Patent Publication Number: US-2013253465-A1

Title: Dispense Interface Component for a Drug Delivery Device

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application is a U.S. National Phase Application pursuant to 35 U.S.C. §371 of International Application No. PCT/EP2011/071132 filed Nov. 28, 2011, which claims priority to European Patent Application No. 10192991.7 filed Nov. 29, 2010 and U.S. Provisional Patent Application No. 61/433,806 filed Jan. 18, 2011. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
    
    
     FIELD OF INVENTION 
     The present patent application relates to medical devices and methods of delivering at least two drug agents from separate reservoirs using a device having a programmable dose setting mechanism and a single dispense interface. Such drug agents may comprise a first and a second medicament. A single dose setting procedure initiated by the user causes the drug delivery device to compute a dose of a second drug agent based on a selected therapeutic dose algorithm. This single dose setting procedure initiated by the user may also cause the drug delivery device to compute a dose of a third drug agent based on a (potentially) different selected therapeutic dose algorithm. Such algorithms may either be previously selected prior to dose setting or at the time that the dose is set. 
     The drug agents may be contained in two or more multiple dose reservoirs, containers or packages, each containing independent (single drug compound) or pre-mixed (co-formulated multiple drug compounds) drug agents. The electro-mechanical dose setting mechanism is of particular benefit where a targeted therapeutic response can be optimized for a specific target patient group. This may be achieved by a microprocessor based drug delivery device that is programmed to control, define, and/or optimize a therapeutic dose profile. A plurality of potential dose profiles may be stored in a memory device operatively coupled to the microprocessor. For example, such stored therapeutic dose profiles may include, but are not limited to, a linear dose profile; a non-linear dose profile; a fixed ratio-fixed dose profile; a fixed dose-variable dose profile; a delayed fixed dose-variable dose profile; or a multi-level, fixed dose variable dose profile as discussed and described in greater detail below. Alternatively, only one dose profile would be stored in a memory device operatively coupled to the microprocessor. 
     A dispense interface component configured for attaching to a drug delivery device may be configured to only pierce the septa of the drug reservoirs of the drug delivery device when the drug delivery device is ready for use. 
     BACKGROUND 
     Certain disease states require treatment using one or more different medicaments. Some drug compounds need to be delivered in a specific relationship with each other in order to deliver the optimum therapeutic dose. The present patent application is of particular benefit where combination therapy is desirable, but not possible in a single formulation for reasons such as, but not limited to, stability, compromised therapeutic performance and toxicology. 
     For example, in some cases it might be beneficial to treat a diabetic with a long acting insulin (also may be referred to as the first or primary medicament) along with a glucagon-like peptide-1 such as GLP-1 or GLP-1 analog (also may be referred to as the second drug or secondary medicament). GLP-1 is derived from the transcription product of the proglucagon gene. GLP-1 is found in the body and is secreted by the intestinal L cell as a gut hormone. GLP-1 possesses several physiological properties that make it (and its analogs) a subject of intensive investigation as a potential treatment of diabetes mellitus. 
     There are a number of potential problems when delivering two active medicaments or “agents” simultaneously. The two active agents may interact with each other during the long-term, shelf life storage of the formulation. Therefore, it is advantageous to store the active components separately and only combine them at the point of delivery, e.g., injection, needle-less injection, pumps, or inhalation. However, the process for combining the two agents and then administering this combination therapy needs to be simple and convenient for the user to perform reliably, repeatedly and safely. 
     A further problem that may often arise is that the quantities and/or proportions of each active agent making up the combination therapy may need to be varied for each user or at different stages of their therapy. For example, one or more active agents may require a titration period to gradually introduce a patient to a “maintenance” dose. A further example would be if one active agent requires a non-adjustable fixed dose while the other active agent is varied. This other active agent may need to be varied in response to a patient&#39;s symptoms or physical condition. Because of such a potential problem, certain pre-mixed formulations comprising two or more active agents may not be suitable as these pre-mixed formulations would have a fixed ratio of the active components, which could not be varied by the healthcare professional or user. 
     Additional problems can arise where a multi-drug compound therapy is required, because many users cannot cope with having to use more than one drug delivery system or make the necessary accurate calculation of the required dose combination. Other problems arise where a drug delivery system requires the user to physically manipulate the drug delivery device or a component of the drug delivery device (e.g., a dose dialing button) so as to set and/or inject a dose. This may be especially true for certain users who are challenged with dexterity or computational difficulties. 
     Accordingly, there exists a need to provide devices and/or methods for the delivery of two or more medicaments in a single injection or delivery step that is simple for the user to perform without complicated physical manipulations of the drug delivery device. Applicants&#39; proposed programmable electro-mechanical drug delivery device overcomes the above-mentioned problems. For example, the proposed drug delivery device provides separate storage containers or cartridge retainers for two or more active drug agents. These active drug agents are then only combined and/or delivered to the patient during a single delivery procedure. These active agents may be administered together in a combined dose or alternatively, these active agents may be combined in a sequential manner, one after the other. This may be just one programmable feature of Applicants&#39; proposed electro-mechanical drug delivery device. 
     In addition, when a user sets a dose of the first or primary medicament, Applicants&#39; proposed electro-mechanical micro-processor based drug delivery device automatically calculates the dose of the second medicament (i.e., non-user settable) based at least in part on a programmed therapeutic dose profile or programmed algorithm. In an alternative arrangement, Applicants&#39; proposed electro-mechanical micro-processor based drug delivery device automatically calculates the dose of the second medicament and/or a third medicament based on a programmed therapeutic dose profile or programmed algorithm. The profile used to compute the dose of the third medicament may or may not be the same type of profile used to compute the dose of the secondary medicament. 
     Applicants&#39; drug delivery device also allows for the opportunity of varying the quantity of the medicaments. For example, one fluid quantity can be varied by changing the properties of the injection device (e.g., setting a user variable dose or changing the device&#39;s “fixed” dose). The second medicament quantity can be changed by manufacturing a variety of secondary drug containing packages with each variant containing a different volume and/or concentration of the second active agent. The user, for example a patient, a healthcare professional or any other person using the device, would then select the most appropriate secondary package or series or combination of series of different packages for a particular treatment regime. 
