Wireless electronics assembly for an injection device

Abstract

A wirelessly enabled electronics assembly for a drug delivery device is described. The electronics assembly includes a processor; a sensor configured to measure a fill level of a drug container and output the measurement to the processor; a wireless module that can be paired with an external device; a power module configured to supply power to the assembly; and a memory storing instructions for execution by the processor. The instructions include: activating the sensor at a first time interval and receiving a measurement signal each time the sensor is activated at the first time interval; determining a change in the fill level of the drug container based on the received measurement signal; and upon detecting a change in the fill level, activating the wireless module for a first duration to enable the external device to pair with the wireless module.

Description

[0001] This specification relates to an electronics assembly with wireless functionality for a drug delivery device.

[0002] There are many existing diseases that require treatment by injecting medication. Such injections can be performed using a drug delivery device, which can be administered by medical personnel or by the patient themselves. For example, type 1 and type 2 diabetes can be treated by the patient themselves by injecting a dose of medication, such as once or several times a day. For example, a pre-filled disposable medication pen or autoinjector can be used as a drug delivery device. Alternatively, a reusable pen or autoinjector can be used. A reusable pen or autoinjector allows an empty medication cartridge to be replaced with a new one. Either pen or autoinjector can have a set of one-way needles that must be replaced before each use.

[0003] The present disclosure relates to a drug delivery device having electronics that can detect certain characteristics related to the drug delivery device (such as the fill level of a medicament within a cartridge in the drug delivery device) and wirelessly transmit these detected characteristics to an external device (such as a mobile phone, tablet, or computer) for viewing by a user. In some cases, the electronics are housed within a stopper or retainer of the cartridge.

[0004] In a representative overview, the electronics assembly is inserted into the stopper of a drug cartridge. The electronics assembly detects the fill level of the drug cartridge (e.g., by detecting the position of the stopper) and, in some cases, the temperature of the drug cartridge or the drug therein. As the patient uses the device, the fill level in the drug cartridge changes, and the electronics assembly senses this change at short intervals (e.g., 5 minutes), and upon detection, this level change activates the Bluetooth transmitter. Thereafter, the patient can pair or connect an external device to the electronics assembly to activate the transmission of measurement data (e.g., delivered dose). After a short period of time (e.g., 10 minutes), if no further change in the fill level in the drug cartridge has been measured and no external device is paired, the Bluetooth transmitter can be automatically set to sleep mode again, and the electronics assembly resumes sensing the next drug delivery operation at regular intervals. After each injection is detected, the device can be re-transferred with the external device. Printed variable data (i.e., batch or expiration date) or the material code of the label can be used as an additional feature during pairing. These can be read with a camera, or can be manually entered by the patient to confirm that the data received from the electronics assembly matches the drug delivery device.

[0005] In a representative example, the electronics assembly is arranged in the cartridge or otherwise positioned in the drug delivery device so that the sensor of the electronics assembly can detect changes in the drive mechanism of the cartridge or drug delivery device, which is used to change the fill level of the cartridge (e.g., filling operation and drug delivery operation). The electronics assembly includes a processor that is configured to initiate data exchange via a Bluetooth wireless module or a similar wireless protocol when determining changes in the fill level. In a first state, the processor instructs the sensor to obtain measurements at a very low frequency (e.g., once every few days) and the wireless module is deactivated. This state is effective before assembling the cartridge or before filling the cartridge. After the stopper including the electronics is assembled with the cartridge, a response can be measured, such as an indication that the medicament has been introduced into the cartridge or that the cartridge has been assembled into the drug delivery device. This detection of a trusted response triggers the processor to switch the activation of the sensor to a higher measurement frequency, for example, once every few minutes. In some cases, the wireless module is activated at this time, which enables pairing with an external device to emit current measurements in a short time. Alternatively, the wireless module can be activated each time the processor determines a change in the measurement result to further reduce power consumption because the wireless module is only activated for "new" measurements rather than for every measurement. A benefit of this arrangement is that no external activation of the electronics assembly is required, which allows the electronics assembly to be a self-contained (e.g., sealed) assembly after production and prior to introduction into the cartridge or drug delivery device.

[0006] The example of the electronic device assembly can be used in a disposable (e.g., disposable) drug delivery device and a multiple use (e.g., reusable) drug delivery device. In an exemplary disposable embodiment, the electronic device assembly is constructed and inserted into the cartridge, at which point the electronic device assembly senses the cartridge in a low-frequency sensing mode, waiting for the introduction of the detection drug, which indicates that the assembly of the disposable drug delivery device is complete. After the medicament is detected, the disposable drug delivery device is ready for standby use, so the electronic device assembly enters a high-frequency sensing mode and waits for the detection drug delivery operation, at which point the electronic device assembly activates the wireless module to allow pairing with an external device in a short time. In an alternative embodiment, the electronic device assembly lacks an initial low-frequency sensing mode, but includes an activation mechanism or sensor configured to detect the assembly of the disposable drug delivery device and activate a high-frequency sensing mode. This activation mechanism can be a switch, and the switch is arranged on the electronic device assembly to be triggered by contact with the drug delivery device during assembly.

[0007] In the example of a reusable drug delivery device, where the electronics assembly is constructed and assembled with a pre-filled cartridge, the electronics assembly may be in a low-frequency sensing state, wherein the sensor is configured to detect, for example, the assembly of the pre-filled cartridge into the drug delivery device, or the electronics assembly may be in a high-frequency sensing mode upon indication of introduction of a medicament into the cartridge and prior to indication of the cartridge to the drug delivery device. In either of the above-described single-use and multiple-use drug delivery device examples, when the drug delivery device is ready for use, the electronics assembly enters the high-frequency sensing mode using a sensor or activation mechanism, thereby enabling faster detection of a subsequent drug delivery operation and faster activation of the wireless module within a given duration after the drug delivery operation is detected.

[0008] In addition to adding wireless connection to drug delivery device, some aspects of the present disclosure also bring some advantages. For example, due to the limited amount of internal power, the shelf life of the sealed electronic device assembly with internal power supply is limited. By limiting sensor activation before the drug delivery device enters the ready-to-use configuration, the shelf life of the electronic device assembly made before the introduction of the drug delivery device or cartridge can be extended. Similarly, by limiting the activation of the wireless module after the drug delivery operation, the shelf life of the electronic device assembly after the drug delivery device is finally made (that is, in a ready-to-use state) can be extended. In the case of extending the shelf life, the electronic device assembly can be separated from the manufacture of the cartridge or drug delivery device and manufactured independently, which also reduces or eliminates the impact on existing production lines.

