DRUG DELIVERY DEVICE WITH IMPROVED DOSE ACCURACY

Abstract

Method of manufacturing a drug delivery device, comprising the steps of (i) providing a plurality of components which in an assembled state form a processor-controlled drug delivery device, (ii) determining a parameter value for at least one component, (iii) assembling the components to form a drug delivery device, and (iv) storing in the processor memory correction data, the correction data being based on one or more differences between a determined parameter value and a corresponding nominal value.

Claims

1. A method of assembling a drug delivery device, comprising the steps of: providing a plurality of components which in an assembled state form a processor-controlled drug delivery device, the drug delivery device comprising a drug-filled cartridge or structure for receiving a drug-filled cartridge, the cartridge comprising an outlet and an axially displaceable piston, the components comprising: a first group of components adapted to move during drug expelling, the first group of components comprising an axially displaceable piston drive member adapted to engage the piston of a cartridge, a second group of components adapted to be stationary during drug expelling but interfacing with a member of the first group, and a processor with memory, determining prior to assembly a parameter value for at least one of: a member of the first group, and a member of the second group, assembling the components to form a drug delivery device, and storing in the processor memory correction data, the correction data being based on one or more differences between a determined parameter value and a corresponding nominal value.

2. A method of assembling a drug delivery device as in claim 1, wherein at least two parameter values are determined for a given member as a function of a given dimension or state, the correction data comprising a number of correction values varying as a function of a state of the drug delivery device.

3. A method of assembling a drug delivery device as in claim 1, wherein the plurality of components in the assembled state form a drug delivery device as defined in claim 8.

4. A method of providing a drug delivery assembly, comprising the steps of: providing a drug-filled cartridge, the cartridge comprising an outlet and an axially displaceable piston, determining at least one parameter value for the cartridge, providing the cartridge with readable information in respect of the determined parameter value(s), providing a processor-controlled drug delivery device comprising: a cartridge holder adapted to receive the cartridge, structure for reading the cartridge readable information, an expelling assembly, and a processor with memory wherein: the readable information provided on the cartridge is in the form of correction data based on the difference between a determined parameter value and a corresponding nominal value, or the readable information provided on the cartridge is in the form of at least one determined parameter value for the cartridge, the processor memory having stored corresponding nominal value data.

5. A method of providing a drug delivery assembly as in claim 4, comprising the further steps of: inserting the cartridge in the cartridge holder, reading the cartridge readable information, and storing in the processor memory correction data, the correction data being based on difference(s) between the determined parameter value(s) and a corresponding nominal value(s).

6. A method of manufacturing a drug cartridge, comprising the steps of: providing a drug-filled cartridge, the cartridge comprising an outlet and an axially displaceable piston, determining at least one parameter value for the cartridge, providing the cartridge with readable information in respect of the determined parameter value(s), the readable information being in the form of correction data based on one or more differences between a determined parameter value and a corresponding nominal value.

7. A method as in claim 1, wherein the parameter value is a dimension.

8. A drug delivery device comprising: a drug-filled cartridge or structure for receiving a drug-filled cartridge, the cartridge comprising an outlet and an axially displaceable piston, an expelling assembly comprising: a first group of components adapted to move during drug expelling, the first group of components comprising an axially displaceable piston drive member adapted to engage the piston of a cartridge, a second group of components adapted to be stationary during drug expelling but interfacing with a member of the first group, dose setting structure allowing a user to set a nominal dose amount of drug to be expelled, a display adapted to display a dose amount, drive structure for moving the piston drive member in a distal direction to thereby expel drug from an inserted cartridge, and a processor comprising a memory, the processor being adapted to control the display to display a dose amount, wherein: a correction value is stored in the memory, the correction value being based on one or more differences between a determined parameter value and a corresponding nominal value for at least one of: a member of the first group, a member of the second group, and a received cartridge, and the processor is adapted to, based on the correction value and a nominally set dose amount, calculate a corrected dose amount and control the display to display the corrected dose amount.

9. A drug delivery device as in claim 8, wherein at least two correction values are stored in the memory, the correction values being correlated to the position of the piston rod, and the processor is adapted to, based on the correction value for the current position of the piston rod and a nominally set dose amount, calculate a corrected dose amount and control the display to display the corrected dose amount.

