Patent Publication Number: US-2022226580-A1

Title: Drug Delivery Device

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application is the national stage entry of International Patent Application No. PCT/EP2020/066373, filed on Jun. 12, 2020, and claims priority to Application No. EP 19305751.0, filed on Jun. 13, 2019, the disclosures of which are incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates to a drug delivery device. 
     BACKGROUND 
     A variety of diseases exists that require regular treatment by delivery, particularly injection of a medicament. Such injection can be performed by using injection devices, which are applied either by medical personnel or by patients themselves. 
     SUMMARY 
     Drug injection devices particularly for usage by patients themselves may be equipped with electronics for user assistance. WO2016/193122A1 discloses for example a pen-formed drug delivery device comprising a drug reservoir with an outlet, a detachable cap adapted to cover the drug reservoir outlet portion in a mounted position on the device body, and drug expelling means comprising dose setting means allowing a user to set a dose amount of drug to be expelled, the set dose printed on a rotatable scale drum being shown in a window. The device is provided with electronic circuitry comprising sensor means adapted to capture a property value related to the dose amount of drug expelled from the reservoir by the expelling means during an expelling event, processor means adapted to determine dose amounts based on captured property values, storage means adapted to store at least one dose amount, display means adapted to display dose related information, e.g. a determined dose amount and a related time value, and a power source. The power source is in the form of a zinc-air battery, which can be deprived of air and thus be inactive until first use. The zinc-air battery comprises a number of air holes in communication with the exterior through one or more channels formed between the battery and openings formed in the pen body exterior surface. The pen cap is provided with sealing surface portions adapted to seal the openings when the cap is in a fully mounted position. When the cap is removed fully or partly from the device body the channel openings are exposed and communication is established between the battery air holes and the exterior, this allowing oxygen-rich air to enter the battery whereby the above-described chemical process starts and a voltage is generated, this allowing the electronic circuitry to power up and to register an expelled dose which then may be displayed in the display means. In one aspect the present disclosure provides a modularization of a drug delivery device with a first and/or a second module, whereby the first and/or second modules are configured for, when aggregated, building up an electronically controlled and/or electronically monitored pen-shaped injection device and to thereby provide functionality for electronically controlled and/or monitored expelling of a liquid drug formulation to an external administration site, the modularization comprising:
         a first module including a liquid drug filled reservoir, a first, downstream, portion of a liquid drug expelling mechanism configured to expel a portion of liquid drug from the liquid drug reservoir when actuated and a self-contained electrical energy source as, in particular, an electrochemical cell or battery, and/or   a second module including a second, upstream, portion of the liquid drug expelling mechanism and an electronic circuitry, the electronic circuitry being configured for controlling and/or monitoring of the state and/or operation of any of the first or second portion of the liquid drug expelling mechanism;   whereby electromechanical interfaces are provided on the first and/or second modules, the electromechanical interfaces being configured to:
           releasable connect the first module and the second module to thereby form a connected mechanical structure and, in more particular, a rigidly connected mechanical structure;   to operationally connect the expelling mechanism portion of the first module to the expelling mechanism portion in the second module; and   to provide an electrical path for supplying energy from the electrical energy source aggregated in the first module to the electronic circuitry included in the second module.   
               