[0009] Another advantage is that the electronics assembly can provide additional information to the user by wirelessly transmitting to an external device. For example, a drug delivery device or cartridge can be provided with an expiration date that can be transmitted to and stored in an external device to help the user confirm printed information and better manage drug delivery. Additional information (e.g., the batch or unique serial number of the drug delivery device or cartridge) can be transmitted to the external device to help the user. Manufacturers can also centrally track this data to help recall, track, and analyze patient behavior and monitor product usage. Additionally, in some embodiments, the electronics assembly includes a temperature sensor, and the electronics assembly can provide temperature data to the external device to, for example, warn the user when a temperature limit is reached. This also allows manufacturers to track patient and transporter compliance with drug temperature handling strategies.

[0010] An exemplary embodiment of the present disclosure is an electronic device assembly for a drug delivery device. The electronic device assembly includes: a processor; a sensor configured to measure a fill level of a drug container of the drug delivery device and output a measurement signal to the processor; a wireless module that can be paired with an external device; a power module configured to power the sensor, the processor, and the wireless transmitter; and at least one non-transitory computer-readable medium storing instructions operable to cause the processor to perform operations. The operations include: activating the sensor at a first time interval and receiving a measurement signal each time the sensor is activated at the first time interval; determining a change in the fill level of the drug container based on the received measurement signal; and upon detecting a change in the fill level, activating the wireless module for a first duration to enable the external device to pair with the wireless module.

[0011] In some cases, the stored instructions include transmitting a change in the fill level of the drug reservoir to the external device and deactivating the wireless module when the wireless module is paired.

[0012] In some cases, the electronics assembly includes a switch arranged to be activated by assembling the electronics assembly into the drug delivery device, such that the switch activates the electronics assembly.

[0013] In some cases, the instructions include activating the sensor at a second time interval and receiving a measurement signal before activating the sensor at the first time interval, the second time interval being longer than the first time interval, determining whether the drug container is empty or filled based on the received measurement signal, and when it is determined that the drug container is filled, stopping activating the sensor at the second time interval and starting activating the sensor at the first time interval.

[0014] In some cases, the first time interval is less than one hour. In some cases, the second time interval is more than 12 hours. In some cases, the first duration is less than 30 minutes.

[0015] In some cases, the instructions include determining a remaining power level of the power module and adjusting the first duration based on the remaining power level. In some cases, the instructions include storing each change in the fill level of the drug reservoir in the memory and, when the wireless module is paired, transmitting each of the stored changes in the fill level of the drug reservoir to the external device and deactivating the wireless module.

[0016] In some cases, the sensor is arranged to be disposed within a stopper, and wherein the stopper is configured to be inserted into the drug container. In some cases, the electronics assembly is configured to be inserted into the stopper. In some cases, the electronics assembly and / or the sensor are integrally formed with the stopper.

[0017] In some cases, the sensor is configured to measure a fill level of the drug container by measuring a position of the stopper in the drug container. In some cases, the instructions include calculating the fill level of the drug container based on the sensed position of the stopper.

[0018] In some cases, the sensor includes an ultrasound transmitter and a corresponding detector, the ultrasound transmitter being configured to transmit an ultrasound signal into the drug container, and the corresponding detector being configured to receive a reflection of the ultrasound signal from the drug container and output the measurement signal to the processor. In some cases, the external electronic device is selected from the group consisting of a smartphone, a smartwatch, a tablet computer, and a personal computer.

[0019] In some cases, the drug delivery device or the drug container includes printed identification or expiration date information, and wherein the instructions include transmitting a confirmation identification corresponding to the printed identification or the expiration date information when the wireless module is paired.

[0020] Another example of the present disclosure is a method for activating a wireless module of an electronics assembly configured to be inserted into a medication container of a medication delivery device. The method includes activating a sensor of the electronics assembly at a first time interval and receiving a measurement signal from the sensor each time the sensor is activated at the first time interval, the sensor being configured to measure a fill level of the medication container; determining a change in the fill level of the medication container based on the received measurement signal; and upon detecting the change in the fill level, activating the wireless module of the electronics assembly for a first duration and enabling pairing of an external device with the wireless module.

[0021] In some cases, the method includes transmitting a change in the fill level of the drug reservoir to the external device and deactivating the wireless module when the wireless module is paired.

[0022] In some cases, the method includes activating the sensor at a second time interval and receiving a measurement signal before activating the sensor at the first time interval, the second time interval being longer than the first time interval, determining whether the drug container is empty or filled based on the received measurement signal, and when it is determined that the drug container is filled, stopping activating the sensor at the second time interval and starting activating the sensor at the first time interval.

[0023] In some cases, the first time interval is less than one hour. In some cases, the second time interval is more than 12 hours.

[0024] In some cases, the method includes storing each change in the fill level of the drug container in the memory, and when the wireless module is paired, transmitting each of the stored changes in the fill level of the drug container to the external device and deactivating the wireless module.

[0025] In some cases, the method includes determining a remaining power level of a power module of the electronics assembly and adjusting the first duration based on the remaining power level.

[0026] Another example of the present disclosure is a system comprising a drug delivery device, the drug delivery device comprising: a housing; a drug container configured to be housed in the housing of the drug delivery device; and a plug disposed in a cavity of the drug container and configured to be driven into the drug container by a drive mechanism of the drug delivery device. The plug or the drug container includes an electronic device assembly, the electronic device assembly including: a processor; a sensor configured to measure a fill level of the drug container and output a measurement signal to the processor; a wireless module that can be paired with an external device; a power module configured to power the sensor, the processor, and the wireless transmitter; and a non-transitory computer-readable medium storing instructions operable to cause the processor to perform operations. The instructions include: activating the sensor at a first time interval and receiving a measurement signal each time the sensor is activated at the first time interval; determining a change in the fill level of the drug container based on the received measurement signal; and upon detecting the change in the fill level, activating the wireless module for a first duration to enable pairing of the external device with the wireless module.

[0027] Figure 1 is an exploded view of the drug delivery device.

[0028] Figure 2A yes Figure 1 A cross-sectional view of a retainer containing an electronic device assembly.

[0029] Figure 2B yes Figure 2A Top view of the stopper.