     SUMMARY 
     The present application allows for a combination of multiple drug compounds within a single electro-mechanical device to achieve a therapeutic dose profile. Such therapeutic dose profile may be a pre-selected profile and may be one of a plurality of dose profiles stored in a memory device contained within the drug delivery device. The electro-mechanical device may comprise two or more such medicaments. The device allows the user to set a multi-drug compound device through one single dose setting mechanism (such as a digital display, a soft-touch operable panel, and/or graphical user interface (GUI)). The device then allows the dispense of at least a plurality of medicaments through a single dispense interface (such as a double-ended needle assembly). This single dose setter can control the electro-mechanical drive unit of the device such that a predefined combination of the individual drug compounds may be administered when a single dose of one of the medicaments is set and dispensed through the single dispense interface. Although principally described in this application as an injection device, the basic principle could be applicable to other forms of drug delivery, such as, but not limited to, inhalation, nasal, ophthalmic, oral, topical, and like forms of drug delivery. 
     By defining the therapeutic relationship between at least a plurality of drug compounds, the proposed microprocessor based drug delivery device helps to ensure that a patient/user receives the optimum therapeutic combination dose from a multi-drug compound device. This microprocessor may comprise a microcontroller. This combination dose may be set and administered without the potential inherent risks that may be associated with multiple inputs, where the user is often called upon to calculate and set the correct dose combination each time that the device is used to administer a dose. The medicaments can be fluids, defined herein as liquids, gases or powders that are capable of flowing and that change shape when acted upon by a force tending to change its shape. Alternatively, one of the medicaments may be a solid where such a solid may be carried, solubilized or otherwise dispensed with another fluid, for example a fluid medicament or a liquid. 
     The proposed electro-mechanical device is of particular benefit to users with dexterity or computational difficulties as the single input and associated predefined therapeutic profile removes the need for a user to calculate a prescribed dose every time they use the device. In addition, the single input allows easier dose setting and dose administration of the combined compounds. The electro-mechanical nature of the preferred drug delivery device also benefits users with dexterity and visual challenges since the proposed drug delivery device may be operated and/or controlled by way of a micro-processor based operator panel. 
     In a preferred embodiment a master drug compound, such as insulin, contained within a multiple dose device could be used with at least a secondary medicament contained within the same device. A third medicament contained within the same device may also be provided. For example, this third medicament could be a long or a short acting insulin. 
     In a preferred arrangement, a computerized electro-mechanical drug delivery device delivers at least one dose of two or more medicaments. This dose may be a combined dose. The device comprises a main body comprising a microprocessor based control unit. An electro-mechanical drive unit is operably coupled to the control unit. The electro-mechanical drive unit is coupled to a primary reservoir and a secondary reservoir. Preferably, the electro-mechanical drive unit is coupled to the primary reservoir and the secondary reservoir by way of a first and second drive trains. The first and the second drive trains may be similar in operation. 
     An operator interface is in communication with the control unit. A single dispense assembly (such as a dispense interface and/or a needle assembly) may be configured for fluid communication with the primary and the secondary reservoir. Activation of the operator panel sets a dose of the primary medicament from the primary reservoir. Based on at least the selected dose of the primary medicament, the control unit computes a dose of the secondary medicament based at least in part on a therapeutic dose profile. In an alternative arrangement, based on at least the selected dose of the primary medicament, the control unit computes a range of a dose of the secondary medicament based at least in part on a therapeutic dose profile. A user may then select a dose of the secondary medicament within the determined range. Based on at least the selected dose of the primary medicament, the control unit may also compute a dose or a range of a dose of the third medicament based at least in part on a therapeutic dose profile. The primary medicament may or may not be administered to an injection site simultaneously with the secondary medicament. 
     In one arrangement, the selected profile may be determined when a cartridge of medicament is inserted into a cartridge retainer of the drug delivery device. A cartridge may comprise one or more reservoirs for storing and releasing one or more medicaments. Separate cartridges for each medicament may be used in a device, or a single cartridge with multiple reservoirs may be used. For example, the cartridge retainer of the device may contain a cartridge identification circuit that when or if the device ‘reads’ a cartridge identifier provided on the inserted cartridge, logic contained in the device could determine which of the plurality of stored profiles is the appropriate profile to select for the particular medicament contained within the cartridge. In one such arrangement, this selection process might therefore be fully automatic. That is, no user intervention is required to select the proper profile. In an alternative embodiment, cartridge identification information may be used to request a profile through a wired or wireless connection, for example a universal serial bus (USB) connection, a Bluetooth™ connection, a cellular connection and/or the like. The profile may be requested from an internet page. The profile may be received by the device through the same wired or wireless connection. The profile may then be stored and applied in the apparatus without any user intervention or after confirmation by a user. 
     Alternatively, this therapeutic profile selection process might be semi-automatic. For example, this therapeutic profile may be suggested and selected via a graphical user interface provided on a digital display. For example, the GUI may prompt the user to confirm which profile they want from a limited range of options or fully configurable by the user, for example by a patient or health care provider. 
     Although the present application specifically mentions insulin, insulin analogs or insulin derivatives, and GLP-1 or GLP-1 analogs as two possible drug combinations, other drugs or drug combinations, such as an analgesics, hormones, beta agonists or corticosteroids, or a combination of any of the above-mentioned drugs could be used with our invention. 
     For the purposes of the present application, the term “insulin” shall mean Insulin, insulin analogs, insulin derivatives or mixtures thereof, including human insulin or a human insulin analogs or derivatives. Examples of insulin analogs are, without limitation, Gly(A21), Arg(B31), Arg(B32) human insulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin, wherein proline in position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin or Des(B30) human insulin. Examples of insulin derivatives are, without limitation, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin; B29-N-(w-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyhepta-decanoyl) human insulin. 
     As used herein the term “GLP-1” shall mean GLP-1, GLP-1 analogs, or mixtures thereof, including without limitation, exenatide (Exendin-4(1-39), a peptide of the sequence H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2), Exendin-3, Liraglutide, or AVE0010 (H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser-Lys-Lys-Lys-Lys-Lys-Lys-NH2). 
     Examples of beta agonists are, without limitation, salbutamol, levosalbutamol, terbutaline, pirbuterol, procaterol, metaproterenol, fenoterol, bitolterol mesylate, salmeterol, formoterol, bambuterol, clenbuterol, indacaterol. 
     Hormones are for example hypophysis hormones or hypothalamus hormones or regulatory active peptides and their antagonists, such as Gonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin, Buserelin, Nafarelin, Goserelin. 
