MEASURING SYSTEM FOR A DRUG DELIVERY DEVICE, A DRUG DELIVERY DEVICE HAVING SUCH A MEASURING SYSTEM, AND METHOD FOR MEASURING THE EXHALED DOSE AND / OR THE SETTED DOSE OF A DRUG DELIVERY DEVICE - Patent application

Abstract

A measuring system for a drug delivery device, a drug delivery device comprising such a measuring system and a method for measuring an expelled dose and / or a set dose of a drug delivery device.Proposed is a measuring system for a drug delivery device, a drug delivery device comprising such a system and related methods, the measuring system comprising: - a dose control member configured to move, e.g. relative to a housing of the drug delivery device, according to a dose expelling operation and / or a dose setting operation, - a sensor unit configured to intermittently observe the position of the dose control member and to generate signals corresponding to one of at least four different data values ​​depending on the position and / or orientation of the dose control member, respectively, and - an electronic processing unit configured to receive the signals of the sensor unit, to adapt a dose-related count depending on the received signals, and to determine whether two consecutive ones of the received signals correspond to adjacent data values ​​in a predetermined repeating sequence of different data values.

Description

[Background technology]

[0001] Drug delivery devices, particularly needle-based and / or pen injection devices, are known to have mechanisms for metering the amount of drug or medication dispensed from the device.

[0002] WO 2019 / 101962 A1 relates to a medication infusion device having a rotary encoder. Summary of the Invention [Problem to be solved by the invention]

[0003] It is an object of the present disclosure to provide an improved measurement system, for example a measurement system with increased reliability and / or accuracy of measurements, in particular of the size of an expelled dose during an expelling operation of a drug delivery device. [Means for solving the problem]

[0004] This object is achieved by the subject matter of the independent claims. Advantageous embodiments and refinements are the subject matter of the dependent claims.

[0005] In the present disclosure, a measurement system (electronic measurement system) for a drug delivery device is proposed, comprising a dose control member configured to move, for example, relative to a housing of the drug delivery device according to a dose expulsion operation and / or a dose setting operation. The measurement system further comprises a sensor unit configured to intermittently observe the position of the dose control member relative to the housing and to generate signals depending on the position and / or orientation of the dose control member, each corresponding to one of at least four different data values, the measurement system further comprises an electronic processing unit configured to receive the signals of the sensor unit, to adapt a dose-related count depending on the received signals, and to determine whether two consecutive of the received signals correspond to adjacent data values ​​in a predefined repeating sequence of different data values.

[0006] In this specification, the dose control member "moves according to a dose ejection operation" may mean that the amount of movement of the dose control member, e.g. the length of linear movement and / or the angle of rotation, is proportional to the amount of drug ejected during the drug ejection operation. The drug delivery device may include a drive unit including a converter unit. The drive unit may include, e.g. an energy storage unit for driving the ejection operation, or may be user-driven or manually driven. The converter unit may be configured to convert energy provided by the user and / or from the energy storage unit into pressure acting on the drug and / or drug container in the drug delivery device to force the drug out of the drug delivery device (eject the drug). The converter unit may include a plunger acting on a syringe. Alternatively, the converter unit may include, e.g. a squeezer acting on a drug tube or bag. The dose control member may be an integral part of the drive unit, e.g. essential for the functioning of the dose ejection operation. Alternatively, the dose control member may be, e.g. mechanically and / or magnetically coupled to at least one moving part of the drive unit, at least during the dose ejection operation.

[0007] In this specification, the dose control member "moves according to a dose setting operation" may mean that the amount of movement of the dose control member, e.g. the length of linear movement and / or the angle of rotation, is proportional to the size of the dose setting. The drug delivery device may include a dose dial unit for selecting an amount of drug in a dose setting operation. The drive unit may be configured to expel the amount of drug selected in a dose setting operation in a dose expelling operation. The dose control member may be an integral part of the dose dial unit, e.g. essential for the function of the dose setting operation. Alternatively, the dose dial member may be coupled, e.g. mechanically and / or magnetically, to at least one movable part of the drive unit, at least during the dose expelling operation.

[0008] In some embodiments, the measurement system may include a single dose control member and a single sensor unit for observing the dose control member in order to observe the movement of the dose control member either during the dose setting operation or during the dose expelling operation. Alternatively, the same dose control member may be coupled to the dial unit, e.g. via a clutch mechanism, at least during the dose setting operation, and coupled to the drive unit, e.g. via a clutch mechanism, at least during the dose expelling operation. As a further alternative, the measurement system may include two dose control members, one moving according to the dose setting operation and one moving according to the dose expelling operation. If both operations are observed, the difference between the set dose and the expelled dose may be detected.

[0009] The "position" of the dose control member may refer to the angular position and / or location of the dose control member. The drug delivery device may include a housing relative to which the position of the dose control member is observed. The housing may include a drug container or may be configured to hold a drug container in a predetermined position relative to the housing. Thus, a position "relative to the housing" may refer to a position relative to a drug container when such a container is in a predetermined position (mounted) in the drug delivery device.

[0010] A component of a device that is "configured" to perform a particular task may refer to a component that performs that task in at least one operational state of the device. The component may be specially formed, programmed, and / or arranged to enable performance of the task.

[0011] In this specification, the sensor unit observing "intermittently" may mean that the sensor unit does not observe continuously, for example to reduce power consumption. The sensor unit may be configured to only activate at certain times. The sensor unit may be configured to switch between a first state in which it does not observe at all and a second state in which the sensor unit observes at predefined intervals, for example at regular intervals. The sensor unit may be configured to observe at a certain sample rate, for example at least in the second state. The electronic processing unit may be configured to activate and / or deactivate the sensor unit at certain times. The electronic processing unit may be configured to set a certain sample rate at which the sensor unit observes. In this specification, an inactive (non-active) sensor unit may mean that at least one essential component of the sensor unit, for example the amplifier circuit and / or the probe circuit, is not powered and / or that the evaluation circuit of the sensor unit or the electronic processing unit is deactivated or ignores (does not evaluate) the signal from the sensor element.

[0012] The sensor unit may include at least one sensor element configured to observe a particular physical property of the observed element (the dose control member), such as reflectance, magnetization, electric polarization (e.g., ferroelectricity), distance, color, conductivity, or a combination of physical properties. The sensor element may be an electronic sensor element. The sensor element may be configured to change at least one electrical property, such as current, electrical resistance, and / or voltage, depending on the value of the observed physical property. The sensor element may be a digital sensor or an analog sensor. A digital sensor may have two states that can be distinguished (i.e., binary 1 and binary 0, or white and black, or any other combination of two states). The sensor element may be an accelerometer, a light sensor, an acoustic sensor, a pressure sensor, a temperature sensor, a proximity sensor, an infrared sensor, an ultrasonic sensor, a color sensor, a humidity sensor, a tilt sensor, a flow sensor, a magnetic / Hall effect sensor, a radiation sensor, a lidar sensor, a current sensor, an optical sensor, a force / torque sensor, a strain gauge, a mechanical switch, etc.

