A drug dosing device and a dose scale for a drug dosing device

Abstract

The present invention relates inter alia to a drug dosing device comprising a dose scale having a plurality of different visual symbols representing a series of increasing dose unit settings in a number of consecutive dose unit settings defined by a dose increment between two consecutive dose unit settings. A first dose increment between two consecutive higher dose unit settings is selected so that dosing ranges of the two higher dose unit settings do not overlap, and a second dose increment between two consecutive lower dose unit settings is selected so that dosing ranges of the two lower dose unit settings do not overlap. The invention also relates to a dose scale.

Description

[0001] 83896PC01

[0002] 1

[0003] A DRUG DOSING DEVICE AND A DOSE SCALE FOR A DRUG DOSING DEVICE FIELD OF THE INVENTION

[0004] The present invention relates inter alia to a drug dosing device comprising a dose scale having a plurality of different visual symbols representing a series of increasing dose unit settings in a number of consecutive dose unit settings defined by a dose increment between two consecutive dose unit settings. A first dose increment between two consecutive higher dose unit settings is selected so that dosing ranges of the two higher dose unit settings do not overlap, and a second dose increment between two consecutive lower dose unit settings is selected so that dosing ranges of the two lower dose unit settings do not overlap. The invention also relates to a dose scale.

[0005] BACKGROUND OF THE INVENTION

[0006] Many dosing devices are today mechanical devices in which a number of parts and push members for pushing a plunger in an ampoule cooperate to dose a selected amount of a drug. The dosed amount is typically counted as a number of dose units, and the ampoule typically contains a high number of dose units so that the same ampoule can be used for repeatedly dosing different amounts of dose units. An actual amount of dose units to be dosed is set by a user, often by rotating a dial-like member of the device having pre-printed numerals. Setting the dose units in such a device, is done by rotating the dial-like member so that a numeral equal to the number of dose units to be dosed lines-up with an indicator line or arrow positioned in a fixed position of the dosing device.

[0007] Existing state of the art marketed multi-dose, needle-based injection system products (e.g. insulin products) and relevant guidelines for such needle-based injection systems (e.g. ISO11608-1) apply a product configuration that allows for a potential overlap in actual delivered dose between neighboring target doses even when disregarding drug concentration variation. This means that users using a multi-dose, needle-based injection system may receive a delivered dose that is closer to a neighboring dose setting than the dose that is targeted for injection.

[0008] Multi-dose, needle-based injection system products must generally meet the dose accuracy requirements of the widely accepted and recognized international standard ISO 11608-1 (Needle-based injection systems for medical use - 83896PC01

[0009] 2

[0010] Requirements and test methods - Part 1: Needle-based injection systems (ISO 11608-1:2022)). Multi-dose, needle-based injection systems capable of delivering several and different doses from a drug product cartridge are being used for the administration of insulins and other drug products. Such multi-dose, needle-based injection systems are designed to deliver doses between a minimum and a maximum dose with constant increments. By example, many insulin multi-dose, needle-based injection systems are capable of delivering doses from 1 III (10 pL) to e.g. 60 III (600 pL) with increments of 1 III (10 pL). For such a pen device, ISO 11608-1 requires an accuracy of ± 1 III (10 pL) in the dose range 1 - 20 III and an accuracy of ± 5% for higher doses.

[0011] Therefore, a typical insulin multi-dose, needle-based injection system could deliver closer to a 9 unit dose than a 10 unit dose when a 10 unit dose is targeted while still meeting product specifications and being used properly. For some therapies this may be inadequate as the patient may not receive the intended amount of drug product. Specifically, for patients in need of a dose adjustment an undesired clinical response may result. As an example, a diabetes patient needing a dose increase from e.g. 10 units to 11 units based on a relevant biomarker assessment (such as the blood sugar level) could receive a delivered dose which is closer to 10 units and potentially experience a worsening of the clinical situation. For larger doses, patients may experience a dose decrease when a dose increase is intended or the opposite. By example, setting a target dose of 50 III (500 pL) may result in a delivery of anything between 47.5 III and 52.5 III (50 III ± 5%) and still satisfy the ISO standard requirements. Or in other words, setting a dose of 48 III or 52 III may both result in the delivery of 50 III. This is sometimes referred to as dose overlap and in the example five dose settings (48, 49, 50, 51, 52) have overlapping accuracy specifications. It is obvious that dose overlap is more likely for high than for low doses.

[0012] Dosing devices are typically based on mechanical elements such as racks, ratches and other mechanical elements combined to provide a constant dose unit increment. That is, the dose scale and the mechanical elements are mutually configured so that the numerals on a dose indicator scale are a series of increasing numbers S (dose unit settings):

[0013]

[0014] .... Sn] 83896PC01

[0015] 3

[0016] where

[0017] [ L < S2< S3.... < Sn]

[0018] The numerical value of the number S is the amount of dose units and two consecutive numerals are numerically distanced by a constant increment, that is S;+i = St+ c

[0019] where c is a constant value, such as 0.5, 1 or 2 etc.

[0020] However, the inventors have realized that mechanical dosing devices deliver dose units within a certain accuracy such as ±X units or ±Y% of the set dose units. Here, X and Y are numbers depending on the actual dosing device used. Above a certain dose threshold, the accuracy is typically the same amount in percentages independently of the number of dose units.

[0021] For the purpose of the discussion below, an accuracy of ±X at a dose unit setting S means that the probability of a dose delivered, within a dosing range S-X < S < S+X is higher than a predefined confidence limit, such as e.g. 95% or 99% and similar for a specification of relative accuracy Y%. Thus, "accuracy" as used herein may include a systematic off set (inaccuracy) as well as variation (precision) in alignment with ISO 11608-1.

[0022] For a dosing device having a dosing accuracy of ±10% throughout a dynamic dose unit setting range from 1 to 105, the following numbers can be determined: s 1 2 3 4 5

[0023] D [0.9;l.l] [1.8;2.2] [2.7;3.3] [3.6;4.4] [4.5;5.5]

[0024] .

[0025] s 100 101 102 103 104

[0026] D [90;110] [90.9;lll.l] [91.8;112.2] [92.7;113.3] [93.6;114.4]

[0027]

[0028] " S" refers to dose unit setting, that is the number of dose units set on a dial-like member and " D" refers to the dosing range [..] in which the actual dose is delivered.

[0029] Investigating e.g. the dose unit setting S=102 and the dose unit setting S = 103, it is revealed that the lowest expected delivery for 103 dose unit setting is "92.7" which falls truly within the dosing range of the 102 dose units setting: 83896PC01

[0030] 4

[0031] [91.8; 112.2]. Thus, the same dose may be delivered for the two dose unit settings 102 and 103. Such an ambiguity is clearly not desirable. Going to even higher dose unit settings, the ambiguity becomes more and more pronounced.

[0032] In other injectors, the accuracy may be ±Y dose units at lower doses and ±X% dose units at higher doses. The issue with dose overlaps remains for such injectors.

[0033] Hence, an improved dosing device would be advantageous, and in particular a more consistent dosing device ensuring no overlap between neighbouring doses would be advantageous.

[0034] OBJECT OF THE INVENTION

[0035] It is an object of the present invention to at least mitigate ambiguities in dosing a drug by a drug dosing device.

[0036] It is an object of the present invention to provide a more consistent dosing of a drug by a drug dosing device.

[0037] It is a further object of the present invention to provide an alternative to the prior art.

[0038] In particular, it may be seen as an object of the present invention to provide a drug dosing device that solves the above-mentioned problems of the prior art with regards to dose overlap.

[0039] In particular, it may be seen as an object of the present invention to provide a drug dosing device that solves the above-mentioned problems of the prior art with regards to dose overlap even at higher dose unit settings.

[0040] In particular, it may be seen as an object of the present invention to provide a drug dosing device comprising a dose scale wherein the number of settable dose unit settings is maximized while avoiding the above-mentioned problems of the prior art with regards to dose overlap. 83896PC01

[0041] 5

[0042] SUMMARY OF THE INVENTION

[0043] Thus, the above-described object and several other objects are intended to be obtained in a first aspect of the invention by providing a drug dosing device, comprising

[0044] • a receptacle configured for fixedly receiving an ampoule;

[0045] • a plunger translationally arranged in said drug dosing device with an end of said plunger positioned to exert a force on a translationally arranged piston of said ampoule to dose one or several dose units of a drug solution from said ampoule, wherein a dose unit is a volume of a drug solution;

[0046] • a metering element configured to co-operate with said plunger to set a number of different travel distances, where each of said travel distances is a distance said plunger can travel translationally in a direction towards said ampoule; • a travel element configured to upon receipt of a trigger event, such as a manual input to said drug dosing device, to move said plunger said travel distance and thereby exert said force on said piston;

[0047] • a dose scale arranged on or coupled to said metering element, said dose scale comprises a plurality of different visual symbols, each of said visual symbols corresponds to a specific number of dose unit settings, where the dose unit settings correspond to the travel distances and the travel distances correspond to the number of dose units;

[0048] wherein

[0049] • said visual symbols represent a series of increasing dose unit settings in a number of consecutive dose unit settings defined by a dose increment between two consecutive dose unit settings, and

[0050] • a first dose increment between two consecutive higher dose unit settings is selected so that dosing ranges of said two higher dose unit settings do not overlap, and a second dose increment between two consecutive lower dose unit settings is selected so that dosing ranges of said two lower dose unit settings do not overlap, wherein the first dose increment is larger than the second dose increment.

[0051] In preferred embodiments, the dose scale is arranged, such as printed, on a fixed part of the drug dosing device, wherein the fixed part may be a housing of the drug dosing device. In such embodiments, the metering element, or another part used to set the dose, may have an indication line or in general an indication 83896PC01

[0052] 6

[0053] symbol, so that a dose unit setting is made by lining-up the visual symbols for the actual dose unit setting with the indication symbol.

[0054] Dosing range as used herein typically refers to the range in which the amount delivered at a dose unit setting expectedly will fall within based on an expected dosing accuracy or concentration accuracy or both. The dosing accuracy is typically an inherent feature of a drug dosing device and can be determined experimentally. The concentration accuracy is typically an inherent feature of the drug solution and can be determined experimentally.

[0055] In another aspect, the invention relates to a dose scale for a drug dosing device, said dose scale comprising a plurality of different visual symbols, each of said visual symbols corresponds to a specific number of dose unit settings, wherein • said visual symbols represent a series of increasing dose unit settings in a number of consecutive dose unit settings defined by a dose increment between two consecutive dose unit settings, and

[0056] • a first dose increment between two consecutive higher dose unit settings is selected so that dosing ranges of said two higher dose unit settings do not overlap, and a second dose increment between two consecutive lower dose unit settings is selected so that dosing ranges of said two lower dose unit settings do not overlap, wherein the first dose increment is larger than the second dose increment.

[0057] A dose scale and a drug dosing device according to the first aspect of the invention have a number of technical advantages. For instance, the dose scale may be restricted to include only a selection of dose unit settings required for the actual purpose of the device, i.e. unnecessary, intermediate dose unit settings may be avoided. The ambiguity, that different dose unit settings may result in the same actual delivered dose may be avoided. A further advantage of a dose scale and a drug dosing device according to the first aspect of the invention is that dose overlap is avoided even at higher dose unit settings. Regulatory and health related concerns with such "overlapping doses" may be relieved.

[0058] Another advantage of a dose scale and a drug dosing device according to preferred embodiments for use with a drug product requiring patient dose level 83896PC01

[0059] 7

[0060] titration using a biomarker is that safety concerns related to potential dose overlaps are eliminated and that the stated labeling is correct.

[0061] A further advantage of a dose scale and a drug dosing device according to preferred embodiments is that the number of dose unit settings of the dose scale is maximized while dose overlap is avoided.

[0062] Terms used herein are used in a manner being ordinary to a skilled person. Some of these terms are elucidated here below:

[0063] " Drug solution" typically refers to a liquid solution (carrier fluid) comprising one or more active pharmaceutical ingredients (APIs). " Volume of a drug" typically refers to a volume of a drug solution comprising one or more active pharmaceutical ingredients. The drug solution may have a number of characteristics such as concentration, viscosity, purity, stability.