10. A drug delivery device as in claim 9, wherein the display is adapted to display dose amounts in increments of a given unit.

11. A drug delivery device as in claim 10, wherein the dose setting structure is adapted to set a nominal dose amount of drug to be expelled in increments which are a fraction of the display increment.

12. A drug delivery device as in claim 9, comprising: a cartridge holder adapted to receive a cartridge, the cartridge being provided with readable information in respect of a determined parameter value for the cartridge, and structure for reading the cartridge readable information, wherein the processor is adapted to calculate a correction value based at least in part on the difference between the cartridge parameter value information and a corresponding stored nominal value.

13. A drug delivery device comprising: a drug-filled cartridge or structure for receiving a drug-filled cartridge, the cartridge comprising an outlet and an axially displaceable piston, an expelling assembly comprising: a first group of components adapted to move during drug expelling, the first group of components comprising an axially displaceable piston drive member adapted to engage the piston of a cartridge, a second group of components adapted to be stationary during drug expelling but interfacing with a member of the first group, dose setting structure allowing a user to set a nominal dose amount of drug to be expelled, the nominal dose amount corresponding to a nominal axial displacement for the piston drive member, a display adapted to display a dose amount, a motor for moving the piston drive member in a distal direction to thereby expel drug from an inserted cartridge, and a processor comprising a memory, the processor being adapted to control the motor to displace the piston drive member axially, wherein: a correction value is stored in the memory, the correction value being based on one or more differences between a determined parameter value and a corresponding nominal value for at least one of: a member of the first group, a member of the second group, and a received cartridge, and the processor is adapted to, based on the correction value and a nominally set dose amount, calculate a corrected axial displacement for the piston drive member and control the motor to move the drive member corresponding to the corrected axial displacement.

14. A drug delivery device as in claim 13, wherein at least two correction values are stored in the memory, the correction values being correlated to the position of the piston rod, and the processor is adapted to, based on the correction value for the current position of the piston rod and a nominally set dose amount, calculate a corrected axial displacement for the piston drive member and control the motor to move the drive member corresponding to the corrected axial displacement.

15. A drug delivery device as in claim 1, wherein the parameter value is a dimension.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0048] In the following exemplary embodiments of the invention will be described with reference to the drawings, wherein

[0049] FIG. 1A shows a pen-formed drug delivery device,

[0050] FIG. 1B shows the pen device of FIG. 1A with the pen cap removed,

[0051] FIG. 2 shows a drug delivery device of the same general type as in FIG. 1A but provided with electronic circuitry and a display,

[0052] FIG. 3 shows an expelling assembly,

[0053] FIG. 4 shows a piston rod,

[0054] FIG. 5 shows a drug cartridge,

[0055] FIGS. 6A-6E show maximum deviations between dialled and given dose for different configurations of a drug delivery device,

[0056] FIGS. 7A and 7B show maximum deviations between dialled and given dose for different configurations of drug delivery devices provided with electronic display compensation, and

[0057] FIGS. 7C and 7D show maximum deviations between dialled and given dose for different configurations of drug delivery devices provided with electronic motor drive compensation.

[0058] In the figures like structures are mainly identified by like reference numerals.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0059] When in the following terms such as upper and lower, right and left, horizontal and vertical or similar relative expressions are used, these only refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only. When the term member or element is used for a given component it generally indicates that in the described embodiment the component is a unitary component, however, the same member or element may alternatively comprise a number of sub-components just as two or more of the described components could be provided as unitary components, e.g. manufactured as a single injection moulded part. The term assembly does not imply that the described components necessary can be assembled to provide a unitary or functional assembly during a given assembly procedure but is merely used to describe components grouped together as being functionally more closely related.

[0060] Before turning to embodiments of the present invention per se, an example of a pre-filled drug delivery will be described, such a device providing the basis for an exemplary embodiment of the present invention. Although the pen-formed drug delivery device 100 shown in FIGS. 1A and 1B may represent a generic drug delivery device, the actually shown device is a FlexTouch pre-filled drug delivery pen as manufactured and sold by Novo Nordisk A/S, Bagsvrd, Denmark.

