Dose counting system

Abstract

A dose counting system of an injection device or a module configured to be used with or applied to an injection device, the dose counting system comprising: a sensor arrangement comprising a first sensor configured to output a first signal and a second sensor configured to output a second signal, wherein the first sensor and the second sensor have an angular offset relative to each other, and wherein the sensor arrangement is configured to detect movement of a rotary encoder system relative to the sensor arrangement during administration of a medicament; and a processor configured to: calculate numerical derivatives of the first signal and the second signal; detect a peak in the derivative value of the first signal and a peak in the derivative value of the second signal when the first derivative signal value and the second derivative signal value exceed a predefined threshold; determine a unit of medicament that has been administered when a peak in the derivative value of the first signal is synchronous with a peak in the derivative value of the second signal, the peak in the derivative value of the first signal and the peak in the derivative value of the second signal have different signs, and the peak in the derivative value of the first signal has a different sign to a previous peak in the derivative value of the first signal; and determine a dose of medicament administered by the injection device by counting the units of medicament administered.

Description

Technical Field

[0001] This disclosure relates to a dose counting system for an injection device or a module configured for use with or applied to an injection device, and a method of operating said dose counting system. Background Technology

[0002] Many diseases require regular treatment with injectable medications. These injections can be administered using an injection device, either by a healthcare professional or by the patient themselves. For example, type 1 and type 2 diabetes can be treated by the patient themselves by injecting insulin doses, such as once or several times a day. For instance, a pre-filled disposable insulin pen can be used as the injection device. Alternatively, a reusable pen can be used. A reusable pen allows for the replacement of empty cartridges with new ones. Either type of pen is typically supplied with a set of disposable needles, which are replaced before each use. The insulin dose to be injected can then be manually selected, for example, by turning the dose knob on the insulin pen and observing the actual dose from the insulin pen's dose window or display. The dose is then injected by inserting the needle into the appropriate skin site and pressing the injection button on the insulin pen. To monitor insulin injections, such as to prevent mishandling of the insulin pen or to record the dose administered, it is desirable to measure information related to the condition and / or use of the injection device, such as information about the injected insulin dose.

[0003] WO 2019 / 101962 A1 describes an injection device comprising: a movable dose programming component including a rotary encoder system having a predetermined angular periodicity; and a sensor arrangement including a first optical sensor and a second optical sensor, the first optical sensor being configured to detect movement of the movable dose programming component relative to the sensor arrangement during drug administration, and the second optical sensor being configured to detect movement of the rotary encoder system relative to the second optical sensor. The first optical sensor is configured to operate in a gated sampling mode at a first frequency, and the second optical sensor is configured to operate in a gated sampling mode at a second frequency lower than the first frequency. The injection device further includes a processor arrangement configured to determine a drug dose administered by the injection device based on the detected movement. WO 2019 / 101962A1 further describes a method for processing signals generated by a sensor arrangement having two optical sensors arranged at a 180° offset such that the signals of the first sensor and the second sensor are out of phase. The method includes the following steps: setting a high threshold and a low threshold for the signals of the first sensor and the second sensor, respectively; and counting dose units selected using the movable dose programming component if the signal of the second sensor passes the high threshold and then passes the low threshold, and if the signal of the first sensor then passes the low threshold and then passes the high threshold. Summary of the Invention

[0004] The first aspect disclosed herein requires a dose counting system for an injection device or a module configured for use with or applied to an injection device, the dose counting system comprising:

[0005] A sensor arrangement comprising a first sensor configured to output a first signal and a second sensor configured to output a second signal, wherein the first sensor and the second sensor have an angular offset relative to each other, and wherein the sensor arrangement is configured to detect movement of a rotary encoder system relative to the respective sensor arrangement during drug administration; and

[0006] The processor is configured as follows:

[0007] Calculate the numerical derivatives of the first signal and the second signal;

[0008] When the values ​​of the first derivative signal and the second derivative signal exceed a predefined threshold, the peak value in the derivative value of the first signal and the peak value in the derivative value of the second signal are detected.

[0009] The number of drug units administered is determined when the peak value of the derivative of the first signal is synchronized with the peak value of the derivative of the second signal, wherein the peak values ​​of the derivative of the first signal and the derivative of the second signal have different signs, and the peak value of the derivative of the first signal has a different sign relative to the preceding peak value in the derivative of the first signal; and

[0010] The dosage of the drug administered by the injection device is determined by counting the units of the drug applied.

[0011] The processor may be further configured to calculate a moving average of a series of values ​​of the first signal and the second signal.

[0012] The moving average may include the mean of a first set of values ​​minus the mean of a second set of values ​​from the same sensor, wherein the first and second sets contain the same number of values. The first and second sets may overlap.

[0013] Alternatively, the processor may be further configured to calculate a moving median of a series of values ​​for the first and second signals. The moving median may include the median of a first set of values ​​minus the median of a second set of values, wherein the first and second sets contain the same number of values. The first and second sets may overlap.

[0014] The injection device may include an injection button configured to be pressed to administer a dose of medication from the injection device. The processor may be further configured to determine that the injection button has been pressed or released when the peak values ​​of the first signal and the second signal have the same sign.

[0015] The processor may be further configured to initiate communication pairing with an external device or perform data synchronization with the external device in response to determining that the injection button has been pressed. The communication pairing may be Bluetooth pairing.

[0016] The processor may be further configured to initiate manual data synchronization in response to determining that the injection button has been released.

[0017] The processor may be further configured to terminate the output dose indication in response to determining that the injection button has been released.

[0018] The rotary encoder system may include an encoder ring comprising a plurality of substantially reflective markings arranged circumferentially around the encoder ring periodically according to the predefined angle.