     Certain aspects of this disclosure may provide a drug delivery device having a first and a second module. Further certain aspects of this disclosure may provide a drug delivery device having a first module, which is configured so that it can be coupled to a second module for building up a pen-shaped injection device. Yet further certain aspects of this disclosure may provide a drug delivery device having a second module, which is configured so that it can be coupled to a first module for building up a pen-shaped injection device. 
     An “injection device” as mentioned before may be considered as a more specific drug delivery device insofar as it includes an expelling mechanism as well as a liquid drug reservoir and thereby allows the user to expel liquid drug therefrom. When fed to a cannula, an injection of the expelled liquid drug into a human or veterinarian body may be effected. The injection may be, for example, sub-cutaneous, intra-muscular or intravenous according to the common understanding of these terms in the medical field. In instances, an injection device may be a dose-controlled injection device for allowing a user to expel a predetermined volume of the liquid drug from the reservoir. In instances, a dose-controlled injection device may be a multi-shot dose-controlled injection device to thereby allow a user to perform multiple dose-controlled expelling operations from the same medicament container. Typical examples thereof can be found in the various diabetes pen injection devices. 
     The term “modularization” as used before and hereinafter shall be understood to apply to every single module as a standalone device as well as to the aggregation of two or more modules. When, in such “modularization”, the scope is semantically limited to a single module or an incomplete aggregation of modules, any reference to a remainder module or remainder aggregation of modules shall be interpreted in terms of interfacing requirements emerging therefrom relative to the single module or an incomplete aggregation of modules in consideration. 
     The qualifiers “upstream” and “downstream” used before in relation with an expelling mechanism shall be understood to attach to the concept of a drivetrain implemented therein and to the flow of mechanical force or power along that drivetrain. In particular, a “downstream” located member of the drivetrain is expected to follow the operation, movement or actuation of an “upstream” member during normal expelling operation. Apparently, “upstream” and “downstream” are relative qualifiers. In a relation between two drivetrain members, the “upstream” located one is closer to the source of mechanical power which causes the expelling drivetrain to operate for expelling. 
     The disclosed modularization of an electronically controlled and/or monitored injection device may be applied for improving the coherence of component lifetime to thereby reduce amount in waste and costs. In particular, the modularization may be implemented in a way that collects several components with a rather reduced lifetime or expected expiration time into one of the modules. Preferably, the drug reservoir and the electrical energy source may be allocated together to the same module whereas the electronic circuitry may be allocated entirely or to an essential extent to another module. This allocation may allow replacement the module comprising the drug container and the electrical energy source at the same time thereby maintaining essential parts of the electronic circuitry with the other module for subsequent re-use. It is an underlying consideration that multiple administration liquid drug injection devices have shelf lifetime of several weeks after first use due to potential risk of medicament degradation which approximately matches with the typical period of power delivery after activation for standard zinc-air cells. On the other hand, for an electronic circuitry a more elongated time of use is desired at least for cost reasons. On the other hand it may be found preferable to keep a short lifetime module free from electronic components to avoid application of waste restrictions beyond the ones applying to empty medicament containers and sharp items. Finally, an appropriate allocation of the components to the modules may help increasing therapy quality by collating operational prerequisites into one item. In an exemplary traditional situation of a re-usable injection pen with an integrated dose capturing and recording unit, in order to safeguard for appropriately captured drug administration, a user has to take care of the charging state of the battery in the dose capturing and to check sufficiency of the remainder in the drug container in view of the upcoming administrations. Failure on either end will prevent the user to perform a properly recorded dose administration as required by the therapy plan. 
     In embodiments, the allocation of the overall mechanical expelling drivetrain to the first module and the second module, respectively, may allocate not only the cartridge bung as the ultimate end portion to the first module but may also include the directly adjacent upstream one or more members, namely the piston rod foot and, in instances, the piston rod into the first module. This may be useful when high structural stability in force flow cycle reaching from the piston rod support along the piston rod, to the bung, the liquid, the vial and the vial support back to the piston to support. This may be especially useful when lower volumes of higher concentrated drug formulations are required to be dispensed at a high precision. 
     In more specific embodiments, the first and/or second module may be configured for aggregating into an axial layout whereby the axial layout has the liquid drug filled reservoir, particularly a drug container, the liquid drug expelling mechanism and the electrical energy source arranged along the longitudinal axis defined by the pen-shaped external appearance of the aggregation of the first and second module. 
     In more specific embodiments, the first module may include a standard medicament cartridge with a liquid drug formulation included in a section of a glass vial, the section of the glass vial being separated from the exterior space by a rubber bung seal, the rubber bung seal being movable along a cylindrical section of the glass vial as the ultimate end of the liquid drug expelling mechanism portion in the first module for transforming mechanical drive force in the expelling mechanism into liquid pressure in the separated glass vial section. 
     In more specific embodiments, the electrical power source may be a button cell located adjacent to the rubber bung seal surface that faces to the exterior. In more particular embodiments, the button cell may be configured to comprise a ridged external structure suitable for transferring an axial load from an abutting drive train member into the rubber bung seal. In an even more particular embodiment, a flat-cylindrical button cell may be arranged to contact the externally facing end of the rubber bung seal with one flat circular pole and to provide the opposite circular pole face as an incoming load plate to an adjacent upstream drivetrain element of the overall expelling drivetrain. In an alternative thereto, the external edge surrounding the opposite pole may be used as the input load support for an upstream drivetrain element in order to avoid promotion of mechanical load over the seal of the button cell or through its internal structure. 
     In embodiments, the upstream drivetrain element abutting against the button cell may be configured to include a portion of the electrical path to the electronic circuitry included in the second module. In more specific embodiments, the upstream drivetrain element abutting against the button cell may be an elongated piston rod which includes an electrically conductive material. In even more specific embodiments, the elongated piston rod may be provided as a composition or aggregate, the composition or aggregate including, in sections, an electrically conductive material and an electrically non-conductive material. 
     In other embodiments, the expelling mechanism may be entirely allocated to the module including the drug reservoir and the electrical energy source. This, in particular, may be useful to implement a re-usable dose recording concept for mechanical self-contained prefilled pen injection devices. In circumstances, the first module may be a self-contained prefilled mechanical pen injection device that principally provides standalone operation for setting and expelling of a multiple of desired doses from a drug reservoir. Solely, the functionality for electronically monitoring the dose setting and/or expelling manoeuvres in order to trace or monitor the drug administration has to be provided by the second module. In such situation, the electrical energy source may be included with the self-contained prefilled mechanical pen injection device in the same module, preferably within the same external casing structure. From the electrical power source electrical power may be supplied to the second module with the dose recording unit by means of an electromechanical coupling or interface. Simplification may be achieved insofar as the second module will directly power up after attachment to the first module. Additionally, the user may be found relieved from the burden of paying attention to the charge state of the electrical energy source as the lifetime thereof may be chosen to safely extend over the maximum shelf lifetime of the drug in the reservoir. In the same way as with traditional pen injection devices the user may limit, without impacting a fully compliant therapy, on checking for sufficient contents in the drug reservoir and non-expiration of shelf-lifetime. As long as these conditions are met, a user may rely on the dimensioning of the energy source to provide sufficient power for operating the dose recording unit in the second module appropriately. 
     In another aspect, the present disclosure provides a modularization for an electronically controlled and/or monitored injection device with a first module, the first module comprising a zinc-air cell, particularly being located at one end of the first module, the zinc-air cell having a number of venting openings, whereby a removable seal is provided for covering the venting openings in a first configuration and to reveal the venting openings in a second configuration, a second module, the second module being configured for attachment to the one end of the first module, the second module comprising electronics, whereby
         a number of mechanical interfaces is provided on the first module and/or the second module for releasable connecting the first module and the second module together to thereby form a mechanical structure, particularly a rigid mechanical structure,   a seal remover is provided on one of the modules, the seal remover being operable to remove the seal from at least one of the venting openings of the zinc-air cell, and whereby the mechanical interface between the first and the second module is configured to operate the seal remover when the first module is attached to the second module at any of the mechanical interfaces.       