[0061] The pen device 100 comprises a cap part 107 and a main part having a proximal body or drive assembly portion with a housing 101 in which a drug expelling mechanism is arranged or integrated, and a distal cartridge holder portion 111 in which a drug-filled transparent cartridge 130 with a distal needle-penetrable septum is arranged and retained in place by a non-removable cartridge holder attached to the proximal portion, the cartridge holder having openings allowing a portion of the cartridge to be inspected as well as distal coupling means 115 allowing a needle assembly to be releasably mounted. The cartridge is provided with a piston driven by a piston rod forming part of the expelling mechanism and may for example contain an insulin, GLP-1 or growth hormone formulation. The mechanism comprises a scale drum member provided with a plurality of dose size indices, the scale drum member being arranged rotationally corresponding to the general axis. The housing comprises a display opening (or window) 102 arranged to show a scale drum member dose size indicia corresponding to a set dose. A proximal-most rotatable dose setting member 180 serves to manually set a desired dose of drug shown in display window 102 and which can then be expelled when the button 190 is actuated. Depending on the type of expelling mechanism embodied in the drug delivery device, the expelling mechanism may comprise a spring as in the shown embodiment which is strained during dose setting and then released to drive the piston rod when the release button is actuated. Alternatively the expelling mechanism may be fully manual in which case the dose member and the actuation button moves proximally during dose setting corresponding to the set dose size, and then is moved distally by the user to expel the set dose, e.g. as in a FlexPen manufactured and sold by Novo Nordisk A/S.

[0062] Although FIGS. 1A and 1B show a drug delivery device of the pre-filled type, i.e. it is supplied with a pre-mounted cartridge and is to be discarded when the cartridge has been emptied, in alternative embodiments the drug delivery device may be designed to allow a loaded cartridge to be replaced, e.g. in the form of a rear-loaded drug delivery device in which the cartridge holder is adapted to be removed from the device main portion, or alternatively in the form of a front-loaded device in which a cartridge is inserted through a distal opening in the cartridge holder which is non-removable attached to the main part of the device.

[0063] FIG. 2 shows a drug delivery device 200 having the same general appearance and being provided with essentially the same type of dose setting and expelling mechanism, however, the device is provided with electronic circuitry comprising a processor with memory, a display controlled by the processor and a sensor adapted to detect the size of a nominally set dose, i.e. the dose set by the user. In the figure a cartridge 230 provided with a piston 214 driven by a piston rod 220 can be seen.

[0064] If the drug delivery device 200 is a disposable prefilled device it is important that the electronic circuitry is provided using cost-effective technologies which is not necessarily designed for a long in-use time. For example, the display may be a printed display formed on a flexible carrier which may also form a substrate for further components being provided as printed electronics, e.g. processor, memory, sensors, energy source. Alternatively one or more of these components may be in the form of discrete components mounted on the flexible carrier. An example of a pre-filled drug delivery device provided with a low-cost electronic label is described in WO 2015/071354. In the shown embodiment the scale drum is not used to show a set dose size, however, it is provided with a plurality of markings or codes which can be detected by the dose size sensors as the scale drum rotates helically during dose setting. The markings may be adapted to be detected by capacitive sensors which e.g. may be formed by a printing process on the flexible substrate. In case the drug delivery device 200 represents a durable device adapted to allow cartridge change, then the electronic circuitry may be provided with more traditional components such as an LCD.

[0065] With reference to FIGS. 3-5 a number of components which can be used to realize the invention will be described, the figures showing three components of the drug delivery device 200 for which one or more parameter values can be determined during an assembly process. More specifically, FIG. 3 shows a dose setting and expelling unit 210 (motor unit), FIG. 4 shows a piston rod 220 adapted to be rotationally driven by the motor unit, and FIG. 5 shows a drug-filled cartridge 230 with an axially displaceable piston 234 adapted to be axially driven by the piston rod.

[0066] The motor unit 210 is set by rotating the rotatable dose setting member 280 which results in the drive output member being rotated correspondingly, however, due to tolerances variations will inevitably occur. The shown motor unit can be set in increments of 15 degrees for a total of 80 increments. Thus during manufacturing a given motor unit may be set in a number of rotational positions (i.e. up to 80) and the corresponding rotation of the output member may be determined and subsequently stored. As appears, to provide such data may be relatively costly. To reduce the amount of data one or more averages may be calculated for a number of dose size ranges.