[0030] Figure 2C yes Figure 2A is set in Figure 1 Cross-sectional view of a stopper within a cartridge of a drug delivery device.

[0031] Figure 3 yes Figures 2A to 2C A cross-sectional schematic of the internal components of the electronics assembly within the stopper.

[0032] Figure 4A yes Figures 2A to 2C is set in Figure 1 Cross-sectional view of the electronic device assembly and the stopper in the drug delivery device.

[0033] Figure 4B yes Figure 4A is set in Figure 1 Cross-sectional view of the electronics assembly and stopper in a drug delivery device in a ready-to-use configuration.

[0034] Figure 4C After the drug delivery operation Figure 4B Cross-sectional view of the electronics assembly, stopper, and drug delivery device.

[0035] Figure 5A is a flow chart depicting a method of controlling activation of a wireless module of an electronics assembly.

[0036] Figure 5B is a flow chart depicting a method of controlling a sensing duration mode of an electronic device component.

[0037] Some injection and medical syringe systems based on cartridges include integrated electronics that support wireless connections. In some examples, a cartridge stopper (sometimes referred to as a stopper) may include a self-contained electronics assembly comprising a sensor, a wireless module, a power module, and a processor with memory. For example, the stopper may receive an insertable electronics assembly that is separated from the stopper. For example, the stopper may be assembled into the stopper or cartridge after sterilization. The electronics assembly may be a self-contained unit that is constructed before assembling the drug delivery device and embedded in the stopper during the final assembly of the drug delivery device. In some examples, the self-contained electronics assembly enables detection of the filling level of the cartridge and enables pairing with an external device (e.g., via Bluetooth or similar wireless protocols) to report the measured filling level. For example, a drug delivery device with a wireless module may enable a smartphone or tablet computer to be paired with the drug delivery device to confirm that an injection has been performed or to receive a measurement from an internal sensor, thereby providing confirmation or measurement of the discharged dose.

[0038] Regardless of the information provided, there is a challenge in balancing the power requirements of the internal wireless module with the size and shelf life limitations of a typical onboard power supply. Two specific examples of challenges, which will be discussed in more detail below, relate to (1) how to extend the shelf life of the integrated electronics assembly before assembly of the drug delivery device or filling of the cartridge occurs, and (2) how to further extend the useful life of the integrated electronics assembly after assembly or filling when the wireless module needs to be used. In some examples of the present disclosure, a solution to the first challenge includes using a sensor to detect when the medicament is filled in the cartridge and then changing to a response detection mode in response to a subsequent injection, as described in more detail below. Additionally, in some examples, a solution to the second challenge includes limiting the operation of the wireless module, and therefore the power consumption, to a short time interval after the injection is detected, as described in more detail below.

[0039] The term "drug" or "agent" is used herein to describe one or more pharmaceutically active compounds. As described below, a drug or agent can include at least one small molecule or macromolecule or a combination thereof in various types of formulations for treating one or more diseases. Exemplary pharmaceutically active compounds can include small molecules; polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids can be incorporated into molecular delivery systems (e.g., vectors, plasmids, or liposomes). Mixtures of one or more of these drugs are also contemplated.

[0040] The term "drug delivery device" should encompass any type of device or system that is configured to distribute a drug amount into the human or animal body. The drug amount can typically be from about 0.5 ml to about 10 ml. Without limitation, a drug delivery device can include a syringe, a needle safety system, a pen injector, an automatic injector, a large volume device (LVD), a pump, an infusion system, or other devices configured for subcutaneous, intramuscular, or intravascular delivery of a drug. Such devices typically include a needle, wherein the needle can include a small gauge needle (e.g., greater than about 24 gauge, and including 27, 29, or 31 gauge).

[0041] The presently described devices can also be customized to operate within desired parameters in combination with a particular drug, for example, within a certain time period (e.g., from about 3 seconds to about 20 seconds for a syringe, from about 5 minutes to about 60 minutes for an LVD), with a low or minimal level of discomfort, or within certain conditions related to human factors, shelf life, expiration date, biocompatibility, environmental factors, etc. These modifications may arise due to various factors (such as, for example, the viscosity of the drug ranging from about 3 cP to about 50 cP).

[0042] The drug or medicament can be contained in a primary package, cartridge or "drug container" adapted for use with a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir or other vessel configured to provide a suitable chamber for storing (e.g., short-term or long-term storage) one or more pharmaceutically active compounds. For example, in some embodiments, the chamber can be designed to store the drug for at least one day (e.g., 1 day to at least 30 days). In some embodiments, the chamber can be designed to store the drug for about 1 month to about 2 years. Storage can occur at room temperature (e.g., about 20°C) or refrigerated temperature (e.g., from about -4°C to about 4°C). In some embodiments, the drug container can be or can include a dual-chamber cartridge configured to store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of drugs) separately, one being stored in each chamber. In such an embodiment, the two chambers of the dual-chamber cartridge can be configured to allow mixing between two or more components of the drug or medicament before and / or during distribution into the human or animal body. For example, the two chambers can be configured so that they are in fluid communication with each other (e.g., via a conduit between the two chambers), allowing the user to mix the two components if desired before dispensing. Alternatively or additionally, the two chambers can be configured to allow mixing of the components when dispensing into a human or animal body.

[0043] Drug delivery devices and medicines described herein can be used to treat and / or prevent many different types of disorders. Exemplary disorders include, for example, diabetes or complications associated with diabetes (e.g., diabetic retinopathy), thromboembolic disorders (e.g., deep vein or pulmonary thromboembolism). Other exemplary disorders are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis.

[0044] Exemplary drugs for treating and / or preventing diabetes or complications associated with diabetes include insulin (e.g., human insulin, or human insulin analogs or derivatives); glucagon-like peptide (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof; dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof; or any mixtures thereof. As used herein, the term "derivative" refers to any substance that is sufficiently similar in structure to the original substance so as to have substantially similar function or activity (e.g., therapeutic effectiveness).

[0045] Exemplary insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin in which the proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and in which the Lys at position B29 can be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0046] Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-Thr B29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogs and GLP-1 receptor agonists are, for example: lixisenatide / AVE0010 / ZP10 / Lyxumia, exenatide / exendin-4 / Byetta / Bydureon / ITCA 650 / AC-2993 (a 39 amino acid peptide derived from the lizard Gila monster), liraglutide / Victoza, semaglutide, taspoglutide, Syncria / albiglutide, dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, langelatide / HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-114, BHM-034. MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN, and Glucagon-Xten.