     It may be advantageous for some purposes that the zin-air cell may be maintained in an inactivated state before the first use of the injection device when the second part is attached to the first part of the drug delivery device. Another advantage may be seen in the comfortable handling by a user since the activation means activate the zinc-air cell when the second part is attached to the first part so that the user does not have to remove the air tight sealing manually as an additional manipulation. If the first part is used as medicament cartridge holder, it can be easily disposed when the cartridge and/or the zinc-air cell is/are empty, and the second part containing the electronics may be reused with another first part. 
     In an implementation, the first module may be a pen with a distal and a proximal end and a dosage button located at the distal end, and wherein the zinc-air cell is located in the dosage button of the body, particularly on top of the dosage button. 
     In an alternative implementation, the first module may be a dispense mechanism of the drug delivery device and the zinc-air cell is located in a bearing of the dispense mechanism. The bearing may comprise a cup-like shaped holder for the zinc-air cell and a cup-like shaped cover for imposing and clipping on the holder, wherein the activation means are integrated in the cover. 
     In yet another alternative implementation, the first module may be a pen with a distal and a proximal end and the zinc-air cell is located in a cell compartment of the first module. The cell compartment may be located at the outside of the first module close to the one end of the first module. 
     The activation means may comprise at least one pin, which is designed to be used as an electrode for electrically connecting a power supply connector of the electronics with a power supply connector of the zinc-air cell. 
     In yet another aspect the present disclosure provides an attachment module for a drug delivery device, the attachment module comprising 
     a flexible body,
 
a flexible display integrated into the flexible body, and
 
electronic circuitry being configured to communicate with electronics of the drug delivery device and to control the flexible display depending on a communication between the electronics of the attachment device and the electronics of the drug delivery device.
 
     As an advantage it may be seen that the attachment module allows a versatile use for example by attaching it at different positions to a drug delivery device allowing a better accommodation to user habits such as attaching at a position where a user holding the drug delivery devices does not cover the display of the attachment device. Another advantage is that the attachment device can be easily detached from the drug delivery device and formed so that it may be hold by a user for comfortably reading information shown on the flexible display. Yet another advantage is that the attachment module may be attached to different drug delivery devices due to its flexibility. 
     The electronic circuitry of the attachment module may be further configured to unlock usage of the drug delivery device depending on the communication. 
     The electronic circuitry of the attachment module may be configured to control the flexible display such that information derived from the operation of the drug delivery device can be displayed, particularly information on one or more delivered injection dosages, time, holding time, cell status, one or more alarms. 
     The attachment module may further comprise user input means, wherein the electronic circuitry is configured to process signals generated by the user input means and to control the flexible display and/or the communication with the drug delivery device depending on the processed signals. 
     The attachment module may further comprise an interface for communication with a computing device, particularly for transmitting data related to the drug delivery device and its usage to the computing device for further processing. 
     In yet another aspect the present disclosure provides a method for operating a supplementary device for a drug delivery device, wherein the supplementary device comprises electronics having at least one processor and at least one storage and the processor is configured to perform the following steps of the method: 
     detecting attachment of the supplementary device to the drug delivery device,
 
detecting a drug delivery with the drug delivery device,
 
recording the detected drug delivery in the storage, and
 
generating at least one signal depending on the recording.
 
     An advantage is that a user may be warned by the signal when for example a medicament cartridge of a drug delivery device is empty and should be disposed. The signal may thus remind the user to remove the supplementary device from the drug delivery device if both are coupled together and not to dispose the supplementary device, since it can be reused with a new disposable drug delivery device. 
     The step of generating at least one signal depending on the recording may comprise one or more of the following: 
     generating a signal after the last drug delivery with the drug delivery device;
 
generating a signal before the end position of a drug delivered with the drug delivery device is reached.
 
     The at least one signal may comprise one or more of the following: 
     an acoustical signal generated with a sound generator of the supplementary device;
 
a visual signal generated with a visual signal indicator of the supplementary device;
 
a tactile signal generated with a tactile signal generator of the supplementary device.
 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
       The figures show: 
         FIG. 1 : a cutaway illustration of a first embodiment of an injection device; 
         FIGS. 2A and 2B : cutaway illustrations of a second embodiment of an injection device; 
         FIG. 2C : a cutaway illustration of an embodiment of a zinc-air cell for application with the embodiments of the injection device; 
         FIGS. 3A and 3B : cutaway illustrations of a third embodiment of an injection device; 
         FIGS. 4A and 4B : cutaway illustrations of a fourth embodiment of an injection device; 
         FIGS. 5A and 5B : cutaway illustrations of a fifth embodiment of an injection device; 
         FIGS. 6A and 6B : cutaway illustrations of a sixth embodiment of an injection device; 
         FIGS. 7A and 7B : an illustration of an embodiment of an attachment device for an injection device; 
         FIG. 8A : a flowchart of an embodiment of a method for operating a supplementary device for a drug delivery device; and 
         FIG. 8B : an schematic illustration of an embodiment of a supplementary device for an injection device. 
     