[0019] The second aspect disclosed herein requires a method for operating a dose counting system of an injection device or configured for use with an injection device or applied to a module of an injection device, wherein the encoding includes:

[0020] A sensor arrangement comprising a first sensor configured to output a first signal and a second sensor configured to output a second signal, wherein the first sensor and the second sensor have an angular offset relative to each other, and wherein the sensor arrangement is configured to detect movement of a rotary encoder system relative to the respective sensor arrangement during drug administration; and

[0021] processor;

[0022] The method includes:

[0023] Calculate the numerical derivatives of the first signal and the second signal;

[0024] When the values ​​of the first derivative signal and the second derivative signal exceed a predefined threshold, the peak value in the derivative value of the first signal and the peak value in the derivative value of the second signal are detected.

[0025] The number of drug units that have been administered is determined when the peak value in the derivative of the first signal is synchronized with the peak value in the derivative of the second signal. The peak value in the derivative of the first signal and the peak value in the derivative of the second signal have different signs, and the peak value in the derivative of the first signal has a different sign relative to the previous peak value in the derivative of the first signal.

[0026] The dosage of the drug administered by the injection device is determined by counting the units of the drug applied.

[0027] The method of the second aspect may further include calculating a moving average of a series of values ​​of the first signal and the second signal. Attached Figure Description

[0028] To better understand the general concepts presented in the preceding sections, implementation schemes will be described with reference to the accompanying drawings, wherein:

[0029] Figure 1 illustrates the injection device according to the first embodiment;

[0030] Figure 2 is a schematic block diagram of the dose counting system;

[0031] Figure 3A is an elevation side view of the first type of encoder system;

[0032] Figure 3B is a plan view of the encoder system shown in Figure 3A;

[0033] Figure 4A is an elevation side view of the second type of encoder system;

[0034] Figure 4B is a plan view of the encoder system shown in Figure 4A;

[0035] Figure 5A is an elevation side view of the eighth type encoder system;

[0036] Figure 5B is a plan view of the encoder system shown in Figure 5A;

[0037] Figure 6 is a detailed view of the encoder system;

[0038] Figure 7 illustrates the changes in signal voltage and derivative signals generated by the two optical sensors of the sensor arrangement during the movement of the movable dose programming component relative to the sensor arrangement as the dose is dispensed by the injection device.

[0039] Figure 8 illustrates the changes in signal voltage and derivative signals generated by two optical sensors arranged in a sensor array during pressing and releasing the dose button in the absence of dose input; and

[0040] Figure 9 shows the Gray code output of an optical dose counting system with an alternative arrangement. Detailed Implementation

[0041] In the following description, embodiments will be illustrated with reference to insulin injection devices. However, this disclosure is not limited to such applications and can be equally well applied to injection devices that dispense other medications.

[0042] Implementation schemes for injection devices, particularly variable-dose injection devices, are provided, which record and / or track data regarding the dose delivered therefrom. This data may include the size of the selected dose, the time and date of administration, the duration of administration, etc. Features described herein include the arrangement of sensing elements, power management techniques (for small batteries), and the arrangement of trigger switches for efficient power utilization.

[0043] Certain embodiments described in this document relate to the injection device of Sanofi, in which an injection button and a grip are combined. The mechanical construction of such an injection device is described in detail in International Patent Application WO 2014 / 033195 A1, which is incorporated herein by reference. Other injection devices with the same kinematic behavior of a selector extension and a trigger button during dose setting and dose dispensing operation modes are referred to, for example, those sold by Eli Lilly. The device and sold by Novo Nordisk Apparatus. Therefore, applying the general principles to these apparatuses is straightforward and self-evident, and further explanation will be omitted. However, the general principles of this disclosure are not limited to this kinematic behavior. Certain other embodiments are conceivable for application to injection devices with separate injection buttons and grip components, such as those described in WO 2004078239. The embodiments described in this document may be particularly based on the embodiments described in WO 2019 / 101962A1, which is incorporated herein by reference.

[0044] In the following discussion, the terms "distal," "distally," and "distalend" refer to the end of the injection device toward which the needle is positioned. The terms "proximal," "proximally," and "proximal end" refer to the opposite end of the injection device toward which the injection button or dosage knob is positioned.

[0045] Figure 1, from WO 2019 / 101962 A1, is an exploded view of a drug delivery device. In this example, the drug delivery device is an injection device 1, such as an injection pen described in WO 2014 / 033195 A1.

[0046] The injection device 1 in Figure 1 is a pre-filled disposable injection pen comprising a housing 10 and containing an insulin container 14 to which a needle 15 can be attached. The needle is protected by an inner needle cap 16 and an outer needle cap 17 or other cap 18. The dose of insulin to be dispensed from the injection device 1 can be programmed or “dialed in” by turning the dose knob 12, and the currently programmed dose is then displayed (e.g., in multiples of units) via a dose window 13. For example, when the injection device 1 is configured to administer human insulin, the dose can be displayed in so-called International Units (IU), one IU being the biological equivalent of approximately 45.5 micrograms of pure crystalline insulin (1 / 22 mg). Other units can be used in the injection device for delivering insulin analogs or other agents. It should be noted that the selected dose can be displayed just as well in a manner different from that shown in the dose window 13 in Figure 1.

[0047] The dosage window 13 may be in the form of a hole in the housing 10, allowing the user to observe a limited portion of the selector sleeve 70, which is configured to move when the dosage knob 12 is turned to provide a visual indication of the currently programmed dosage. When turned during programming, the dosage knob 12 rotates in a helical path relative to the housing 10.

[0048] In this example, the dosage knob 12 includes one or more configurations 71a, 71b, 71c to facilitate attachment of the data collection device.

[0049] The injection device 1 can be configured such that turning the dose knob 12 produces a mechanical click to provide acoustic feedback to the user. The selector sleeve 70 interacts mechanically with a piston in the insulin container 14. In this embodiment, the dose knob 12 also functions as an injection button. The dose knob can house a separate pressable button or can be an integral component pressed by the user to initiate the drug delivery process. When the needle 15 is inserted into the patient's skin and the injection button 12 is then pushed in the axial direction, the insulin dose displayed in the display window 13 is dispensed from the injection device 1. Most of the dose is actually injected into the patient while the needle 15 of the injection device 1 remains in the skin for a period of time after the dose knob 12 is pushed. The dispensing of the insulin dose can also cause a mechanical click, however, it is different from the sound produced when the dose knob 12 is rotated during dose selection.