[0013] The generated signal may be a digital or analog signal. The signal of the sensor unit may include the readings (signal values) of one or more sensor elements of the sensor unit. A signal "corresponding" to a data value may mean that a range of possible signal values ​​is associated with that data value, for example to accommodate deviations in the measurement process due to measurement errors and / or manufacturing inaccuracies. The signals may be uniquely identifiable in order to associate them with a particular data value. The readings of a single sensor element may be associated with 0 if the signal value is below a certain value and with 1 if it is above, or vice versa. Alternatively, the possible readings of a single sensor element may be divided into more than two ranges, for example 3, 4, 5, 6, 7, 8, 9, 10 or more ranges. Different ranges of signal values ​​may be associated with different data values. The range associated with a particular data value may be static, i.e., predetermined or preprogrammed, or may be dynamic, e.g., dependent on one or more prior measurements, e.g., to accommodate degradation of the sensor unit and / or the energy source powering the sensor unit. A particular or minimum amount of movement by the dose control member may be required for the sensor unit to generate signals corresponding to different data values. The sensor unit and dose control member may be configured such that the data values ​​corresponding to the signals generated by the sensor unit change at intervals of equidistant movement (position change) of the dose control member.

[0014] The electronic processing unit may include a processor unit configured to execute a specific machine-readable code and / or an application specific integrated circuit (ASIC). The electronic processing unit may include a memory unit for storing at least the dose-related count. The electronic processing unit may further include a clock unit, for example a real-time clock. The electronic processing unit may be electrically connected to the sensor unit. The electronic processing unit may be configured to associate a signal value of the signal received from the sensor unit with a corresponding data value. Alternatively, the sensor unit may be configured to directly provide a corresponding data value instead of the signal value of the received signal. The sensor unit and the electronic processing unit may share a common integrated circuit (IC). The sensor unit may be configured to directly store a data value corresponding to the observed signal in the memory of the electronic processing unit. The electronic processing unit may be configured to go into a sleep state upon receiving a signal from the sensor unit and may be configured to evaluate the received signal after waking up from the sleep state. The electronic processing unit may be configured to store at least the latest data value in the memory unit. The electronic processing unit may be configured to compare a first data value evaluated after waking up from the sleep state with a last data value evaluated before entering the sleep state. The electronic processing unit may be configured to compare a first data value generated in a current dose setting operation and / or dose expulsion operation with a last data value generated in a immediately preceding dose setting operation and / or dose expulsion operation.

[0015] The electronic processing unit may be configured to ignore pairs of consecutive signals if the corresponding data values ​​are the same.

[0016] The electronic processing unit may be configured to increase and / or decrease the dose-related count in response to the received signal. The dose-related count may be a data value representative of the amount of drug dispensed during a current dose-dispensing operation, the total amount of drug dispensed from a currently attached drug container, or the total amount of drug dispensed during the life of the drug delivery device and / or measurement system. The electronic processing unit may be configured to adapt more than one dose count in response to the received signal. Alternatively, the dose-related count may be a data value representative of the amount of drug selected in a dose setting operation that the user intends to dispense in the next dose-dispensing operation. As a further alternative, the dose-related count may represent the amount of drug remaining in the drug container.

[0017] A "repeating sequence" of data values ​​may be a sequence that is repeated after a certain number of elements N, such that the Mth element of the sequence is identical to the (MN)th element of the sequence. The certain number of elements N may be identical to the number of distinct data values. The repeating sequence may include each of the distinct data values ​​at least once, e.g., exactly once. Two data values ​​are "adjacent" in a repeating sequence if one of the two data values ​​is equal to the nth data value of the repeating sequence and the other of the two data values ​​is equal to the nth+1 data value. A repeating sequence may consist of a basic sequence that is repeated multiple times, e.g., at least 4 times, e.g., at least 10 times, e.g., at least 20 times, e.g., indefinitely.

[0018] The dose control member and the sensor unit may be configured such that the sensor unit continuously observes the dose control member, e.g. at a very high sample rate, and when the dose control member moves in one direction to increase the delivered or set dose, or in a direction associated with an increase in the delivered or set dose, a predetermined repeating sequence is generated, e.g. in the electronic processing unit. Herein, consecutive signals corresponding to the same data value may be considered as the same signal and / or may be ignored.

[0019] According to a further embodiment, the electronic processing unit may be configured to determine the direction of movement of the dose control member based on the two consecutive signals and the predetermined repeating sequence, if at least two consecutive signals are associated. The two consecutive signals may include a leading signal and a trailing signal. The trailing signal may be generated after the leading signal. The leading signal may correspond to a first data value (one of the different data values). The trailing signal may correspond to a second data value (one of the different data values). The electronic processing unit may be configured to associate the two signals with a direction of increasing the set dose or the delivered dose (forward direction) if the second data value immediately follows the first data value in the repeating sequence. The electronic processing unit may be configured to increase the dose-related count, for example by one, if the two signals correspond to adjacent signals and the forward direction is determined. The electronic processing unit may be configured to associate the two signals with a direction of decreasing the set dose or the delivered dose (reverse direction) if the first data value immediately follows the second data value in the repeating sequence. The electronic processing unit may be configured to decrease the dose-related count, for example by 1, if the two signals correspond to adjacent signals and an opposite direction is determined. According to further embodiments, the repeating sequence may be reversed such that the association with the direction is also reversed. For example, improved accuracy of dose measurement may be achieved since the device can detect a reverse rotation and therefore respond accordingly to a change in the dose count.

[0020] In other embodiments, the electronic processing unit may be configured to increase the sample rate of the sensor unit if two successive signals do not correspond to adjacent ones in the repeating sequence of different signals. In the first operating mode, a low sample rate may be selected to only detect whether the movement of the dose control member has started. The electronic processing unit may be configured to switch the sensor unit to a high sample rate in the second operating mode if it is determined that the dose control member is moving. The high sample rate may be associated with a sample rate at which the sensor unit may obtain corresponding data signals that reproduce the repeating sequence for at least any movement rate (speed and / or rotation speed) that is below the expected and / or typical maximum movement rate. In a preferred embodiment, the low sample rate may be associated with a sample rate at which the sensor unit may obtain corresponding data signals that reproduce at least every second of the repeating sequence for at least any movement rate (speed and / or rotation speed) that is below the expected and / or typical maximum movement rate. Thus, the electronic processing unit may be configured to increase the sample rate as soon as the movement of the dose control member has started. Alternatively or additionally, the electronic processing unit may be configured to set the sensor unit to a higher sample rate in the third operating mode. The higher sample rate may be associated with a sample rate at which the sensor unit may obtain corresponding data signals reproducing the repeating sequence for at least any movement rate (speed and / or rotation rate) below the extended movement rate. The extended movement rate may be at least as large as the expected and / or typical maximum movement rate, such as at least 1.3 times, such as at least 1.5 times, such as at least 2 times. This may improve the accuracy of dose detection, in particular because the system may prevent ambiguous situations where the accelerating movement does not allow the system to distinguish between a single transition and a transition of the full length of the repeating sequence plus one transition.

[0021] The subsequence of the repeating sequence may span from the first (initial first) occurrence of the second data value in the repeating sequence to the second (initial second) occurrence of the second data value in the repeating sequence.