    
    
     DETAILED DESCRIPTION 
     In the following, embodiments of the present disclosure will be described with reference to injection devices, particularly a two-part dispensable injection device in the form of a pen. The present disclosure is however not limited to such application and may equally well be deployed with other types of drug delivery devices, particularly with another shape than a pen. 
     The below described embodiments relate to a modularized pen-shaped injection device comprising two modules, which upon aggregation may build up an electronically controlled and/or monitored injection device, which provides functionality for electronically controlling and/or monitoring expelling of a liquid drug formulation to an external administration site. 
     A first embodiment of an injection device will now be described with reference to  FIG. 1 . The injection device is a two-part device comprising a dispensable injector having a body  10 ″ in the form of a pen having a proximal end P and a distal end D and a supplementary device  12 ″ for attachment to the distal end D of the body  10 ″. The proximal end P of the body  10 ″ is directed towards the injection site of a patient during an injection while the distal end D is directed away from the injection site. 
     The body  10 ″ comprises an outer housing  11 ″. The outer housing  11 ″ is an elongate tube. The outer housing  11 ″ includes a cartridge holder or syringe holder (not shown) which supports a cartridge or syringe containing liquid medicament (not shown) and has a mechanical interface to a supplementary device  12 ″ containing an electric drivetrain for causing dispensing of the medicament during injection by the body  10 ″. A cell compartment  24  is located at the outside of the outer housing  11 ″. The cell compartment  24  is provided for housing a zinc-air cell  14 ″. 
     The body  10 ″ with the zinc-air cell  14 ″ forms the dispensable part of the injection device, which may be dispensed when the cell and/or cartridge with the liquid medicament is/are empty. 
     The supplementary device  12 ″ is designed as an attachment for the distal end D of the body  10 ″. It comprises an electric drivetrain with a mechanical interface for interfacing with the mechanical interface of the body  10 ″. The electric drivetrain comprises an electric motor  26   a , a gear  26   b , and a drive screw  26   c . The motor  26   a  is controlled by electronics  16 ″ for implementing control and/or measurement functionality of the injection device and which also performs a sensing of the drivetrain in order to ensure the reliability of the drivetrain. The electronics  16 ″ can also store and/or receive and/or transmit data regarding the usage of the injection device. It may furthermore control a display of the supplementary device  12 ″. The electronics  16  may for example comprise a microcontroller configured with firmware for measuring and recording usage of the injection device such as time, holding time, cell status, one or more alarms, one or more delivered injection dosages. 
     Activation means in the form of pins  18 ″ are located at the attachment side of the supplementary device  12 ″ opposite to the cell compartment  24  housing the zin-air cell  18 ″. In this embodiment, the pins  18 ″ are part of the supplementary device  12 ″ and integrated in the device  12 ″. 
     Usage of the injection device is explained in the following: for the first use, the supplementary device  12 ″ has to be attached to the body  10 ″, as shown in  FIG. 1 . When the supplementary device  12 ″ is attached to the body  10 ″ so that the mechanical interfaces are coupled and the drive screw  26   c  can put a force in a bung in the body  10 ″ to cause dispense of a medicament, the pins  18 ″ of the activation means have pierced the air tight sealing of the zinc-air cell  14 ″ so that air may pass through the pierced air holes in the air tight sealing and activate power supply through the pins  18 ″ from the now activated zinc-air cell  14 ″. 
     A second embodiment of an injection device will now be described with reference to  FIGS. 2A, 2B and 2C . The injection device is a two-part device comprising a dispensable injector having a body  10  in the form of a pen having a proximal end P and a distal end D and a supplementary device  12  for attachment to the distal end D of the body portion  10 . The proximal end P of the body  10  is directed towards the injection site of a patient during an injection while the distal end D is directed away from the injection site. 
     The body  10  comprises an outer housing  11 . The outer housing  11  is an elongate tube. The outer housing  11  includes a cartridge holder or syringe holder (not shown) which supports a cartridge or syringe containing liquid medicament (not shown). 
     The outer housing  11  also houses a dispense mechanism for causing dispensing of the medicament during injection. The dispense mechanism comprises a dosage button  20 , which may be pushed onto the outer housing  11 . The dosage button  20  is mechanically coupled to a piston  13  of the cartridge (not shown). The dispense mechanism is configured to move the piston axially along the cartridge in a proximal direction to dispense medicament through for example a needle (not shown) at the proximal end. The dosage button  20  may apply a force to the piston  13  in response to an actuation input provided by a user. Here, the actuation input that triggers application of a force to the piston  13  is received by way of the dose dispense or dosage button  20  that is located at the distal end D of the body  10  of the injection device. 
     A zinc-air (Zn/O 2 ) cell  14  with an air tight sealing is located on top of the dosage button  20 . Due to the air tight sealing, the zinc-air cell is inactive until a first use, when one or more air holes are created in the air tight sealing for activating the zinc-air cell  14 . 
       FIG. 2C  shows the zinc-air cell  14  in a cutaway illustration: zinc powder  14   a  is contained in an anode can  14   b  and electrically separated from an outer cathode can  14   g  by an insulator gasket  14   c . The outer can  14   g  is provided with openings  14   i . A sealing layer  14   h  is provided in the outside of the outer can  14   g  to provide an air tight sealing of the openings  14   i . When air holes are created in the sealing layer  14   h , air can enter through the openings  14   i  through a teflon membrane  14   f  into an air electrode  14   e , which is separated from the zinc powder anode  14   a  by means of a separator  14   d . The sealing layer  14   h  may be for example implemented by air tightly integrating the zinc-air cell  14  in the dosage button  20 , for example by injection moulding, wherein the moulding material should be a soft material, for example TPE (thermoplastic elastomer), and/or a thin material to allow piercing for activating the zinc-air cell  14 . The piercing allows air to enter through the openings  14   i  and the Teflon membrane  14   f  into the air electrode  14   e  starting the chemical reaction to generate electric power. 