[0050] In this embodiment, during insulin dose delivery, the dose knob 12 returns to its initial position (without rotation) in axial movement, while the selector sleeve 70 rotates back to its initial position, for example, displaying a dose of zero units.

[0051] The injection device 1 can be used for several injections until the insulin container 14 is emptied or the medication in the injection device 1 reaches its expiration date (e.g., 28 days after the first use).

[0052] Furthermore, before using the injection device 1 for the first time, a so-called "preparation injection" may be necessary to remove air from the insulin container 14 and needle 15, for example by selecting two units of insulin and pressing the dosage knob 12 while keeping the needle 15 of the injection device 1 facing upwards. For ease of presentation, it will be assumed below that the ejected volume substantially corresponds to the injected dose, such that, for example, the dose of medication expelled from the injection device 1 is equal to the dose received by the user. However, the difference between the ejected volume and the injected dose (e.g., loss) may need to be considered.

[0053] As explained above, the dosage knob 12 also functions as an injection button, allowing the same component to be used for selection and dispensing.

[0054] Figures 3A and 3B illustrate an encoder system 500 according to certain embodiments. The encoder system can be configured for use with the injection device 1 described above. As shown in Figures 3A and 3B, the primary sensor 215a and secondary sensor 215b are configured for a specially adapted region at the proximal end of the selector sleeve 70. In this embodiment, the primary sensor 215a and secondary sensor 215b are infrared (IR) reflective sensors. Therefore, the specially adapted proximal region of the selector sleeve 70 is divided into a reflective region 70a and a non-reflective (or absorptive) region 70b. A portion of the selector sleeve 70 including the reflective region 70a and the non-reflective (or absorptive) region 70b may be referred to as an encoder ring.

[0055] Having two sensors facilitates the power management techniques described below. The primary sensor 215a is arranged at a frequency corresponding to the resolution (e.g., 1 IU) required for the dose history requirements applicable to a particular drug or dosing regimen, targeting a series of alternating reflective regions 70a and non-reflective regions 70b. Compared to the primary sensor 215a, the secondary sensor 215b is arranged at a reduced frequency targeting the series of alternating reflective regions 70a and non-reflective regions 70b. It should be understood that the encoder system 500 can operate solely with the primary sensor 215a to measure the dispensed dose. The secondary sensor 215b facilitates the power management techniques described below.

[0056] Figures 3A and 3B show two sets of coding regions 70a and 70b, concentric with an outer region and an inner region, respectively. However, any suitable arrangement of the two coding regions 70a and 70b is possible. Although regions 70a and 70b are shown as crenellated regions, it should be remembered that other shapes and configurations are also possible.

[0057] A dose counting system 700 is schematically shown in Figure 2. The dose counting system 700 may be an integral part of the injection device 1 or part of a module configured to be attached to the injection device 1. The dose counting system 700 includes a processor arrangement 23 and memory units 24, 25. The processor arrangement includes one or more processors, such as a microprocessor, digital signal processor (DSP), application-specific integrated circuit (ASIC), field-programmable gate array (FPGA), etc.; the memory units include program memory 24 and main memory 25, which can store software executed by the processor arrangement 23.

[0058] The dose counting system 700 controls the sensor arrangement 215, which includes one or more sensors 215a, 215b.

[0059] Provide output 27, which may be for use via a wireless network (such as Wi-Fi or A wireless communication interface for communicating with another device; or an interface for a wired communication link, such as a socket for receiving a Universal Serial Bus (USB), mini-USB, or micro-USB connector. For example, data can be output to a data collection device attached to device 1.

[0060] It also includes a power switch 28 and a battery 29.

[0061] Power Management

[0062] Minimizing the power consumption of the dose counting system 700 is advantageous, allowing for a smaller size of the battery 29 that needs to be packaged into the device 1. The sensors 215a and 215b used in this embodiment require a certain amount of power to operate. This embodiment is arranged such that sensors 215a and 215b can be intermittently switched on and off at a controlled frequency (i.e., in gated sampling mode). An inherent limit is placed on the maximum rotational speed that can be counted by the sampled encoder system before aliasing occurs. Aliasing is a phenomenon where the sampling rate is less than the rate at which the sensed area passes through the sensor, meaning that counting errors may occur when area changes are missed. The secondary sensor 215b, with a reduced frequency compared to the primary frequency 215a, can tolerate higher rotational speeds before it also becomes aliased. Although the secondary sensor 215b cannot distinguish doses allocated with the same resolution as the primary sensor 215a, its output remains reliable at higher speeds. Therefore, the two sensors 215a and 215b are used in combination to accurately determine the dose delivered up to a first threshold rotational speed (dispensing speed). Sensors 215a and 215b can then be used to determine the approximate dose delivered up to a second (higher) threshold dispensing rate. At speeds above the second threshold rate, sensors 215a and 215b will not be able to accurately or approximately determine the delivered dose, therefore the second threshold is set above a speed that is physically impossible for the injection device 12 to achieve.

[0063] A first speed threshold is determined by the sampling rate of the primary sensor 215a and the frequency of encoder region switching, the frequency being fixed at the resolution required for the intended drug or dosing regimen (e.g., one switching per 1 IU). A second speed threshold is determined by the sampling rate of the secondary sensor 215b and the frequency of encoder region switching. The first threshold is set such that the system can cover the maximum dispensing speed range to accurately report the dispensed dose.

[0064] The exemplary embodiment shown in Figure 3B has a main sensor 215a that switches for a region switch once per 1 IU dose delivery and a secondary sensor 215b that switches for a region switch once per 6 IU dose delivery. Other options are also possible, including switching once per 2 IU, once per 4 IU, once per 8 IU, and once per IU unit. These options are each possible because in the encoder system 500 shown in Figure 3B, there are 24 individual regions 70a, 70b per revolution. Typically, if the number of individual regions 70a, 70b per revolution is n units, there will be an option for a region switch every m units, where m is any integer factor greater than 1 and less than n.