[0022] According to another embodiment, if two consecutive signals are not adjacent in the repeating sequence, the electronic processing unit may be configured to increase the dose-related count in relation to (e.g. proportionally) the first distance from the first data value to the second occurrence of the second data value along the partial sequence if the second distance from the first occurrence of the second data value to the first data value along the partial sequence is greater than a certain value, e.g. greater than 1. The electronic processing unit may be configured to increase the dose-related count in relation to the first distance from the first data value to the second data value along the repeating sequence if the second distance from the first data value to the second data value along the reversed repeating sequence is greater than a certain value, e.g. greater than 1. The electronic processing unit may be configured to increase the dose-related count in relation to the first distance if the second distance is not greater than the first distance. The electronic processing unit may be configured to increase the dose-related count by the first distance. Assuming that movement of the dose control member in the dose-increasing direction is more likely than movement in the reverse direction, a reduction in error conditions may be achieved and dose measurement accuracy may be improved. The "distance" along a sequence may be the count of value changes (transitions) along the sequence. The distance may be the difference in the indexes of the sequences. The distance from the Nth element of a sequence to the (N+m)th element of a sequence may be m.

[0023] In other words, the electronic processing unit may be configured to determine (calculate) a first distance between a first data value and a second data value in a forward direction along the repeat sequence, and to determine (calculate) a second distance from the first data value to the second data value in a reverse direction along the repeat sequence. The electronic processing unit may be configured to increase the dose-related count in relation to (e.g. proportional to) the first distance if the second distance is greater than a certain value, e.g. greater than 1. The processing unit may be configured to assume a minimum distance from a first signal of two consecutive signals along the repeat sequence to a second signal of two consecutive signals, and assume that the most likely direction of rotation of the dose control member is the direction that increases the delivered dose, and to increase the dose-related count in relation to (e.g. proportional to) the implied number of missed data values ​​of the repeat sequence. By such measures, a reduction in dose measurement errors may be achieved and dose measurement accuracy may be improved.

[0024] Movement of the dose control member relative to the housing in a direction opposite to that required to increase the delivered or set dose may at least be prevented. The drive mechanism of the drug delivery device may comprise at least one blocking member, e.g. a ratchet, that allows only movements that lead to an increase in the ejected drug. The blocking member may provide a certain amount of margin for movements against the dose increase direction, exceeding which margin is only possible by using an excessive amount of force and / or leading to a (partial) destruction of the drug delivery device. This allows the electronic processing unit to associate a certain change in the detection position (change in the data value corresponding to the received signal of the sensor unit) with a movement in the forward direction.

[0025] Furthermore, the dose control member may be configured to rotate, for example, in relation to and / or in proportion to the dose setting and / or the delivered dose, and the sensor unit configured to generate signals corresponding to different data values ​​depending on the angular position of the dose control member. The sensor unit, e.g. at least a sensor element of the sensor unit, may be immovably arranged with respect to and / or on the housing. Alternatively, the sensor unit, e.g. at least a sensor element of the sensor unit, may be immovably arranged on or with respect to the dose control member, thereby allowing easy integration into existing designs. Alternatively, the dose control member may be configured and / or arranged to move linearly or helically.

[0026] The given repeating sequence may be associated with a Gray code sequence, for example a 2-bit Gray code sequence. A "Gray code sequence" may be a sequence of binary codes of a particular length, where successive elements of the sequence differ by only one bit of the binary code. A Gray code sequence may include all possible combinations of binary bits of a given binary code length. A 2-bit Gray code sequence may consist of the sequence [00;01;11;10]. Alternatively, the repeating sequence may be associated with a 3-bit Gray code sequence. Exemplarily, a 3-bit Gray code sequence may consist of the sequence [000;001;011;111;110;100] or the sequence [000;001;011;010;110;111;101;100]. Similarly, the repeating sequence may be associated with a Gray code of a higher bit length, which allows for error detection and correction.

[0027] According to further embodiments, for example when the sensor unit is fixed (immovably) relative to the housing, the dose control member comprises a series of sensing regions, where adjacent sensing regions have different physical properties. According to alternative embodiments, for example when the sensor unit is fixed relative to the dose control member, the series of sensing regions may be arranged on the housing or on an element fixed relative to the housing. In this specification, "having different physical properties" may mean that the sensing regions differ in the value of at least one physical property observed by at least one sensor element of the sensor unit. The value of the physical property of the sensing region and / or the sensor response (e.g. sensor voltage or sensor current) generated by each sensor element of the sensor unit when observing each sensing region may differ here by at least 10%, such as at least 11%, for example at least 100% between any two adjacent regions. Compared to a sensing region with a physical property that varies continuously along its surface, this does not require high resolution for sensor sensitivity. The set of sensing regions may consist of at least 2, such as at least 4, such as at least 6, such as at least 8, such as at least 10, such as at least 12 sensing regions.

[0028] The sensor unit may include at least two sensor elements observing the dose control member. The two sensor elements may be of the same type, for example configured to observe (measure) the same physical property. Alternatively, the sensor elements may be configured to observe different physical properties, for example of the same sensing area. The sensor areas may have the same physical property, for example having values ​​that differ by less than 10%, for example by less than 5%. The sensing areas, for example at least the sensing areas having the same physical property, may have the same size or different sizes. In this specification, the "size" of a sensing area may refer to the extension of the sensing area, for example according to a direction of movement relative to the sensor unit. At least two of the sensor elements may be arranged to observe different sensing areas simultaneously. Two of the sensor elements may be arranged to observe different sensing areas at least at some times and the same sensing area at least at different times. At least two of the sensor elements, for example two identical sensor elements, may be configured to observe the same sensing area at different times. The sensor elements may be configured to observe the dose control member synchronously. The sensor elements may sample simultaneously and may have the same sample rate. The sensor elements may be arranged to observe the dose control member out of phase. According to an alternative embodiment, the two sensor elements may be configured to never observe the same sensing area. The sensing areas may form a first series of sensing areas observed by the first sensor element and a second series of sensing areas observed by the second sensor element. The second series of sensing elements may be larger than the first series of sensing elements, for example twice as large.

[0029] A full rotation (360°) of the dose control member may correspond to a multiple of the basic sequence of the repeating sequence, for example 1, 2, 3, 4, 5, 6, 7 or 8 repetitions of the basic sequence, although other configurations are possible.

[0030] According to another embodiment, the dose control member comprises a ring-shaped portion, the sensing regions being arranged along its periphery. At least two of the sensor elements, e.g. any two of (a subset of) the sensor elements, may be arranged such that when one of the sensor elements is oriented towards the transition between the two sensing regions, the other sensor element is not oriented towards the transition between the two sensing regions, e.g. oriented towards the center of another sensing region. This allows easy implementation of repeat sequences.

[0031] Further proposed is a drug delivery device comprising a measurement system according to any one of the preceding claims or configured to be coupled, e.g. removably coupled, with such a measurement system. The housing of the drug delivery device may comprise an electronic and / or mechanical interface. The measurement system may comprise a separate housing comprising an electronic and / or mechanical interface configured to connect with the interface of the housing. The interface may comprise means for releasably locking the measurement system to the drug delivery device. The drug delivery device may be an injection device. The drug delivery device may be a needle-based injection device. The drug delivery device may be a pen-type device. The pen-type device comprises a form similar to a pen, e.g. a fountain pen, thereby allowing easy handling of the medical device by the user, e.g. for self-administration. The drug delivery device may be a handheld device.