[0064] " Dose unit setting" referenced herein as " S" refers to a symbol, such as a numeral, on a dose scale according to preferred embodiments of the invention. In embodiments, where the symbol is a numeral, the value of the numeral is preferably the number of dose units. In some preferred embodiments, the numerals are integers.

[0065] "dose unit settings do not overlap" refers to that two consecutive dose unit settings shown in a dose scale are truly separate in their expected actual delivered dose amounts. That is, as an example, an actual delivered amount of an ithdose unit setting Si is expected, when taking into account the dosing accuracy being the accuracy of the drug dosing device of x%, where x% preferably includes the delivered volume and / or the drug concentration accuracies, within a first dosing range Dte [S, -x%; Si + x%],and the actual delivered amount of a consecutive dose unit setting is expected within a second dosing range Di+1e [Si+1- x%; Si+1+ x%]. Thus, dose unit settings that do not overlap typically refers to that the two dosing ranges Dtand Di+1do not intersect (i.e. St+x% < Si+1-x%), whereas overlap refers to that the two dosing ranges intersect, i.e. they have a certain actual delivered dosing range in common. 83896PC01

[0066] 8

[0067] "determinable" typically refers to that one or more dose unit settings although being determined in one manner are determinable in another manner.

[0068] "consecutive dose unit setting" preferably refers to a series of symbols such as numbers. In embodiments, where the dose unit setting is represented by a numeral, consecutive dose unit settings S refers to a sequence of numerals, where the value of the numerals is increasing.

[0069] In some preferred embodiments, the accuracy of the dosed drug solution may be similar to the volume accuracy. Here, the volume accuracy preferably refers to the actual volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting. This may apply if the drug concentration variation is not significant and can be neglected.

[0070] In some preferred embodiments, the accuracy of the dosed drug solution may be similar to the drug concentration accuracy. Here, the drug concentration accuracy preferably refers to the actual concentration variation of the active pharmaceutical ingredient between different cartridges of the same nominal concentration. Hence, drug concentration accuracy, typically refers to the accuracy of the amount of the active pharmaceutical ingredient in a specific volume of solution of the active pharmaceutical ingredient, such as a confidence interval for the amount of active pharmaceutical ingredient in a specific volume of solution of the active pharmaceutical ingredient. This may apply if the drug concentration variation is significant and cannot be neglected.

[0071] In some preferred embodiments, the accuracy of the dosed drug solution may be the cumulative effect of the volume accuracy and the drug concentration accuracy. This may apply if both the volume variation and the drug concentration variation are significant and cannot be neglected.

[0072] In some preferred embodiments, the accuracy of the dosed drug solution may be the volume accuracy. In some preferred embodiments, the accuracy of the dosed drug solution may be the drug concentration accuracy. In some preferred embodiments, the accuracy of the dosed drug solution may be the cumulative effect of the volume accuracy and the drug concentration accuracy. In some 83896PC01

[0073] 9

[0074] preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 0.1 to 20 III and ± X% for higher doses, wherein X is a variable selected from 2.05 to 5.

[0075] The formulation "selected from" used in the above paragraph and in other contexts herein where "a variable is selected from" does not refer to a random or personal selection of a number for the accuracy, but refers to a selection of an injection device having the accuracy, that is the accuracy of the injection device selected is X and / or Y either expressed in percentage of, absolute Ill's or volume [I, ml, pl],

[0076] IU as used herein refers to International Units which is a measure of drug amount or dose. E.g. insulins are typically provided in a concentration of 100 lU / mL.

[0077] Therefore, in this case 1 IU = 10 pL.

[0078] In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 0.1 to 20 IU and ± X% for higher doses, wherein X is a variable selected from 2.1 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 0.1 to 20 IU and ± X% for higher doses, wherein X is a variable selected from 2.2 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 0.1 to 20 IU and ± X% for higher doses, wherein X is a variable selected from 2.5 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 0.1 to 20 IU and ± X% for higher doses, wherein X is a variable selected from 3 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 0.1 to 20 IU and ± X% for higher doses, wherein X is a variable selected from 4 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 0.1 IU and ± X% for higher doses, wherein X is at least 2.05. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 0.1 IU and ± X% for higher doses, wherein X is at least 2.1. In some 83896PC01

[0079] 10

[0080] preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 0.1 III and ± X% for higher doses, wherein X is at least 2.2. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 0.1 III and ± X% for higher doses, wherein X is at least 2.5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 0.1 III and ± X% for higher doses, wherein X is at least 3. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 0.1 III and ± X% for higher doses, wherein X is at least 4.

[0081] In some preferred embodiments, the accuracy of the dosed drug solution may be the volume accuracy. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 1 to 20 pl and ± X% for higher doses, wherein X is a variable selected from 2.05 % to 5 %. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 1 to 20 pl and ± X% for higher doses, wherein X is a variable selected from 2.1 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 1 to 20 pl and ± X% for higher doses, wherein X is a variable selected from 2.2 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 1 to 20 pl and ± X% for higher doses, wherein X is a variable selected from 2.5 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 1 to 20 pl and ± X% for higher doses, wherein X is a variable selected from 3 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is a variable selected from 1 to 20 pl and ± X% for higher doses, wherein X is a variable selected from 4 to 5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 1 pl and ± X% for higher doses, wherein X is at least 2.05. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 1 pl and ± X% for higher doses, 83896PC01

[0082] 11

[0083] wherein X is at least 2.1. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 1 pl and ± X% for higher doses, wherein X is at least 2.2. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 1 pl and ± X% for higher doses, wherein X is at least 2.5. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 1 pl and ± X% for higher doses, wherein X is at least 3. In some preferred embodiments the accuracy of the dosed drug solution may be in a range of ± Y for lower doses, wherein Y is at least 1 pl and ± X% for higher doses, wherein X is at least 4.

[0084] Dose unit settings which do not overlap may be considered in accordance with at least two alike scenarios. With reference to a drug being a solution comprising an active pharmaceutical ingredient the two scenarios are disclosed here below.

[0085] In a first scenario, non-dose overlap where drug concentration variation is neglected, may be evaluated as follows:

[0086] S=Dose unit setting e.g. S=10 pL or 150 pg

[0087] x%=dosing accuracy of the drug dosing device, e.g. +-10%

[0088] CAPi=drug concentration of API mg / ml, e.g. 15 mg / ml

[0089] V= total volume dosed (pL)

[0090] Dose= total amount of drug dosed (mg)=V*CAPi

[0091] Vmax=S+x%=10μL+10%=11μL Vmin=S-x%=10μL-10%=9μL

[0092] Thus, the different values (Si) of the dose unit setting are to be selected so that the dosing ranges:

[0093] Vi=[Vmin,i; Vmax,i] and Vi+1=[Vmin,i+1; Vmax,i+1] do not overlap.

[0094] This may also be expressed in amounts of API as follows:

[0095] Dosemax= Vmax* CAPI=11μL*15mg / ml=165μg

[0096] Dosemin= Vmin* CAPI=9μL*15mg / ml=135μg 83896PC01

[0097] 12

[0098] Thus, the different values of Si and Si+i are to be selected so that the dosing ranges:

[0099] Di=[Dmin,i;Dmax,i] and Di+1=[Dmin,i+1;Dmax,i+1] do not overlap.

[0100] For a drug solution having a concentration CAPI =15 mg / ml and a drug dosing device having an accuracy of 10%, the following dose unit setting scales, S without dose overlap may be determined:

[0101] s

[0102] [pL] 10 13 16 20 25 31 D

[0103] [μL] [9;11] [11.7;14.3] [14.4;17.6] [18;22] [22.5;27.5] [27.9;34.1] S

[0104] 150 195 240 300 375 465 [pg]

[0105] D

[0106]

[0107] [pg] [135;165] [176;215] [216;264] [270;330] [338;413] [419;512]

[0108] Where S [pl] refers to a drug dosing device with a volume-based dose unit setting scale and S [pg] refers to a drug dosing device with a dose-based dose unit setting scale.

[0109] As a comparison, using a state-of the art dose scale, dose overlap occurs as highlighted by bold digits in the following table, e.g. a dose unit setting scale comprising a constant dose increment of 5 [pl]; 75 [pg]:

[0110] S

[0111] [μL] 10 15 20 25 30 35 D [μL] [9;11] [13.5;16.5] [18;22] [22.5;27.5] [27;33] [31.5;38.5] S

[0112] 150 225 300 375 450 525 [pg]

[0113] D

[0114]

[0115] [pg] [135;165] [203;248] [270;330] [338;413] [405;495] [473;578]

[0116] In a second scenario, non-dose overlap where drug concentration variation is not neglected, may be evaluated as follows:

[0117] S=Dose unit setting e.g. S=10 pL or 250 pg

[0118] x%= dosing accuracy of the drug dosing device, wherein the dosing accuracy is the cumulative effect of the volume accuracy (e.g. ±10 %) and the drug concentration accuracy (e.g. ±10 %) CAPi=drug concentration of API mg / ml, e.g. 25 mg / ml 83896PC01

[0119] 13

[0120] V= total amount (volume) dosed

[0121] y%=drug concentration accuracy e.g. +-10%

[0122] Dose=m= total amount of API dosed (mg)=V*CAPi

[0123] Vmax=S+x%=10μL + 10%=11μL Vmin=S-x%=10μL-10%=9μL

[0124] If the variation of delivered volume and drug concentration are both uniformly distributed, a non-overlapping dose scale can be conservatively calculated as follows:

[0125] Dosemax= Vmax*CAPI,max=11μL*(25mg / ml+10%) = 11μL*27.5mg / ml=303μg Dosemin= Vmin*CAPI,min=9μL*(25mg / ml-10%)=9μL*22.5mg / ml=203μg

[0126] Thus, the different values of Si and Si+i are to be selected so that the dosing ranges:

[0127] Di=[Dmin,i;Dmax,i] and Di+1=[Dmin,i+1;Dmax,i+1]

[0128] do not overlap.

[0129] For a drug having a concentration CAPI=25 mg / ml, a volume accuracy of 10% and a drug concentration accuracy of 10% the following dose unit setting scales, S without dose overlap may be determined:

[0130] s

[0131] [pL] 10 15 23 35 53 80 D

[0132] [pL] [9;11] [13.5;16.5] [20.7;25.3] [31.5;38.5] [47.7;58.3] [72;88] S

[0133] 250 375 575 875 1325 2000 [pg]

[0134] D

[0135]

[0136] [pg] [203;303] [304;454] [466;696] [709;1059] [1073;1603] [1620;2420]

[0137] Where S [pl] refers to a drug dosing device with a volume-based dose unit setting scale and S [pg] refers to a drug dosing device with a dose-based dose unit setting scale.

[0138] As a comparison, dose overlap occurs using a state-of the art dose scale as highlighted by bold digits in the following table, e.g. a dose scale comprising a constant dose increment of 5 [pl_]; 125 [pg]: 83896PC01

[0139] 14

[0140] s

[0141] [pL] 10 15 20 25 30 35 D

[0142] [μL] [9;11] [13.5;16.5] [18;22] [22.5;27.5] [27;33] [31.5;38.5] S 250 375 500 625 750 875 [μg]

[0143] D

[0144]

[0145] [pg] [203;303] [304;454] [405;605] [506;756] [608;908] [709;1059]

[0146] As an alternative of the second scenario, non-dose overlap where drug concentration variation is not neglected and assuming that the delivered volume and the drug concentration are both normally distributed, a non-overlapping dose scale can be determined or is determinable as follows:

[0147] S=Dose unit setting e.g. S=10 pL or 250 pg

[0148] x%= dosing accuracy of the drug dosing device, wherein the dosing accuracy is the cumulative effect of the volume accuracy (e.g. ±10 %) and the drug concentration accuracy (e.g. ±10 %) CAPi=drug concentration of API mg / ml, e.g. 25 mg / ml

[0149] V= total amount (volume) dosed

[0150] Dose=mAPi= total amount of API dosed (mg)=V*CAPi

[0151] If dose volume or concentration is normally distributed, dose overlap can in principle not be completely avoided, but it can be reduced to a low and known level by defining the 10 % variation of volume and concentration to include e.g. 95% or 99% or 99.9% of all volumes or concentrations.