[0065] The slower the sampling frequency of the two sensors 215a and 215b, the lower the power consumption required, and therefore the smaller the required battery 29. Therefore, in practical applications, minimizing the sampling frequency through design is optimal.

[0066] The following implementation relates to an alternative sensing technology to determine the number of drug units that have been dispensed from device 1.

[0067] Similar to the embodiment described above, two sensors 215 are mounted in the injection button 12 and configured to sense the relative rotational position of the selector sleeve 70 relative to the injection button during dose dispensing. This relative rotation can be equivalent to the dispensed dose size and is used for the purpose of generating, storing, or displaying dose history information.

[0068] As shown in Figure 4A, two sensors 215 from this embodiment are configured for specially adapted regions 70a and 70b of the selector sleeve 70. In this embodiment, an IR reflective sensor is used, thus dividing the region of the selector sleeve 70 into a reflective segment 70a and an absorptive segment 70b. Segments 70a and 70b may also be referred to herein as markings.

[0069] Unlike the encoder system 500 described above with respect to Figures 3A and 3B, the encoder system 900 shown in Figures 4A and 4B has two IR sensors 215, targeting the same type of regions 70a and 70b. In other words, the sensors 215 are arranged such that they simultaneously face the reflective region 70a or both face the absorptive region 70b. During dose dispensing, for each dose unit dispensed, the selector sleeve 70 rotates 15° counterclockwise relative to the injection button 12. Alternate marking elements are located in a 30° (or two-unit) section. The sensors 215 are arranged out of phase with each other such that the angle between them is equal to an odd number of units (e.g., 15°, 45°, 75°, etc.), as shown in Figure 4B.

[0070] The encoder system 900 shown in Figure 4B has 12 units per revolution, i.e., 12 alternating regions 70a, 70b. Typically, implementations operate at any multiple of 4 units per revolution. The angle α between the sensors 215 can be represented by Equation 1, where m and n are both any integers, and 4m units are allocated per revolution.

[0071]

[0072] Equation 1 - Angle between sensors

[0073] Figure 10 shows how the outputs of sensors A and B change when the selector sleeve 70 is rotated counterclockwise during drug dispensing.

[0074] The combination of two sensors, A and B, produces a 2-bit Gray code output (11, 01, 00, 10). The 2-bit code sequence repeats every four units. This coded output facilitates the detection of both positive (counter-clockwise) and negative (clockwise) rotation. For example, when the sensor reads "11," changing it to "01" will indicate positive rotation, while changing it to "10" will indicate negative rotation. This orientation-sensitive system is superior to purely incremental systems in its ability to accurately determine the actual dispensed dose volume in cases where negative rotation may occur. For example, when the user releases the injection button 12, the mechanism that has over-rotated at the end of the dose stops before "retracting."

[0075] An encoder system according to an additional embodiment will now be described with reference to Figures 5A and 5B. This encoder system can be used to record the dose delivered from an injection device. The concept of this encoder system is based on a light guide used to transmit the state of an indicator mark to a reflective sensor physically located away from the mark. The embodiments shown in Figures 5A and 5B use an optical add-on module configured to be attached to the injection device. For simplicity, the housing of the add-on module is omitted, and only the sensor and optical components are shown in Figures 5A and 5B. The add-on module also includes a dose counting system 700, such as shown in Figure 2. This add-on module can be configured to be added to a suitably configured pen injection device to record the dose selected and delivered from the device. The add-on module can be configured to replace the selector knob / injection button of the injection pen, or alternatively, can be fitted onto an existing selector knob / injection button. In these embodiments, the indicator mark is formed by the relative rotation of a digital sleeve or selector sleeve with the add-on module, which houses at least one optical sensor. This feature can be valuable to many device users as a memory aid or to support detailed recording of dose history. The additional module can be configured to connect to an external device, such as a smartphone or tablet computer, or similar device, to enable periodic download of dose history from the module. However, the concept of an encoder system can also be applied to any device with indicator markings and sensor separation devices, such as the injection device 1 of Figure 1, where the module can be implemented in the dose knob 12, which can be removable.

[0076] According to the concept of an encoder system, a collimating optics is arranged between the working surface of at least one optical sensor, which can serve as an IR reflection sensor, and a movable dose programming component. The collimating optics may include one or more discrete collimating lenses and one or more light guides. The lens geometry can be selected to parallelize (“collimate”) the emitted radiation from at least one optical sensor before it is transmitted through the light guide between the at least one sensor and the target (i.e., the indicator mark).

[0077] Figure 5A illustrates the basic components of an embodiment of module 1000 implementing this encoder concept: an indicator mark 1008 can be formed by relative rotation of a digital sleeve 1006 about a rotation axis 1010, wherein the indicator mark 1008 in the illustrated embodiment is achieved by radially projecting teeth, which are formed, for example, on the top of the digital sleeve or selector sleeve 70 of the injection device 1; the optical sensor 215c and collimating optics include two collimating lenses 1004a, 1004b and a light guide in the form of a light guide 1002 for transmitting the state of the indicator mark 1008 to the sensor 215c positioned remotely from the mark. The collimating optics 1002, 1004a, 1004b and the optical sensor 215c can be positioned relative to surrounding components within the injection device and are particularly associated with additional modules. As can be seen, the collimating optical device, including lenses 1004a, 1004 and light guide tube 1002, is arranged between the active side of optical sensor 215c (i.e., the IR emission and reception side) and the indicator mark 1008 formed by digital sleeve 1006.

[0078] Figure 5B shows a housing 1012 according to an embodiment of module 1000, which houses two optical sensors 215c (indicated by their positions shown as bold rectangles in the housing 1012) and their corresponding collimating lenses 1004a, 1004b. It is envisioned that the collimating lenses 1004a, 1004b, implemented here as discrete lenses, are held relative to the near-end faces of the optical sensors 215c and the light guide by means of supports or other positioning geometries that are features of the housing 1012.