     The body  10  with the zinc-air cell  14  forms the dispensable part of the injection device, which may be dispensed when the cell and/or cartridge with the liquid medicament is/are empty. 
     A further part of the injection device is formed by the supplementary device  12 , which is designed as a clip-on attachment for the distal end D of the body  10 , particularly on the dosage button  20 . The supplementary device  12  comprises electronics  16  for implementing control and/or measurement functionality of the injection device. The electronics  16  may for example comprise a microcontroller configured with firmware for measuring and recording usage of the injection device such as time, holding time, cell status, one or more alarms, one or more delivered injection dosages. 
     Activation means in the form of pins  18  with tips  18   a  are located at the bottom side of the electronics  16 . In this embodiment, the pins  18  are part of the supplementary device  12  and integrated in the device  12 . 
     Usage of the injection device is explained in the following: for the first use, the supplementary device  12  has to be clipped on the body  10 , namely on the dosage button  20  as shown in  FIGS. 2A and 2B . In  FIG. 2A , the supplementary device  12  is not yet completely clipped on the dosage button  20 , and  FIG. 2B  shows it completely clipped on the dosage button  20 . As shown in  FIG. 2B , when the supplementary device  12  completely covers the dosage button  20 , the tips  18   a  of the pins  18  of the activation means at the bottom side of the electronics  16  have pierced the air tight sealing of the zinc-air cell  14  so that air may pass through the pierced air holes in the air tight sealing and through the openings  14   i  and the Teflon membrane  14   f  into the air electrode  14   e.    
     A third embodiment of an injection device will now be described with reference to  FIGS. 3A and 3B . The injection device comprises a first part  10 ′ and a second part  12 ′ for attachment to one end of the first part  10 ′. 
     The first part  10 ′ is a dispense mechanism of the drug delivery device for causing dispensing of the medicament during injection. The dispense mechanism comprises a bearing  22  for a zinc-air cell  14 ′ and activation means  18 ′. The bearing  22  comprises a cup-like shaped holder  22   a  for the zinc-air cell  14 ′, which is mechanically coupled to a piston  13 ′ of the cartridge (not shown). The dispense mechanism is configured to move the piston  13 ′ axially along a cartridge in a proximal direction to dispense medicament through for example a needle (not shown) at a proximal end. The bearing  22  further comprises a cup-like shaped cover  22   b  for imposing and clipping on the holder  22   a . The bearing  22  forms a button with which a force may be applied to the piston  13 ′ in response to an actuation input provided by a user. Here, the actuation input that triggers application of a force to the piston  13 ′ is received by way of the bearing  22  that is located at the distal end D of the body  10 ′ of the injection device. 
     The zinc-air (Zn/O 2 ) cell  14 ′ with an air tight sealing is located in the holder  22   a  and covered by the cover  22   b . The zinc-air cell  14 ′ can be for example integrated in the holder  22   a  by injection moulding. Due to the air tight sealing, the zinc-air cell is inactive until a first use, when one or more air holes are created in the air tight sealing for activating the zinc-air cell  14 ′. The zinc-air cell  14 ′ may be similar or even identical to the one shown in  FIG. 2C . 
     The first  10 ′ with the zinc-air cell  14 ′ may belong to a dispensable part of the drug delivery device, which may be dispensed when the cell and/or cartridge with the liquid medicament is/are empty. 
     The second part  12 ′ is designed as a bung for attachment to the cover  22   b  and comprises electronics  16 ′ for implementing control and/or measurement functionality of the injection device. The electronics  16 ′ may for example comprise a microcontroller configured with firmware for measuring and recording usage of the injection device such as time, holding time, cell status, one or more alarms, one or more delivered injection dosages. 
     Activation means in the form of pins  18 ′ with tips  18   a ′ are integrated in the cover  22   b  of the first part  10 ′. Thus, when the cover  22   b  is clipped on the holder  22   a , tips  18   a ′ of the pins  18 ′ pierce the air tight sealing of the zinc-air cell  14 ′, which is then activated. In this embodiment, the pins  18 ′ are integrated in the first part  10 ′, namely the cover  22   b.    
     Usage of the injection device is explained in the following: for the first use, the bung  12 ′ has to be attached to the cover  22   b  and pressed down to clip the cover  22   b  on the holder  22   b  as shown in  FIGS. 3A and 3B . In  FIG. 3A , the bung  12 ′ is not yet attached to the cover  22   b , and  FIG. 3B  shows it attached to the cover  22   b  and pressed down with the cover  22   b  clipped on the holder  22   a . As shown in  FIG. 3B , when the bung  12 ′ is attached to the cover  22   b  and the cover  22   b  is clipped on the holder  22   a , the tips  18   a ′ of the pins  18 ′ of the activation means integrated in the cover  22   b  have pierced the air tight sealing of the zinc-air cell  14  so that air may pass through the pierced air holes in the air tight sealing and through the openings  14   i  and the Teflon membrane  14   f  into the air electrode  14   e . The other side of the pins  18 ′ may pierce the bung  12 ′ to get into contact with the electronics  16 ′. 
     In the above described embodiments, the pins  18 ,  18 ′ may also be designed that they could be used as electrodes supplying the electronics  16 ,  16 ′. 
     A fourth embodiment of an injection device will now be described with reference to  FIGS. 4A and 4B . The injection device is a two-part device comprising a dispensable injector having a body  10 ′″ in the form of a pen having a proximal end P and a distal end D and a supplementary device  12 ′″ for attachment to the distal end D of the body portion  10 ′″. The proximal end P of the body  10  is directed towards the injection site of a patient during an injection while the distal end D is directed away from the injection site. 