[0152] The distribution of the product of two normal distributions (dose = volume * concentration) is approximately normally distributed provided the variations are smaller than the mean values for both distributions (see e.g. Antonio Seijas- Macias, Amilcar Oliveira: AN APPROACH TO DISTRIBUTION OF THE PRODUCT OF TWO NORMAL VARIABLES. Discussiones Mathematicae. Probability and Statistics 32 (2012) 87-99). Then the relative variation of the new normal distribution of the function (Asv+c) reflecting both volume and drug concentration variation can be determined according to: 83896PC01

[0153] 15

[0154] A

[0155]

[0156] sv+C= √(Δsv2+ ΔsC2)

[0157] wherein Asvis the relative variation of the normal distributed volume and Asc is the relative variation of the drug concentration defined to ensure an acceptable 5 low and known probability of dose overlap.

[0158] In the case that Asvis 10% and Asc is 10%, Asv+c can be determined according to:

[0159] A

[0160]

[0161] sv+C= √(Δsv2+ Δsc2) = √(0.12+ 0.12) = 0.1414 = 14.14%

[0162] 0

[0163] Likewise, the combined variation Asv+ccan be determined for multiples of variations, e.g. double, triple or even higher multiplied variations.

[0164] Thus, the different values of Si and Si+iare to be selected so that the dosing

[0165] 5 ranges:

[0166] Di= [Dmin,i Dmax,i] and Di+1=[Dmin,i+1;Dmax,i+1]

[0167] do not overlap.

[0168] 0

[0169] For a drug having a concentration CAPI=25 mg / ml, a volume accuracy of 10% and a drug concentration accuracy of 10% the following dose unit setting scales, S without dose overlap may be determined:

[0170] s

[0171] [pL] 10 13,3 17,7 23,6 31,4 41,8 D

[0172] [PL] [9.0; 11.0] [12.0; 14.6] [15.9; 19.5] [21.2;26.0] [28.3;34.5] [37.6;46.0] S

[0173] [pg] 250 333 443 590 785 1045 D

[0174]

[0175] [pg] [214.7;285.4] [285.9;380.1] [380.4;505.6] [506.6;673.4] [674.0;896.0] [897.2;1192.8] 5

[0176] Where S [pl] refers to a delivery device with a volume-based dose unit setting scale and S [pg] refers to a delivery device with a dose-based dose unit setting scale. 83896PC01

[0177] 16

[0178] As a comparison, dose overlap occurs using a state-of the art dose scale as highlighted by bold digits in the following table, e.g. a dose scale comprising a constant dose increment of 5 [pl]; 125 [pg]:

[0179] s

[0180] [μL] 10 15 20 25 30 35 D [μL] [9;11] [13.5;16.5] [18;22] [22.5;27.5] [27;33] [31.5;38.5] s

[0181] 250 375 500 625 750 875 [pg]

[0182] D

[0183]

[0184] [μg] [215;285] [322;428] [429;571] [537;713] [644;856] [751;999]

[0185] Accordingly, a dose scale may have numerals (or symbols) for the dose unit setting which refers to the total volume of the solution including the active pharmaceutical ingredient delivered within a range D, and / or a have numerals (or symbols) for the dose unit setting, which refers to the amount of active pharmaceutical ingredient, e.g. in mg, pg or i.u. (international unit) delivered within a range D'.

[0186] " Linear dose scale" typically refers to a dose scale in which the increment between two consecutive dose unit settings, S, within a series of dose unit settings is a constant value.

[0187] " Non-linear dose scale" typically refers to a dose scale in which the increment between two consecutive dose unit settings, S, increases with higher dose unit settings.

[0188] " Predefined threshold" is preferably determined as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if a certain linear or non-linear dose scale applied at low dose unit settings were applied throughout all dose unit settings.

[0189] BRIEF DESCRIPTION OF THE FIGURES

[0190] The present invention and in particular preferred embodiments thereof will now be described in more details with reference to the accompanying figures. The figures show ways of implementing the present invention and are not to be construed as 83896PC01

[0191] 17

[0192] being limiting to other possible embodiments falling within the scope of the attached claim set.

[0193] Fig. 1 schematically illustrates, in a sequence of five figures, dosing of a drug solution by a drug dosing device according to a first embodiment of the invention;

[0194] Fig. 2 schematically illustrates a preferred embodiment of an inspection window provided in a housing of a drug dosing device according to an embodiment of the invention.

[0195] Fig. 3A and 3B each schematically illustrates preferred embodiments of a series of increasing numerals.

[0196] Fig. 4A schematically illustrate a metering element and 4B schematically illustrate a selection element according to a preferred embodiment of the invention; in Fig.

[0197] 4A the metering element is disclosed isolated and in Fig. 4B, the selection element is illustrated as comprised in a drug dosing device (illustrated only in part) according to a preferred embodiment. Kindly observe that a housing of the drug dosing device is indicated by broken lines.

[0198] Fig. 5 schematically illustrates a section of a preferred embodiment of a metering element with an indication of a dose scale in a 3-dimensional view.

[0199] DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0200] Reference is made to Fig. 1 schematically illustrating in cross sectional views a drug dosing device 1 according to a first embodiment. The device 1 has a receptacle 2 configured for fixedly receiving an ampoule 3. The receptacle 2 is formed within a housing 11 of the device 1 at a first end of the drug dosing device 1. Interior of the drug dosing device 1, an end of the ampoule 3 abuts a stop member 16. A cap 17 through which the needle 18 extends is placed typically by being screwed-on at the first end of the drug dosing device 1. Thus, the combination of the receptacle 2, the stop member 16 and the cap 17 fixes the ampoule 3 within the housing 11.

[0201] Dosing of drug from the ampoule 3 is provided inter alia by a plunger 4. The plunger 4 is translationally and non-rotationally arranged inside the drug dosing 83896PC01

[0202] 18

[0203] device 1. The ampoule 3 has a piston 9 which is translationally arranged in the ampoule 3 so that when the piston 9 is moved towards the needle 18, liquid contained in the ampoule flows out through the needle 18. As illustrated in Fig. 1, an end of the plunger 4 is positioned to exert a force on the translationally arranged piston 9 of the ampoule 3 so as to deliver dose units of drug from the ampoule when the plunger 4 is moved towards the needle 18. Herein, a dose unit is a volume of a drug.

[0204] The volume of drug solution to be delivered, that is the number of dose units to be delivered, is set by the metering element 5. The metering element 5 is configured to co-operate with the plunger 4 to set a number of different travel distances 6, where each of such travel distances 6 is a distance the plunger 4 can travel translationally in a direction towards said ampoule 3. The travel distance 6 is delimited by the travel stop 7 which is an element placed in a fixed position within the device, so that when the metering element 5 moves towards the needle, this movement is stopped when the metering element 5 abuts the travel stop 7. As the travel distance 6 is directly proportional to the volume of drug solution ejected, setting a travel distance corresponds to setting a number of dose units to be dosed.

[0205] In the embodiment of Fig. 1, the metering element 5 has an internal thread and an end of the plunger 4 extending into the metering element 5 has an external thread mating with the internal thread. Thus, when the metering element 5 is rotated, it moves outwardly (because the plunger is non-rotational) and the number of rotations corresponds to a travel distance 6.

[0206] The device shown in Fig. 1, also has a travel element 10 which is configured to move the plunger 4 the set travel distance 6 upon receipt of an input and thereby exert said force on said piston 9 and effectuate drug solution ejection. In the embodiment of Fig. 1, the travel element 10 is an end of the metering element accessible to a user to an extent where the user can move, by pushing the travel element 10, the plunger 4 the distance defined by the set travel distance 6.

[0207] It is noted, that the travel element 10 may be configured to move the plunger 4 by a manual input to the drug dosing device 1 wherein such manual input triggers 83896PC01

[0208] 19

[0209] movement of the travel element 10. Thus, a manual input may be referred to as a trigger event.

[0210] In another embodiment (not illustrated) the translational movement of the plunger 4 is effectuated by a spring. Upon setting the metering element 5, the spring is tensioned and kept in tensioned state by a latch. The latch is released by a trigger event, typically being a manually applied force exerted onto a trigger element which releases the latch. When the latch is released, the spring extends and provides the translational movement of the plunger 4.

[0211] Fig. 1 illustrates three different configurations of the drug dosing device 1, labelled a), b) and c) in Fig. 1. The configuration labelled d) in Fig. 1 is the same configuration as illustrated in Fig. 1 a), and e) is the same configuration as b). Fig. 1, a) illustrates a configuration in which a travel distance 6 is not set. Fig. 1, b) illustrates a configuration in which a travel distance 6 is set by rotating the metering element 5. Fig. 1, c) illustrates a configuration in which drug is ejected by pushing the travel element 10. As it appears from the Fig.l, the position of the travel element 10 is the same in Fig. 1A and Fig. ID, although the piston 9 has moved according to the travel distance 6.

[0212] To allow for re-setting the dose scale to e.g. zero, the metering element 5 may be configured to not change its longitudinal position relatively to the plunger 4 when rotated in an opposite direction than when setting the travel distance 6. This may be accomplished by the metering element 5 having a ratchet wheel and a pawl.

[0213] In the illustrated embodiment, the drug dosing device has a dose scale arranged on or in an outer surface of the metering element 5. Alternatively, the dose scale may be mechanically coupled to the metering element 5. The drug dosing device has a window allowing visual reading of the dose scale, e.g. as illustrated in Fig.

[0214] 2. The dose scale may have a plurality of different visual symbols, where each of the symbols corresponds to a specific number of dose units. Such a symbol may be a number of dots, where the number of dots corresponds to a specific number of dose units. A symbol may alternatively be a colour, where a specific colour corresponds to a specific number of dose units. A symbol may alternatively be a number, where the number corresponds to the number of dose units. A symbol 83896PC01

[0215] 20

[0216] may alternatively be a number, where the number corresponds to the volume of drug solution to be administered. A symbol may alternatively be a number, where the number corresponds to the amount of the active pharmaceutical ingredient to be administered.

[0217] The symbols of the dose scale represent a series of increasing dose unit settings being defined by a dose increment between two consecutive dose unit settings, and where at least one of the dose increments between two consecutive higher dose unit settings is larger than a dose increment between two consecutive lower dose unit settings.

[0218] Reference is made to fig. 2. schematically illustrating in a cross-sectional view of the setting of dose units (8) in a drug dosing device. The drug dosing device has an inspection window (14) and an indicator (12) that is configured to line up with a numeral indicative of the dose units (8) of a metering element (5).

[0219] According to preferred embodiments, for at least some of the visual symbols, the dose increment between two consecutive dose unit settings is increasing with increasing dose unit settings. " Some of the symbols typically" refers to at least one non-linear dose scale having at least three different dose increments lncLor at least three linear dose scales having a different dose increment / nc(, where e.g. for three dose increments:

[0220] Inc1< Inc2< lnc3.

[0221] In particular preferred embodiments, the symbols of the dose scale are numerals, and one such example is illustrated in Fig. 1. The metering element 5 is illustrated in an isolated view at the lower part of Fig. 1 and the numerals "100", "160" and "320" are shown which each represents a dose unit setting S. Numeral 100 corresponds to 100 dose units, 160 corresponds to 160 dose units, and 320 corresponds to 320 dose units.