[0079] Essentially, all the points mentioned above relate to a more robust coding mechanism system where optical (reflective) sensors form the active elements in the optical encoder. By more effectively capturing the movement of the digital sleeve relative to the dosage button, reduced power consumption and extended battery life can be achieved through lower optical sensor transmitter power and the use of algorithms requiring less microcontroller operation. The encoder system described herein is equally applicable to devices included in disposable or reusable injection units, or any device incorporating an optical encoder arrangement with a similar light guide structure.

[0080] Figure 6 shows a partial view of the digital sleeve 400 and the arrangement of teeth or marks 402 on the digital sleeve. The marks 402 are substantially reflective. For example, the marks 402 may be made of or coated with a reflective material, or the reflective material may be printed on the surface of the marks 402. The marks 402 are spaced apart from each other at an angle of 30 degrees, such that twelve marks 402 are evenly spaced around the circumference of the digital sleeve 400. Figure 6 also shows exemplary positions of two light guides associated with corresponding optical sensors, indicated by ellipses numbered 1 and 2. The light guides are separated at an angle of 45 degrees, such that the difference between the angular spacing of the light guides and the angular spacing of the marks 402 is 15 degrees, and the signals from the two sensors are out of phase. In some embodiments of the injection device, the digital sleeve 400 is configured to rotate 15 degrees for each dose unit selected or delivered. The arrangement shown in Figure 6 thus allows for the measurement of the number of dose units selected or delivered using signals from both sensors. Although this embodiment has been described with respect to optical sensing and reflective marking, in some other embodiments, inductive sensing, capacitive sensing, or magnetic sensing may be used. For example, marking 402 may include a conductive or magnetic region passing under an inductive, capacitive, or magnetic sensor to determine the amount of rotation of digital sleeve 400.

[0081] Next, an implementation scheme for an algorithm for processing signals, particularly signal voltages, generated by the optical sensors of the sensor arrangement described above with respect to the injection device and modules is described. The algorithm is implemented as a computer program executed by one or more processors, such as those in the processor arrangement 23 included in the dose counting system 700 shown in FIG. 2.

[0082] The algorithm is implemented to process signals delivered by the one or more optical sensors 215a, 215b, 215c, i.e., to decode a selected drug dose for delivery by an injection device or to be delivered by an injection device. The algorithm is preferably applicable to devices with indicator markers and sensor separation devices with light guides, such as the modules described above.

[0083] The relative rotation between the dosage button and the digital sleeve can be optically encoded using an incremental encoder (e.g., a quadrature encoder), where two or more optical sensors, particularly reflective IR sensors, axially observe a crenellation or radially projecting tooth or mark formed on the top surface of the digital sleeve. The encoder system can be implemented as an add-on module, meaning that even after calibration, the position of the detected crenellation or tooth can vary relative to the position of the optical sensors due to variations in the manufacturing process of the injection device to which the module is assembled. Therefore, the signal may vary between devices and during typical use. Additionally, the axial position of the optical sensors may also change relative to the crenellation when the dosage button is pressed and released.

[0084] The algorithm described below can be implemented in the injection device or an add-on module, specifically for the purpose of recording the dose delivered from the injection device. This functionality could be valuable to many injection device users as a memory aid or to support detailed recording of dose history. It is conceivable that the electronic device implementing the algorithm could be configured to connect to a mobile device, such as a smartphone or similar device, to enable the periodic download of dose history from the electronic device.

[0085] The algorithm is configured to detect the relative rotation of a serration or tooth on a digital sleeve relative to a non-rotating component such as a dosage button. The presence or absence of the serration or tooth feature provides a binary code that can be used to count the number of units dispensed from the injection device. The voltage output of the optical sensor can typically be approximated as a sine curve. The algorithm is capable of detecting the presence of serration or tooth features on all devices, which may have any combination of geometric tolerances in terms of physical characteristics.

[0086] Furthermore, when the dosage button moves axially toward or away from the bevel or tooth feature at the start and end of dosage injection, the signal changes generated by the optical sensor should not be incorrectly interpreted as rotation of the bevel or tooth feature. Therefore, the algorithm can adapt to significant amplitude modulation of the signal generated by the optical sensor.

[0087] All algorithms involve a system in which two optical sensors are arranged with a 180° phase shift, such that the signal voltages generated by the two sensors are out of phase.

[0088] The implementation of the algorithm provides improved noise resilience and false positive reduction, and is unaffected by offset drift (amplitude modulation) and sensor amplitude variations.

[0089] The first image in Figure 7 illustrates a typical variation in the signal voltages generated by the two optical sensors upon dose administration. The first sensor signal voltage is shown by a thicker line, while the second sensor signal voltage is shown by a lighter line. These two optical sensors may have different gain profiles. The signal voltages are amplitude modulated. Different gain profiles may cause the two optical sensors to generate significantly different signal voltages, which are then sent to the processor for processing. Different gain profiles can result, for example, from tolerances associated with electronic components. In this system, the two optical sensors are arranged with a 180° phase shift, causing the signal voltages generated by the two sensors to be out of phase.

[0090] The second image in Figure 7 illustrates the numerical derivative of the signal change process of the first image. The applied drug unit is detected by the algorithm when peaks (positive and negative) are present simultaneously in the derivatives of the first and second signal voltages. The small series of peaks at the beginning of the derivative graph (only in the first sensor signal) are caused by pressing the injection button and the accompanying axial movement. This is not counted as an applied drug unit because there is no corresponding peak with the opposite sign in the second sensor signal. At the end of the derivative graph, the peaks in the derivatives of both the first and second sensors are caused by releasing the injection button. Again, these peaks are not counted as applied drug units because the peaks in the two sensors do not have opposite signs.

[0091] The first image in Figure 8 illustrates the typical variation in signal voltages generated by the two optical sensors when the injection button is pressed when no dose is being dispensed into the injection device. The first sensor signal voltage is shown by a thicker line, while the second sensor signal voltage is shown by a lighter line.