[0047] An exemplary oligonucleotide is, for example, mipomersen / Kynamro, a cholesterol-reducing antisense therapeutic used to treat familial hypercholesterolemia.

[0048] Exemplary DPP4 inhibitors are vildagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0049] Exemplary hormones include pituitary or hypothalamic hormones or regulatory activity peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, tocopherol), growth hormone (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin and goserelin.

[0050] Exemplary polysaccharides include glucosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or derivatives thereof or sulfated polysaccharides (for example, the polysulfated forms of the above-mentioned polysaccharides), and / or pharmaceutically acceptable salts thereof. The example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. The example of a hyaluronic acid derivative is Hylan G-F20 / Synvisc, which is a sodium hyaluronate.

[0051] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind to antigens. The antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single-chain antibody. In some embodiments, the antibody has effector functions and can repair complement. In some embodiments, the antibody has reduced or no ability to bind to Fc receptors. For example, the antibody can be an isotype or subtype, an antibody fragment, or a mutant that does not support binding to Fc receptors, for example, it has a mutagenized or deleted Fc receptor binding region.

[0052] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy chain and / or light chain polypeptide) that does not comprise a full-length antibody polypeptide but still comprises at least a portion of a full-length antibody polypeptide capable of binding to an antigen. An antibody fragment can include a cleavage portion of a full-length antibody polypeptide, although the term is not limited to such cleavage fragments. Antibody fragments that can be used in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments (such as bispecific, trispecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies)), miniantibodies, chelated recombinant antibodies, triabodies or diabodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and antibodies containing VHH. Additional examples of antigen-binding antibody fragments are known in the art.

[0053] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences within the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences within the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the correct positioning of the CDR sequences to allow antigen binding. Although the framework regions themselves are typically not directly involved in antigen binding, as is known in the art, certain residues within the framework regions of certain antibodies may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDRs to interact with the antigen.

[0054] Exemplary antibodies are anti-PCSK-9 mAb (e.g., Alirocumab), anti-IL-6 mAb (e.g., Sarilumab), and anti-IL-4 mAb (e.g., Dupilumab).

[0055] The compounds described herein can be used in pharmaceutical formulations comprising (a) one or more compounds or pharmaceutically acceptable salts thereof, and (b) a pharmaceutically acceptable carrier. The compounds can also be used in pharmaceutical formulations that include one or more other active pharmaceutical ingredients or in pharmaceutical formulations in which a compound of the invention or a pharmaceutically acceptable salt thereof is the sole active ingredient. Thus, the pharmaceutical formulations of the present disclosure encompass any formulation prepared by mixing a compound described herein and a pharmaceutically acceptable carrier.

[0056] Pharmaceutically acceptable salts of any drug described herein are also intended to be used in drug delivery devices. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts are, for example, HCl or HBr salts. Basic salts are, for example, salts with a cation selected from an alkali metal or alkaline earth metal, for example, Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 are independently represented by hydrogen, an optionally substituted C1 C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Other examples of pharmaceutically acceptable salts are known to those skilled in the art.

[0057] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolate or ethanolate.

[0058] Figure 1FIG2 is an exploded view of a drug delivery device 100, which can be a disposable or reusable drug delivery device. Drug delivery device 100 includes a housing 110 containing a cartridge 114 and a cartridge housing 104 in which cartridge 114 is disposed. A stopper or stopper 200 is disposed within cartridge housing 104 of cartridge 114 and can be advanced within cartridge housing 104 during use to expel drug from cartridge 114. A needle assembly 115 can be attached to cartridge housing 104. Needle 109 of needle assembly 115 is protected prior to use by inner and outer needle caps 116 and 117, which in turn can be covered by cap 118. The medicament or drug dose to be expelled from drug delivery device 100 can be selected by rotating dose knob 112, and the selected dose is displayed via dose window or display 113.

[0059] As further described below, the drug delivery device 100 can include one or more electronic components 122, 124, some of which can be included as self-contained electronics assemblies within the retainer 200 of the cartridge 114. In some examples, the electronic components 122, 124 are located within other portions of the drug delivery device while enabling sensors of the electronic components 122, 124 to determine or measure the fill level of the cartridge 114.

[0060] Continuing with the operation of the drug delivery device 100, turning the dose knob 112 causes a mechanical click to provide acoustic feedback to the user. The number displayed in the dose display 113 is printed on a sleeve that is housed in the housing 110 and mechanically interacts with a plunger configured to interact with the cartridge 114. When the needle 109 is inserted into the patient's body and the injection button 111 is subsequently pushed, the drug dose displayed in the display 113 is discharged from the drug delivery device 100. During injection, a drive mechanism (shown as the outline of the plunger arm) drives the stopper 200 into the cartridge 114 to discharge the drug. The stopper 200 acts as a barrier to prevent fluids and gases from leaking into and out of the cartridge 114 and can prevent evaporation of H2O and other fluids. In some embodiments, the sealing function is provided by an elastic sealing element that contacts the container wall, but still allows the stopper 200 to slide. A higher percentage of the dose is actually injected into the patient's body when the needle 109 of the drug delivery device 100 remains in the patient's skin for a certain period of time after pushing the injection button 111. In some examples, the drug delivery device 100 is a single-use device or a disposable device, and those skilled in the art will understand that the electronic components 122, 124 used in the drug delivery device 100 can similarly perform similar functions in a single-use drug delivery device or a disposable drug delivery device.

[0061] Figure 2Ais a cross-sectional view of an embodiment of a retainer 200 for a drug delivery device 100. The retainer 200 includes a housing 202 and a core 204 containing electronic components 122, 124, which in some embodiments are embedded in the material of the core 204. In some cases, the core 204 is configured to be inserted into the housing 202 of the retainer 200 after manufacture. For example, the core 204 can be inserted into the housing after the housing 202 is positioned in the cartridge 114 of the drug delivery device 100. In other cases, the housing 202 is assembled with the core 204 having the electronic components 122, 124 for later insertion into the cartridge 114. In some cases, the housing 202 includes a sealing element 208 (e.g., an O-ring) that is arranged to provide a sealing interface with the inner surface of the cartridge 114 when the housing 202 is inserted into the cartridge 114. In some cases, housing 202 and core 204 are manufactured as a single component with or without electronic components 122 , 124 .