[0222] In embodiments where the symbols for the dose unit settings S are numerals corresponding to the number of dose units, the numerals of the dose scale are preferably a series of increasing numerals: 83896PC01

[0223] 21

[0224]

[0225] ■■■ -^n]

[0226] where

[0227] [St< S2< S3.... < Sn]

[0228] Two consecutive numerals are numerically distanced by an increment, e.g. between the i and i + 1 numerals:

[0229]

[0230] Inci+1,i= Si+1— Si

[0231] According to preferred embodiments, the drug dosing device doses dose units with an accuracy, such as ±15% or ±10% or ±5%. For such drug dosing devices, dose increments are typically selected so that the dosing ranges of two consecutive dose unit settings comprised in the dose scale do not overlap. Such a dose increment between the two consecutive dose unit settings may be selected to be larger than a dose increment between two lower consecutive dose unit settings including the accuracy.

[0232] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0233] Di∈ [Si— x%; Si+ x%]

[0234] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0235] Di+1∈ [Si+1— x%; Si+1+ x%]

[0236] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting. For this, the symbols referring 83896PC01

[0237] 22

[0238] to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0239] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0240] Di∈ [Si— x%; Si+ x%]

[0241] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and x% is a variable selected from 2.05 to 5. The expected accuracy covers in a nonlimiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0242] Di+1∈ [Si+1— x%; Si+1+ x%]

[0243] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is a variable selected from 2.05 to 5. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0244] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0245] Di∈ [Si— x%; Si+ x%] 83896PC01

[0246] 23

[0247] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and x% is a variable selected from 2.1 to 5. The expected accuracy covers in a nonlimiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0248] Di+1∈ [Si+1— x%; Si+1+ x%]

[0249] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is a variable selected from 2.1 to 5. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0250] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0251] Di∈ [Si— x%; Si+ x%]

[0252] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and x% is a variable selected from 2.2 to 5. The expected accuracy covers in a nonlimiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0253] D

[0254]

[0255] Di+1∈ [Si+1— x%; Si+1+ x%] 83896PC01

[0256] 24

[0257] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is a variable selected from 2.2 to 5. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0258] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0259] Di∈ [Si— x%; Si+ x%]

[0260] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and x% is a variable selected from 2.5 to 5. The expected accuracy covers in a nonlimiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0261] Di+1∈ [Si+1— x%; Si+1+ x%]

[0262] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is a variable selected from 2.5 to 5. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0263] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of: 83896PC01

[0264] 25

[0265] Di∈ [Si— x%; Si+ x%]

[0266] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and x% is a variable selected from 3 to 5. The expected accuracy covers in a nonlimiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0267] Di+1∈ [Si+1— x%; Si+1+ x%]

[0268] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is a variable selected from 3 to 5. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0269] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0270] Di∈ [Si— x%; Si+ x%]

[0271] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and x% is a variable selected from 4 to 5. The expected accuracy covers in a nonlimiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of: 83896PC01

[0272] 26

[0273] Di+1∈ [Si+1— x%; Si+1+ x%]

[0274] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is a variable selected from 4 to 5. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0275] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0276] Di∈ [Si— x%; Si+ x%]

[0277] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and x% is at least 2.05. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0278] Di+1∈ [Si+1— x%; Si+1+ x%]

[0279] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 2.05. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap. 83896PC01

[0280] 27

[0281] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0282] Di∈ [Si— x%; Si+ x%]

[0283] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 2.1. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0284] Di+1∈ [Si+1— x%; Si+1+ x%]

[0285] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 2.1. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0286] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0287] Di∈ [Si— x%; Si+ x%]

[0288] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 2.2. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected 83896PC01

[0289] 28

[0290] concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0291] Di+1∈ [Si+1— x%; Si+1+ x%]

[0292] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 2.2. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0293] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0294] Di∈ [Si— x%; Si+ x%]

[0295] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 2.5. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0296] Di+1∈ [Si+1— x%; Si+1+ x%]

[0297] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 2.5. For this, the symbols referring to the lower dose unit setting and the higher dose unit 83896PC01

[0298] 29

[0299] setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0300] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0301] Di∈ [Si— x%; Si+ x%]

[0302] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 3. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0303] Di+1∈ [Si+1— x%; Si+1+ x%]

[0304] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 3. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0305] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0306] Di∈ [Si— x%; Si+ x%] 83896PC01

[0307] 30

[0308] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 4. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0309] Di+1∈ [Si+1— x%; Si+1+ x%]

[0310] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 4. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0311] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0312] Di∈ [Si— x%; Si+ x%]

[0313] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 5. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0314] D

[0315]

[0316] Di+1∈ [Si+1— x%; Si+1+ x%] 83896PC01

[0317] 31

[0318] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 5. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0319] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0320] Di∈ [Si— x%; Si+ x%]

[0321] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 6. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0322] Di+1∈ [Si+1— x%; Si+1+ x%]

[0323] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 6. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0324] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of: 83896PC01

[0325] 32

[0326] Di∈ [Si— x%; Si+ x%]

[0327] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 7. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0328] Di+1∈ [Si+1— x%; Si+1+ x%]

[0329] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 7. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0330] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0331] Di∈ [Si— x%; Si+ x%]

[0332] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 8. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of: 83896PC01

[0333] 33

[0334] f

[0335]

[0336] \+l t^i+1 + X° / o]

[0337] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 8. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0338] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0339] Di∈ [Si— x%; Si+ x%]

[0340] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 9. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0341] Di+1∈ [Si+1— x%; Si+1+ x%]

[0342] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 9. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0343] According to preferred embodiments, for at least two of the consecutive dose unit settings S, a lower and higher dose unit setting are determined so that their 83896PC01

[0344] 34

[0345] dosing ranges do not overlap. In this regard, a lower of the consecutive dose unit settings corresponds to dose units within the dosing range D of:

[0346] Di∈ [Si— x%; Si+ x%]

[0347] where Si is the numeral of the lower dose unit setting and x% is the dosing accuracy being an expected accuracy in dosing for the lower dose unit setting and % is at least 10. The expected accuracy covers in a non-limiting manner expected volume variation of the ejected volume of the drug solution between different drug solution ejections of the same dose unit setting, expected concentration variations of the active pharmaceutical ingredient (API) between different cartridges of the same nominal concentration or both. Similarly, a higher of the consecutive dose units setting corresponds to dose units within the dosing range of:

[0348] Di+1∈ [Si+1— x%; Si+1+ x%]

[0349] where Si+i is the numeral of the higher dose unit setting and x% is an expected accuracy of dosing at said higher dose unit setting and x% is at least 10. For this, the symbols referring to the lower dose unit setting and the higher dose unit setting respectively, correspond to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0350] As an example, the following numbers refer to dose unit settings for a drug dosing device having a drug dosing accuracy of ±10% where the dosing ranges do not overlap (" S" is dose unit setting and " D" is dosing range):

[0351] s 10 13 16 20 25 31 38 47 Dmin — S-10% 9 11.7 14.4 18 22.5 27.9 34.2 42.3

[0352]

[0353] Dmax= S+10% 11 14.3 17.6 22 27.5 34.1 41.8 51.7

[0354] Again, the drug dosing accuracy of ±10% may cover volume variation, concentration variation of the API in the drug solution or both. 83896PC01

[0355] 35

[0356] According to preferred embodiments, for at least two of said consecutive dose unit settings, a higher of said dose unit settings, St+i, is determined or determinable by:

[0357] Si+1= Si+ Inci+1,i

[0358] where Inci+1,iis determined or determinable as:

[0359] Inci+1,i= roundup (Six% + Si+1x% + Δ).

[0360] Here roundup rounds the result up to nearest integer and Inci+1,iis the dose increment between the dose unit settings Si+1and Si. The roundup function can be left out in case the numerals do not have to be given in integers. x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both, and A is a value selected, to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. The dose scale can be determined or is determinable by:

[0361] Si+1= Si+ Inci+1,i= Si+ roundup (Six% + Si+1x% + Δ).

[0362] This condition can is solvable by an iterative method, and such iterative method may be initiated by selection of S1= 10, Δ= 5, and X% = 0.1 (as an example). By this the condition reads:

[0363] S2= 10 + roundup (10 · 0.1 + S2· 0.1 + 5) = 10 + roundup(6 + 0.1 · S2).

[0364] The solution to this condition can be found by iteration, starting e.g. by guessing S2= 16 and checking whether this number fulfils the condition. 16 does not fulfil, so another number is selected and after some iterations it can be found that S2= 18 matches the condition. A preferred iterative method is the bisection method. Once S2= 18 has been determined, S3can be determined in the same manner.

[0365] Alternatively, for at least two of said consecutive dose unit settings, a higher of said dose unit settings, St+i, is determined or determinable by:

[0366] Si+1= Si+ Inci+1,i

[0367] where Inci+1,iis determined or determinable as: 83896PC01

[0368] Inci+1,i= roundup (Six% + Six% + Δ) = roundup (2Six% + Δ), where Δ implicitly includes the difference between Si+1·x% and Si·x% = Si+1·x% - Si·x% = Inci+1,i·x%.

[0369] So by including (Inci+1,i· x%) in Δ the dose scale can be determined or is determinable by:

[0370] Si+1= Si+ Inci+1,i= Si+ roundup (2 · Six% + Δ)

[0371] In the example below, with x% = 10%, Δ in: Si+1= Si+ roundup(2 · Six% + Δ) is selected Δ=2%Sito avoid dose overlap and to achieve a high number of dose unit settings within a dose scale range S∈ [10:47].

[0372] s 10 13 16 20 25 31 38 47 Dmin — S- 10% 9,0 11,7 14,4 18,0 22,5 27,9 34,2 42,3 Dmax=

[0373]

[0374] S+10% 11,0 14,3 17,6 22,0 27,5 34,1 41,8 51,7

[0375] As a comparison, setting A=0%S / dose overlap occurs as highlighted by bold digits in the following table:

[0376] S 10 12 15 18 22 27 33 40 Dmin — S-10% 9 10,8 13,5 16,2 19,8 24,3 29,7 36

[0377]

[0378] Dmax= S+10% 11 13,2 16,5 19,8 24,2 29,7 36,3 44

[0379] Alternatively, the dose increments are determined based on:

[0380] Inci+1,i> roundup (Six% + Si+1x% + Δ)

[0381] where the values for:

[0382]

[0383] are pre-selected and adjusted, or removed from the series, if: 83896PC01

[0384] 37

[0385] Inci+l i< roundup (S(x% + Si+1x% + A).

[0386] According to preferred embodiments, the dose increment, is determined or determinable based on:

[0387] Inci+1,i= roundup (Six% + Si+1x% + Δ).

[0388] Here roundup rounds the result up to nearest integer and Inci+1,iis the dose increment between the dose unit settings Si+1and Si. The roundup function can be left out in case the numerals do not have to be given in integers. x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both, and A is a constant value selected to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. Accordingly, such a dose scale has a non-linear dose scale and can be determined or is determinable by:

[0389] Si+1= Si+ Inci+1,i= Si+ roundup (Six% + Si+1x% + Δ).

[0390] Alternatively, the dose increment, is determined or determinable based on:

[0391] Inci+1,i= roundup (Six% + Six% + Δ) = roundup (2Six% + Δ)

[0392] where (Inci+1,i·x%) is included in Δ and Δ is a constant value selected, to ensure that the dosing ranges of two consecutive dose unit settings do not overlap.

[0393] Accordingly, such a dose scale is a non-linear dose scale and can be determined or is determinable by:

[0394] Si+1= Si+ Inci+1,i= Si+ roundup (2 · Six% + Δ).

[0395] According to preferred embodiments, the dose increment, is determined or determinable based on:

[0396] Inci+1,i= roundup (Six% + Si+1x% + Δ1).

[0397] Here roundup rounds the result up to nearest integer and Inci+1,iis the dose increment between the dose unit settings Si+1and Si. The roundup function can be left out in case the numerals do not have to be given in integers. x% is a value 83896PC01

[0398] 38

[0399] selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both, and A, is a constant value selected to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. Here, A, is a first constant value (A below a predefined threshold and a second constant value (A2) above the predefined threshold and A s smaller than A2(A1< A2). The predefined threshold is selected as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if a dose increment according to:

[0400] Inci+1,i= roundup (Six% + Si+1x% + Δ1)

[0401] applied between low dose unit settings were applied throughout all dose unit settings. Accordingly, such a dose scale comprises two non-linear dose scales, and the first non-linear dose scale can be determined or is determinable by:

[0402] Si+1= Si+ Inci+1,i= Si+ roundup (Six% + Si+1x% + Δ1),

[0403] for lower dose unit settings below the predefined threshold and the second nonlinear dose scale can be determined or is determinable by:

[0404] Si+1= Si+ Inci+1,i= Si+ roundup (Six% + Si+1x% + Δ2)

[0405] for higher dose unit settings above the predefined threshold.

