis of the auto-injector with a second variant of the locking slider—device cap interaction in the locked state (FIG. 4c) and in the unlocked state (FIG. 4d). In this variant the radially flexible locking arm 11c is part of the device cap 11, and the locking ledges thereof, in the locked state, engage a recess 10c formed in the housing 10. The locking arm may be part of an inner sleeve of the device cap, or may be part of a metallic remover sleeve of the device cap 11, adapted to engage a rigid needle shield 12a sealing the needle of the pre-filled syringe 12.

[0069] FIG. 4e to FIG. 4h depict an off-center longitudinal section along a plane tangential to the inner sleeve of the device cap (FIG. 4e and FIG. 4f) and a cross section perpendicular to the main axis (FIG. 4g and FIG. 4h) of the auto-injector with a third variant of the locking slider—device cap interaction in the locked state (FIG. 4e and FIG. 4g) and in the unlocked state (FIG. 4f and FIG. 4h). In this variant, removal of the device cap 11 includes first a rotation by a few degrees as depicted in FIG. 4g and FIG. 4h, followed by a combined rotational-axial unscrewing movement. The plane of the perpendicular cross section is indicated with a broken line in FIG. 4f, and the intersection of the perpendicular and the longitudinal section plane is depicted by a dash-dot line in FIG. 4h. A rotating cam 11d extending radially outwards from the inner sleeve 11a of the device cap 11 is guided by a cam-path 10d in the housing, wherein a locking cam 15d extending radially inward from the locking slider 15 into the cam path prevents the rotating cam 11d from being rotated in the locked state. In the unlocked state, the locking slider 15 is shifted proximally, and the locking cam 15d is moved out of the blocking engagement with the rotating cam 11d.

[0070] Alternative to the shape memory alloy based materials, the actuators may include a magnetic core shifted by the magnetic field of an electromagnet or a solenoid; a DC motor, a stepper motor, or a linear motor, all with or without gearing, Further possibilities include actuators based on a piezo-effect, a bimetal, electroactive polymers, air cushion, or an H2 cell, or a one-time operational melting fuse.

[0071] The locking arm or the recess of the previous variants may be part of the cover sleeve instead of the housing. The locking arm may be arranged to flex radially inward upon locking slider retraction and device cap retrieval. The distal head of the locking slider may be positioned, in the locked state, between two off-center flexible locking arms of the device cap engaging two recesses of the housing facing each other. Upon locking slider retraction, these two locking arms may be deflected towards each other in a tangential direction. Alternative variants of the locking slider—device cap interaction include a distally oriented locking arm of the device cap or a distally oriented claw of the remover sleeve abutting a proximally oriented stop surface of the housing, and a locking slider being rotated or shifted distally to urge the locking arm out of engagement with the stop surface. Further concepts involve pivotal levers, or a lock wheel that may be rotated in the unlocked state by less than 180° by the device cap being removed, against a biasing spring.

[0072] The electronic unit being integrated in the delivery device may comprise a visual, audible and/or tactile status indicator indicating to a user a status of the system. The status of the system may include a device status of the delivery device or a delivery status of a drug dispensing process. The status indicator may be simple and limited to a few Light Emitting Diodes LEDs in traffic-light colors and/or an audible signal generator for generating language-independent beep sounds or simple melodies. In particular, the status information may include an indication about a lapse of a minimum holding, delay, or dwell time following completion of a substance dispensing activity to inform the user that it is now safe to remove the delivery device. The status indicator may explicitly exclude any advanced human-machine interfacing capability, and be limited to a few, specifically less than ten, messages conveyable to the user. In particular, the delivery device may be devoid of a display, screen, or projector for visually transmitting readable instructions, and likewise exclude an artificial speech assistant for reading out loud the instructions.

[0073] FIG. 5a and FIG. 5b depict a partial axial section of an auto-injector according to a second embodiment of the invention in a locked or shipping state (FIG. 5a), and an isometric view of the plunger rod (FIG. 5b). The auto-injector includes a housing 10 defining a main or longitudinal device axis, a prefilled syringe 12, a cover sleeve 13, an electronic unit 14, a battery 14a, a plunger rod 19, and a trigger component 20 mounted rotationally and axially fix in the housing 10. A lock sleeve 13a is arranged proximally to and in force-fit contact with the cover sleeve 13, and biased by a cover sleeve spring 13b in a distal direction. An injection sleeve 13c in contact with a proximal flange of the prefilled syringe 12 has radially flexible arms with inward-oriented cams kept in engagement with a first recess 19a of the plunger rod by an adjacent blocking surface of a mechanics holder 10e solidly mounted in the housing 10. The plunger rod 19 comprises, in addition to the first recess 19a perpendicular to the main axis, a second, axial recess 19b, and a third recess 19c with a distally oriented guiding surface that is oblique with respect to the main axis, in other words neither parallel nor perpendicular thereto.