[0062] In some cases, the materials of the housing 202 and the core 204 are selected because they have the ability to allow sensor signals to pass through. For example, non-metallic materials such as polymers or ceramics or very thin metals (e.g., less than 0.1 mm thick) can be used. The electronic components 122, 124 may include, for example, sensors, energy sources, microcontrollers and / or wireless transceivers. The electronic components 122, 124 are only representative. Any number of electronic devices may be present. The sensor may be a sensor / transceiver device, such as, for example, a piezoelectric device, an acoustic sensor, or an electromagnetic sensor. The sensor / transceiver can transmit a signal, such as, for example, ultrasound, sound, light, or other signal, through the stopper 200 and measure a response, which in some embodiments can be used to determine the position of the stopper 200 in the cartridge 114 or to determine whether an injection has occurred. In some embodiments, the sensor comprises an ultrasonic sensor having an ultrasonic transmitter and an acoustic sensor, wherein the sensor is arranged to transmit an ultrasonic signal into the cartridge 114 using the ultrasonic transmitter, and the acoustic sensor is positioned to receive a reflection of the ultrasonic signal from the cartridge 114, the reflection being caused by the fill level of the medicament in the cartridge 114 or the presence of the medicament in the cartridge 114. The position of the stopper 200 before and after the injection corresponds to a change in the amount of medicament remaining in the cartridge 114, which can indicate the amount of medicament or dose expelled from the cartridge 114. In some embodiments, the response received by the sensor is provided to a controller (e.g., a processor located in the stopper 200 or elsewhere in the drug delivery device 100), which can receive the response and calculate the state of the cartridge 114. The state of the cartridge 114 can correspond to the fill level of the medicament in the cartridge 114, the position of the stopper 200, or the amount of the dose.

[0063] In some embodiments, the energy source is a battery or an energy storage device. The wireless module can communicate with an external electronic device and with the sensor and the energy source. The external electronic device (which can be a controller, a smart phone, a tablet computer or a computer) can transmit the data received from the sensor to an external database. The communication with the external device can be one-way or two-way. The data transmitted to the external database from the sensor device can include information related to the identity of the device, such as a unique number, calibration data, production batch information, device material information, data related to storage time and production time, and information related to sensor measurement (for example, measurement time, sensor measurement results such as temperature, distance, light signal and acoustic signal, etc.). The wireless module can use any known wireless communication technology to communicate, including, for example, Bluetooth, NFC or radio frequency.

[0064] In some embodiments, the housing 202 of the stopper 200 is constructed of a material such as metal, a polymer (e.g., COC, PA, PP, PE, POM, PS, ABS, COP, etc.), glass, or ceramic. In some embodiments, the electronic device or electronic component 122, 124 includes one or more of the following: a sensor, a power source (e.g., a battery), a controller or processor, a wireless communication module (e.g., Bluetooth, NFC, Bluetooth LE, any RF, IrDA), a memory, an on / off switch, a thermistor, a pressure sensor, etc. In some embodiments, the electronic component 122, 124 includes an on / off mechanism configured to trigger the electronic component 122, 124 by, for example, contact of a component of the drug delivery device 100 (e.g., force from a drive mechanism) on the stopper 200 during assembly of the drug delivery device 100.

[0065] Figure 2B 2 is a top view of the retainer 200. The housing 202 surrounds the core 204 and interacts with a sealing element 208 that forms a sealing interface with the cartridge 114 when the retainer 200 is introduced into the cartridge 114. The sealing interface can form at least a portion of a sterile barrier within the cartridge 114 that is used to maintain the sterility of the medicament to be delivered by the drug delivery device 100.

[0066] Figure 2C is a cross-sectional view of the stopper 200 provided in the cartridge 114. Figure 2A and Figure 2B Various features of the illustrated retainer 200 are depicted. The cartridge 114 includes a housing 602 that interfaces with the sealing element 208 of the retainer 200 to seal the open end of the cartridge 114. In some embodiments, the medicament is disposed in the space between the cap 604 of the cartridge 114 and the housing 202 of the retainer 200.

[0067] In some embodiments, different measurement methods are used to measure the position of the stopper 200. A signal is generated that changes with the movement of the stopper 200 relative to the fixed position in the system or cartridge 114. This fixed position can be inside the cartridge 114. In some cases, for example, the fixed position is on the diaphragm area of ​​the cartridge 114 or on another rigid wall of the cartridge 114. Alternatively, an element can be introduced into the cartridge for the purpose of providing a fixed reference. In other embodiments, the fixed reference can be outside the cartridge, such as on the housing of the drug delivery device 100. In some embodiments, the sensor measures the change in the light signal by emitting light from a light source (e.g., LED) to a fixed area and receiving the emitted light with a photodetector. The intensity of the emission can be related to the distance. Another possibility is to measure the time required for the signal (e.g., acoustic signal) to travel from a transmitter to a fixed position and back to a receiver positioned near the transmitter. In another embodiment, a signal (optical, acoustic, capacitive, etc.) can be sent from a fixed location to a receiver in the moving stop 200 to measure changes in the signal during stop travel and correlate it to the stop position in the cartridge 114.

[0068] In an example, a transmitter (e.g., one of the electronic components 122 or 124) transmits an acoustic wave at a first time t1. The first time t1 (e.g., the time of emission of the acoustic wave) can be provided to an external device. The acoustic wave propagates from the transmitter in the retainer 200 toward the distal end of the cartridge 114 (i.e., the end having the cap 604) and reflects (e.g., bounces back) from a surface of the cartridge 114 or a reflector disposed at the distal end of the cartridge 114. The reflection of the acoustic wave (e.g., a reflected wave) propagates from the distal end of the cartridge 114 toward the sensor in the retainer 200. The reflected wave is received at a second time t2. The speed of the acoustic wave is the known speed of sound S of the medicament in the cartridge 114. The time elapsed between the emission and reception of the acoustic wave is t2 − t1. The elapsed time is multiplied by the speed of sound to determine the distance traveled by the wave from the transmitter to the distal end of the cartridge 114 and back to the sensor. The distance traveled is divided by two to determine the distance D between the retainer 200 and the distal end of the cartridge 114. The amount V of medication in the cartridge 114 (e.g., the amount of medication enclosed in the cartridge 114 between the stopper 200 and the distal end) is determined by multiplying the determined distance by the cross-sectional area A of the cartridge 114. Thus, V = A*(t2 - t1)*S / 2. The detected difference in the determined amount of medication in the cartridge 114 before and after the drug delivery operation corresponds to the dose administered to the patient.