[0406] Alternatively, the dose increment, is determined or is determinable based on:

[0407] Inci+1,i= roundup (Six% + Six% + Δ1) = roundup (2Six% + Δ1),

[0408] where A, includes (Jnci+l i-x%) and A, is a constant value selected, to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. Here, A, is a first constant value (A below a predefined threshold and a second constant value (A2) above the predefined threshold and A s smaller than A2(A1< A2). The predefined threshold is selected as the first dose unit setting in a series of dose 83896PC01

[0409] 39

[0410] unit settings, which would overlap a succeeding increased dose unit setting if the increment according to:

[0411] Inci+1,i= roundup (2Six% + Δ1)

[0412] applied between low dose unit settings were applied throughout all dose unit settings. Accordingly, such a dose scale comprises two non-linear dose scales, and the first non-linear dose scale can be determined or is determinable by:

[0413] Si+1= Si+ Inci+1,i= Si+ roundup (2 · Six% + Δ1),

[0414] for lower dose unit settings below the predefined threshold and the second nonlinear dose scale by:

[0415] Si+1= Si+ Inci+1,i= Si+ roundup (2 · Six% + Δ2)

[0416] for higher dose unit settings above the predefined threshold.

[0417] The invention is not limited to a first and a second non-linear dose scale, as a third, fourth or higher number of non-linear dose scales may be used, by defining multiple predefined thresholds that separate the individual non-linear dose scales and each non-linear dose scale has a different value of A,. In preferred embodiments, a dose scale may have a piecewise non-linear dose scale having a number of successive non-linear dose scales. For each of the non-linear dose scales, the dose increment can be determined or is determinable by:

[0418] Inci+1,i= roundup (Six% + Si+1x% + Δ1), or by

[0419] Inci+1,i= roundup (2Six% + Δ1)

[0420] wherein Δ1is larger for a subsequent non-linear dose scale than for a preceding non-linear dose scale.

[0421] According to preferred embodiments, the dose increment, is determined or is determinable based on: 83896PC01

[0422] 40

[0423] Inci+1,i= roundup (Six% + Si+1x% + Δ).

[0424] Here roundup rounds the result up to nearest integer and Inci+1,iis the dose increment between the dose unit settings Si+1and Si. The roundup function can be left out in case the numerals do not have to be given in integers. x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both, and A is a value increasing with dose unit settings selected, to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. Accordingly, such a dose scale is a non-linear dose scale and can be determined or is determinable by:

[0425] Si+1= Si+ Inci+1,i= Si+ roundup (Six% + Si+1x% + Δ).

[0426] Alternatively, the dose increment, is determined or determinable based on:

[0427] Inci+1,i= roundup (Six% + Six% + Δ) = roundup (2Six% + Δ),

[0428] here Δ includes (Inci+1,i·x%) and Δ is a value increasing with dose unit settings selected, to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. Accordingly, such a dose scale is a non-linear dose scale and can be determined or is determinable by:

[0429] Si+1= Si+ Inci+1,i= Si+ roundup (2 · Six% + Δ).

[0430] According to preferred embodiments, Inci+1,iis a value increasing with dose unit settings. For instance, the value of Inci+1,ibetween two consecutive dose unit settings may be determined as a percentage of the lower of the two dose unit setting, such as:

[0431] Inci+1,i= Si+ y%Si

[0432] where the value of y% is selected to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. 83896PC01

[0433] 41

[0434] According to preferred embodiments, the dose increment, is determined or determinable based on:

[0435] Inci+1,i= roundup (Six% + Si+1x% + Δi).

[0436] Here roundup rounds the result up to nearest integer and Inc is the dose increment. The roundup function can be left out in case the numerals do not have to be given in integers. x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both, and A, is a value increasing with dose unit settings selected to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. Here, A, is a first number (A increasing with dose unit settings below a predefined threshold and a second number (A2) increasing with dose unit settings above the predefined threshold and A s smaller than A2(A1< A2). The predefined threshold is selected as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if the dose increment according to:

[0437] Inci+1,i= roundup (Six% + Si+1x% + Δ1)

[0438] applied between low dose unit settings were applied throughout all dose unit settings. Accordingly, such a dose scale comprises two non-linear dose scales, and the first dose scale can be determined or is determinable by:

[0439] Si+1= Si+ Inci+1,i= Si+ roundup (Six% + Si+1x% + Δ1),

[0440] for lower dose unit settings below the predefined threshold and the second dose scale by:

[0441] Si+1= Si+ Inci+1,i= Si+ roundup (Six% + Si+1x% + Δ2)

[0442] for higher dose unit settings above the predefined threshold.

[0443] Alternatively, the dose increment, is determined or determinable based on: 83896PC01

[0444] 42

[0445] Inci+1,i= roundup (Six% + Six% + Δi) = roundup (2Six% + Δi),

[0446] where Δiincludes (Inci+1,i· x%) and Δiis a value selected, to ensure that the dosing ranges of two consecutive dose unit settings do not overlap. Here, A, is a first value (A increasing with dose unit settings below a predefined threshold and a second value (A2) increasing with dose unit settings above the predefined threshold and A s smaller than A2(A1< A2). The predefined threshold is selected as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if the dose increment according to:

[0447] Inci+1,i= roundup (2Six% + Δ1)

[0448] applied between low dose unit settings were applied throughout all dose unit settings. Accordingly, such a dose scale has two non-linear dose scales, and the first non-linear dose scale can be determined or is determinable by:

[0449] Si+1= Si+ Inci+1,i= Si+ roundup (2 · Six% + Δ1),

[0450] for lower dose unit settings below the predefined threshold and the second nonlinear dose scale by:

[0451] Si+1= Si+ Inci+1,i= Si+ roundup (2 · Six% + Δ2)

[0452] for higher dose unit settings above the predefined threshold.

[0453] The invention is not limited to a first and a second non-linear dose scale, as a third, fourth or higher number of non-linear dose scales may be used, by defining multiple predefined thresholds that separate the individual non-linear dose scales and each non-linear dose scale has a different value of A,. In preferred embodiments, a dose scale may have a piecewise non-linear dose scale having a number of successive non-linear dose scales. For each of the non-linear dose scale, the dose increment is determined or determinable by:

[0454] Inci+1,i= roundup (Six% + Si+1x% + Δi) , or by

[0455] Inci+1,i= roundup (2Six% + Δi) 83896PC01

[0456] wherein A;is larger for a subsequent non-linear dose scale than for a preceding non-linear dose scale. In preferred embodiments the dose scale may have a piecewise non-linear dose scale having a number of successive non-linear dose scales wherein for each non-linear dose scale

[0457]

[0458] is a constant value or a value increasing with dose unit setting.

[0459] By definition, to ensure against dose overlap, Ind must fulfil:

[0460] Inci> Six% + Si+1x% = x%(Si+ Si+1),

[0461] where In is defined by

[0462] Si+1= Si+ Inci.

[0463] Therefore (by eliminating Si+1), dose overlap is avoided by selecting Ind such that:

[0464] 2Stx%

[0465] Inci > - - —.

[0466] 1 - x%

[0467] Here, x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both. This incrementation provides a densest dose scale without dose overlap.

[0468] According to preferred embodiments, for at least two of said consecutive dose unit settings, a higher of said dose unit settings, Si+i, is determined or determinable by

[0469] Si+1= Si+ Inci+1,i

[0470] where Inci+1,iis determined or determinable by:

[0471] ('ll a ■ 2Spx%

[0472] / nci+1;i= a ■ roundup — - — —

[0473]

[0474] where α is a numeral and x% is an expected dosing accuracy in dosing at the ithrespectively the i+1thdose unit setting. Here, x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers 83896PC01

[0475] 44

[0476] volume variation, concentration variation of the API in the drug solution or both. In some embodiments a is 0.1. In some embodiments a is 0.5. In some embodiments a is 1.0. In some embodiments a is 2.0. a is preferably selected in dependency of a preferred numbering of the dose unit settings. In preferred embodiments:

[0477] • α = 2.0 is used to provide a dose scale with even numbers only,

[0478] • α = 0.1 is used to provide a dose scale with single decimals

[0479] • a = 0.5 is used to provide a dose scale with half unit increments, and

[0480] • α = 1.0 is used to provide a dose scale with integers,

[0481] as detailed here below.

[0482] By use of the roundup function and α = 1, the densest possible integer dose scale can be achieved by:

[0483] / 2Stx% \

[0484] Inct= roundup I - - — I

[0485]

[0486] \ J. X / § /

[0487] By use of the roundup function and α = 0.5, a non-overlapping half-integer dose scale can be achieved by:

[0488] / 2 • 2Six%\

[0489] Inc, = 0.5 ■ roundup I— - — I.

[0490]

[0491] \ J. X / O /

[0492] By use of the roundup function and α = 0.1, a non-overlapping single-decimal dose scale can be achieved by:

[0493] / 10 • 2S(x%

[0494] Inc, = 0.1 ■ roundup — - — —

[0495]

[0496] As an example, the following numbers refer to the densest possible single-decimal dose unit settings for a drug dosing device having a drug dosing accuracy of ±10% where the dosed units do not overlap (" S" is dose unit setting and " D" is dosing range):

[0497] s 0.5 0.7 0.9 1.2 1.5 1.9 2.4 3.0

[0498]

[0499] Dmin — S-10% 0.45 0.63 0.81 1.08 1.35 1.71 2.16 2.7 83896PC01

[0500] 45

[0501] I Dmax— S+10% I 0.55 I 0.77 I 0.99 | 1.32 | 1.65 | 2.09 | 2.64 | 3.3 |

[0502] Alternatively, for at least two of said consecutive dose unit settings, a higher of said dose unit settings, Si+i, is determined or determinable by

[0503] Si+1= Si+ Inci+1,i

[0504] where Inci+1,iis determined or determinable by:

[0505] 2S(x%

[0506] ,

[0507]

[0508] nc'=l^%+ £

[0509] Here ε is a small number, such as a constant value in the order of 0.01-0.1 or a variable such as 1 permille of Si.

[0510] According to preferred embodiments, the dose scale comprises a linear dose scale, such as for instance determined or determinable by:

[0511] Si+1= Si+ k.

[0512] Here k is a constant value selected to ensure that the dosing ranges of two consecutive dose unit settings Si and Si+i do not overlap. In some embodiments k is determined or determinable by:

[0513] k = Smax− Smax-1= Incmax,max-1> (Smaxx% + Smax-1x%)

[0514] wherein Smax is the highest dose unit setting within the linear dose scale and x% is an expected accuracy in dosing at the ithrespectively the i+lthdose unit settings, where accuracy covers volume variation, concentration variation of the API in the drug solution or both.

[0515] According to preferred embodiments, a consecutive dose unit setting (S / + ) is determined or determinable by:

[0516] Si+1= Si+ ki

[0517] wherein kiis a first constant value, k1, up till dose unit settings being larger than a predefined threshold, and a second constant value k2for dose unit settings 83896PC01

[0518] 46

[0519] being larger than said predefined threshold, where the second constant value k.2 is larger than the first constant value ki, kr< k2. Accordingly, such a dose scale has a first linear dose scale below the predefined threshold and a second linear dose scale above the predefined threshold, that is for / =1 to n where n corresponds to the predefined threshold:

[0520] Si+1= Si+ k1Wherein ki is a constant value, such as an integer that ensures that the dosing ranges of two consecutive dose unit settings do not overlap. Alternatively, ki is a constant value that can be determined or is determinable by:

[0521]

[0522] k1= Sn− Sn-1= Incn,n-1> (Snx% + Sn-1x%)

[0523] and for / =n+l to m where m corresponds to the maximal dose unit setting:

[0524] Si+1= Si+ k2

[0525] Wherein k2 is a constant value, such as an integer that ensures that the dosing ranges of two consecutive dose unit settings do not overlap. Alternatively, k2 is a constant value that can be determined or is determinable by:

[0526] ^

[0527]

[0528] -2—^m-1 ~ > (SmX° / o +.