     In one preferred arrangement, the proposed electro-mechanical drug delivery device has a single dispense interface. This interface may be configured for fluid communication with the primary reservoir and with a secondary reservoir of medicament containing at least one drug agent. The drug dispense interface can be a type of outlet that allows the two or more medicaments to exit the system and be delivered to the patient. 
     In one preferred arrangement, the secondary reservoir contains multiple doses of medicament. The system may be designed such that a single activation of a dose button causes the user set dose of medicament to be expelled from the primary reservoir. As a result, a dose of medicament from the second reservoir is determined based on a preprogrammed therapeutic profile and this combination of medicaments will be expelled through the single dispense interface. By user settable dose it is meant that the user (e.g., patient or health care provider) can enter the dose of the primary medicament by way of the device so as to set a desired dose. Additionally, the user settable dose can be set remotely through a communications port such as a wireless communication port (e.g., Bluetooth, WiFi, satellite, etc.). Alternatively, the user settable dose can be set through a wired communications port such as a Universal Serial Bus (USB) communications port. Additionally, the dose may be set by another device, such as a blood glucose monitor after performing a therapeutic treatment algorithm. 
     By calculated dose, it is meant that the user (or any other input) cannot independently set or select a dose of medicament from the secondary reservoir but rather it is computed to achieve a predefined therapeutic profile of a combination of both primary and secondary medicaments. In other words, when the user (or another input as described above) sets the dose of the primary medicament in the primary reservoir, the dose of the second medicament is determined by the microprocessor control unit. This combination of medicaments is then administered via a single interface. 
     1. The combination of compounds as discrete units or as a mixed unit can be delivered to the body via a double-ended needle assembly. This would provide a combination drug injection system that, from a user&#39;s perspective, would be achieved in a manner that closely matches the currently available injection devices that use standard needle assemblies. One possible delivery procedure may involve the following steps: 
     2. Attach a dispense interface to a distal end of the electro-mechanical injection device. The dispense interface comprises a first and a second proximal needle. The first and second needles pierce a first reservoir containing a primary compound and a second reservoir containing a secondary compound, respectively.
         1. Attach a dose dispenser, such as a double-ended needle assembly, to a distal end of the dispense interface. In this manner, a proximal end of the needle assembly is in fluidic communication with both the primary compound and secondary compound.   2. Dial up/set a desired dose of the primary compound from the injection device, for example, via a graphical user interface (GUI).   3. After the user sets the dose of the primary compound, the micro-processor controlled control unit determines or computes a dose of the secondary compound and preferably determines or computes this second dose based on a previously stored therapeutic dose profile. Where the drug delivery device includes a third medicament, the micro-processor controlled control unit computes a dose of the third medicament based on the same or a different therapeutic dose profile. It is this computed combination of medicaments that will then be injected by the user. The therapeutic dose profile may be user selectable.   1. Optionally, after the second dose has been computed, the device may be placed in an armed condition. In such an optional armed condition, this may be achieved by pressing and/or holding an “OK” button on a control panel. This condition may provide for greater than a predefined period of time before the device can be used to dispense the combined dose.   2. Then, the user will insert or apply the distal end of the dose dispenser (e.g., a double ended needle assembly) into the desired injection site. The dose of the combination of the primary compound and the secondary compound (and potentially a third medicament) is administered by activating an injection user interface (e.g., an injection button).       

     The proposed drug delivery system may be designed in such a way as to limit its use to exclusive primary and secondary reservoirs through employment of dedicated or coded cartridge features. In some situations, it may be beneficial from a therapeutic and safety point of view to ensure that the primary reservoir can be a standard drug containing vial or cartridge. This would allow the user to deliver a combined therapy when a secondary reservoir is included in the device. It would also allow delivery of the primary compound independently through a standard dose dispenser in situations where the combined therapy is not required. This could include situations, such as, but not limited to, dose splitting (i.e., delivering the complete dose of the primary therapy in two separate injections) or top-up of the primary compound in a way that would prevent the potential risk of double dosing of the secondary compound that such scenarios might otherwise present. 
     In some cases, it may be beneficial for a dispense interface component to remain attached to the drug delivery device, but not pierce the cartridges when the drug delivery device is not being used for an injection. This may beneficially improve sterility of the drug delivery device and the medicament in the drug delivery device. Thus, a dispense interface component that is configured to only pierce the drug cartridges during use may be provided. The dispense interface may comprise an outlet needle. The dispense interface may be configured for attachment of a needle assembly. 
     Generally, the dispense interface component may include a main body, a first piercing portion, a second piercing portion, and a biasing element. The main body is configured for connection to the drug delivery device. The first piercing portion is for piercing a first cartridge contained within the drug delivery device, and the first piercing portion is connected to the main body. The second piercing portion is for piercing a second cartridge contained with the drug delivery device, and the second piercing portion is connected to the main body. The at least one biasing element is operably coupled to the main body, wherein the at least one biasing element is configured to, when the load on the at least one biasing element is less than or equal to a threshold load, bias (i) the first piercing portion away from the first cartridge and (ii) the second piercing portion away from the second cartridge, thereby preventing the first piercing portion from piercing the first cartridge and the second piercing portion from piercing the second cartridge. Conversely, when the load on the at least one biasing element is greater than the threshold load, as a result of the application of a axial force resulting from, for example, the attachment of a detachable single injection interface, the first and second piercing portions are forced towards the cartridge causing them to pierce the respective cartridge septums in preparation for dispense of the dose. 
     A particular benefit of the proposed drug delivery device is that the use of two or more multi-dose reservoirs makes it possible to tailor dose regimes when required, for example where a titration period is necessary for a particular drug. The secondary reservoir, third reservoir, and/or other reservoirs may be supplied in a number of titration levels with certain differentiation features such as, but not limited to, aesthetic design of features or graphics, numbering or the like symbols, so that a user could be instructed to use the supplied secondary reservoirs in a specific order to facilitate titration. Alternatively, a prescribing physician or health care provider may provide the patient with a number of “level one” titration secondary reservoirs and then when these were finished, the physician could then prescribe the next level. Alternatively, a single strength formulation could be provided and the device could be designed to deliver a pre-defined fraction of the full intended dose during the titration period. Such a fraction could be gradually increasing, stepped or any therapeutically beneficial or desirable variant thereof. One advantage of such a titration program is that the primary device remains constant throughout the administration process.