     The body  10 ′″ comprises a medicament cartridge  11 ′″ containing a liquid drug formulation, which is included in a section  100  of a glass vial. The section  100  is separated from the exterior space by a rubber bung seal  102 , which can be moved along a cylindrical section of the glass vial. Attached to the side of the rubber bung seal  102 , which is exposed to the exterior space, is a first part  110  of an electromechanical interface of the body  10 ′″ and supplementary device  12 ′″. This first part  110  contains a zinc-air cell  14 , two channels  112  extending from the side of the part  110  to the zinc-air cell  14  allowing to pass air to the zinc-air cell  14  from the exterior space, electrical contacts  18   a ′″ for contacting the zinc-air cell contacts with electrical contacts  18 ′″ of the supplementary device  12 ′″, and a recess  108  for mechanically coupling the first part  110  to a second part  104  of the electromechanical interface of the supplementary device  12 ″. A seal  114  air-tightly covers the open end of the cartridge  11 ′″ and avoiding activation of the zinc-air cell  14 . The outer housing  11 ′″ is an elongate tube. The first part  110  is hold within the cartridge  11 ′″ by protrusions provided at the distal end D of the cartridge  11 ′″ in order to avoid falling out. 
     The supplementary device  12 ′″ comprises the second part  104  of the electromechanical interface, which has a coupling side with the electrical contacts  18 ′″ and a protrusion  106  shaped to fit into the recess  108  of the first part  110 . The contacts  18 ′″ are electrically connected to an electronic circuitry  16  housed in the second part  104  and provided to be powered by the zinc-air cell  14  via the electrical contacts  18 ′″ and  18   a′″.    
     For using the injection device, the modules  10 ′″ and  12 ′″ have to be coupled. This is done by manually removing the seal  114  so that air can pass from the exterior space and the channels  112  to the zinc-air cell  14 , and, thus, activating the cell  14 . Furthermore, the second part  104  of the electromechanical interface of the supplementary device  12 ′″ has to be coupled to the first part  110  by attaching the side of the second part  104  comprising the electrical contacts  18 ′″ and the protrusion  106  to the side of the first part  110  with the recession  108  and the electrical contacts  18   a ′″, as shown in  FIG. 4B . 
     To expel a portion of the liquid drug formulation, pressure in an axial direction of the first and second parts  110 ,  104  may be exerted downwards on the section  116  of the second part  104  in order to move downwards the first part  110  and the rubber bung  102 . 
     The electronic circuitry  16  being powered by the activated zinc-air cell  14  via the electrical contacts  18 ′″, 18   a ′″ may be configured to electronically control and/or monitor the expelling of the liquid drug formulation. For example, the electronic circuitry  16  may be configured to measure the distance of the downwards moving of the second part  104 , the first part  110  and the rubber bung  102  and to calculate from the measured distance the expelled amount of the liquid drug formulation. The electronical circuitry  16  may for instance be also configured to control a liquid drug expelling mechanism (not shown) for downwards moving the second part  104 , the first part  110  and the rubber bung  102 . The mechanism may for comprise an electric motor and a gear with a drive screw for driving the second part  104  downwards (similar for example to the mechanism  26   a ,  26   b ,  26   c  of the embodiment shown in  FIG. 1 ). 
     A fifth embodiment of an injection device will now be described with reference to  FIGS. 5A and 5B . The fifth embodiment is similar to the fourth embodiment and differs merely in the implementation of the air tightly sealing of the zinc-air cell  14 : the sealing comprises two seals  114 ′ each covering one of the entrances of the two channels  112  extending from the side of the part  110  to the zinc-air cell  14  allowing to pass air to the zinc-air cell  14  from the exterior space. The seals  114 ′ may extend beyond the edge of the medicament cartridge  11 ′″ and may be fixed to the edge, for example adhered to the edge. The other ends of the seals  114 ′ may be removably adhered over the entrances of the two channels  112  so that when the first part  110  is moved downwards, the seals  114 ′ are pulled away from the entrances of the two channels  112 , thus, removing the air tight sealing of the channels  112 . Thus, upon first usage of the injection device, i.e. when both modules  10 ′″ and  12 ′″ are coupled together and the second part  104 , the first part  110 , and the rubber bung  102  are moved downwards to expel a dosage of the liquid drug formulation, the seals  114 ′ are pulled from the entrances of the two channels  112  so that air can pass from the exterior space and the channels  112  to the zinc-air cell  14  and, thus, activate the cell  14 . 
       FIGS. 6A and 6B  show a sixth embodiment of an injection device, which will now be described with reference to these Figures. Also, the sixth is similar to the fourth and fifth embodiments, but it differs in the implementation of the first part  110 ′ and the air tightly sealing of the zinc-air cell  14  located within the first part  110 ′. As can be seen in the  FIGS. 6A and 6B , the first part  110 ′ comprises one channel  112 ′ extending from the left to the right side of the part  110 ′. The zinc-air cell  14  is located in the part  110 ′, wherein one side of it is exposed to the channel  112 ′. Thus, when air enters the channel  122 ′ it may pass through the channel to the exposed side of the zinc-air cell  14  and may activate the cell  14 . The exposed side of the cell  14  is in an unused condition covered by a seal  114 ″, for example removably adhered to the exposed side and extending through the channel  112 ′ beyond the edge of the medicament cartridge  11 ′″ and may be fixed to the edge, for example adhered to the edge. When the first part  110 ′ is moved downwards, the seal  114 ′ is pulled away from the exposed side of the zinc-air cell  14  so that air passing through the channel  112 ′ can activate the zinc-air cell  14 . Thus, upon first usage of the injection device, i.e. when both modules  10 ′″ and  12 ′″ are coupled together and the second part  104 , the first part  110 ′, and the rubber bung  102  are moved downwards to expel a dosage of the liquid drug formulation, the seal  114 ″ is pulled from the exposed side of the zinc-air cell  14  so that air can pass from the exterior space and the channel  112 ′ to the zinc-air cell  14  and, thus, activate the cell  14 . 
     In the following, an embodiment of an attachment device  30  for a drug delivery device  40  is described with reference to  FIGS. 7A and 7B . 
     The drug delivery device  40  may be a pen shaped injection device having an elongate body  40  with a distal end D and a proximal end P. At the proximal end P, a syringe may be provided for injection of a medicament from a cartridge inside the body  40  into a patient&#39;s body. At the distal end D, a dispense button  46  and a dosage selector  48  may be provided. The dosage to be injected may be selected with the dosage selector  48 , and the dispense may be initiated by a patient by pressing the dispense button  46 . An internal mechanism may then be triggered by the pressing of the dispense button  46  to inject the selected dosage through the syringe into the patient&#39;s body. 