[0069] Figure 3 is a schematic cross-sectional view of the internal components of the electronic device assembly 340, which may be, for example Figure 1124. An electronics assembly 340 is shown disposed within the retainer 200, which itself is mounted within the open end of the cartridge 114. The electronics assembly 340 includes a sensor 341, a transmitter 342, a processor 343, a memory 344, a wireless module 345, and a power module 346. The sensor 341 and transmitter 342 are arranged within the electronics assembly such that, when the electronics assembly 340 is disposed within the retainer 200, the transmitter 342 can transmit a sensing signal into the interior volume 303 of the cartridge 114, and the sensor 341 can detect a return or reflected signal from the interior volume 303. The processor 343 is operably coupled to all elements of the electronics assembly 340 and controls the activation of the sensors 341, transmitter 342, and wireless module 345. The memory 344 stores instructions for use by the processor 343 in operating the components of the electronics assembly 340, as described above and discussed in more detail with respect to the following figures.

[0070] In operation, wireless module 345 is configured to communicate with external electronic devices to transmit information from electronics assembly 340. Power module 346 is configured to provide power to all components of electronics assembly 340. In some embodiments, electronics assembly 340 includes a capacitive device that includes capacitive circuitry configured to wirelessly receive power from, for example, a smartphone via a near field communication protocol (NFC) signal, or other inductively charged means through a typical wireless charging device, to provide energy to wireless module 345.

[0071] Figure 4A is a cross-sectional view of the electronics assembly 340 in the retainer 200 configured to be disposed in the drug delivery device 100. The retainer 200 includes a housing 202 that holds the electronics assembly 340 and a cap 410 that is configured to seal the electronics assembly 340 into the retainer 200. Figure 4A The cap 410 is shown to be installed (497) during assembly of the cartridge 114 before the medicament is filled into the cartridge's interior volume 303. In this way, Figure 4A 4 shows an assembly step in which the electronics assembly 340 operates in a low frequency sensing mode to detect when the interior volume 303 is filled with medicament using the sensing signal 470 .

[0072] exist Figure 4AIn the low frequency sensing mode, the wireless module of the electronic device assembly 340 is disabled and the electronic device assembly 340 is in a very low power state to extend the shelf life of the electronic device assembly 340 until the electronic device assembly 340 detects that the cartridge 114 is ready. In some embodiments, in addition to or instead of the low frequency sensing mode, the electronic device assembly 340 includes an activation mechanism configured to trigger the electronic device assembly 340 by being installed in the stopper 200 or the drug delivery device 100, such as Figure 4B As shown in .

[0073] Figure 4B is a cross-sectional view of the electronics assembly 340 and the stopper 200 disposed in the drug delivery device 100 in a ready-to-use configuration. Figure 4B A cartridge 114 and a stopper 200 housing an electronics assembly 340 are shown, wherein the cartridge 114 is mounted in the drug delivery device 100 and the plunger 106 is arranged to drive the stopper 200 and the electronics assembly 340 into the cartridge 114. The cap 410 has sealed the electronics assembly 340 within the interior region of the stopper 200. The interior volume 303 of the cartridge 114 has been filled with the medicament 40, and the electronics assembly 340 is sensing (via a sensing signal 470) the presence of the medicament 40 in the interior volume 303. The detection of the medicament 40 in the cartridge 114 by the electronics assembly triggers the electronics assembly 340 to change from a low frequency sensing mode to a high frequency sensing mode so that subsequent drug delivery operations can be detected within a reasonable timescale (i.e., so that the user does not have to wait too long for the wireless module to be activated). In Figure 4B , the plunger 106 is driven by an actuator or drive mechanism of the drug delivery device 100 containing the cartridge 114. In operation, the plunger 106 is driven (as indicated by arrow 498) against the stopper 200 and applies a force to move the stopper 200 into the cartridge 114 so as to drive a portion of the medicament 40 in the cartridge 114.

[0074] Figure 4C is a cross-sectional view of the electronics assembly 340 , the stopper 200 , and the drug delivery device 100 after a drug delivery operation. Figure 4CThe plunger 106 of the drug delivery device 100 is shown contacting the stopper 200 and having driven the stopper 200 into the cartridge 114 (as indicated by arrow 499) for a drug delivery operation (e.g., injection via needle 109). In operation, the electronics assembly 340 is in high frequency mode after having detected the presence of the medicament 40 and transmits a sensing signal 470, which in some embodiments is responsive to the position of the stopper 200 in the cartridge 114. The sensing signal 470 is processed by the electronics assembly 340, and the electronics assembly 340 detects the movement of the stopper 200 or the fill level of the cartridge 114 after the illustrated drug delivery operation. In response to detecting the injection, the wireless module of the electronics assembly 340 is activated for a short duration to enable pairing with the external device 480.

[0075] Figure 4C The external device 480 is shown initiating wireless communication 481 with the electronics assembly 340, and the wireless module of the electronics assembly 340 responding with a return wireless communication 482. In some cases, the return wireless communication 482 to the external device 480 includes a detected change in the fill level of the cartridge 114. In some cases, the return wireless communication 482 includes a history of detected changes in the fill level of the cartridge 114, enabling the external device 480 to receive all or part of the previous drug delivery history of the cartridge 114 or drug delivery device 100. The history of detected changes can include, for example, a previous change, multiple previous changes (e.g., a certain number or within a certain time period), or a complete history of detected changes. In some cases, the return wireless communication 482 includes temperature information or a temperature history sensed by the electronics assembly 340. In some cases, the return wireless communication 482 includes batch or expiration date information for the medicament, cartridge, or drug delivery device. The return wireless communication 482 can also include any other parameters or changes sensed, detected, or determined by any or all components of the electronics assembly 340. In some embodiments, the return wireless communication 482 includes the status of the electronics assembly or certain components of the electronics assembly, such as remaining power. In some cases, the plunger 106 is a plunger of a syringe, wherein the cartridge 114 is a syringe housing (e.g., a disposable drug delivery device).