         1. In a preferred arrangement, the drug delivery device is used more than once and therefore is multi-use. Such a device may or may not have a replaceable reservoir of the primary drug compound, but the presently disclosed arrangements are equally applicable to both scenarios. It is possible to have a suite of different secondary reservoirs for various conditions that could be prescribed as one-off extra medication to patients already using a standard drug delivery device.       

     A further feature of a preferred arrangement is that both medicaments are delivered via one injection needle or dose dispenser and in one injection step. This offers a convenient benefit to the user in terms of reduced user steps compared to administering two separate injections. This convenience benefit may also result in improved compliance with the prescribed therapy, particularly for users who find injections unpleasant, or who have dexterity or computational difficulties. The use of one injection instead of two reduces the possibility for user errors and so may increase patient safety. 
     In a further aspect, an apparatus is described comprising a control unit configured to receive information on a dose of a primary medicament. The control unit is further configured to determine a dose of a fluid agent based at least in part on said dose of said primary medicament and a therapeutic dose profile. The fluid agent may be a medicament, for example a liquid medicament or a liquid solution of a medicament. 
     In a further aspect, a method is disclosed comprising receiving at a control unit information on a therapeutic dose profile. The method further comprises receiving at the control unit information on a dose of a primary medicament, determining at the control unit a dose of a fluid agent based at least in part on said information on said dose of said primary medicament and the therapeutic dose profile, and initiating administration of said dose of said primary medicament and said dose of said fluid agent in accordance with the therapeutic dose profile. 
     These as well as other advantages of various aspects of the present invention will become apparent to those of ordinary skill in the art by reading the following detailed description, with appropriate reference to the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Exemplary embodiments are described herein with reference to the drawings, in which: 
         FIG. 1   a  illustrates a plan view of a programmable drug delivery device in accordance with one aspect of the present invention and  FIG. 1   b  illustrates a plan view of a programmable drug delivery device with an end cap removed in accordance with one aspect of the present invention; 
         FIG. 2  illustrates a perspective view of the delivery device illustrated in  FIGS. 1   a  and  1   b  with an end cap of the device removed; 
         FIG. 3  illustrates a perspective view of a cartridge holder and a back side of the delivery device illustrated in  FIG. 1   b;    
         FIG. 4  illustrates a perspective view of a proximal end of the delivery device illustrated in  FIG. 1   b;    
         FIG. 5   a  illustrates a plan view of a digital display of the delivery device after the device has been turned on but before a dose is set; 
         FIG. 5   b  illustrates a plan view of the digital display illustrated in  FIG. 5   a  after a dose has been set; 
         FIG. 6  illustrates a perspective view of the delivery device distal end showing the cartridge; 
         FIG. 7  illustrates a flowchart of one algorithm that can be programmed into the drug delivery device illustrated in  FIGS. 1   a  and  1   b;    
         FIG. 8  illustrates a flowchart of another algorithm that can be programmed into the drug delivery device illustrated in  FIGS. 1   a  and  1   b;    
         FIG. 9  illustrates a perspective view of the cartridge holder illustrated in  FIG. 3  with one cartridge retainer in an open position; 
         FIG. 10  illustrates one type of cartridge dedication system that may be used with the cartridge holder; 
         FIG. 11  illustrates a dispense interface and a dose dispenser that may be removably mounted on a distal end of the delivery device illustrated in  FIGS. 1   a ,  1   b , and  2 ; 
         FIG. 12  illustrates the dispense interface and the dose dispenser illustrated in  FIG. 11  mounted on a distal end of the delivery device illustrated in  FIGS. 1   a ,  1   b , and  2 ; 
         FIG. 13  illustrates one arrangement of the dose dispenser that may be mounted on a distal end of the delivery device; 
         FIG. 14  illustrates a perspective view of the dispense interface illustrated in  FIG. 11 ; 
         FIG. 15  illustrates another perspective view of the dispense interface illustrated in  FIG. 11 ; 
         FIG. 16  illustrates a cross-sectional view of the dispense interface illustrated in  FIGS. 11 and 12 ; 
         FIG. 17  illustrates an exploded view of the dispense interface illustrated in  FIG. 11 ; 
         FIG. 18  illustrates another exploded view of the dispense interface illustrated in  FIG. 11 ; 
         FIG. 19  illustrates a cross-sectional view of the dispense interface and dose dispenser mounted onto a drug delivery device, such as the device illustrated in  FIGS. 1   a  and  1   b;    
         FIG. 20  illustrates a block diagram functional description of a control unit for operation of the drug delivery device illustrated in  FIG. 11 ; 
         FIG. 21  illustrates a printed circuit board assembly of the drug delivery device illustrated in  FIG. 11 ; 
         FIG. 22  illustrates a schematic view of a drive mechanism for use with the drug delivery device illustrated in  FIGS. 1   a  and  1   b;    
         FIG. 23  illustrates another schematic view of the drive mechanism illustrated in  FIG. 22 ; 
         FIGS. 24   a  and  24   b  illustrate a motion detection system that may be used with the drive mechanism illustrated in  FIG. 22 ; 
         FIG. 25  illustrates a schematic view of an alternative drive mechanism for use with the drug delivery device illustrated in  FIGS. 1   a  and  1   b;    
         FIG. 26  illustrates a schematic view of the alternative drive mechanism illustrated in  FIG. 25  with certain elements removed; 
         FIG. 27  illustrates a schematic view of a telescope piston rod and gearing arrangement illustrated in  FIG. 26 ; 
         FIG. 28  illustrates a schematic view of a telescope piston rod arrangement illustrated in  FIG. 27 ; 
         FIG. 29  illustrates a schematic view of one piston rod arrangement illustrated in  FIG. 27 ; 
         FIG. 30  illustrates a potential deliverable therapy of a known two input and two compound combination device; 
         FIGS. 31   a  and  31   b  illustrates a first arrangement of a predefined therapeutic profile that may be programmed into Applicants&#39; programmable drug delivery device; 
         FIG. 32  illustrates one arrangement of a predefined fixed ratio therapeutic profile that may be programmed into the drug delivery device; 
         FIG. 33  illustrates an alternative arrangement of a predefined fixed ratio therapeutic profile that may be programmed into a drug delivery device comprising three medicaments; 