[0092] The second image in Figure 8 illustrates the derivative values ​​of the signal changes in the first image. At the beginning of the derivative graph, a series of positive peaks in both the first and second sensor signals are caused by pressing the injection button. Therefore, the pressing of the injection button is detected by the algorithm but is not counted as the administration of a dose unit. At the end of the derivative graph, a series of negative peaks in both the first and second sensor signals are caused by releasing the injection button. Therefore, the release of the injection button is detected by the algorithm but is not counted as the administration of a dose unit. Thus, the signals caused by pressing and releasing the injection button are not incorrectly identified as drug administration events.

[0093] To determine the dosage of the drug administered by the injection device, the algorithm calculates the numerical derivatives of a first signal and a second signal. The algorithm then identifies the maximum and minimum values ​​of the derivative values ​​of the two sensor signals. The algorithm defines a derivative peak threshold, which determines the magnitude at which a derivative peak needs to be recognized as a peak value. This derivative peak threshold can be set during manufacturing or during sensor calibration. Due to differences in gain curves, the algorithm can define different derivative peak thresholds for the first and second sensors. When the first derivative signal value and the second derivative signal value exceed the derivative peak threshold or their respective derivative peak thresholds, the algorithm detects a peak value in the derivative values ​​of the first signal and a peak value in the derivative values ​​of the second signal.

[0094] The algorithm determines the number of drug units applied when the following three criteria are met:

[0095] (a) The peak values ​​of the derivative values ​​of the first and second signals are detected simultaneously. The degree to which the detected peak values ​​in the two derivative signals must be reached simultaneously can be predefined in the algorithm. For example, it can be anticipated that the peak values ​​will not occur precisely simultaneously due to manufacturing tolerances in the dose counting system. The algorithm can therefore define a synchronization threshold, and if the peak values ​​of the derivative values ​​of the first and second signals appear within this threshold, they are considered simultaneous.

[0096] (b) The peak value of the derivative of the first signal has a different sign than the peak value of the derivative of the second signal. The two sensors are arranged such that their signals are out of phase. Therefore, when the signal from the second sensor increases, the signal from the first sensor should decrease, and vice versa, resulting in opposite signs for their respective derivative values; and

[0097] (c) The peak value in the derivative of the first signal has a different sign than the previous peak value in the derivative of the first signal. This standard helps ensure that the peak value in the derivative represents a mark passing in front of the sensor, rather than a button being pressed or released.

[0098] The algorithm then determines the dosage of the drug administered by the injection device by counting the number of drug units applied.

[0099] To further improve the robustness of the peak detection step, the algorithm can calculate a moving average or moving median of a series of values ​​for the first and second signals.

[0100] When using a moving average, it can comprise the average of a first set of sensor values ​​minus the average of a second set of sensor values, where the first and second sets contain the same number of values ​​and may overlap. In a simple example, a moving average of eight values ​​can be calculated, for example, Average = ..., mean(1 to 8), mean(2 to 9), mean(3 to 10), etc. The first and last seven samples from each sensor can be used without any averaging, or can be averaged using available information, for example, Average = 1, mean(1 to 2), mean(1 to 3), mean(1 to 4), ..., mean(1 to 7), mean(1 to 8), mean(2 to 9), mean(3 to 10), etc. Alternatively, the first seven values ​​can be ignored entirely. Since the sensor sampling rate is in the kHz range, this will result in a delay of less than 1 / 100th of a second, thus preventing missed doses. In another example, greater overlap is used in the averaging calculation. The average can be calculated as the average of sensor values ​​6 to 13 minus the average of sensor values ​​2 to 9. This average can be said to have an average of eight and a distance of four. Once the average value has been calculated as described above, the derivative of the average signal is calculated.

[0101] When using a moving median, it can comprise the median of a first set of sensor values ​​minus the median of a second set of sensor values, wherein the first and second sets contain the same number of values ​​and may overlap. For example, the average can be calculated as the median of peak values ​​6 to 12 minus the median of peak values ​​3 to 9. This average can be described as having an average of seven and a distance (or overlap) of three. Once the average has been calculated as described above, the derivative of the average signal is calculated.

[0102] The algorithm discussed above is unaffected by offset drift (amplitude modulation) and sensor amplitude variations because the original sensor data is averaged before applying the derivative.

[0103] As discussed earlier, the injection device includes an injection button configured to be pressed by a user to administer a dose of medication from the injection device. The algorithm is configured such that pressing and releasing the injection button is not incorrectly identified as administering a dose of medication. The algorithm achieves this by determining that the injection button has been pressed or released when the peaks in the first and second signals have the same sign, as can be seen in the second image of Figures 7 and 8.

[0104] The processor of the dose counting system can be configured to trigger further action in response to detecting that the injection button has been pressed or released. For example, in response to determining that the injection button has been pressed, the processor can use a (not shown) wireless transceiver unit of the injection device or module to initiate communication pairing with an external device. This communication pairing may be Bluetooth pairing.

[0105] Upon determining that the injection button has been released, the processor can initiate manual data synchronization. Typically, dose data is synchronized automatically at the end of each dosing event. This will also cause data synchronization if the algorithm detects button press and release without dose delivery.

[0106] As a further example, in response to determining that the injection button has been released, the processor can cause the output dose indication to end. This can take the form of an audible alarm or visual information display on the display of the injection device or module. The end of the dose indication can also indicate the time the user should hold the needle of the injection device in their skin after the injection device has reached zero units, prior to a dwell time countdown triggered by detecting button release.

[0107] As discussed earlier, a rotary encoder system may include an encoder ring having a plurality of substantially reflective markings arranged circumferentially. Each of these markings may have a concave or convex shape. This shape increases the signal gradient received by the first and second sensors, and thus increases the amplitude of the derivatives of these signals.

[0108] Although the above embodiments have been described with respect to data collection from insulin injection pens, it should be noted that embodiments of the present invention can be used for other purposes, such as monitoring the injection of other drugs.