[0529] The predefined threshold is determined or determinable as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if the first linear scale applied at low dose unit settings were applied throughout all dose unit settings. x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both.

[0530] The invention is not limited to a first and a second linear dose scale, as a third, fourth or higher number of linear dose scales may be used, by defining multiple consecutive predefined thresholds and increasing values of kjin between the thresholds. 83896PC01

[0531] 47

[0532] Reference is made to fig. 3B schematically illustrating a dose scale comprising a plurality of linear dose scales. The dose increment is a constant value below a predefined threshold and another constant value above the predefined threshold. In this illustrated embodiment, one predefined threshold is selected to be the 120 dose unit setting, below which the increment, ki is 10 dose units. Above the 120 dose unit setting, constant increments, k2 of 20 dose units are used between 120 and 200 dose units, and between 230 and 290 dose units a constant increment, ks of 30 dose units are used. Between 290 and 410, the dose increment k4 is constant with the value 40 dose units. Finally, above 410, the dose increment, given the highest dose unit setting of 510 is ks = 50 dose units. The constant value(s) k is(are) selected so that two consecutive dose unit settings comprised in the dose scale do not overlap.

[0533] Fig. 3B is based on the following table:

[0534] Dosing State-of-the-Art drug dosing Scale according preferred accuracy (x) device embodiment

[0535] Overlap Dose unit Overlap Dose unit

[0536] Setting, S,

[0537] setting (pL)

[0538] (ML)

[0539] 10 No 10 no

[0540] 20 (ki=10) no

[0541] 20 No

[0542] 30 (ki=10) no

[0543] 30 No 40 (ki=10) no

[0544] 50 (ki=10) no

[0545] 40 No

[0546] 60 (ki=10) no

[0547] x=5 pL 50 No 70 (ki=10) no

[0548] 80 (ki=10) no

[0549] 60 No

[0550] 90 (ki=10) no

[0551] 70 No 100 (ki=10) no

[0552] 80 No

[0553] 90 No

[0554] 100 No

[0555]

[0556] 83896PC01

[0557] 48

[0558] 110 yes

[0559] 120 yes 120 (k2=20) no

[0560] 130 yes

[0561] 140 yes 140 (k2=20) no

[0562] 150 yes

[0563] 160 yes 160 (k2=20) no

[0564] 170 yes

[0565] 180 yes 180 (k2=20) no

[0566] 190 yes

[0567] 200 yes 200 (k2=20) no

[0568] 210 yes

[0569] 220 yes

[0570] 230 yes 230 ( / c?=30) no

[0571] 240 yes

[0572] 250 yes

[0573] 260 yes 260 ( / c?=30) no

[0574] 270 yes

[0575] 280 yes

[0576] 290 yes 290 ( / c?=30) no

[0577] 300 yes

[0578] 310 yes

[0579] 320 yes

[0580] 330 yes 330 (k4=40) no

[0581] 340 yes

[0582] 350 yes

[0583] 360 yes

[0584] 370 yes 370 (k4=40) no

[0585] 380 yes

[0586] 390 yes

[0587] 400 yes

[0588] 410 yes 410 (k4=40) no

[0589] 420 yes

[0590] 430 yes

[0591] 440 yes

[0592] 450 yes

[0593] x% = 5 %

[0594] 460 yes 460 (k4=40) no

[0595] 470 yes

[0596] 480 yes

[0597] 490 yes

[0598] 500 yes

[0599] 510 yes 510 (k4=40) no

[0600]

[0601] In this table k1, k2, k3and k4are the constants in Si+1= Si+ k. x is a constant value (5 pL) up to dose setting 100 pL and above 100 pL x% is a percentage (5%) of the dose unit setting. 83896PC01

[0602] 49

[0603] In preferred embodiment, a dose scale may have a piecewise linear dose scale having a number of successive linear dose scales. For each of the linear dose scales, the dose increment is a constant value which is larger for a subsequent linear dose scale than for a preceding linear dose scale and each of said constant values being selected so that two consecutive dose unit settings comprised in said dose scale do not overlap. Accordingly, such a dose scale has a number of linear dose scales that are each separated by a predefined threshold. One such example is shown in the table here below:

[0604] S 6 9 12 18 24 30 42 54 10% S-x 5,4 8,1 10,8 16,2 21,6 27,0 37,8 48,6 10% S+x 6,6 9,9 13,2 19,8 26,4 33,0 46,2 59,4

[0605]

[0606] k (3) 3 3 6 6 6 12 12

[0607] According to preferred embodiments, the dose scale comprises a first linear dose scale at low dose unit settings up to a predefined threshold, and a second nonlinear dose scale at high dose unit settings above the predefined threshold. The predefined threshold is determined as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if the first linear scale applied at low dose unit settings were applied throughout all dose unit settings.

[0608] According to preferred embodiments, the dose scale comprises a linear dose scale at low dose unit settings and a non-linear dose scale at high dose unit settings. The dose unit settings of the dose scales are determined or determinable in the following manner. For / =1 to n where n corresponds to the predefined threshold the linear dose scale can be determined or is determinable by:

[0609] Si+i = St + k

[0610] and the predefined threshold is preferably determined as the first dose unit setting in a series of dose unit settings, which would otherwise overlap a succeeding increased dose unit setting if the linear dose scale applied at low dose unit settings were applied throughout all dose unit settings. Here, k is a constant value, such as an integer that ensures that the dosing ranges of two consecutive 83896PC01

[0611] 50

[0612] dose unit settings do not overlap. Alternatively, k is a constant value that can be determined or is determinable by:

[0613] /

[0614]

[0615] c k1= Sn− Sn-1= Incn,n-1> (Snx% + Sn-1x%) > (Snx% +

[0616] Here, x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both.

[0617] For / =n+l to m where m corresponds to the maximum dose unit setting the nonlinear dose scale can be determined or is determinable by:

[0618] S

[0619]

[0620] i+i = + Inci+l iwherein

[0621] Inci+1,i= roundup (Six% + Si+1x% + A)

[0622] which can be solved in an iterative manner e.g. by a bisection method. Here, A is a value larger than zero, selected to ensure that the dosing ranges of two consecutive dose unit settings do not overlap and x% is defined as above.

[0623] According to preferred embodiments, the dose scale comprises a linear dose scale at low dose unit settings and a non-linear dose scale at high dose unit settings. The dose unit settings of the dose scale are determined or determinable in the following manner. For / =1 to n where n corresponds to the predefined threshold the linear dose scale can be determined or is determinable by:

[0624] Si+i = St + k

[0625] and the predefined threshold is preferably determined or determinable as the first dose unit setting in a series of dose unit settings, which would otherwise overlap a succeeding increased dose unit setting if the linear dose scale applied at low dose unit settings were applied throughout all dose unit settings. Here, k is a constant value, such as an integer that ensures that the dosing ranges of two consecutive dose unit settings do not overlap. Alternatively, k is a constant value that can be determined or is determinable by: 83896PC01

[0626] 51

[0627]

[0628] Sn$n— 1 ^^n,n— 1 > " F §n—

[0629] Here, x% is a value selected, typically representing the dosing accuracy of the drug dosing device where accuracy covers volume variation, concentration variation of the API in the drug solution or both.

[0630] For / =n+l to m where m corresponds to the maximum dose unit setting the nonlinear dose scale can be determined or is determinable by:

[0631] Si+1= Si+ Inci+1,i

[0632] where

[0633] / l / <z • 2Si%%\

[0634] / nc(= a ■ roundup — - — — J

[0635]

[0636] where a is a numeral and x% is defined as above.

[0637] According to preferred embodiments, for at least two of the consecutive dose unit settings, a higher one of said dose unit settings is determined or determinable by a factor multiplied to a lower one of said dose unit settings, that is:

[0638] Si+1 = p *St.

[0639] Where p is a factor being a positive number larger than 1. In some embodiments the factor p is 2. In some embodiments the factor p is 3. In some embodiments the factor p is 4.

[0640] Fig. 3A illustrates another embodiment in which the increments are doubled between two consecutive dose unit settings, that is:

[0641] Si+1 = 2 *Si.

[0642] Accordingly, Fig. 3A schematically illustrates a dose scale comprising a non-linear dose scale. The dose increments are based on a non-linear increase, with a 100% increase, or as stated above Si+1= 2 *St. This produces dose unit settings which do 83896PC01

[0643] 52

[0644] not overlap when the dose accuracy x% < 33%, where x% covers volume variation, concentration variation of the API in the drug solution or both.

[0645] Scale according preferred Dosing State-of-the-Art Pen

[0646] embodiment

[0647] accuracy

[0648] Dose unit setting Dose unit setting, (x) Overlap Overlap (ML) S, (pL)

[0649] 10 no 10 no 20 no 20 no 30 no

[0650] 40 no 40 no 50 no

[0651] x=5 pL

[0652] 60 no

[0653] 70 no

[0654] 80 no 80 no 90 no

[0655] 100 no

[0656] 110 yes

[0657] 120 yes

[0658] 130 yes

[0659] 140 yes

[0660] 150 yes

[0661] 160 yes 160 no 170 yes

[0662] 180 yes

[0663] x% = 5 %

[0664] 190 yes

[0665] 200 yes

[0666] 210 yes

[0667] 220 yes

[0668] 230 yes

[0669] 240 yes

[0670] 250 yes

[0671] 260 yes

[0672]

[0673] 83896PC01

[0674] 53

[0675] 270 yes

[0676] 280 yes

[0677] 290 yes

[0678] 300 yes

[0679] 310 yes

[0680] 320 yes 320 no

[0681]

[0682] According to preferred embodiments, the dose increment is non-linearly increased by a first non-linear dose scale up till dose unit settings being larger than a predefined threshold, and increased by a second non-linear dose scale for dose unit settings being larger than said predefined threshold. For example, the first non-linear dose scale may be determined or determinable by:

[0683] Si+1= a eb,i* St

[0684] where a and b are constants and b is a constant being larger 0 if a is larger than 1 and otherwise larger than 1.0. Further, the second non-linear dose scale may be determined or determinable by:

[0685] Si+1= a ec*1* St

[0686] where c > b is a constant being larger than 0 if a is larger than 1 and otherwise larger than 1.0. The predefined threshold is determined or determinable as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if the first non-linear dose scale applied at low dose unit settings were applied throughout all dose unit settings.

[0687] According to preferred embodiments, the smallest dose increment of the second non-linear dose scale is equal to or larger than a highest dose increment of the first non-linear dose scale.

[0688] According to one embodiment, a dose scale may be a piecewise dose scale comprising multiple non-linear dose scales. According to one embodiment, a dose scale may be a piecewise dose scale comprising multiple linear dose scales.

[0689] According to one embodiment, a dose scale may be a piecewise dose scale comprising a combination of one -linear and multiple non-linear dose scales. 83896PC01

[0690] 54

[0691] According to one embodiment, a dose scale may be a piecewise dose scale comprising a combination of one non-linear and multiple linear dose scales.

[0692] According to one embodiment, a dose scale may be a piecewise dose scale comprising a combination of multiple linear and multiple non-linear dose scales. According to one embodiment, a dose scale being a piecewise dose scale comprising a combination of multiple linear or multiple non-linear dose scales may be a system composed of multiple drug dosing devices each having one or multiple dose scales. One such example is shown in the table here below:

[0693] S 6 9 12 18 24 30 42 54 66 10% S-x 5,4 8,1 10,8 16,2 21,6 27,0 37,8 48,6 59,4 10% S+x 6,6 9,9 13,2 19,8 26,4 33,0 46,2 59,4 72,6

[0694]

[0695] k (3) 3 3 6 6 6 12 12 12

[0696] Here the drug dosing system is composed of three drug dosing devices, where the first device has a linear scale from 6 to 12 with increment 3, the second device has a linear scale from 18 to 30 with increment 6, and the third device has a linear scale from 42 to 66 with increment 12.