     The drug delivery device  40  may further house electronics  42  adapted to perform tasks such as for example measuring a delivered injection dosage, time, holding time, cell status, and/or outputting one or more alarms, for example when the medicament cartridge and/or the cell is empty. The electronics  42  may be further adapted for communication and data exchange with another electronics, particularly via radio transmission such as for example according to the Bluetooth® standard or a near field communication (NFC) standard. 
     The attachment device  30  for the drug delivery device  40  comprises a flexible body  32 , in which a flexible display  34 , particularly a flexible OLED (Organic Light Emitting Diode) display, is integrated. The attachment device  30  is bendable so that it can be twisted around the body  40  of the drug delivery device and placed at a position preferred by a user. For example, a user can position the attachment device  30  at the body  40  so that the display  34  is not covered by her/his hands when using the drug delivery device. 
       FIG. 7B  shows the attachment device  30  detached from the body  40  of the drug delivery device and bended in a flat handheld mode, in which it can be for example hold by a user or laid down on a table. 
     As shown in  FIG. 7B , the attachment device  30  can also comprise user input means  38  in form of buttons and/or the flexible display  34  may comprise touch screen functionality in order to receive user inputs. Electronics  36  is integrated in the flexible body  32 , which is configured to control the display  34 , to process signals generated by the user inputs means  38 , and/or to communicate with the electronics  42  of the drug delivery device  40  and/or a computing device  50  such as a mobile computing device, for example a smartphone, a laptop and/or a tablet computer. The communication  44  with the electronics  42  of the drug delivery device may be wired or wireless. For a wired communication, the electrical contacts may by integrated in the flexible body and also electrical contacts may be integrated in the body  40  of the drug delivery device, for example several contacts at different positions at the body  40  in order to allow to place the attachment device  30  at different positions at the body  40 . Electrical contacts may be also provided on the flexible body  32  for connecting the attachment device  30  with the computing device  50 , for example a micro-USB (Universal Serial Bus) connector. A wireless communication  44  with the electronics  42  may be performed via a particularly short-range radio communication such as according to the Bluetooth® standard or a near field communication (NFC) standard. A wireless communication  52  with the computing device  50  may be performed via a short-range radio communication such as according to the Bluetooth® standard or a near field communication (NFC) standard, or via a wider range radio communication such as according to the IEEE802.11 standard. 
     A communication  44  between the electronics  36  of the attachment device  30  and the electronics  42  of the drug delivery device  40  can established upon a user input via the user input means  38  and/or via a touch screen input if the display  34  has touch screen functionality and/or automatically when the attachment device  30  is twisted around the body  40 . For example, a switch integrated in the flexible body  32  may be activated upon bending the body  32  so that the electronics  36  is switched into a mode in which a communication  44  with the electronics  42  of the drug delivery device  40  can be established. 
     The electronics  36  of the attachment device  30  may receive data from and transmit data to the electronics  42  of the drug delivery device  40  via an established communication  44 . For example, the electronics  36  may receive data regarding the use of the drug delivery device  40 , such as delivered injection dosages, time, holding time, device&#39;s  40  cell status, one or more alarms, and/or transmit data to control use of the drug delivery device  40 , such as an unlocking code allowing a user to operate the drug delivery device  40 . 
     The electronics  36  is configured to control the display  34  such that information received via a communication  44  from the drug delivery device  40  is displayed. The electronics  36  may be further configured to process signals generated by the user inputs means  38  and/or a touch screen. Also, the electronics  36  may be configured to control the communication  44  depending on the processed signals generated by the user inputs means  38  and/or a touch screen. For example, after attaching the device  30  to the drug delivery device  40 , a user may press one of the user input means  38  in order to establish a communication  44  and after establishment of the communication  44  send an unlock code via the communication  44  to the electronics  42  of the drug delivery device  40  to enable an injection by a patient. The electronics  36  may be further configured to enable customization of the information displayed on the display  34 , for example the arrangement and/or kind of displayed information. 
     Furthermore, the attachment device  30  can be configured to be assigned to a certain user by means of a user identification stored by the electronics  36  so that it can only be used by that user and not by other users. In order to identify the user, the electronics  36  may be configured to request a code a user has to input via the user input means  38  or a touch screen before allowing to use the attachment device  30 . 
     The electronics  36  of the attachment device  30  may be further configured to store data received from the electronics  42  of the drug delivery device  40 . The stored data can then be transmitted via a communication  52  to a computing device  50  for further processing, for example evaluation and/or storing in a therapy ID card of a patient. The communication  52  can be also configured to customize the attachment device  30 , for example to adapt it to user requirements such as assigning it to a certain user, customizing the information to be displayed on the display  34 . For a comfortable customization, the computing device  50  may be configured by a dedicated software such as an app for programming the attachment device  30  and/or evaluating data received from the electronics  36 . 