[0067] For the piston rod 220 the pitch of each thread 221 along the length thereof may be measured. Alternatively, the pitch variation for a given piston rod having a specific location in a multi-cavity mould tool may be known from measurement of the mould, each cavity being provided with a code which can be identified, e.g. a code on the piston rod head 222. Indeed, by this method variations introduced by the mould process per se will not be detected. To reduce the amount of data one or more averages may be calculated for a number of sections of the piston rod. The shown housing nut portion 225 is not part of the piston rod.

[0068] For the cartridge 230 the diameter along the length thereof may be measured. For ease of measurement the external diameter may be determined. Indeed, by this method variations introduced by the thickness of the glass wall will not be detected. To reduce the amount of data one or more averages may be calculated for a number of sections of the cartridge. As disclosed above, if a given cartridge is to be used in a durable device provided with a corresponding reader, the cartridge may be provided with readable information in respect of the determined parameter value(s), i.e. in the form of a printed label.

[0069] After or during assembly of a given device correction data can be stored in the device processor memory, the correction data being based on one or more differences between a determined parameter value and a corresponding nominal value. For example, if the piston rod and the cartridge have been measured a correction table may be calculated, the table having correction values as a function of piston rod position. The actual position of the piston rod may be determined by e.g. detection of scale drum rotation as described above. For a given device the variations of the two components along the length thereof may for some positions cancel each other whereas for other positions they may be added. In addition, also the dose size will influence the calculated correction for a given expelled dose.

[0070] For a motor driven drug delivery device the basic concept is the same as for the above-described spring-driven device although the components having a relevant variability may not be the same. For example, the piston rod may be manufactured by machining and may thus have stricter tolerances. As a motor driven device will be designed to allow the cartridge to be replaced, a measured cartridge would have to be provided with a readable code and the device with a corresponding code reader. In contrast to the above-described spring-driven device it would be possible to use the correction data to control the motor such that the nominally set dose amount is very close to the dose actually expelled. Examples of motor-driven drug delivery devices which may be used as a platform for this aspect of the present invention are described in e.g. EP 2015/065544.

[0071] In the following aspects of the present invention will be illustrated by a number of examples.

[0072] 1A. Reference Drug Delivery Device Example

[0073] In an exemplary drug delivery device the cartridge has an inner nominal diameter of 9.25 mm with a tolerance of +/0.1 mm corresponding to an inner cross section area of 67.2006+/1.4608 mm.sup.2. The piston rod has nominal thread inclination of 3.6+/0.04 mm/rev corresponding to a linear movement per degree of rotation of 0.01+/0.00011111 mm/deg. The nominal offset is 0+/0.02 mm. Drug concentration is 0.1 IU/mm.sup.3.

[0074] Standard and Regulations requirements are for dose sizes in the range 0-20 units (IU) set to +/1 IU, and for dose sizes larger than 20 IU+/5%.

[0075] Based on the above dimensions and tolerances deviations between dialled and expelled doses can be calculated and are illustrated in FIG. 6A in which the full line represents standard and regulation requirements and the dotted line represents maximum device variations due to mechanical tolerances. As seen in the figure an out-dosing of 20 IU can get closest to allowable limits. Thus, an out-dosing of 20 IU will be used in the following examples and illustrations.

[0076] For a drug delivery in which the piston rod rotates 15 degrees per increment of 1 IU dialing 20 IU will result in a piston rod rotation of 300 degrees.

TABLE-US-00001 Linear movement of piston: Nominal 300 degrees 0.01 mm/deg 3 mm Max. 300 degrees 0.01011111 mm/deg + Offset 3.053333 mm Volume displacement of piston: Nominal 3 mm 67.2006 mm.sup.2 201.6019 mm.sup.3 Max. 3.053333 mm 68.6615 mm.sup.2 209.6464 mm.sup.3 Dose size of displaced volume: Nominal 201.6019 mm3 0.1 IU/mm.sup.3 20.16 IU Max. 209.6464 mm3 0.1 IU/mm.sup.3 20.96 IU Dose size deviation from nominal dose: 20.96 20.16 = 0.80 IU

[0077] As appears, dialing 20 IU may within the limits of the allowed tolerances result in an overdosing of 0.8 IU which is thus acceptable within the +/1 IU tolerance limits for doses up to 20 IU.