         FIG. 34  illustrates an alternative arrangement of a predefined fixed ratio therapeutic profile that may be programmed into a drug delivery device comprising four medicaments; 
         FIG. 35  illustrates another alternative arrangement of a predefined fixed ratio therapeutic profile having discrete dose steps and that may be programmed into the drug delivery device; 
         FIG. 36  illustrates an arrangement of a predefined non-linear fixed ratio therapeutic profile having a decreasing rate of change and that may be programmed into the drug delivery device; 
         FIG. 37  illustrates an alternative arrangement of a predefined non-linear fixed ratio therapeutic profile having a decreasing rate of change and that may be programmed into the drug delivery device; 
         FIG. 38  illustrates an arrangement of a predefined non-linear fixed ratio therapeutic profile having an increasing rate of change and that may be programmed into the drug delivery device; 
         FIG. 39  illustrates an alternative arrangement of a predefined non-linear fixed ratio therapeutic profile having an increasing rate of change and that may be programmed into the drug delivery device; 
         FIG. 40  illustrates an arrangement of a predefined fixed ratio-fixed dose therapeutic profile having a low dose threshold and that may be programmed into the drug delivery device; 
         FIG. 41  illustrates an alternative arrangement of a predefined fixed ratio-fixed dose therapeutic profile having a high dose threshold and that may be programmed into the drug delivery device; 
         FIG. 42  illustrates an alternative arrangement of a predefined fixed ratio-fixed dose therapeutic profile having a low dose threshold and that may be programmed into a drug delivery device for use with at least three medicaments; 
         FIG. 43  illustrates an arrangement of a predefined fixed dose-variable dose therapeutic profile that may be programmed into the drug delivery device; 
         FIG. 44  illustrates an alternative arrangement of a predefined fixed dose-variable dose therapeutic profile that may be programmed into the drug delivery device and for use with at least three medicaments; 
         FIG. 45  illustrates an arrangement of a predefined delayed fixed dose-variable dose therapeutic profile having a low threshold and that may be programmed into the drug delivery device; 
         FIG. 46  illustrates an arrangement of a predefined delayed fixed dose-variable dose therapeutic profile having a high threshold and that may be programmed into the drug delivery device; 
         FIG. 47  illustrates an alternative arrangement of a predefined delayed fixed dose-variable dose therapeutic profile having a low dose threshold and that may be programmed into the drug delivery device; 
         FIG. 48  illustrates an arrangement of a predefined delayed fixed dose-variable dose therapeutic profile having offset dose thresholds and that may be programmed into the drug delivery device; 
         FIG. 49  illustrates an arrangement of a predefined multi-level fixed dose-variable dose therapeutic profile having a slow ramp up and that may be programmed into the drug delivery device; 
         FIG. 50  illustrates an arrangement of a predefined multi-level fixed dose-variable dose therapeutic profile having a fast ramp up and that may be programmed into the drug delivery device; 
         FIG. 51  illustrates a perspective view of an example dispense interface component; 
         FIG. 52   a  illustrates a cross-sectional view of the dispense interface component of  FIG. 51 ; 
         FIG. 52   b  illustrates a close-up cross-sectional view of an example sealed area of the dispense interface component of  FIG. 51 ; 
         FIG. 52   c  illustrates an example top-cross-sectional view of the dispense interface component of  FIG. 51 ; 
         FIG. 53  illustrates a cross-sectional view of another example dispense interface component; 
         FIG. 54  illustrates a cross-sectional view of another example dispense interface component having a cover; 
         FIG. 55  illustrates a cross-sectional view of another example dispense interface component having a cover; and 
         FIG. 56  illustrates a cross-sectional view of another example dispense interface component having a cover. 
     
    
    
     DETAILED DESCRIPTION 
     Like elements, elements of the same kind and identically acting elements may be provided with the same reference numerals in the figures. 
       FIGS. 1   a  and  1   b  illustrate plan views of a programmable drug delivery device  10  in accordance with one aspect of the present invention.  FIG. 1   a  illustrates the device  10  when an end cap  18  is on the device  10 . In  FIG. 1   b , the device  10  is illustrated in a ready mode in that the end cap  18  is off and the device  10  has been turned on so that the digital display  80  is illuminated. When the device is activated with the cap on only cartridge contents, battery status and last dose information will be available for display. When the cover is removed the dose setting screen will be available.  FIG. 2  illustrates a perspective view of the delivery device  10  illustrated in  FIGS. 1   a  and  1   b  with the end cap  18  of the device  10  removed. In  FIG. 2 , the device is turned on so that the digital display is illuminated.  FIG. 3  illustrates a perspective view of a cartridge holder and the back side of the delivery device illustrated in  FIGS. 1   a  and  1   b .  FIG. 4  illustrates a perspective view of a proximal end of the delivery device  10 . 
     Referring now to  FIG. 1 through 4 , there can be seen a micro-processor controlled electro-mechanical drug delivery device  10  in accordance with the present invention. Preferably, this drug delivery device  10  is generally rectangular in shape comprising generally rounded ends so as to easily fit in a user&#39;s shirt pocket and is also compact enough to fit in a hand bag. 
     As will be described in greater detail below, the drug delivery device  10  contains a micro-processor control unit that operates an electro-mechanical drive that is used to deliver at least two drugs (a first or primary medicament and a second or secondary medicament) during a single dosing operation. This enables the drug delivery device  10  to provide, for example, a primary medicament such as a long acting insulin along with a secondary medicament such as a GLP1 as a combination therapy. Such combination therapy may be defined by one of a plurality of therapeutic profiles stored in a memory device that is coupled to the micro-processor contained within the device  10 . 
     The drug delivery device illustrated in  FIG. 1 through 4  comprises a main body  14  that extends from a proximal end  16  to a distal end  15 . At the distal end  15 , a removable end cap or cover  18  is provided. This end cap  18  and the distal end  15  of the main body  14  work together to provide a snap fit or form fit connection so that once the cover  18  is slid onto the distal end  15  of the main body  14 , this frictional fit between the cap and the main body outer surface  20  prevents the cover from inadvertently falling off the main body. Other types of connection mechanisms may also be used such as frictional fits or snap fits provided by way of a clip feature. 