[0076] Figure 5A is a flow chart depicting a method of controlling activation of the wireless module 345 of the electronics assembly 340. In some examples, Figure 5A and Figure 5BThe logic is stored in the memory 344 of the electronics assembly 340 and executed by the processor 343. With the electronics assembly 340 in the ready state (501), the processor 343 activates the sensor (i.e., sensor 341 and transmitter 342) (502) to detect the condition of the cartridge 114, either by previously detecting the medicament in the cartridge 114 or by triggering the activation mechanism as described above. The processor receives a signal from the sensor 341 (503) and determines whether a change in the fill level of the cartridge 114 is sensed (504). In some cases, the change in the fill level of the cartridge 114 can be sensed as a change in the position of the stopper 200 in the cartridge 114. If no change is determined, the processor 343 waits for a period of time (hereinafter referred to as time A) (511), which can be, for example, 5 minutes, 10 minutes, 15 minutes, or between 1 minute and 1 hour, or some time in between. Typically, time A is selected to balance the average detection time and power consumption of the electronics assembly 340. In some cases, the sensing operation uses very little power compared to the wireless module 345, so the duration of Time A (high frequency mode) may be short enough to allow the user to wait only a few minutes at most after the injection for the electronics assembly 340 to pair with the external device 480. In some cases, Time A may be selected dynamically. For example, if the medication is administered only once a day, Time A may be set to 12 hours after the injection is detected and then reduced to 5 minutes thereafter to anticipate the next day's drug delivery operation.

[0077] Continuing, if a change in the fill level of the cartridge 114 is determined, the processor 343 activates the wireless module 345 for a short duration (hereinafter referred to as time B), which can be, for example, 5 minutes, 10 minutes, 15 minutes, or between 1 minute and 1 hour, or some time in between. Typically, time B is selected to balance the high power consumption of the wireless module 345 with the flexibility of giving the user a larger time window to initiate wireless device pairing. In some embodiments, after determining a change in fill level, if the initial detection is performed during a drug delivery operation rather than immediately after the operation is completed, the processor 343 instructs further sensing operations to occur quickly until no further changes are detected. In addition, in some embodiments, the processor 343 stores the detected change in fill level in the memory 344 (506). When the wireless module 345 is activated, the external device 480 is able to pair with the electronic device assembly 340. When the wireless module 345 is activated, the processor checks whether a pairing is detected (507). If a pairing is not detected, the processor checks whether time B has expired (508). If no pairing is detected at the end of time B, the wireless module 345 is deactivated (510) and the electronic device assembly returns to the high frequency sensing mode (i.e., the ready state 501). When a pairing is detected, the wireless module 345 transmits the detected change to the external device 480 (509) and deactivates the wireless module 345 (510). After deactivation, as described above, the processor 343 can return to the high frequency mode to detect a subsequent drug delivery operation, or wait for a time A* (which can be the same as time A, or a different time specifically selected so that it will only occur after a drug delivery operation is detected) (511) and then return to the high frequency detection mode.

[0078] Figure 5B is a flow chart depicting a method of controlling a sensing duration mode of the electronics assembly 340. As discussed in more detail above, in some cases, the electronics assembly 340 is brought into a ready state 501 using an activation mechanism prior to final assembly of the drug delivery device, and in some cases, the electronics assembly 340 uses a low frequency sensing mode (e.g., Figure 5B) to detect the ready state 501. In the low frequency sensing mode, the electronics assembly 340 is in an assembled state, which may include the final assembly of the components of the electronics assembly 340 before filling the cartridge with the medicament or an activation step during the assembly of the electronics assembly into the cartridge 114 or the drug delivery device (i.e., the final assembly of the drug delivery device to make it ready) (520). In this assembled state, the processor 343 activates the sensors (i.e., the sensor 341 and the transmitter 342) (521) to detect the state of the cartridge 114. The processor receives a signal from the sensor 341 (522) and determines whether the medicament is detected in the cartridge 114 (523). In some cases, the filling of the medicament in the cartridge 114 can be sensed as a change in the position of the stopper 200 in the cartridge 114. If it is determined that there is no fill 523, the processor 343 waits 524 for a certain period of time (hereinafter referred to as time C), which can be, for example, 12 hours, 24 hours, 48 ​​hours, between 1 hour and 1 day, or some time in between. In some cases, time C is selected to balance the power usage of the electronics assembly 340 to enable the electronics assembly to have a long shelf life after construction and the expected time between filling the drug delivery device with medicament and the expected use by the patient. Time C can be selected to ensure that the electronics assembly is in a ready state 501 before the drug delivery device has been delivered to the patient for use. When medicament is detected in the cartridge 114, the processor stores the initially sensed value in the memory 344 (526) for later use in determining whether the fill level has changed to indicate that a drug delivery operation has occurred.

[0079] Described above are apparatus and methods for providing energy to electronic circuit systems in cartridge systems (e.g., those disclosed herein) using a power module (PM) (which may include, for example, a battery or other power storage device using technologies such as lithium-ion, nickel-metal hydride, nickel-cadmium, zinc-air, etc.).

[0080] Aspects of the systems disclosed above enable a medical injector to impart certain features to the cartridge of a drug delivery device (e.g., a pen injector) using "smart" technology by attaching included electronic components (e.g., RFID, sensors). When the electronics are integrated into the cartridge's stopper, one or more components may be active (e.g., sensors for measuring certain properties of the syringe or cartridge) and require an energy source, which can typically be a battery. An alternative is to use an energy harvesting device as a power source substitute for a battery. In some cases, a light source such as an LED or laser light source is included in the drug delivery device, and the electronics assembly includes a receiver (e.g., a photovoltaic cell or a light sensor) configured to receive light from the light source. In some cases, the receiver is configured to turn the electronics assembly on or off upon receiving or terminating light incident on the receiver, or in some cases, the receiver powers the electronics assembly by converting received light into electrical energy.

[0081] Embodiments of the present disclosure may also be applied to pre-filled single and dual chamber syringes that may not use a cartridge. The examples described above for the electronics assembly in the stopper of a cartridge may also be used with other drug containers, such as disposable pre-filled syringes or reusable / refillable cartridges. In some cases, the electronics assembly is housed in the cartridge or drug delivery device in a manner that enables the electronics assembly to sense changes in the fill level of the cartridge or syringe after injection. In some cases, components of the electronics assembly are located outside the stopper or in different parts of the cartridge or drug delivery device.