[0078] 1B: Example for Drug Delivery Device with Double Cartridge Inner Diameter Tolerances

[0079] An exemplary drug delivery device has a cartridge with an inner nominal diameter of 9.25 mm with a tolerance of +/0.2 mm corresponding to an inner cross section area of 67.2006+/2.9374 mm.sup.2. Otherwise the values are the same as in example A1.

[0080] Based on the above dimensions and tolerances deviations between dialled and expelled doses can be calculated and are illustrated in FIG. 6B in which the full line represents standard and regulation requirements and the dotted line represents maximum device variations due to mechanical tolerances. As seen in the figure, doubling the cartridge diameter tolerance will bring performance variations well outside allowed limits.

[0081] Corresponding to the calculation in example A1 a maximum dose size deviation for a nominal 20 IU dose will be (21.42-20.16) IU=1.26 IU.

[0082] 1C: Example for Drug Delivery Device with Double Piston Rod Inclination Tolerances

[0083] An exemplary drug delivery device has a piston rod with nominal thread inclination of 3.6+/0.08 mm/rev corresponding to a linear movement per degree of rotation of 0.01+/0.00022222 mm/deg, and a nominal offset of 0+/0.04 mm. Otherwise the values are the same as in example A1.

[0084] Based on the above dimensions and tolerances deviations between dialled and expelled doses can be calculated and are illustrated in FIG. 6C in which the full line represents standard and regulation requirements and the dotted line represents maximum device variations due to mechanical tolerances. As seen in the figure, doubling the piston rod inclination tolerance will bring performance variations well outside allowed limits. However, not quite as much as if the cartridge inner diameter was doubled.

[0085] Corresponding to the calculation in example A1 a maximum dose size deviation for a nominal 20 IU dose will be (21.33-20.16) IU=1.17 IU.

[0086] 1D: Example for Drug Delivery Device with Double Mechanical Tolerances

[0087] An exemplary drug delivery device has a cartridge with an inner nominal diameter of 9.25 mm with a tolerance of +/0.2 mm corresponding to an inner cross section area of 67.2006+/2.9374 mm.sup.2, as well as a piston rod with nominal thread inclination of 3.6+/0.08 mm/rev corresponding to a linear movement per degree of rotation of 0.01+/0.00022222 mm/deg, and a nominal offset of 0+/0.04 mm. Otherwise the values are the same as in example A1.

[0088] Based on the above dimensions and tolerances deviations between dialled and expelled doses can be calculated and are illustrated in FIG. 6D in which the full line represents standard and regulation requirements and the dotted line represents maximum device variations due to mechanical tolerances. As seen in the figure, doubling the mechanical tolerances for both cartridge and piston rod will bring performance variations well outside allowed limits.

[0089] Corresponding to the calculation in example A1 a maximum dose size deviation for a nominal 20 IU dose will be (21.79-20.16) IU=1.63 IU.

[0090] 1E: Example for Drug Delivery Device with Triple Drug Concentration

[0091] In an exemplary drug delivery device the cartridge drug concentration is 0.3 IU/mm.sup.3. Correspondingly, the device has a piston rod with nominal thread inclination of 1.2+/0.04 mm/rev corresponding to a linear movement per degree of rotation of 0.00333333+/0.00011111 mm/deg, and a nominal offset of 0+/0.02 mm. Otherwise the values are the same as in example A1.

[0092] Based on the above drug concentration, dimensions and tolerances deviations between dialled and expelled doses can be calculated and are illustrated in FIG. 6E in which the full line represents standard and regulation requirements and the dotted line represents maximum device variations due to mechanical tolerances. As seen in the figure, maintaining the mechanical tolerances and tripling the drug concentration will bring performance variations far outside allowed limits.

[0093] Corresponding to the calculation in example A1 a maximum dose size deviation for a nominal 20 IU dose will be (21.70-20.16) IU=1.54 IU.