     As will be described in greater detail below, the main body  14  contains a micro-processor control unit, an electro-mechanical drive train, and at least two medicament reservoirs. When the end cap or cover  18  is removed from the device  10  (as illustrated in  FIGS. 1   b ,  2 ,  3 , and  4 ), a dispense interface  200  (see  FIG. 3 ) is mounted to the distal end  15  of the main body  14 , and a dose dispenser (e.g., a needle assembly) is attached to the interface. The drug delivery device  10  can be used to administer a computed dose of a second medicament (secondary drug compound) and a variable dose of a first medicament (primary drug compound) through a single needle assembly, such as a double ended needle assembly. 
     A control panel region  60  is provided near the proximal end of the main body  14 . Preferably, this control panel region  60  comprises a digital display  80  along with a plurality of human interface elements that can be manipulated by a user to set and inject a combined dose. In this arrangement, the control panel region comprises a first dose setting button  62 , a second dose setting button  64  and a third button  66  designated with the symbol “OK.” As illustrated, the first dose setting button  62  resides above the second dose button  64  which is positioned above the OK button  66 . Alternative button arrangements may also be used. As just one example, the first buttons  62  and a second button  64  may, as a pair, be rotated through 90 degrees and sit underneath the screen, with each button being adjacent to a screen area. In such an arrangement, the first and second buttons could be used as soft keys to interact with icons on the user digital display  80 . In addition, along the most proximal end of the main body, an injection button  74  is also provided (see e.g.,  FIG. 4 ). 
     Utilizing micro-processor controlled human interface elements such as an operator panel (e.g., hard keys, buttons or soft keys with the key legend appearing on the display screen), setting the dose of the primary medicament allows the control unit to compute or determine the fixed dose of the second medicament. In one preferred arrangement, a computerized electronic control unit computes the dose of the second medicament. Most preferably, the computerized electronic control unit computes the dose of the second medicament based at least in part on a therapeutic dose profile that is stored in a memory device coupled to the micro-processor. Such a therapeutic profile may or may not be user or caregiver selectable. Alternatively, this profile may not be user selectable. As will be explained in greater detail below, a plurality of different such dose profiles may be stored on a memory storage device in the drug delivery device. In one arrangement, the preferred memory storage device comprises Flash memory of the micro-processor. An optional storage device could comprise an EEPROM that is coupled via a serial communication bus to the micro-processor of the control unit. 
       FIG. 2  illustrates a perspective view of the drug delivery device  10  of  FIGS. 1   a  and  1   b  with the cover  18  removed so as to illustrate the main body  14  and a cartridge holder  40 . By removing the cover  18  from the device, a user is provided access to the cartridge holder  40  and also the dispense interface  200 . In one preferred arrangement, this cartridge holder  40  can be removably attached to the main body  14 . In this arrangement, and as illustrated in  FIG. 6 , the cartridge holder  40  may contain at least two cartridge retainers  50  and  52 . Each retainer is configured so as to contain one medicament reservoir, such as a glass cartridge. Preferably, each cartridge contains a different medicament. However, in alternative drug delivery device arrangements, more than two cartridge retainers may be contained within the cartridge housing. 
     In one preferred arrangement, each cartridge retainer  50 ,  52  may be provided with a cartridge detecting system, such as the cartridge detecting system illustrated and described with respect to  FIG. 10 . Such a cartridge detecting system may comprise a mechanical or electrical switch that can be used to determine if a cartridge has been correctly inserted into the retainers  50  and  52 . Ideally, such a detection system can determine if the correct size cartridge has been properly inserted into the retainer. 
     In addition, at the distal end of the cartridge holder  40 , the drug delivery device illustrated in  FIG. 2  includes a dispense interface  200 . As will be described in relation to  FIG. 11 , this dispense interface  200  includes a main outer body  212  that is removably attached to a distal end  42  of the cartridge housing  40 . As can be seen in  FIGS. 2 and 3 , a distal end  214  of the dispense interface  200  preferably comprises a needle hub  216 . This needle hub  216  may be configured so as to allow a dose dispenser, such as a conventional pen type injection needle assembly, to be removably mounted to the drug delivery device  10 . 
     At a first end or a proximal end  16  of the main housing  14 , there is provided a control panel region  60 . This control panel region  60  comprises a digital display, preferably an Organic Light Emitting Diode (OLED) display  80  along with a plurality of user interface keys such as push buttons. Alternatively, this region could comprise a touch screen and icons on the display. A further option would be a display screen with a joystick, a control wheel and/or possibly push buttons. In addition, the control panel region may also comprise a swipe section so as to either increase or decrease the dose size or provide other means by which a user could operate the device  10 . Preferably, the human interface controls may be configured to provide tactile, audible and/or visual feedback. 
     The digital display  80  may be part of a user interface that allows the user to interact with the device  10 . As explained in greater detail below, this display provides a visual indication of device operation such as dose setting, dose administration, injection history, device errors, etc. The digital display  80  can also display various drug delivery device parameters. For example, the display can be programmed to display an identified medicament contained in either medicament containers and also provide a visual confirmation that the correct cartridge and therefore medicament is being used. In addition, the display can also provide dose history information such as the time since the last dose has been administered, battery level, dose size set, device status, dose dispense status, dose history information, warnings, and errors. 
     In addition, the display  80  may also provide the time and date and be used to set a current time and date. The display may also be used to provide the user with training information as to how the device should be used and operated. Alternatively, the display may be used to educate the user on diabetes or other therapy information via instructional videos. The display may also be used to communicate with, or receive feedback from a health care professional via the wireless or wired communication link such as USB to a PC and then potentially via the internet, or via a mobile phone coupled to the device using a wired or wireless link such as a Bluetooth™ link, a WLAN link, and/or the like. The display may also be used to configure a device communication link: that is, used for device set up and enter passwords for a data link, such as a Bluetooth data link. In addition, the display may be used to provide drug delivery device priming information or possibly an indication of the orientation and/or relative position of the device. For example, a micro-electro-mechanical accelerometer could be provided within the device so that the device will have the intelligence to know if the user is using the device to perform a safety or priming shot (i.e., having the distal end of the device pointing upwards) or using the device to perform a dose administration step (i.e., having the distal end of the device pointing downwards). 
     The display may also potentially be used as a diary or life style calendar and perhaps communicate with a patient&#39;s BGM and perhaps store and display blood glucose data. The display could also indicate a dwell period, possibly proportional to a dose size, following the delivery of a dose. The display could indicate if the device is armed i.e., ready to deliver a dose and also be used to provide an indication if the dose is outside of expected limits. 