[0032] The drug delivery device may include at least one reservoir filled with a medicament, or a receptacle for receiving such a reservoir. The reservoir may contain sufficient amounts of the medicament for multiple doses to be expelled by the device.

[0033] If the measurement system is integrated into the device, and if the device is a drug delivery device, the device can preferably be used with multiple containers. In other words, the device may be a reusable device. Of course, the measurement system can also be used with reusable medical devices as an add-on module. The user may simply need to replace the empty container in the receptacle with a new container and reconnect the receptacle to the drive mechanism of the device.

[0034] The drug delivery device may be a variable dose device in which the size of the dose to be delivered can be set within ranges defined by a mechanism of the device.

[0035] As used herein, the terms "drug" or "medicament" are used interchangeably to refer to a pharmaceutical formulation containing one or more active pharmaceutical ingredients or pharma- ceutically acceptable salts or solvates thereof and, optionally, a pharma- ceutically acceptable carrier. An active pharmaceutical ingredient ("API"), in its broadest sense, is a chemical structure that has a biological effect on humans or animals. In pharmacology, drugs or agents are used to treat, cure, prevent, or diagnose disease, or to otherwise enhance physical or mental comfort. Drugs or agents may be used for a limited period of time, or periodically for chronic conditions.

[0036] As described below, a drug or agent may include at least one API, or a combination thereof, in various types of formulations for the treatment of one or more diseases. Examples of APIs may include small molecules with 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 DNA 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.

[0037] The drug or agent may be contained in a primary package or "drug container" adapted for use with the drug delivery device. The drug container may be, for example, a cartridge, a syringe, a reservoir, or other sturdy or flexible vessel configured to provide a suitable chamber for storage (e.g., short-term or long-term storage) of one or more drugs. For example, in some examples, the chamber may be designed to store the drug for at least one day (e.g., from one day to at least 11 days). In some examples, the chamber may be designed to store the drug for about one month to about two years. Storage may be at room temperature (e.g., about 20°C) or at refrigerated temperatures (e.g., about -4°C to about 4°C). In some examples, the drug container may be or include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation to be administered (e.g., an API and a diluent or two different drugs), one in each chamber. In such examples, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components before and / or during ejection into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with one another (e.g., via a conduit between the two chambers) to allow mixing of the two components when desired by a user prior to ejection. Alternatively or additionally, the two chambers may be configured to allow mixing of the components as they are ejected into the human or animal body.

[0038] The drugs or agents contained in the drug delivery devices described herein may be used for the treatment and / or prevention of many different types of medical diseases. Examples of diseases include, for example, diabetes or complications related to diabetes, such as diabetic retinopathy, thromboembolism, such as deep vein thromboembolism or pulmonary thromboembolism. Further examples of diseases are 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, but are not limited to, those as described in handbooks such as the Rote Liste 2014, for example, in major groups 12 (antidiabetic drugs) or 86 (oncology drugs), and the Merck Index 15th Edition.

[0039] Examples of APIs for the treatment and / or prevention of type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin, e.g., human insulin, or a human insulin analog or derivative, glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist or an analog or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharma- ceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the terms "analog" and "derivative" refer to a polypeptide having a molecular structure that can be formally derived from the structure of a naturally occurring peptide, e.g., the structure of human insulin, by deleting and / or substituting at least one amino acid residue that occurs naturally in the naturally occurring peptide and / or by adding at least one amino acid residue. The added and / or substituted amino acid residue can be either an encoded amino acid residue or another naturally occurring residue or a purely synthetic amino acid residue. Insulin analogs are also referred to as "insulin receptor ligands". In particular, the term "derivative" refers to a polypeptide having a molecular structure that can be formally derived from the structure of a naturally occurring peptide, e.g., the structure of human insulin, in which one or more organic substituents (e.g., fatty acids) are attached to one or more of the amino acids. Optionally, one or more of the amino acids occurring in the naturally occurring peptide can be deleted and / or replaced with other amino acids, including non-coded amino acids, or amino acids, including non-coded amino acids, can be added to the naturally occurring peptide.

[0040] Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulin glulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28) human insulin (insulin aspart); human insulin in which the proline in position B28 can be replaced by Asp, Lys, Leu, Val or Ala and the Lys in position B29 can be replaced by Pro; Ala(B26) human insulin; Des(B28-B11) human insulin; Des(B27) human insulin and Des(B11) human insulin.

[0041] Examples of insulin derivatives are e.g. B29-N-myristoyl-des(B11) human insulin, Lys(B29)(N-tetradecanoyl)-des(B11) human insulin (insulin detemir, Levemir®); B29-N-palmitoyl-des(B11) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B11-N-myristoyl-ThrB29LysB11 human insulin; B11-N-palmitoyl-ThrB29LysB11 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B11) human insulin, B29-N-ω-carboxypentadecanoyl-γ-L-glutamyl-des(B11) human insulin (insulin deglu, Tresiba®); B29-N-(N-lithocholyl-γ-glutamyl)-des(B11) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B11) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0042] Examples of GLP-1, GLP-1 analogs, and GLP-1 receptor agonists include, for example, lixisenatide (Lyxumia®), exenatide (Exendin-4, Byetta®, Bydureon®, a 39 amino acid peptide produced by the salivary glands of the Gila monster), liraglutide (Victoza®), semaglutide, taspoglutide, albiglutide (Syncria®), dulaglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (Efpeglenatide), HM-15211, CM-3, GLP-1 Eligen. , ORMD-0901, NN-9423, NN-9709, NN-9924, NN-9926, NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-1191, MAR-701, MAR709, ZP-2929, ZP-1122, ZP-DI -70, TT-401 (Pegapamodtide), BHM-034, MOD-6011, CAM-2036, DA-15864, ARI-2651, ARI-2255, Tirzepatide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN and Glucagon-Xten.

[0043] Examples of oligonucleotides are, for example, mipomersen sodium (Kynamro®), a cholesterol-lowering antisense therapeutic for the treatment of familial hypercholesterolemia, or RG012 for the treatment of Alport Syndrome.

[0044] Examples of DPP4 inhibitors are linagliptin, vildagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0045] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, choriogonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0046] Examples of polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or very low molecular weight heparin or derivatives thereof, or sulfated polysaccharides, such as the 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 sodium hyaluronate Hylan G-F20 (Synvisc®).

[0047] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of an immunoglobulin molecule include F(ab) and F(ab')2 fragments that retain the ability to bind antigen. An 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 antibody (e.g., a murine antibody), or a single chain antibody. In some embodiments, an antibody has effector functions and can fix complement. In some embodiments, an antibody has reduced or no ability to bind to Fc receptors. For example, an antibody can be an isotype or subtype, an antibody fragment or a variant that does not support binding to Fc receptors, e.g., has a mutated or deleted Fc receptor binding region. The term antibody also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable region antibody-like binding proteins with cross-linking domain orientation (CODV).

[0048] The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and / or light chain polypeptide) that does not include the full-length antibody polypeptide, but still includes at least a portion of the full-length antibody polypeptide that can bind to an antigen. An antibody fragment can include a truncated portion of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments useful 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, tetraspecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), monovalent or multivalent antibody fragments, such as bivalent, trivalent, tetravalent and multivalent antibodies, minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are well known in the art.