[0094] 1F: Example for Drug Delivery Device with Triple Drug Concentration and Compensation by Reduced Tolerances

[0095] In an exemplary drug delivery device the cartridge drug concentration is 0.3 IU/mm.sup.3. To compensate for the higher drug concentration the cartridge has an inner nominal diameter of 9.25 mm with a tolerance of +/0.05 mm corresponding to an inner cross section area of 67.2006+/0.7285 mm.sup.2. The piston rod has nominal thread inclination of 1.2+/0.02 mm/rev corresponding to a linear movement per degree of rotation of 0.00333333+/0.00005556 mm/deg. The nominal offset is 0+/0.02 mm.

[0096] Based on the above drug concentration, dimensions and tolerances deviations between dialled and expelled doses can be calculated and are illustrated in FIG. 6F in which the full line represents standard and regulation requirements and the dotted line represents maximum device variations due to mechanical tolerances. As seen in the figure, tripling the drug concentration requires the mechanical tolerances reduced to less than half to keep performance variations just inside allowed limits.

[0097] Corresponding to the calculation in example A1 a maximum dose size deviation for a nominal 20 IU dose will be (21.13-20.16) IU=0.97 IU.

[0098] As illustrated by the above examples decreasing tolerances and/or increasing drug concentration will bring the possible performance variations outside allowed limits. Correspondingly, in the following examples will be given which will illustrate how aspects of the present invention can be used to reduce performance variations for a given drug delivery device having given tolerances.

[0099] 2A: Example for Drug Delivery Device with Double Mechanical Tolerances and Electronic Display Compensation

[0100] An exemplary drug delivery device has a cartridge, piston rod and drug concentration with dimensions and tolerances as set out in example 1D above, each increment of 1 IU corresponding to a piston rod rotation of 15 degrees.

[0101] Based on the above drug concentration, dimensions and tolerances deviations between dialled and expelled doses can be calculated and are illustrated in FIG. 7A in which the full line represents standard and regulation requirements, the dotted line represents maximum device variations due to mechanical tolerances.

[0102] However, in accordance with an aspect of the present invention the drug delivery device is provided with an electronically controlled display that will compensate for the difference between the nominally set value and the calculated value for the drug amount to be expelled. More specifically, the calculated value for a given set dose size will be rounded down to the nearest integer value which will then be displayed, e.g. a dose of 47 IU is dialled, a dose of 50.5 IU is calculated, and a dose 50 IU is displayed, this resulting in an over-dosing deviation of 0.5 IU. In FIG. 7A the bold dotted line shows variations in out-dosing compared to displayed values. As also seen in FIG. 7A, the electronic display compensation reduces the actual variations in out-dosing to less than the reference example, even if the mechanical tolerances have been doubled.

[0103] FIG. 7A illustrates maximum variations, however, a given component such as a cartridge or piston rod will not have maximum tolerances over the entire dose range.

[0104] As dimensions for both cartridge inner diameter and piston rod inclination may vary along the length of the members, it would be necessary for optimal compensation to determine the actual dimensions along the length of the members with a high resolution. However, for practical purposes the dimensions may be determined as an average for a number of ranges, e.g. 10 ranges for the entire drug volume of e.g. 300 IU of insulin.

[0105] In the following example dimensions for an exemplary device has been determined which are representative for a dose of 20 IU being expelled from a given device in a given state, i.e. the 20 IU may correspond to the piston rod in the initial position or any other position in which 20 IU can be expelled from the cartridge. The dimensions are imaginary and thus not based on actual measurements.

[0106] Measurement Values

[0107] Inner diameter: 9.44 mm

[0108] Inclination of threading: 3.67 mm/rev.

[0109] Calculation Results

[0110] Cross section area: 69.98965777 mm.sup.2

[0111] Actual piston movement/click: 0.152916667 mm

[0112] Actual out-dosing/click: 1.070258517 IU

[0113] Display Correction factor: 1.070258517

[0114] Correspondingly, when the user sets a dose of 19 IU this will correspond to 19 IU1.070258517=20.33 IU being expelled, which will be rounded and displayed as 20 IU, a deviation of 0.33 IU.