     In addition, by manipulating certain other buttons, the display can be used to display information stored in the control unit. For example, such stored information could include user or patient information. Such user or patient information could include their name, their address, their health number, contact details, their prescribed medication or dosage regime. 
     In addition, there is also the opportunity to include calendar information, which could include blood glucose readings, the size of last dose taken, exercise taken, state of health, the time these events occurred including meal times, etc. Certain key events can also be stored and viewed. For example, such key events could include device failures that could potentially result in an over or under dose, cartridge changes, priming shots, reading the dose history, removing the cap, removing the dose dispenser, removing the dispense interface, time since manufacture, time since first use along with other similar types of information and data. 
     The digital display could also allow the user access to a time reference maintained by the device. Such a time reference could keep track of the current time and date. This clock may be set by the user via the interface or alternatively, via a data link (e.g., USB or IRDA) provided on the device. In addition, the time reference may be provided with a permanently connected battery backup so as to maintain the passage of time if and when the main battery has been removed or is flat. This time reference may be used to determine when the last dose was taken, which can then be displayed on the display. This time reference may also be used to store certain key events. Such events could include the time and date of the following: the last dose; whether any drug delivery device errors occurred; cartridge changes; any parameter changes, any changes in therapeutic profiles; dispense interface changes; and time since manufacture. 
     As previously mentioned,  FIG. 1   b  illustrates one arrangement of the drug delivery device  10  after the user has turned the device on. One way in which a user may turn the device on is for the user to press the “OK” button  66  provided on the control panel region  60 . Alternatively, the device  10  can be programmed to be turned on by removing the end cap  18 . The OK button  66  may then be used when the device  10  has gone into a sleep mode after a certain period of inactivity. The sleep mode may be indicated by a possibly blank display screen. Preferably, when the cap  18  is placed back upon the device, it may be possible to review via the display  80  certain dose or dosing history data by pressing one of the human interface elements, such as the OK button  66 . 
     Once the device is turned on, the digital display  80  illuminates and provides the user certain device information, preferably information relating to the medicaments contained within the cartridge holder  40 . For example, as illustrated in  FIGS. 1 and 5 , the user is provided with certain information relating to both the primary medicament (Drug A) and the secondary medicament (Drug B). Preferably, the display comprises at least two display regions  82 ,  86  containing medicament information. The first display region  82  provides the user information relating to the primary medicament: the type of medicament—“Drug A” and the amount of Drug A that has been selected by the user—“0 Units.” In addition, the second display region  86  provides the user with information relating to the secondary medicament: the type of medicament—“Drug B” and the amount of Drug B that has been calculated by the device based on the amount of Drug A selected by the user and on the particular therapeutic profile—“0μ, Grams.” As those of ordinary skill in the art will recognize, if in an alternative arrangement the drug delivery device  10  contained three medicaments and then used to administer a combination therapy of these three medicaments, the digital display  80  would be modified so as to comprise at least three display regions containing information for at least these three medicaments. 
     Where the size of the second dose is determined from the size of the first it may not be necessary to indicate the size of the second dose and hence an alternative embodiment of the display graphics may be used, for example an “O.k.” indication, such as a green dot, a green check mark, or the letters “O.k.”. 
     Aside from the digital display  80 , the control panel region  60  further comprises various user interface keys. For example, as illustrated in  FIGS. 1   a ,  1   b ,  2  and  4 , the control panel region  60  of the drug delivery device  10  further provides the following user interface keys:
         a. a first dose setting button  62 ,   b. a second dose setting button  64 , and   c. an OK or Enter button  66 .       

     The first and second dose buttons  62 ,  64  may be manipulated so as to allow a user of the device  10  to either increase or decrease a selected dose of the primary medicament “Drug A” to be delivered. For example, to set or increase a primary medicament dose amount, a user could toggle the first dose setting button  62 . The first display region  82  would provide a visual indication to the user of the amount he or she is setting. 
     In the event that a user wants to decrease a previously set dose, the second dose setting button  64  may be toggled or pushed so as to decrease the set dose. Once the user has selected the amount of the primary medicament, the user may then push the “OK” button  66 . Pushing the OK button  66  may instruct the device  10  to compute the corresponding dose of the secondary medicament “Drug B”. Alternatively, the dose of the secondary medicament may be determined when the dose of the first medicament is set or changed. 
     In an alternative display arrangement, the display  80  can display the calculated amount of the secondary medicament Drug B for every incremental change of Drug A. Thereafter, the OK button  66  could then be used. For example, pressing and holding this OK button  66  for a certain period of (e.g., 2 seconds) could be used by the user to confirm the set and calculated dose and thereby arming the device  10  ready for delivery. The combined dose could then be dispensed through a single dose dispenser by pressing the injection button  74 . In one preferred arrangement, the device armed condition may be available for a limited period, for example, 20 seconds or so. In an alternative arrangement, the arm feature may not be included. 
       FIG. 5   a  illustrates the display  80  of device  10  illustrated in  FIG. 1   b  after the device has been turned on but before a user sets a first dose of the primary medicament Drug A.  FIG. 5   b  illustrates this display  80  after a user has set a first dose of the primary medicament Drug A and after the device has computed the corresponding amount of the secondary medicament Drug B. As illustrated in  FIG. 5   b , the user has set a 15 Unit dose of the primary medicament Drug A and this is confirmed by what is displayed in the first display region  82 . After the device  10  computes the secondary dose of the second medicament Drug B, this is also indicated by what is displayed in the second region  86 . For example, in this situation, the device  10  calculated a dose of 20μ Grams for Drug B based in part on a 15 Unit dose of the primary medicament Drug A and based in part on one of the algorithms stored within the device. 
     This combined dose, 15 Units of the primary medicament Drug A and 20μ Grams of the secondary medicament Drug B, can then be injected. As may be seen from  FIG. 4 , at a proximal end of the main body  14  of the device  10 , an injection button  74  is provided for injecting this combined dose. Alternatively, this dose inject button  74  could be provided elsewhere on the main housing  14  such as on the control panel region  60 . 
     Other information that may be taken into account when calculating the amount of the second medicament may be the time interval since the previous dose of either the first or the second medicament. For example, the following description provides an example algorithm and process that may be used in the calculation of the size of the dose to be dispensed from the second medicament. This algorithm maybe illustrated in a flowchart  150  provided as  FIG. 7 . 