[0697] According to preferred embodiments, the dose unit setting may be determined in or determinable by the following manner. For / =1 to n where n corresponds to the predefined threshold:

[0698] Si = Si-1+ roundup (S X% + Si-jx / o + Aj ).

[0699] And, for i = n+l to m where m corresponds to the maximal dose unit setting:

[0700] Si+1= S, + roundup (Si+1x% + SLx% + A2)

[0701] wherein A2> At. A i and A 2 are constants or a number increasing with dose unit settings.

[0702] Reference is made to Figs. 4A and 4B schematically illustrating an optional selection element 5 of a preferred embodiment of a drug dosing device. 83896PC01

[0703] 55

[0704] According to preferred embodiments, the selection element 13 mechanically cooperates with the metering element 5 to releasably retain the metering element 5 in a number of positions where each of said positions corresponds to one of said visual symbols.

[0705] According to preferred embodiments, the selection element (13) provides a tactile and / or acoustic feedback upon being releasably retained. According to preferred embodiments of figs. 4A and 4B the metering element 5 comprises a number of indentations 15 which are configured to receive a pawl in the illustrated embodiment being a sphere which is partly received in an indentation. The pawl -or sphere is biased by a spring towards the metering element 5. The spring is in the illustrated embodiment housed in the travel stop 7. The spring force is selected so as to allow rotation of the metering element by hands while still allowing the pawl to engage with one of the indentations, when the pawl lines-up with an indentation 15. By the pawl engaging with an indentation the selection element 13 provides a tactile and / or acoustic feedback upon being releasably retained.

[0706] Thereby, there is a clear indication to the user, that a certain dose unit setting is selected, thereby assisting a user to set a dose unit setting which corresponds to one of the numerals or symbols, whereby dosing within overlapping dosing regions is at least mitigated.

[0707] According to preferred embodiments, the selection element 13 is releasable by hand. While it may be preferred that the release of the selection element 13 requires e.g. a special designed tool, it is generally preferred that the selection element 13 is releasable by hand. Released by hand typically refers to that a user can rotate the metering element by hand.

[0708] According to preferred embodiments, the manually operated travel element 10 is a section of said metering element 5 extending outside a housing 11 of said device. As illustrated by Fig. 1, the manually operated travel element 10 may be a section of the metering element 5 extending outside a housing 11 of the device to an extend allowing the user to push the metering element 5 to its position where is abuts the travel stop 7. In other embodiments, the plunger 4 is spring activated 83896PC01

[0709] 56

[0710] and the travel element 10 may be a push button which releases a tension stored in the spring onto the plunger 4.

[0711] In preferred embodiments, like the one of Fig. 1, the plunger 4 is typically non-rotationally arranged in said device, which may be provided by one or more notches protruding inwardly from the housing 2 and engaging with a groove provided in the plunger. The metering element 5 is typically rotatably arranged in the device.

[0712] As illustrated in Fig. 1, the plunger 4 has a threaded section 19 at least a part of which extends into and engages a threaded bore 20 provided in the metering element 5. By this, the travel is defined by rotating the metering element 5, as also disclosed above.

[0713] Reference is made to Fig. 5 which illustrates a section of a further embodiment of a metering element 5. The plane indicated by 21 is a cut plane along which the section illustrated is cut-away from the full metering device 5.

[0714] According to preferred embodiments, the metering element 5 comprises a helix having an outer surface 22 upon which said symbols are provided as illustrated in fig. 5. In the illustrated embodiment, the symbols are integers representing dose units.

[0715] The metering element 5 further comprises indentations 15 having the function disclosed in connection with Figs. 4A and 4B (detailed below), although the pawl of the selection element in the embodiment of Fig. 5 acts in radial direction whereas the pawl of the selection element in the embodiment of Figs. 4A and 4B acts in a longitudinal direction. The selection element of Fig. 5 is typically configured as disclosed in connection with Figs. 4A and 4B.

[0716] Although the present invention has been described in connection with the specified embodiments, it should not be construed as being in any way limited to the presented examples. The scope of the present invention is set out by the accompanying claim set. In the context of the claims, the terms "comprising" or "comprises" do not exclude other possible elements or steps. Also, the mentioning 83896PC01

[0717] 57

[0718] of references such as "a" or "an" etc. should not be construed as excluding a plurality. The use of reference signs in the claims with respect to elements indicated in the figures shall also not be construed as limiting the scope of the invention. Furthermore, individual features mentioned in different claims, may possibly be advantageously combined, and the mentioning of these features in different claims does not exclude that a combination of features is not possible and advantageous.

[0719] LIST OF REFERENCE SYMBOLS USED:

[0720] 1 Liquid drug dosing device

[0721] 2 Receptacle

[0722] 3 Ampoule

[0723] 4 Plunger

[0724] 5 Metering element

[0725] 6 Travel

[0726] 7 Travel stop

[0727] 8 Dose units

[0728] 9 Piston

[0729] 10 Travel element

[0730] 11 Housing

[0731] 12 Indicator

[0732] 13 Selection element

[0733] 14 Inspection window

[0734] 15 Indentation

[0735] 16 Stop member

[0736] 17 Cap

[0737] 18 Needle

[0738] 19 Threaded section

[0739] 20 Threaded bore

[0740] 21 Cut plane

[0741] 22 Outer surface

[0742] S Dose unit setting

[0743] D Dosing range

[0744] k Value used for a linear scale

[0745] A Value used for a non-linear scale 83896PC01

[0746] 58

[0747] ITEMIZED LIST OF PREFERRED EMBODIMENTS

[0748] Item 1. A drug dosing device (1), comprising

[0749] • a receptacle (2) configured for fixedly receiving an ampoule (3);

[0750] • a plunger (4) translationally arranged in said drug dosing device (1) with an end of said plunger (4) positioned to exert a force on a translationally arranged piston (9) of said ampoule (3) to dose one or more dose units of a drug solution from said ampoule (3), wherein a dose unit is a volume of a drug solution;

[0751] • a metering element (5) configured to co-operate with said plunger (4) to set a number of different travel distances (6), where each of said travel distances (6) is a distance said plunger (4) can travel translationally in a direction towards said ampoule (3);

[0752] • a travel element (10) configured to upon receipt of a trigger event, such as a manual input to said drug dosing device (1), to move said plunger (4) said travel distance (6) and thereby exert said force on said piston (9);

[0753] • a dose scale (8) arranged on or coupled to said metering element (5), said dose scale (8) comprises a plurality of different visual symbols, each of said visual symbols corresponds to a specific number of dose unit settings (S), where the dose unit settings correspond to the travel distances and the travel distances correspond to the number of dose units;

[0754] wherein

[0755] • said visual symbols represent a series of increasing dose unit settings (S) in a number of consecutive dose unit settings (S) defined by a dose increment Inc) between two consecutive dose unit settings, and

[0756] • a first dose increment between two consecutive higher dose unit settings is selected so that dosing ranges of said two higher dose unit settings do not overlap, and a second dose increment between two consecutive lower dose unit settings is selected so that dosing ranges of said two lower dose unit settings do not overlap, wherein the first dose increment is larger than the second dose increment.

[0757] Item 2. A drug dosing device according to item 1, wherein for at least some of said visual symbols, said dose increment between two consecutive dose unit settings is increasing with increasing dose unit settings. 83896PC01

[0758] 59

[0759] Item 3. A drug dosing device according to item 1 or 2, wherein for at least two of said consecutive dose unit settings (S)

[0760] • a lower of said consecutive dose unit settings corresponds to dose units within a dosing range of Dte [S, -x%; SL+ %%], where Si is the dose unit setting of said lower dose unit setting and x% is an expected accuracy in dosing for said lower dose unit setting,

[0761] • a higher of said consecutive dose units settings corresponds to dose units within a dosing range of Di+1∈ [Si+1− x%; Si+1+ x%], where Si+i is the dose unit setting of said higher dose unit setting and x% is an expected accuracy in dosing at said higher dose unit setting, and

[0762] • the symbols referring to said lower dose unit setting and said higher dose unit setting corresponds to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

[0763] Item 4. A drug dosing device according to item 3, wherein x% is at least 2.05 %, preferably at least 2.1 %, preferably at least 2.2 %, preferably at least 2.5 %, preferably at least 3 %, preferably at least 4 %, preferably 5 %, preferably at least 6 %, preferably at least 7 %, preferably at least 8 %, preferably at least 9 %, preferably at least 10 %, and preferably less than 30%.

[0764] Item 5. A drug dosing device according to any one of items 1-4, wherein for at least two of said consecutive dose unit settings, a higher of said dose unit settings, Si+i, is determined or determinable by

[0765] Si+1= Si+ Inci+1,i

[0766] where Incl+is determined or determinable as

[0767] roundup (S(x% + Si+1x% + A), or

[0768] roundup (2S(x% + A).;

[0769] where A being one or more constants or a number increasing with dose unit setting and is selected so that the dosing ranges of two consecutive dose unit settings comprised in said dose scale (8) do not overlap, and x% is an expected accuracy in dosing at the ithrespectively the i+lthdose unit settings. 83896PC01

[0770] 60

[0771] Item 6. A drug dosing device according to item 5, wherein A is a constant value ( ).

[0772] Item 7. A drug dosing device according to item 5, wherein A is a first constant value Atbelow a predefined threshold, and a second constant value A2above said predefined threshold, wherein A1< A2.

[0773] Item 8. A drug dosing device according to item 5, wherein A is a value increasing with dose unit settings.

[0774] Item 9. A drug dosing device according to item 5, wherein A is a first number Atincreasing with dose unit settings below a predefined threshold, and a second number A2increasing with dose unit settings above a predefined threshold, wherein A1< A2.

[0775] Item 10. A drug dosing device according to any one of items 1-4, wherein for at least two of said consecutive dose unit settings, a higher of said dose unit settings, St+i, is determined or determinable by

[0776] Si+1= Si+ Inci+1,i

[0777] where Incl+is determined or determinable as

[0778] / l / <z • 2S(x%\

[0779] Inci+1: = a ■ roundup — - — —

[0780]

[0781] ' \ 1 — x% /

[0782] where a is a numeral and x% is an expected accuracy in dosing at the ithrespectively the i+lthdose unit settings.

[0783] Item 11. A drug dosing device according to any one of items 1-4, wherein a consecutive dose unit setting (Si+1) is determined or determinable by Si+1= Si+ kiwhere kiis a constant value and a first constant value, k1, up till dose unit settings being larger than a predefined threshold, and a second constant value, k2for dose unit settings being larger than said predefined threshold, said second constant value, k2, being larger than said first constant value, k1.

[0784] Item 12. A drug dosing device (1) according to any one of items 1-4, wherein said dose scale comprises a piecewise linear dose scale having a number of successive linear dose scales, wherein for each of said linear dose scales said dose increment 83896PC01

[0785] 61

[0786] is a constant value which is larger for a subsequent linear dose scale than for a preceding linear dose scale wherein each of said constant values being selected so that two consecutive dose unit settings comprised in said dose scale do not overlap.

[0787] Item 13. A drug dosing device according to any one of items 1-4, wherein said dose scale comprises a linear dose scale at low dose unit settings up to a predefined threshold, and a non-linear dose scale at high dose unit settings above the predefined threshold, wherein the predefined threshold is determined as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if the linear dose scale applied at low dose unit settings were applied throughout all dose unit settings.

[0788] Item 14. A drug dosing device according to item 13, wherein said dose increment Inci+1,i, of said non-linear dose scale is determined or determinable as

[0789] Inci+1,i= roundup (Six% + Si+1x% + A)

[0790] where x% is an expected dosing accuracy of said device, and A is a value larger than zero selected, to ensure that the dosing ranges of two consecutive dose unit settings do not overlap.