[0115] 2B: Example for Drug Delivery Device with Triple Drug Concentration and Electronic Display Compensation

[0116] An exemplary drug delivery device has a cartridge, piston rod and drug concentration with dimensions and tolerances as set out in example 1E above, each increment of 1 IU corresponding to a piston rod rotation of 15 degrees. Corresponding to example 2A the drug delivery device is provided with an electronically controlled display that will compensate for the difference between the nominally set value and the calculated value for the drug amount to be expelled by rounding down the calculated value for a given set dose size to the nearest integer value which will then be displayed.

[0117] Based on the above drug concentration, dimensions and tolerances deviations between dialled and expelled doses can be calculated and are illustrated in FIG. 7B in which the full line represents standard and regulation requirements, the dotted line represents maximum device variations due to mechanical tolerances, and the bold dotted line shows variations in out-dosing compared to displayed values. As also seen, an increase in concentration may require clicks for half units to reduce rounding errors.

[0118] 2C: Example for Drug Delivery Device with Double Mechanical Tolerances and Electronic Piston Rod Drive

[0119] An exemplary drug delivery device has a cartridge, piston rod and drug concentration with dimensions and tolerances as set out in example 1D above, each increment of 1 IU corresponding to a piston rod rotation of 15 degrees.

[0120] Based on the above drug concentration, dimensions and tolerances deviations between dialed and expelled doses can be calculated and are illustrated in FIG. 7C in which the full line represents standard and regulation requirements, the dotted line represents maximum device variations due to mechanical tolerances.

[0121] However, in accordance with a further aspect of the present invention the drug delivery device is provided with an electronically controlled motor drive that will adjust the amount of piston rod rotation for a given nominally set dose size such that the expelled amount of drug corresponds to the set amount of drug. In example 2A above a display correction factor of 1.070258517 was calculated. The corresponding piston rod turn correction factor for the same measured values is the inverse value thereof: 0.934354.

[0122] Calculation Example for a Set Dose of 20 IU

[0123] Nominal turn angle for piston rod: 2015 deg=300 deg

[0124] Actual piston rod rotation: (300 deg0.934354)+1=281,306 mm/deg

[0125] (A worst case inaccuracy of the motor drive of +/1.0 deg is assumed)

[0126] Actual piston movement: (281.3061 deg0.01019 mm/deg)+0.04 mm=2,908 mm

[0127] (A worst case offset due to elasticity and friction of 0.04 mm is assumed)

[0128] Actual volume displaced: 2,908 mm(Tr(9.45 mm/2).sup.2=203.9444922 mm.sup.3

[0129] Actual Dose expelled: 203,944 mm.sup.30.1 IU/mm.sup.3=20.39444922

[0130] In FIG. 7C the bold dotted line shows variations in out-dosing compared to set values. As seen, the electronic motor drive compensation reduces the actual variations in out-dosing to far less than those of the reference example, even if mechanical tolerances have been doubled. As exemplified in the above calculation example variation cannot be corrected completely due to properties of the drive system per se.

[0131] 2D: Example for Drug Delivery Device with Triple Drug Concentration and Electronic Piston Rod Drive

[0132] An exemplary drug delivery device has a cartridge, piston rod and drug concentration with dimensions and tolerances as set out in example 1E above, each increment of 1 IU corresponding to a piston rod rotation of 15 degrees. Corresponding to example 2C the drug delivery device is provided with an electronically controlled motor drive that will adjust the amount of piston rod rotation for a given nominally set dose size such that the expelled amount of drug corresponds to the set amount of drug.

[0133] Based on the above drug concentration, dimensions and tolerances deviations between dialed and expelled doses can be calculated and are illustrated in FIG. 7D in which the full line represents standard and regulation requirements, the dotted line represents maximum device variations due to mechanical tolerances, and the bold dotted line shows variations in out-dosing compared to displayed values. As also seen, the electronic motor drive compensation reduces the actual variations in out-dosing to far less than those of the reference example, even if mechanical tolerances are maintained and the concentration tripled.

[0134] In the above description of exemplary embodiments, the different structures and means providing the described functionality for the different components have been described to a degree to which the concept of the present invention will be apparent to the skilled reader. The detailed construction and specification for the different components are considered the object of a normal design procedure performed by the skilled person along the lines set out in the present specification.