[0049] 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 but are primarily responsible for maintaining the proper arrangement of the CDR sequences to allow antigen binding. Although the framework region itself is usually not directly involved in antigen binding, as is well known in the art, certain residues within the framework region of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids within the CDRs to interact with the antigen.

[0050] Examples of antibodies are anti-PCSK-9 mAb (e.g., alirocumab), anti-IL-6 mAb (e.g., sarilumab), and anti-IL-4 mAb (e.g., dupilumab).

[0051] Pharmaceutically acceptable salts of any of the APIs described herein are contemplated for use with the drug or medicament in the drug delivery device. Pharmaceutically acceptable salts include, for example, acid addition salts and base salts.

[0052] Those skilled in the art will appreciate that modifications (addition and / or removal) of the various components of the APIs, formulations, devices, methods, systems, and embodiments described herein may be made without departing from the full scope and spirit of the invention, which encompasses such modifications and all equivalents thereof.

[0053] An exemplary drug delivery device may include a needle-based injection system as described in Table 1 of Section 5.2 of ISO11608-1:2014(E). As described in ISO11608-1:2014(E), needle-based injection systems can be broadly divided into multi-dose container systems and single-dose (with partial or complete evacuation) container systems. The container may be a replaceable container or a one-piece non-replaceable container.

[0054] As further described in ISO11608-1:2014(E), a multi-dose container system may include a needle-based injection device with a replaceable container. In such a system, each container holds multiple doses and the size may be fixed or variable (pre-set by the user). Another multi-dose container system may include a needle-based injection device with a unitary non-replaceable container. In such a system, each container holds multiple doses and the size may be fixed or variable (pre-set by the user).

[0055] As further described in ISO11608-1:2014(E), the single dose container system may include a needle-based injection device with a replaceable container. In one example of such a system, each container holds one dose and the entire deliverable volume is expelled (full expelled). In a further example, each container holds one dose and a portion of the deliverable volume is expelled (partial expelled). Also, as described in ISO11608-1:2014(E), the single dose container system may include a needle-based injection device with a one-piece non-replaceable container. In one example of such a system, each container holds one dose and the entire deliverable volume is expelled (full expelled). In a further example, each container holds one dose and a portion of the deliverable volume is expelled (partial expelled).

[0056] In this specification, "distal" is used to designate a direction, end, or surface that is or will be arranged to face or face toward the discharge end of the drug delivery device or a component thereof and / or faces away from the proximal end. On the other hand, "proximal" is used to designate a direction, end, or surface that is or will be arranged to face away from the discharge end and / or the distal end of the drug delivery device or a component thereof. The distal end may be the end closest to the discharge end and / or furthest from the proximal end, and the proximal end may be the end furthest from the discharge end. The proximal surface may face away from the distal end and / or towards the proximal end. The distal surface may face towards the distal end and / or away from the proximal end. The discharge end may be, for example, the needle end where the needle unit is present or will be attached to the device.

[0057] Further, a method for measuring an ejected dose and / or a set dose of a drug delivery device is proposed, comprising: intermittently observing a position and / or orientation of a dose control member moving according to a dose ejection operation and / or a dose setting operation; generating signals corresponding to one of at least four different data values, respectively, in response to the position and / or orientation of the dose control member; adapting a dose-related count in response to the generated signals; and determining whether consecutive two of the generated signals correspond to adjacent data values ​​in a predetermined repeating sequence of different data values.

[0058] Adapting the dose-related count may include determining the direction of movement of the dose control member. Adapting the dose-related count may include increasing the dose-related count if movement of the dose control member in a dose-increasing direction (forward direction) is determined. Adapting the dose-related count may include decreasing the dose-related count if movement of the dose control member in a dose-decreasing direction (reverse direction) is determined. If two consecutive signals are not adjacent in the repeating sequence, the dose-related count may be increased in relation to the distance from a first data value corresponding to a first signal of the generated signal along the partial sequence to a later occurrence of a second data value corresponding to a second signal of the generated signal, if the distance from a previous occurrence of the second data value along the partial sequence to the first data value is greater than a certain value, e.g., greater than 1. In other words, the dose-related count may be increased in relation to the implied number of missed data values ​​of the repeating sequence, assuming a minimum distance from a first signal of two consecutive signals along the repeating sequence to a second signal of the two consecutive signals, assuming the most likely direction of rotation of the dose control member is the direction of increasing the delivered dose.

[0059] The method may further include, for example, storing the dose-related count in a memory unit of a metering system of the drug delivery device.

[0060] In one embodiment, a method for measuring an expelled dose and / or a set dose by a drug delivery device according to one of the embodiments of the present disclosure is provided.

[0061] Furthermore, machine readable code is proposed which, when executed in an electronic processing unit of a measurement system, causes the system to behave and operate like the measurement system described above. The machine readable code may be provided in the form of an update to existing machine readable code present in the measurement system.

[0062] Furthermore, a data storage medium, e.g. a compact disc, a flash drive, a memory card, a cloud storage or a data stream, is proposed which comprises said machine-readable code or a machine-readable code (update) which reproduces said machine-readable code of the measurement system. [Brief description of the drawings]

[0063] [Figure 1] 1 shows a schematic diagram of a drug delivery device including a measurement system. [Diagram 2] 2 shows a schematic cross-sectional view taken along marker A in FIG. 1. [Diagram 3] 1 shows a subsequence of a repeating sequence according to a Gray code sequence. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0064] In the figures, identical elements, identically functioning elements, or elements of the same type may be labeled with the same reference numbers.

[0065] 1 shows a drug delivery device 20. The drug delivery device 20 includes an electronic measurement system (measurement system) 10 for the drug delivery device 20. The measurement system 10 includes an electronic processing unit 12. The measurement system 10 includes a sensor unit 14. The measurement system 10 is configured to measure the amount of drug expelled from the drug delivery device 20.

[0066] The electronic processing unit 12 may include a memory unit for storing the measured amount of drug expelled. The electronic processing unit 12 may further include a communication unit 14 for transmitting the measured amount of drug and other data, such as the time the drug was administered, to an external device.

[0067] The drug delivery device 20 is a needle-based injection device (also called NIS-needle-based injection system). The drug delivery device 20 is a pen-type device. The drug delivery device 20 includes an elongated housing 22. The drug delivery device 20 includes a receptacle 26 for receiving a container 25. The container 25 is filled with a medication. The container 25 may be replaced with a different one by partially disassembling the drug delivery device 20, for example, an empty container may be replaced with a full one. The drug delivery device 20 includes a needle 27 at a first end in fluid communication with the container 25. The drug delivery device 20 includes a cap 24, which may be mechanically connected to the housing 22 and covers the needle 27 when connected to the housing 22. The drug delivery device 20 includes a dose dial 23 rotatably connected to the housing 22 at a second end opposite the needle 27. By rotating the dose dial 23, a dose of drug to be expelled from the drug delivery device 20 (and injected into the body) can be selected. The dose dial 23 also functions as an ejection mechanism to initiate ejection of drug when pressed along the cylinder axis. Alternatively, a separate button pressed manually by the user or a needle shield that retracts upon insertion of the needle 27 into the body, thereby triggering ejection, may be provided to perform that function. The drug delivery device 20 includes a drive unit 29 and a plunger 28. The drive unit 29 drives the plunger 28 into the container 25 a distance specific to the set dose.