     Now, an embodiment of a method for operating a supplementary device  60  for a drug delivery device  70  is described with reference to  FIGS. 8A and 8B . The supplementary device  60  is a re-usable add-on device for a disposable drug delivery device  70 . Typically, the supplementary device  60  may contain some electronics for controlling and monitoring the usage of the drug delivery device  60 . For example, it may contain control electronics to assist a user of the drug delivery device  70  in the correct usage, particularly the injection of a medicament. It may also comprise monitoring electronics for determining the number of usage of the drug delivery device  70 , for example for recording the injected dosages of a medicament, the time and date of each injection. 
     The method serves to output at least one signal depending on a recording of drug deliveries with the drug delivery device  70 . The outputting of a signal may assist a user of the disposable drug delivery device  70  in preventing a disposal of the reusable supplementary device  60 , or in other words warn a user to detach the supplementary device  60  from the drug delivery device  70  when disposing the later. 
     The method is implemented as an algorithm to be executed by the supplementary device  60 . The algorithm may signal a user of the disposable drug delivery device  70  recordings of detected drug deliveries, particularly signal when the disposable drug delivery device  70  is empty. 
     An embodiment of the algorithm is explained in detail with reference to the flowchart shown in  FIG. 8A  and the schematic illustration of the supplementary device  60  attached to the distal end D of the drug delivery device  70  shown in  FIG. 8B . 
     The algorithm is implemented as firmware stored in a memory  64  of the supplementary device  60 , which is executed by a processor  62 . The supplementary device  60  may comprise several signalling means, particularly a sound generator  66   a  such as a loudspeaker, a visual signal indicator  66   b  such as a LED (Light Emitting Diode), a tactile signal generator  66   c  such as a vibrating alert motor. 
     A sensor (not shown) may be provided to detect an attachment of the supplementary device  60  to the drug delivery device  70 . The sensor may be also implemented as a contact  68 , which can be contacted with a counter-contact  74  of the drug delivery device  70 , or as a contactless sensor, for example a hall sensor, which may detect a magnetic field created by a magnet of the drug delivery device  70 . 
     The drug delivery device  70  may comprise electronics  72  for measuring drug deliveries, for example an electronic counter for simply counting the delivered dosages, and the counter-contact  74  for the contact  68 . Data exchange between the processor  62  and the electronics  72  may be wireless or wired as shown in  FIG. 8B  by means of the contacts  68 ,  74  through which a wired data link may be established between the processor  62  and the electronics  72  upon attachment of the supplementary device  60  to the drug delivery device  70 . 
     In a first sept S 10  after starting, the algorithm checks if the supplementary device  60  is attached to the drug delivery device  70  by means of the sensor. For example, the processor  62  receive a signal from the electronics  72  via a wired data link established via the contacts  68  and  74 . If a wireless sensor is used, the processor  62  may receive a signal from the sensor signalling an attachment of the supplementary device  60  to the drug delivery device  70 , for example a signal from a hall sensor detecting a magnetic field in its vicinity. If attachment of the supplementary device  60  to the drug delivery device  70  is detected in step S 10 , the algorithm continues with the second step S 12 . 
     In step S 12 , the algorithm detects if a drug is/was delivered with the drug delivery device  70 . Particularly, the processor  62  can request information on drug delivery from the electronics  72  of the drug delivery device  70 , for example via a data link established via the contacts  68  and  74 . It is also possible that the processor  62  detects a drug delivery by means of a sensor (not shown) integrated in the supplementary device  60  or the drug delivery device  70  and provided for detecting a drug delivery. Such a sensor could be used when only the supplementary device  60  contains electronics, and the disposable drug delivery device  70  contains only a mechanics for dispensing a medicament from a cartridge. The detected drug delivery may be a count of every dispensed dosage, for example x dispensed dosages, a count for total dispensed dosage, for example y total dispensed dosage, or a last dosage counter, for example xth dispensed dosage. It is also possible that a counter starts with the maximum number of dosages contained in a cartridge and is counted down with every dispensed dosage, and the detected drug delivery is the actually read out counter value. 
     The detected drug delivery is in a third step S 14  recorded in the storage  64  by the processor  62 . The recording may also comprise a date and/or time stamp, and a unique identifier of the drug delivery device  70  or the medicament cartridge contained in the device  70  in order to be able to assign the recordings to the drug device  70 . With the unique identifier the supplementary device could be used with different drug delivery devices  70 . 
     After the recording step S 14 , the algorithm continues in a fourth step S 16  with generating at least one signal depending on the recording performed in the previous step S 14 . In detail, the processor may check in step S 16  whether the recording performed in step S 14  fulfils one or more predetermined criteria. 
     One criterion may be that the last dosage was delivered by the drug delivery device  70 . Another criterion may comprise the position before the end position is reached in the drug delivery device, for example when a medicament cartridge contains only remaining dosage. 
     The processor may check the fulfilment of the criteria for example by comparing the detected drug delivery recorded in step S 14  with a maximum number of possible dosages, or if a count-down counter falls below a predefined threshold such as 1 or 2 (for number of remaining dosages), or if a dosage counter exceeds a predefined threshold such as a maximum number of dosages. 
     If the processor  62  detects that the one or more predetermined criteria are fulfilled, it may generate a control signal for one or more of the signalling means. For example, the processor  62  may control the sound generator  66   a  to generate a sound signal, the visual signal indicator  66   b  to generate a visible signal, and/or the tactile signal generator  66   c  to generate a tactile feedback signal such as a vibration of the supplementary device  60 . Thus, a user may note that the last dosage contained in the cartridge of the drug delivery device  70  was dispensed, or only one further dosage remains for injection, and the drug delivery device  70  has to be replaced now or soon with a new one and the supplementary device  60  containing the electronics for controlling the drug dispense with the drug delivery device  70  should be removed from the drug delivery device  70  and not be disposed.