[0791] Item 15. A drug dosing device according to item 13, wherein said dose increment Inci+1,iof said non-linear dose scale is determined or determinable as

[0792] (V / a. ■ 2Six%\

[0793] / nc(= a ■ roundup I — - — — I

[0794]

[0795] \ J. X / O /

[0796] where a is a numeral and x% is an expected dosing accuracy of said device.

[0797] Item 16. A drug dosing device according to any one of items 1-4, wherein for at least two of said consecutive dose unit settings a higher one of said dose unit setting is determined or determinable by a factor multiplied to the lower one of said dose unit setting, wherein said factor being a positive number larger than one, such as two, three or even four.

[0798] Item 17. A drug dosing device according to any one of items 1-4, wherein said dose increment is non-linearly increased by a first non-linear scale up till dose unit 83896PC01

[0799] 62

[0800] settings being larger than a predefined threshold, and increased by a second nonlinear scale for dose unit settings being larger than said predefined threshold.

[0801] Item 18. A drug dosing device according to item 17, wherein a smallest dose increment of the second non-linear scale is equal to or larger than a highest increment of the first non-linear scale.

[0802] Item 19. A drug dosing device according to any one of items 1-18, comprising a selection element (13) mechanically co-operating with said metering element (5) to releasably retain said metering element (5) in a number of positions where each of said positions corresponds to one of said visual symbols.

[0803] Item 20. A drug dosing device according to item 19, wherein said selection element (13) provides a tactile and / or acoustic feedback upon being releasably retained.

[0804] Item 21. A drug dosing device according to item 19 or 20, wherein said selection element (13) is releasably by hand.

[0805] Item 22. A drug dosing device according to any one of items 1-21, wherein said manually operated travel element (10) is a section of said metering element (5) extending outside a housing (11) of said device.

[0806] Item 23. A drug dosing device according to any one of items 1-22, wherein said metering element (5) comprising a helix having an outer surface (22) upon which said symbols are provided.

[0807] Item 24. A drug dosing device according any one of items 1-23, wherein

[0808] • said plunger (4) is non-rotationally arranged in said device and said metering element (5) is rotatably arranged in said device,

[0809] • said plunger (4) has a threaded section (19) at least a part of which extends into and engages a threaded bore (20) provided in said metering element (5),

[0810] whereby said travel is defined by rotating said metering element (5). 83896PC01

[0811] 63

[0812] Item 25. A kit of parts comprising a number, such as two, three, four or even a higher number of drug dosing devices according to any one of the preceding items, wherein at least some said symbols of said dose scale of each of said devices in said kit of parts are different from each other.

[0813] Item 26. A dose scale (8) for a drug dosing device according to any one of items 1 to 24, said dose scale (8) comprises a plurality of different visual symbols, each of said visual symbols corresponds to a specific number of dose unit settings (S), wherein

[0814] • said visual symbols represent a series of increasing dose unit settings (S) in a number of consecutive dose unit settings (S) defined by a dose increment (Inc) between two consecutive dose unit settings, and

[0815] • a first dose increment between two consecutive higher dose unit settings is selected so that dosing ranges of said two higher dose unit settings do not overlap, and a second dose increment between two consecutive lower dose unit settings is selected so that dosing ranges of said two lower dose unit settings do not overlap, wherein the first dose increment is larger than the second dose increment.

Claims

83896PC0164CLAIMS1. A drug dosing device (1), comprising• a receptacle (2) configured for fixedly receiving an ampoule (3);• a plunger (4) translationally arranged in said drug dosing device (1) with an end of said plunger (4) positioned to exert a force on a translationally arranged piston (9) of said ampoule (3) to dose one or more dose units of a drug solution from said ampoule (3), wherein a dose unit is a volume of a drug solution;• a metering element (5) configured to co-operate with said plunger (4) to set a number of different travel distances (6), where each of said travel distances (6) is a distance said plunger (4) can travel translationally in a direction towards said ampoule (3);• a travel element (10) configured to upon receipt of a trigger event, such as a manual input to said drug dosing device (1), to move said plunger (4) said travel distance (6) and thereby exert said force on said piston (9);• a dose scale (8) arranged on or coupled to said metering element (5), said dose scale (8) comprises a plurality of different visual symbols, each of said visual symbols corresponds to a specific number of dose unit settings (S), where the dose unit settings correspond to the travel distances and the travel distances correspond to the number of dose units;wherein• said visual symbols represent a series of increasing dose unit settings (S) in a number of consecutive dose unit settings (S) defined by a dose increment Inc) between two consecutive dose unit settings, and• a first dose increment between two consecutive higher dose unit settings is selected so that dosing ranges of said two higher dose unit settings do not overlap, and a second dose increment between two consecutive lower dose unit settings is selected so that dosing ranges of said two lower dose unit settings do not overlap, wherein the first dose increment is larger than the second dose increment.

2. A drug dosing device according to claim 1, wherein for at least some of said visual symbols, said dose increment between two consecutive dose unit settings is increasing with increasing dose unit settings.83896PC01653. A drug dosing device according to claim 1 or 2, wherein for at least two of said consecutive dose unit settings (S)• a lower of said consecutive dose unit settings corresponds to dose units within a dosing range of Di∈ [Si− x%; Si+ x%], where Si is the dose unit setting of said lower dose unit setting and x% is an expected accuracy in dosing for said lower dose unit setting,• a higher of said consecutive dose units settings corresponds to dose units within a dosing range of Di+1∈ [Si+1− x%; Si+1+ x%], where Si+i is the dose unit setting of said higher dose unit setting and x% is an expected accuracy in dosing at said higher dose unit setting, and• the symbols referring to said lower dose unit setting and said higher dose unit setting corresponds to dose unit settings for which the two dosing ranges Di and Di+i do not overlap.

4. A drug dosing device according to claim 3, wherein x% is at least 2.05 %, preferably at least 2.1 %, preferably at least 2.2 %, preferably at least 2.5 %, preferably at least 3 %, preferably at least 4 %, preferably at least 5 %, preferably at least 6 %, preferably at least 7 %, preferably at least 8 %, preferably at least 9 %, preferably at least 10 %, and preferably less than 30%.

5. A drug dosing device according to any one of claims 1-4, wherein for at least two of said consecutive dose unit settings, a higher of said dose unit settings, Si+i, is determined or determinable bySi+1= Si+ Inci+1,iwhere Incl+is determined or determinable asroundup (S(x% + Si+1x% + A), orroundup (2S(x% + A).;where A being one or more constants or a number increasing with dose unit setting and is selected so that the dosing ranges of two consecutive dose unit settings comprised in said dose scale (8) do not overlap, and x% is an expected accuracy in dosing at the ithrespectively the i+lthdose unit settings.

6. A drug dosing device according to claim 5, wherein A is a constant value ( ).83896PC01667. A drug dosing device according to claim 5, wherein A is a first constant value Atbelow a predefined threshold, and a second constant value A2above said predefined threshold, wherein A1< A2.

8. A drug dosing device according to claim 5, wherein A is a value increasing with dose unit settings.

9. A drug dosing device according to claim 5, wherein A is a first number Atincreasing with dose unit settings below a predefined threshold, and a second number A2increasing with dose unit settings above a predefined threshold, wherein A1< A2.

10. A drug dosing device according to any one of claims 1-4, wherein for at least two of said consecutive dose unit settings, a higher of said dose unit settings, St+i, is determined or determinable bySi+1= Si+ Inci+1,iwhere Incl+is determined or determinable as / l / <z • 2S(x%\Inci+1: = a ■ roundup — - — —' \ 1 — x% / where a is a numeral and x% is an expected accuracy in dosing at the ithrespectively the i+lthdose unit settings.

11. A drug dosing device according to any one of claims 1-4, wherein a consecutive dose unit setting (Si+1) is determined or determinable by Si+1= Si+ kiwhere kiis a constant value and a first constant value, k1, up till dose unit settings being larger than a predefined threshold, and a second constant value, k2for dose unit settings being larger than said predefined threshold, said second constant value, k2, being larger than said first constant value, k1.

12. A drug dosing device (1) according to any one of claims 1-4, wherein said dose scale comprises a piecewise linear dose scale having a number of successive linear dose scales, wherein for each of said linear dose scales said dose increment is a constant value which is larger for a subsequent linear dose scale than for a preceding linear dose scale wherein each of said constant values being selected so83896PC0167that two consecutive dose unit settings comprised in said dose scale do not overlap.

13. A drug dosing device according to any one of claims 1-4, wherein said dose scale comprises a linear dose scale at low dose unit settings up to a predefined threshold, and a non-linear dose scale at high dose unit settings above the predefined threshold, wherein the predefined threshold is determined as the first dose unit setting in a series of dose unit settings, which would overlap a succeeding increased dose unit setting if the linear dose scale applied at low dose unit settings were applied throughout all dose unit settings.

14. A drug dosing device according to claim 13, wherein said dose increment Inci+1,i, of said non-linear dose scale is determined or determinable asInci+1,i= roundup (Six% + Si+1x% + A)where x% is an expected dosing accuracy of said device, and A is a value larger than zero selected, to ensure that the dosing ranges of two consecutive dose unit settings do not overlap.

15. A drug dosing device according to claim 13, wherein said dose increment Inci+1,iof said non-linear dose scale is determined or determinable as(V / a. ■ 2Six%\ / nc(= a ■ roundup — - — — Jwhere a is a numeral and x% is an expected dosing accuracy of said device.

16. A drug dosing device according to any one of claims 1-4, wherein for at least two of said consecutive dose unit settings a higher one of said dose unit setting is determined or determinable by a factor multiplied to the lower one of said dose unit setting, wherein said factor being a positive number larger than one, such as two, three or even four.

17. A drug dosing device according to any one of claims 1-4, wherein said dose increment is non-linearly increased by a first non-linear scale up till dose unit settings being larger than a predefined threshold, and increased by a second nonlinear scale for dose unit settings being larger than said predefined threshold.83896PC016818. A drug dosing device according to claim 17, wherein a smallest dose increment of the second non-linear scale is equal to or larger than a highest increment of the first non-linear scale.

19. A drug dosing device according to any one of claims 1-18, comprising a selection element (13) mechanically co-operating with said metering element (5) to releasably retain said metering element (5) in a number of positions where each of said positions corresponds to one of said visual symbols.

20. A drug dosing device according to claim 19, wherein said selection element (13) provides a tactile and / or acoustic feedback upon being releasably retained.

21. A drug dosing device according to claim 19 or 20, wherein said selection element (13) is releasably by hand.

22. A drug dosing device according to any one of claims 1-21, wherein said manually operated travel element (10) is a section of said metering element (5) extending outside a housing (11) of said device.

23. A drug dosing device according to any one of claims 1-22, wherein said metering element (5) comprising a helix having an outer surface (22) upon which said symbols are provided.

24. A drug dosing device according any one of claims 1-23, wherein• said plunger (4) is non-rotationally arranged in said device and said metering element (5) is rotatably arranged in said device,• said plunger (4) has a threaded section (19) at least a part of which extends into and engages a threaded bore (20) provided in said metering element (5),whereby said travel is defined by rotating said metering element (5).

25. A kit of parts comprising a number, such as two, three, four or even a higher number of drug dosing devices according to any one of claims 1 to 24, wherein at83896PC0169least some said symbols of said dose scale of each of said devices in said kit of parts are different from each other.

26. A dose scale (8) for a drug dosing device according to any one of claims 1 to 24, said dose scale (8) comprises a plurality of different visual symbols, each of said visual symbols corresponds to a specific number of dose unit settings (S), wherein• said visual symbols represent a series of increasing dose unit settings (S) in a number of consecutive dose unit settings (S) defined by a dose increment (Inc) between two consecutive dose unit settings, and• a first dose increment between two consecutive higher dose unit settings is selected so that dosing ranges of said two higher dose unit settings do not overlap, and a second dose increment between two consecutive lower dose unit settings is selected so that dosing ranges of said two lower dose unit settings do not overlap, wherein the first dose increment is larger than the second dose increment.

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