[0068] The electronic measurement system 10 comprises a dose control member 11 configured to move relative to a housing 22 of the drug delivery device 20 according to a dose expulsion operation. According to other embodiments, the dose control member is configured to move according to a dose setting operation or both operations.

[0069] The electronic measurement system 10 includes a sensor unit 14. The sensor unit 14 is electrically connected to the electronic processing unit 12. The sensor unit 14 is configured to intermittently monitor the position of the dose control member 11. The sensor unit 14 is configured to generate a signal corresponding to one of four different data values ​​A, B, C or D, respectively, depending on the position of the dose control member 11. The electronic measurement system 10 further includes an energy source, e.g. a battery, for powering the electronic processing unit 12 and the sensor unit 14.

[0070] To drive the plunger 28, the drive unit 29 produces a rotational motion that is translated into linear motion of the plunger 28. The dose control member 11 is configured to rotate an amount proportional to the amount of linear motion of the plunger 28.

[0071] The electronic processing unit 12 is configured to receive the signal of the sensor unit 14 and to adapt the dose-related count in response to the received signal. The electronic processing unit 12 is configured to determine whether two consecutive data values ​​of the received signal are adjacent in a predetermined repeating sequence of four different data values ​​A, B, C and D [...A,B,C,D,A,B,C,D,...].

[0072] The sensor unit 14 comprises two sensor elements 16, 18 which observe the dose control member 11 (compare in FIG. 2). The sensor elements 16, 18 are optical sensors. The sensor elements 16, 18 are configured to observe the reflectivity of the dose control member 11. The sensor elements 16, 18 are configured to emit light (in this case infrared light) towards the dose control member 11 and to detect how much light is received by the sensor elements 16, 18.

[0073] The dosage control member 11 includes a series of sensing regions L, G, where adjacent sensing regions L, H have different physical properties. The series of sensing regions includes 12 sensing regions L, H. Each of the sensing regions L, H occupies 30° of the dosage control member. Half of the sensing regions L have low reflectivity (for IR light). The other half of the sensing regions H have high reflectivity (for IR light). The sensing regions L with low reflectivity and the sensing regions H with high reflectivity are arranged alternately. Other embodiments may use more or fewer sensing regions. Using more sensing regions allows for higher resolution, and fewer sensing regions allows for lower sample rates and lower energy consumption. The sensing regions L with lower physical property values ​​are made of a different material than the sensing regions H with higher physical property values. The sensing area L with low reflectivity is recessed to increase the distance between the sensor and the sensing area L with low reflectivity, thereby further reducing the signal output by the sensor when observing the low reflectivity area. This improves the contrast between the areas and the corresponding difference in the signal output from the sensor when observing the two areas. The first type of sensing area H (in this case the one with the high physical property value) may be constituted by the substrate of the dose control member 11. The other sensing areas L may be formed by an additive process, for example by adding material to the substrate between the first type of sensing areas H, for example by injection molding, or by form-fitting and / or gluing one or more additional parts.

[0074] The dose control member 11 is an integral part of the drive unit 29 and transfers energy to the plunger 28. The dose control member 11 comprises a ring-shaped portion. The ring-shaped portion is arranged at a proximal end of the dose control member 11. The sensing areas L, H are arranged along the circumference of the ring-shaped portion. The sensing areas are arranged on a radially outer surface of the ring-shaped portion. The sensor elements 16, 18 are arranged at a distance from the ring-shaped portion in a radially outward direction from the dose control member 11. The sensor elements 16, 18 are fixed with respect to the housing 22. The sensor elements 16, 18 are arranged such that when one of the sensor elements 16, 18 is oriented towards the transition between the two sensing areas L, H, the other sensor element 16, 18 is not oriented towards the transition between the two sensing areas (L, H). The other sensor element 16, 18 is oriented towards the centre of another sensing area L, H. The sensor elements 16, 18 are arranged to simultaneously (at any given time) view different sensing areas L, H, and to view the same sensing areas L, H at different times. The sensing areas L, H each occupy the same amount of space in the dose control member (in this case 30°). The sensor elements 16, 18 are angularly spaced apart by an angle α relative to the center of the ring-shaped portion of the dose control member. The angle α is 135°.

[0075] During operation of the device, when exhaling (or dialing in accordance with other embodiments), a pair of sensors are mechanically coupled to an encoding component (encoder ring).

[0076] The sensor unit 12 is configured to generate signals corresponding to different data values ​​A, B, C or D depending on the angular position of the dose control member 11. The predetermined repeating sequence [..., A, B, C, D, A, B, C, D, ...] is associated with a 2-bit Gray code (compare in Fig. 3). According to the physical properties of the respective observed sensing areas L, H, the first sensor element 16 generates a first sensor signal S1 having a value 0 (low physical property value) or 1 (high physical property value). According to the physical properties of the respective observed sensing areas L, H, the second sensor element 18 generates a second sensor signal S2 having a value 0 (low physical property value) or 1 (high physical property value). The dose control member 11 and the sensor unit 14 are configured such that when the sensor unit 14 continuously observes the dose control member 11 and the dose control member 11 moves unidirectionally in a direction R to increase the delivered or set dose, a predetermined repeating sequence [..., A, B, C, D, A, B, C, D,...] is generated.

[0077] In the case of optical sensors, depending on the last dispensed dose, each sensor can be pointing either to the black or white area. The center of each sensor is nominally located at an angle away from the transition edge. The response of the sensor is defined as a binary 1 when pointing to the white area and a binary 0 when pointing to the black area. The configuration in which the sensors nominally point to one of two states and transitions occur between these states is also applicable to other sensor technologies as described above.

[0078] In a position of the dosage control member 11 where both sensor elements 16, 18 are directed towards the sensing area L having a low physical characteristic value (IR reflectance), the sensor unit 14 generates from the sensor unit 14 a signal "00" associated with a first data value of the different data value A. In a position of the dosage control member 11 where the first sensor element 16 is directed towards the sensing area H having a high physical characteristic value and the second sensor element 18 is directed towards the sensing area L having a low physical characteristic value, the sensor unit 14 generates from the sensor unit 14 a signal "10" associated with a second data value of the different data value B. In a position of the dosage control member 11 where both sensor elements 16, 18 are directed towards the sensing area H having a high physical characteristic value, the sensor unit 14 generates from the sensor unit 14 a signal "11" associated with a third data value of the different data value C. In a position of the dose control member 11 where the first sensor element 16 is directed towards the sensing area L having a low physical characteristic value and the second sensor element 18 is directed towards the sensing area H having a high physical characteristic value, the sensor unit 14 generates a signal "10" associated with a fourth data value of a different data value D from the sensor unit 14. In the repeating sequence [..., A, B, C, D, A, B, C, D, ...], the first data value of the data value A is followed by the second data value of the data value B. In the repeating sequence [..., A, B, C, D, A, B, C, D, ...], the second data value of the data value B is followed by the third data value of the data value C. In the repeating sequence [..., A, B, C, D, A, B, C, D, ...], the third data value of the data value C is followed by the fourth data value of the data value D. In a repeating sequence [...,A,B,C,D,A,B,C,D,...], a fourth data value of data value D is followed by a first data value of data value A. The positions depicted in Figure 2 herein relate to signal "10" from sensor unit 14 and correspond to a second data value of different data value B. The different data values ​​A, B, C and D are identical to each signal of sensor unit 14.