[0109] The terms “drug” or “pharmaceutical” are used synonymously herein and describe pharmaceutical preparations comprising one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally pharmaceutically acceptable carriers. In the broadest sense, an active pharmaceutical ingredient (“API”) is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or pharmaceutical preparation is used to treat, cure, prevent, or diagnose a disease, or to otherwise enhance physical or mental health. Drugs or pharmaceutical preparations may be used for a limited duration or periodically for chronic disorders.

[0110] As described below, a drug or pharmaceutical preparation may include at least one API or combination thereof in various types of formulations for the treatment of one or more diseases. Examples of APIs may include small molecules (having a molecular weight of 500 Da or less); 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 may be incorporated into molecular delivery systems (such as vectors, plasmids, or liposomes). Mixtures of one or more drugs are also contemplated.

[0111] Drugs or pharmaceutical preparations may be contained in primary packaging or "drug containers" suitable for use with drug delivery devices. Drug containers may be, for example, cartridges, syringes, reservoirs, or other robust or flexible vessels configured to provide suitable chambers for storing (e.g., short-term or long-term storage) one or more drugs. For example, in some cases, the chambers may be designed to store the drug for at least one day (e.g., from 1 day to at least 30 days). In some cases, the chambers may be designed to store the drug for about one month to about two years. Storage may be carried out at room temperature (e.g., about 20°C) or at refrigerated temperatures (e.g., from about -4°C to about 4°C). In some cases, drug containers may be or may include dual-chamber cartridges configured to separately store two or more components of the drug formulation to be administered (e.g., API and diluent, or two different drugs), one component in each chamber. In this case, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components before and / or during administration to a human or animal. For example, the two chambers can be configured such that they are in fluid communication with each other (e.g., by means of a conduit between the two chambers) and allow the user to mix the two components before dispensing if needed. Alternatively or additionally, the two chambers can be configured to allow mixing during dispensing of the components into a human or animal body.

[0112] Drugs or agents contained in drug delivery devices as described herein can be used to treat and / or prevent many different types of medical disorders. Examples of disorders include, for example, diabetes or diabetes-related complications (such as diabetic retinopathy), and thromboembolic disorders (such as deep vein or pulmonary thromboembolism). Other examples of disorders include acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis. Examples of APIs and drugs are those described in the following manuals: such as the 2014 German Medical Doctor's Drug Handbook (RoteListe), for example, but not limited to main group 12 (antidiabetic drugs) or 86 (oncology drugs); and the 15th edition of the Merck Index.

[0113] Examples of APIs used to treat and / or prevent type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin (e.g., human insulin, or human insulin analogs or derivatives); glucagon-like peptide-1 (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 mixture thereof. As used herein, the terms “analyte” and “derivative” refer to a polypeptide having a molecular structure that is formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin) by deletion and / or exchange of at least one amino acid residue present in a naturally occurring peptide and / or by addition of at least one amino acid residue. The added and / or exchanged amino acid residues may be encoding amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogs are also referred to as “insulin receptor ligands”. Specifically, the term "derivative" refers to a polypeptide having a molecular structure that is formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin), wherein one or more organic substituents (e.g., fatty acids) are bound to one or more amino acids. Optionally, one or more amino acids present in a naturally occurring peptide may have been deleted and / or substituted with other amino acids (including non-coding amino acids), or amino acids (including non-coding amino acids) may have been added to a naturally occurring peptide.

[0114] Examples of insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (glargine insulin); Lys(B3), Glu(B29) human insulin (glutamate insulin); Lys(B28), Pro(B29) human insulin (lispro insulin); Asp(B28) human insulin (aspart insulin); human insulin wherein the proline at position B28 is replaced by Asp, Lys, Leu, Val, or Ala and wherein 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.

[0115] Examples of insulin derivatives are, for example, B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (detemir insulin, B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin, B29-N-ω-carboxypentadecanoyl-γ-L-glutamyl-des(B30) human insulin (degludec insulin) ); B29-N-(N-lithochyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0116] Examples of GLP-1, GLP-1 analogs, and GLP-1 receptor agonists include, for example, lixilatin. Exenatide (Exoctinopeptide-4, Liraglutide, a 39-amino acid peptide produced by the salivary glands of the Gila monster. Semaglutide, Taspoglutide, Albiglutide Dulaglutide rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langnatide / HM-11260C, CM-3, GLP-1Eligen, 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-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, exenatide-XTEN, and glucagon-Xten.

[0117] Examples of oligonucleotides include: imipenem sodium. It is a cholesterol-reducing antisense agent used to treat familial hypercholesterolemia.

[0118] Examples of DPP4 inhibitors include vidagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0119] Examples of hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, fertility-stimulating hormone), growth hormone (growth hormone), desmopressin, terlipressin, gosorelin, triptorelin, leuprorelin, buserorelin, nafarelin, and goserelin.

[0120] Examples of polysaccharides include glucosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or their derivatives, or sulfated polysaccharides (e.g., polysulfated forms of the above polysaccharides), and / or their pharmaceutically acceptable salts. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan GF 20. It is a type of sodium hyaluronate.

[0121] As used herein, the term "antibody" refers to an immunoglobulin molecule or its antigen-binding portion. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments that retain the ability to bind antigens. Antibodies can be polyclonal antibodies, monoclonal antibodies, recombinant antibodies, chimeric antibodies, deimmunized or humanized antibodies, fully human antibodies, non-human (e.g., murine) antibodies, or single-chain antibodies. In some embodiments, antibodies have effector function and can fix complement. In some embodiments, antibodies have reduced or no ability to bind Fc receptors. For example, antibodies can be isotypes or subtypes, antibody fragments, or mutants that do not support binding to Fc receptors, for example, they have a mutagenic or missing Fc receptor-binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or antibody-like binding proteins with bivariate cross-binding domain orientation (CODV).