[0074] A solenoidal compression spring (not shown) is arranged inside the sleeve-shaped plunger rod as a drive or injection spring and exerts an axial force on the plunger rod. The mechanics holder 10e includes a proximally oriented counter guiding surface such that under an unobstructed axial bias of the drive spring, the plunger rod 19 first moves in a screwing movement, including a rotation by a few degrees, before pursuing a pure axial movement. The angular width of the first recess 19a corresponds to said rotational movement, such that the flexible arms of the injection sleeve 13c, and the injection sleeve as a whole, move only axially.

[0075] FIG. 6a and FIG. 6b depict an isometric view of the trigger component (FIG. 6a) and a cross section perpendicular to the main axis in a plane denoted by the broken line in FIG. 5a in a shipping state of the auto-injector according to the second embodiment (FIG. 6b). The trigger component includes a device operation lock with a thermosensitive element 20a and a latch 20b. In a locked state, the latch 20b engages the second recess 19b of the piston rod and prevents the latter from rotating by compensating or absorbing the torque generated by the drive spring via the guiding surfaces of recess 19c and mechanics holder 10e. Due to the orientation of the guiding surfaces, the torque acts in clockwise direction when viewed in distal direction, resulting in a compressive strain on the thermosensitive element 20a. The thermosensitive element 20a connects the latch 20b to a body of the trigger component 20 and ultimately to the housing 10. The thermosensitive element thus forms a direct, force-fit connection or link between the housing and the latch. A heating element as the actuator is part of the electronic unit 14 and located adjacent to the thermosensitive element 20a, and may generate sufficient heating power to cause the latter to melt.

[0076] In alternative embodiments, an axial instead of a rotational lock, with a latch being connected to the housing in axial direction, may be employed to directly prevent an axial dispense movement of the piston rod or other movable component. Further alternatively, the thermosensitive element may include a form-fit blocking surface preventing a flexibly and even elastically mounted latch from being driven out of engagement with the biased plunger rod. Advantageously, the unconnected or unblocked latch is retained in a position or space where it may no longer interfere with the piston rod or other movable component.

[0077] When the cover sleeve as the manually operated trigger element is pushed against the injection site and retracted proximally, a pin or other protrusion at the proximal end of the lock sleeve operates a switch or other trigger element operation detector of the electronic unit. If the unlock command has been received beforehand, the electronic unit instantaneously powers the heating element. Alternatively, an injection validation request is issued by the injection device upon trigger element operation, and receipt of an unlocking approval in response is awaited before the heating element is operated. Heat from the latter is conducted to the thermosensitive element, which results in weakening and destruction of the thermosensitive element, unlocking of the latch, and ultimately a movement of the piston rod in distal direction. The injection sleeve is dragged proximally until the flexible arms are free to flex radially and decouple from the piston rod, which results in tissue penetration of the needle of the pre-filed syringe. The penetration depth corresponds to the distance between the first recess of the plunger rod and the distal end of the adjacent blocking surface of the mechanics holder in the shipping state.

[0078] While the invention has been described in detail in the drawings and foregoing description, such description is to be considered illustrative or exemplary and not restrictive. Variations to the disclosed embodiments can be understood and effected by those skilled in the art and practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. The mere fact that certain elements or steps are recited in distinct claims shall not preclude the existence of further meaningful combinations of these elements or steps.

TABLE-US-00001 LIST OF REFERENCE NUMERALS  1 injection device  2 Gateway  3 therapy management system  4 Pharmacy  5 health care professional  6 health portal  7 electronic patient file 10 housing 10a locking ledge 10b locking arm 10c recess 10d cam path 10e mechanics holder 11 device cap 11a inner sleeve 11b recess 11c locking arm 11d rotating cam 12 prefilled syringe 12a needle shield 13 cover sleeve 13a Lock sleeve 13b Cover sleeve spring 13c Injection sleeve 14 electronic unit 14a battery 15 locking slider 15a base 15b arm 15c tip 15d locking cam 16 actuator bracket 16a actuator arm 16b transverse ledge 17a, b SMA wire 18 anchor 18a blocking surface 18b pulley 19 Plunger rod 19a, b, c recess 20 Trigger component 20a Thermosensitive element 20b latch