[0079] A user of the drug delivery device 20 may begin using the device by using the dose dial 23 to select the dose (amount of drug) to be expelled in a set dose operation. During the set dose operation, the sensor unit 14 is deactivated and does not provide a signal for determining a data value representative of the position of the dose control member 11. The electronic control 12 unit may be deactivated or in a sleep mode at this stage.

[0080] When the user initiates a dose delivery operation by pressing the dose dial 23 in a first stage or by a different mechanism, for example by closing the contacts when a first depression depth of the dose dial 23 is reached, the sensor unit 14 is activated and set to a first sample rate. The electronic processing unit 12 may also be activated to evaluate the signal of the sensor unit. The dose-related count is set to zero. The electronic processing unit 12 is configured to read from memory a stored data value corresponding to the last received signal of the sensor unit 14 of a previous dose delivery operation to enable comparison with the newly generated signal. Alternatively, the first data value for comparison may be a factory preset value. The sensor unit may also be activated to establish and obtain a reset position when changing the drug container.

[0081] The drive unit 29 comprises (among other possible components of the drive unit 29) a locking mechanism for preventing movement of the plunger 28 and the dose control member 11. In a second stage, e.g. after reaching a second depression depth of the dose dial (later / deeper than the first depression depth), the drive unit 29 is unlocked for expelling the drug by releasing the locking mechanism at least in direction R, increasing the delivered dose. Movement of the dose control member 11 relative to the housing opposite direction R for increasing the delivered dose is at least prevented by the locking mechanism at any stage.

[0082] If any one of the sensor elements changes from 0 to 1 or 1 to 0, i.e. a transition occurs, it is interpreted as one unit being dispensed, but depending on the configuration of the system it may also be interpreted as multiple single units or part of a single unit. By implementing Gray coding it is possible to determine whether the unit increases or decreases the overall dose count. Furthermore, the mechanism is designed so that the dose only increases in normal operation. Any consecutive transitions indicating a decrease in the overall dose count suggest a mechanical and / or electrical failure, or momentary vibration in the opposite direction, so-called "jitter".

[0083] The electronic processing unit 12 is configured to increase the sample rate of the sensor unit 14 if two successive signals do not correspond to adjacent ones in the repeating sequence of different signals A, B, C or D [..., A, B, C, D, A, B, C, D, ...]. The electronic processing unit 12 is configured to increase the sample rate of the sensor unit 14 at least after a first movement of the dose control member 11 (any change in the data values ​​A, B, C or D corresponding to the signal received from the sensor unit 14) is detected. In particular, if the dose dial 23 is pressed very hard, the first few transitions of the different data values ​​A, B, C or D in the repeating sequence [..., A, B, C, D, A, B, C, D, ...] may be missed due to a delayed start-up of the sensor unit 14.

[0084] When the amount of drug according to the set dose has been expelled, the drive mechanism reaches an end position where the forward movement in the direction R is blocked again by the locking mechanism. In particular, at the end of the dose expelling operation, momentary vibrations (jitter movements) of the drive unit 29 and / or parts of the dose control member 11 may occur, e.g. due to flexibility of parts and mechanisms, leading to the sensor unit 14 providing a signal which repeatedly switches between two data values. The electronic processing unit 12 is configured to determine the direction of movement of the dose control member 11 based on two successive signals and a predefined repeating sequence [..., A, B, C, D, A, B, C, D,...]. If the electronic processing unit 12 determines that the successive signals relate to two adjacent data values ​​(A, B), (B, C), (C, D), (D, A) in the forward direction R, the electronic processing unit 12 increments the dose-related count by one. If the electronic processing unit 12 determines that the successive signals relate to two adjacent data values ​​(B,A), (C,B), (D,C), (A,D) in the opposite forward direction R, the electronic processing unit 12 decrements the dose-related count by one. If the electronic processing unit 12 determines that the successive signals relate to two adjacent data values ​​(B,A), (C,B), (D,C), (A,D) in the opposite forward direction R repeatedly, the electronic processing unit 12 generates an error since such a movement should not be possible within the limitations of the drug delivery device 20 without significant device failure. An error message or warning may be provided to the user acoustically and / or visually.

[0085] When dispensing at higher rates approaching and exceeding the sampling rate of the measurement system (encoder system), successively measured transitions may not correspond to successive Gray code transitions. In the example of an optical sensor system, the expected set of transitions is "11" → "01" → "00" → "10". However, when the system goes from "11" to "00", it is not clear whether the transition is forward or reverse, i.e., "11" → "01" → "00" (forward) or "11" → "10" → "00" (reverse). This is called a double transition, and the direction may not be determined since either the "01" or "10" position is effectively skipped.

[0086] The two successive signals include a leading signal corresponding to a first data value A, B, C or D and a trailing signal corresponding to a second data value C, D, A or B. The subsequence spans from a first occurrence of the second data value C, D, A or B in the repeating sequence [...,A,B,C,D,A,B,C,D,...] to a second occurrence of the second data value C, D, A or B in the repeating sequence [...,A,B,C,D,A,B,C,D,...]. For example, if the second data value is C, the subsequence is [C,D,A,B,C].

[0087] The electronic processing unit is configured to determine a first distance from a first data value to a second data value in a forward direction along the repeat sequence, which can be interpreted as determining a distance (first distance) from a first data value A, B, C, D to a second occurrence of a second data value C, D, A or B along the subsequence. The electronic processing unit is further configured to determine a second distance from a first data value to a second data value in a backward direction along the repeat sequence, which can be interpreted as determining a distance (second distance) from a first occurrence of a second data value C, D, A or B to a first data value A, B, C or D along the subsequence.

[0088] If two consecutive signals do not correspond to adjacent ones in the repeating sequence [..., A, B, C, D, A, B, C, D, ...], the electronic processing unit 12 is configured to increase the dose-related count in relation to the first distance (always by 2 in the case of only four distinct data values) if the second distance is greater than a certain value, in this case greater than 1.

[0089] A double transition is always interpreted as moving forward, i.e. increasing the overall dose count (dose related count). This is because it is physically impossible to drive the mechanism backwards more than one transition without some fault or misuse condition. In effect, the embedded software is written to take into account the physical characteristics of the entire system. This ensures that double transitions do not cause unnecessary fault conditions while improving dose recording accuracy.

[0090] For example, the system is quickly dispensed and a double transition is detected. The previous dose count was 20 units, but using the system structure described herein, the double transition adds 2 units to the dose count, resulting in a dose of 22 units. The next transition is as expected and increases the dose count by 1, bringing it to 23 units.