[0122] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy chain and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not contain the full-length antibody polypeptide but still contains at least a portion of the full-length antibody polypeptide capable of binding an antigen. Antibody fragments may contain cleaved portions of the full-length antibody polypeptide, although the term is not limited to such cleaved fragments. Antibody fragments that can be used in this 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, tetraspecific, and multispecific antibodies (e.g., double-chain, triple-chain, and quadruple-chain antibodies)), monovalent or multivalent antibody fragments (such as bivalent, trivalent, quadruvalent, and multivalent antibodies), microantibodies, chelated recombinant antibodies, tri- or bispecific antibodies, intracellular antibodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camel-derived antibodies, and antibodies containing VHH. Further examples of antigen-binding antibody fragments are known in the art.

[0123] The term "complementarity-determining region" or "CDR" refers to a short polypeptide sequence within the variable region of both heavy and light chain polypeptides, primarily responsible for mediating specific antigen recognition. The term "frame region" refers to an amino acid sequence within the variable region of both heavy and light chain polypeptides that is not a CDR sequence, and is primarily responsible for maintaining the correct positioning of the CDR sequence to allow antigen binding. Although frame regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues within the frame regions of some antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0124] Examples of antibodies are anti-PCSK-9 mAbs (e.g., alirocumab), anti-IL-6 mAbs (e.g., sarilumab), and anti-IL-4 mAbs (e.g., dupilumab).

[0125] Pharmaceutically acceptable salts of any API described herein are also contemplated for use in drugs or pharmaceutical preparations in drug delivery devices. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

[0126] Those skilled in the art will understand that various modifications (additions and / or removals) can be made to the APIs, formulations, devices, methods, systems, and embodiments described herein without departing from the full scope and spirit of the invention, which covers such variations and any and all equivalents.

Claims

1. A dose counting system (700) for use with an injection device (1) or a module thereof, the dose counting system comprising: A sensor arrangement (215) includes a first sensor (215a) configured to output a first signal and a second sensor (215b) configured to output a second signal, wherein the first sensor (215a) and the second sensor (215b) have an angular offset relative to each other, and wherein the sensor arrangement (215) is configured to detect movement of a rotary encoder system (500, 900) relative to the sensor arrangement (215) during drug administration; as well as Processor (23), which is configured as follows: Calculate the numerical derivatives of the first signal and the second signal; When the values ​​of the first derivative signal and the second derivative signal exceed a predefined threshold, the peak value in the derivative value of the first signal and the peak value in the derivative value of the second signal are detected. The number of drug units administered is determined when the peak value of the derivative of the first signal is synchronized with the peak value of the derivative of the second signal, wherein the peak values ​​of the derivative of the first signal and the derivative of the second signal have different signs, and the peak value of the derivative of the first signal has a different sign relative to the preceding peak value in the derivative of the first signal; and The dosage of the drug administered by the injection device is determined by counting the units of the drug applied.

2. The dose counting system (700) according to claim 1, wherein the processor (23) is further configured to calculate a moving average of a series of values ​​of the first signal and the second signal.

3. The dose counting system (700) according to claim 2, wherein the moving average includes the mean of a first set of values ​​minus the mean of a second set of values ​​from the same sensor, wherein the first set and the second set contain the same number of values.

4. The dose counting system (700) according to claim 3, wherein the first group and the second group overlap.

5. The dose counting system (700) according to claim 2, wherein the processor (23) is further configured to calculate the moving median of a series of values ​​of the first signal and the second signal.

6. The dose counting system (700) of claim 5, wherein the moving median comprises the median of a first set of values ​​minus the median of a second set of values, wherein the first set and the second set contain the same number of values.

7. The dose counting system (700) according to any of the preceding claims, wherein the injection device (1) includes an injection button (12) configured to be pressed to administer a dose of medicine from the injection device.

8. The dose counting system (700) according to claim 7, wherein the processor (23) is further configured to determine that the injection button (12) has been pressed or released when the peak values ​​in the first signal and the second signal have the same sign.

9. The dose counting system (700) according to claim 8, wherein the processor (23) is further configured to initiate communication pairing with an external device or perform data synchronization with the external device in response to determining that the injection button (12) has been pressed.

10. The dose counting system (700) according to claim 9, wherein the communication pairing is Bluetooth pairing.

11. The dose counting system (700) according to any one of claims 7 to 10, wherein the processor (23) is further configured to initiate manual data synchronization in response to determining that the injection button (12) has been released.

12. The dose counting system (700) according to any one of claims 7 to 11, wherein the processor (23) is further configured to cause the end of the output dose indication in response to determining that the injection button (12) has been released.

13. The dose counting system (700) according to any of the preceding claims, wherein the rotary encoder system (500, 900) includes an encoder ring (70, 400, 1006) including a plurality of substantially reflective marks (70a) arranged circumferentially around the encoder ring periodically according to a predefined angle.

14. A method of operating an injection device (1) or being configured to be used with or applied to a module of an injection device, the dose counting system comprising: A sensor arrangement (215) includes a first sensor (215a) configured to output a first signal and a second sensor (215b) configured to output a second signal, wherein the first sensor (215a) and the second sensor (215b) have an angular offset relative to each other, and wherein the sensor arrangement (215) is configured to detect movement of a rotary encoder system (500, 900) relative to the sensor arrangement during drug administration; as well as Processor (23); The method includes: Calculate the numerical derivatives of the first signal and the second signal; When the values ​​of the first derivative signal and the second derivative signal exceed a predefined threshold, the peak value in the derivative value of the first signal and the peak value in the derivative value of the second signal are detected. The number of drug units that have been administered is determined when the peak value in the derivative of the first signal is synchronized with the peak value in the derivative of the second signal. The peak value in the derivative of the first signal and the peak value in the derivative of the second signal have different signs, and the peak value in the derivative of the first signal has a different sign relative to the previous peak value in the derivative of the first signal. The dosage of the drug administered by the injection device is determined by counting the units of the drug applied.

15. A method of operating an injection device (1) or a dose counting system (700) configured for use with or applied to a module of an injection device according to claim 14, wherein the method further comprises calculating a moving average of a series of values ​​of the first signal and the second signal.

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