[0082] Some of the features described can be implemented in digital electronic circuitry, or in computer hardware, firmware, software, or a combination thereof. The apparatus can be implemented in a computer program product tangibly embodied in an information carrier (e.g., in a machine-readable storage device) for execution by a programmable processor; and the method steps can be performed by a programmable processor executing a program of instructions to perform the functions of the described embodiments by operating on input data and generating output. The features described can advantageously be implemented in one or more computer programs that can be executed on a programmable system comprising at least one programmable processor coupled to receive data and instructions from and transmit data and instructions to a data storage system, at least one input device, and at least one output device. A computer program is a set of instructions that can be used, directly or indirectly, in a computer to perform an activity or cause a result. Computer programs can be written in any form of programming language, including compiled or interpreted languages, and can be deployed in any form, including as stand-alone programs or as modules, components, subroutines, or other units suitable for use in a computing environment.

[0083] Those skilled in the art will understand that modifications (such as, for example, adjustments, additions, or removals) may be made to the various components of the materials, formulations, apparatuses, methods, systems, devices, and embodiments described herein without departing from the overall scope and spirit of the inventive concept, and that the present invention covers such modifications and any equivalents thereof.

[0084] Many embodiments of the present disclosure have been described. However, it should be understood that various modifications can be made without departing from the spirit and scope of the present disclosure. Therefore, other embodiments are also within the scope of the following claims.

[0085] Many embodiments of the present disclosure have been described. However, it should be understood that various modifications can be made without departing from the spirit and scope of the present disclosure. Therefore, other embodiments are also within the scope of the following claims.

Claims

1. An electronics assembly (340) for a drug delivery device (100), the electronics assembly comprising: processor(343); a sensor (341) arranged to measure a fill level of a drug container of the drug delivery device (100) and to output a measurement signal to the processor (343); a wireless module (345) capable of pairing with an external device (480); a power module (346) arranged to supply power to the sensor (341), the processor (343) and the wireless module (345); as well as At least one non-transitory computer-readable medium storing instructions operable to cause the processor (343) to perform operations comprising: activating the sensor (341) at a first time interval and receiving the measurement signal, determining whether the drug container contains a drug based on the received measurement signal, stopping activating the sensor (341) at the first time interval when it is determined that the drug container contains a drug, starting activating the sensor (341) at a second time interval and receiving the measurement signal, wherein the second time interval is shorter than the first time interval for each activation of the sensor (341) at the second time interval, determining a change in the filling level of the drug container based on the received measurement signal, and activating the wireless module (345) for a first duration to allow the external device (480) to pair with the wireless module (345) when the change in the filling level is detected.

2. The electronics assembly (340) of claim 1, wherein the instructions stored on the at least one non-transitory computer-readable medium comprise: When the wireless module (345) is paired, the change in the fill level of the drug container is transmitted to the external device (480) and the wireless module (345) is deactivated.

3. The electronic device assembly (340) according to claim 1 or 2, wherein the electronic device assembly (340) includes a switch, which is arranged to be activated by assembling the electronic device assembly (340) into the drug delivery device (100), so that the switch activates the electronic device assembly (340).

4. The electronics assembly (340) of claim 1 or 2, wherein the second time interval is less than one hour.

5. The electronics assembly (340) of claim 1 or 2, wherein the first time interval exceeds 12 hours and the first duration is less than 30 minutes.

6. The electronics assembly (340) of claim 1 or 2, wherein the instructions stored on the at least one non-transitory computer-readable medium comprise: A remaining power level of the power module (346) is determined and the first duration is adjusted based on the remaining power level.

7. The electronics assembly (340) of claim 1 or 2, wherein the instructions stored on the at least one non-transitory computer-readable medium comprise: Each change in the fill level of the drug container is stored in a memory (344), and when the wireless module (345) is paired, each of the stored changes in the fill level of the drug container is transmitted to the external device (480) and the wireless module (345) is deactivated.

8. The electronics assembly (340) according to claim 1 or 2, wherein the sensor (341) is arranged to be disposed inside a stopper, and wherein the stopper is configured to be inserted into the drug container.

9. The electronics assembly (340) of claim 8, wherein the electronics assembly (340) is configured to be inserted into the plug.

10. The electronics assembly (340) according to claim 8, wherein the electronics assembly (340) and / or the sensor (341) are formed integrally with the plug.

11. The electronic device assembly (340) of claim 8, wherein the sensor (341) is configured to measure the fill level of the drug container by measuring a position of the stopper in the drug container, and wherein the instructions include calculating the fill level of the drug container based on the sensed position of the stopper.

12. The electronic device assembly (340) according to claim 1 or 2, wherein the sensor (341) comprises an ultrasonic transmitter and a corresponding detector, the ultrasonic transmitter being configured to transmit an ultrasonic signal into the drug container, and the corresponding detector being configured to receive a reflection of the ultrasonic signal from the drug container and output the measurement signal to the processor.

13. The electronics assembly (340) of claim 1 or 2, wherein the external device (480) is selected from the group consisting of a smartphone, a smartwatch, a tablet computer, and a personal computer.

14. The electronics assembly (340) of claim 1 or 2, wherein the drug delivery device (100) or the drug container includes printed identification or expiration date information, and wherein the instructions stored on the at least one non-transitory computer-readable medium include: When the wireless module (345) is paired, a confirmation mark corresponding to the printed mark or the validity period information is transmitted.

15. A system comprising: A drug delivery device (100), comprising a housing; a drug container configured to be received in the housing of the drug delivery device; as well as a stopper disposed in the cavity of the drug container and configured to be driven into the drug container by a drive mechanism of the drug delivery device, wherein the stopper or the drug container comprises an electronic device assembly (340), the electronic device assembly comprising: processor(343); a sensor (341) arranged to measure the fill level of the drug container and output a measurement signal to the processor; a wireless module (345) capable of pairing with an external device (480); a power module (346) arranged to supply power to the sensor (341), the processor and the wireless module (345); and At least one non-transitory computer-readable medium storing instructions operable to cause the processor (343) to perform operations comprising: activating the sensor (341) at a first time interval and receiving the measurement signal, determining whether the drug container contains a drug based on the received measurement signal, stopping activating the sensor (341) at the first time interval when it is determined that the drug container contains a drug, starting activating the sensor (341) at a second time interval and receiving the measurement signal, wherein the second time interval is shorter than the first time interval for each activation of the sensor (341) at the second time interval, determining a change in the filling level of the drug container based on the received measurement signal, and activating the wireless module (345) for a first duration to allow the external device (480) to pair with the wireless module (345) when the change in the filling level is detected.

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