[0091] The electronic processing unit may determine that the dose delivery operation is complete when the dose button is released. Alternatively, the electronic processing unit may determine that the dose delivery operation is complete when the electronic processing unit 12 determines that the drive unit 29 has stopped due to no change in the data value corresponding to the signal of the sensor unit 14. The electronic processing unit 12 is configured to store the measured dose-related counts in memory, for example together with a timestamp. Additionally, the data value A, B, C or D corresponding to the most recent signal of the sensor unit 14 is committed to the memory.

[0092] This procedure achieves an approach to identify and address non-sequential Gray code transitions detected by a pen injection system using a pair of sensors, which takes into account the physical characteristics of the system, improves dose recording accuracy, and reduces unnecessary identification of fault conditions.

[0093] The present embodiment is configured to switch to the faster sample rate if any transition (including double transitions) is detected, such that most physically possible accelerations will not lead to missed transitions when the slower sample rate is active (i.e. triple or more transition events). Furthermore, for triple or more transitions to exist when the faster sample rate is active, the mechanical speed of the system must be greater than twice the faster sample rate. The sample rate is selected such that such speeds are physically impossible in the mechanism, such that the sensor system is configured to be robust against losing counts under fast injection events.

[0094] In other embodiments, there may be, for example, eight different data values. Thus, the electronic processing unit may be configured to increment a dose-related count in relation to the calculated number of missed transitions (1, 2, 3, 4, or 5) and to increment the dose count by (2, 3, 4, 5, or 6). Thus, a sixth calculated missed transition is interpreted as one reverse transition and decreases the dose count by 1. Furthermore, the electronic processing unit may be configured to record an error if the number of missed transitions is above a set threshold (e.g., 2, 3, 4, or 5).

[0095] In alternative embodiments, the sensor unit may have only a single sensor element, but the sensing region has several different values ​​or value ranges in the physical property being observed, and the sensor element is configured to individually distinguish these different values ​​or value ranges, each corresponding to a different data value.

[0096] In a further embodiment, the sensor unit may include three sensor elements arranged at 0°, 130° and 260° to generate a 3-bit Gray code (or at least a Gray-like code) instead of the proposed two.

[0097] Also, in alternative embodiments, the sensing region may be located, for example, on an axial surface of the ring away from the needle and / or on the proximal end of the dose control member, and the sensor element may be located axially distal or proximal to the dose control member, for example, away from the needle. [Explanation of symbols]

[0098] 10 Measurement System 11 Dose control elements 12 Electronic Processing Unit 14 Sensor unit 16 Sensor Elements 18 Sensor elements 20 Drug Delivery Devices 22 Housing 23 Dose Dial 24 Cap 25 Container 26 Receptacle 27 needles 28 Plunger 29 Drive unit A Data Value B Data Value C Data Value D Data Value H Sensing Area L Sensing Area R direction S1 Sensor signal S2 Sensor signal

Claims

1. A measurement system for a drug delivery device (20), comprising: a dose control member (11) adapted to move, for example relative to the housing (22) of said drug delivery device (20), according to a dose expulsion operation and / or a dose setting operation; a sensor unit (14) for intermittently monitoring the position of said dose control member (11), said sensor unit being configured to generate signals, each signal corresponding to one of at least four different data values ​​(A, B, C or D) depending on the position of said dose control member (11); an electronic processing unit (12) configured to receive the signals of the sensor unit (14), to adapt a dose-related count depending on the received signals, and to determine whether two consecutive ones of the received signals correspond to adjacent data values ​​in a predetermined repeating sequence of the different data values ​​(A, B, C and D); a measurement system,

2. 2. The measurement system of claim 1, wherein the dose control member (11) and the sensor unit (14) are configured such that the predetermined repeating sequence is generated when the sensor unit (14) continuously observes the dose control member (11) and the dose control member (11) moves in one direction (R) to increase the delivered or set dose.

3. 3. The measuring system according to claim 1 or 2, wherein the electronic processing unit (12) is configured to determine the direction of movement of the dose control member (11) based on the two successive signals and the predetermined repetitive sequence.

4. 4. The measurement system according to claim 1, wherein the electronic processing unit (12) is configured to increase the sample rate of the sensor unit (14) if the two consecutive signals do not correspond to adjacent data values ​​in the repeated sequence of different signals.

5. The two consecutive signals include a leading signal corresponding to a first data value (A, B, C, D) and a trailing signal corresponding to a second data value (A, B, C, D), and the two consecutive signals 5. The measurement system of claim 1, wherein the electronic processing unit is configured to determine a first distance from the first data value (A, B, C, D) to the second data value (A, B, C, D) in a forward direction along the repeating sequence if the signals do not correspond to adjacent ones in the repeating sequence, and to determine a second distance from the first data value (A, B, C, D) to the second data value (A, B, C, D) in a reverse direction along the repeating sequence, and wherein the electronic processing unit is configured to increment the dose-related count associated with the first distance if the second distance is greater than a certain value, for example greater than 1.

6. 6. The measuring system according to claim 1, wherein movement of the dose control member (11) relative to the housing (22) opposite to the direction (R) for increasing the delivered or set dose is at least prevented.

7. 7. The measuring system according to claim 1, wherein the dose control member (11) is configured to rotate and the sensor unit (14) is configured to generate the signals corresponding to the different data values ​​(A, B, C or D) depending on the angular position of the dose control member (11).

8. Measurement system according to any one of claims 1 to 7, wherein the predetermined repeating sequence is associated with a Gray code, for example a 2-bit Gray code.

9. 9. The measuring system according to claim 1, wherein the dose control member (11) comprises a series of sensing areas (L, H), adjacent sensing areas (L, H) having different physical properties, and / or the sensor unit comprises at least two sensor elements (16, 18) observing the dose control member (11).

10. 10. The measurement system of claim 9, wherein at least two of the sensor elements (16, 18) are arranged to observe different sensing areas (L, H) at least some of the time and to observe the same sensing area (L, H) at least some of the time.

11. 11. The measuring system of claim 10, wherein the dose control member (11) comprises a ring-shaped portion, the sensing areas (L, H) are arranged along the periphery of the ring-shaped portion, and the sensor elements (16, 18) are arranged such that when one of the sensor elements (16, 18) is directed toward the transition between two sensing areas (L, H), the other sensor element (16, 18) is not directed toward the transition between the two sensing areas (L, H), but is, for example, directed toward the center of another sensing area (L, H).

12. A drug delivery device comprising a measurement system (10) according to any one of claims 1 to 11 or configured to be coupled, for example removably coupled, with such a measurement system.

13. 13. A drug delivery device according to claim 12, comprising at least one container (25) filled with a drug or a receptacle (26) for receiving such a container (25).

14. 14. The drug delivery device of claim 12 or 13, which is a needle-based injection device, such as a pen-type device.

15. A method for measuring an expelled dose and / or a set dose of a drug delivery device, for example a drug delivery device (20) according to any one of claims 12 to 14, comprising the steps of: - the position and movement of the dose control member (11) according to the dose expelling and / or dose setting operations; and intermittently observing the position and / or orientation of the object. - generating a signal corresponding to one of at least four different data values ​​(A, B, C or D) in response to the position and / or orientation of said dose control member (11); - adapting a dose-related count in response to said generated signal; determining whether two successive ones of said generated signals correspond to adjacent data values ​​in said predetermined repeating sequence of different data values; A method comprising:

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