     As may be seen from the flowchart  150  provided in  FIG. 7 , first a user begins the dose selection process by turning the device on at step  134 . Then, at step  136 , the user selects the size of the dose to be delivered from the first medicament M1 in the first cartridge and then presses the OK button to confirm. At step  138 , the microcontroller determines if the selected dose size of the first medicament M1 is less than a minimum dose threshold for the first medicament (e.g., 5 units). If it is determined that the selected dose size is indeed less than the minimum dose threshold, the process proceeds to step  144  where the calculated dose of the second medicament M2 is then computed as a zero dose. Then, the process moves to step  146  where the dose (comprising only a selected dose of the primary medicament) is administered. 
     If the selected dose size is determined to be greater than or equal to this minimum dose threshold, the process  150  proceeds to step  140 . At step  140 , the microcontroller determines if the time interval since the previous injection is less than, or equal to the predefined threshold (e.g., 18 hours). If the answer to this inquiry is yes, the process  150  proceeds to step  144  where the size of the dose from the second medicament M2 would be calculated as equal to a zero (“0”) dose. Then, the process moves to step  146  where the dose (comprising only a selected dose of the primary medicament) is administered. 
     Alternatively, if the answer to both inquiries at steps  138  and  140  are no, then process  150  would proceed to the step  142 . At step  142 , the microcontroller would compute the dose of the secondary medicament M2 based at least in part on a stored therapeutic profile. If a third medicament would be provided in the drug delivery device, the microcontroller would compute a dose of a third medicament based at least in part on a stored therapeutic profile as well. This later profile may or may not be the same profile that is used to calculate the dose of the secondary medicament. 
     Therefore, if a user selects a dose size of the primary medicament M1 at step  136  that is equal to, or greater than, a certain minimum dose threshold for the first medicament (e.g., 5 units), and the time interval since the previous injections is greater than the predefined threshold (e.g., 18 hours) then the predefined dose of the secondary medicament from the second cartridge (e.g., 0.5 units) will be delivered when the injection is administered at step  146 . 
     Applicants&#39; drug delivery device  10  may also be programmed with an auto titration algorithm. As just one example, such an algorithm may be used where the dose of the second medicament needs to be increased over a period of time to allow a patient to get used to the second medicament, such as is the case for a GLP1 or GLP1 analogs. An exemplary auto titration algorithm is presented in a flowchart  160  illustrated in  FIG. 8 . 
     In one arrangement, after the device is turned on at step  164 , a user initiates an auto titration mode of operation by manipulating one of the keys provided on the control panel. This is represented at step  166 . Alternatively, this auto titration mode of operation could be automatically activated. For example, the auto titration mode of operation could be automatically activated when the drug delivery device  10  is first used, for example, when a battery is first connected to the device, when the battery is first charged, or when a profile is loaded into the device and selected by a user. After step  166 , a prompt on the digital display  80  may ask a user for a password and then to confirm that the auto titration algorithm is indeed desired by the patient. In an alternative embodiment, a prompt on the digital display  80  may ask the user for a confirmation only. 
     Aside from using a stored algorithm for operating the device in an auto titration mode, this auto titration mode might be achieved via providing a user with cartridges containing the same medicament but with different strengths or concentrations. One disadvantage of such a scenario is that the provider of such cartridges would have to produce cartridges in at least two different strength concentrations of drugs rather than through smaller doses from a standard strength cartridge. If different strength cartridges are used, then the device may be programmed not to provide the auto-titration functionality. If this functionality is optional and patient determined, then such a function could be accessed through the digital display  80  via a ‘menu’ button (or other similar user interface element). 
     At step  168 , a user selects a dose of the primary medicament M1. Then, at step  170 , the microcontroller determines if the selected dose size is less than a minimum dose threshold for the first medicament (e.g., 5 units). If the microcontroller determines that the selected dose size is less than a minimum dose threshold for the first medicament, the process  160  proceeds to step  176 . At step  176 , the microcontroller determines that the calculated dose of the secondary medicament M2 should be a zero (“0”) dose. 
     If at step  170  the microcontroller determines that the selected dose size of M1 is not less than a minimum dose threshold for the first medicament, the process  160  proceeds to step  172 . At step  172 , the microcontroller computes a time interval since the previous dose administration and determines if this computed time interval is less than, or equal to a predefined threshold (e.g., 18 hours). If at step  172  the microcontroller determines that this computed time interval is less than, or equal to a predefined threshold, the process  160  proceeds on to step  176 . At step  176 , the microcontroller determines that the calculated dose of the secondary medicament M2 should be a zero (“0”) dose. 
     Alternatively, if at step  172 , the microcontroller determines that this computed time interval since the previous injection is not less than, or equal to a predefined threshold, the process proceeds to step  174 . 
     If the microcontroller determines that the selected dose size is equal to, or greater than, the minimum dose threshold for the first medicament (e.g., 5 units) at step  170  and determines that the time interval since the previous injection is greater than the predefined threshold (e.g., 18 hours) at step  172 , the process proceeds to step  174 . At step  174 , the microcontroller determines whether the time interval since the auto-titration feature was activated is less than a predefined threshold (e.g., 1 week). If at step  174  the microcontroller determines that the time interval since the auto-titration feature was activated is greater than this predefined threshold, the process  160  moves to step  176  where a zero “0” dose of M2 is determined. 
     Alternatively, if the microcontroller determines that the time interval since the auto-titration feature was activated is less than the predefined threshold at step  174 , the process moves to step  178 . At step  178 , the microcontroller determines a predefined starting dose of the secondary medicament based in part on a therapeutic profile. Then, at step  180 , the predefined starting dose from the second cartridge (e.g., 0.25 micro Grams) M2 along with the previously selected dose of the primary medicament M1 from step  168  will be delivered during an injection step. 
     Therefore, in accordance with the auto titration flowchart  160 , if the selected dose size is equal to, or greater than, the minimum dose threshold for the first medicament (e.g., 5 units) and the time interval since the previous injections is greater than the predefined threshold (e.g., 18 hours) and the time interval since the auto-titration feature was activated is greater than a predefined threshold (e.g., 1 week) then the predefined maintenance dose from the second cartridge (e.g., 0.5 units) will be delivered when the injection is taken at step  180 . If the calculated responses to the steps  170  and  172  are yes or if the response to step  174  is no, then the dose that is administered would comprise only the selected dose of the primary medicament from step  168 . 
     Aside from the user interface keys, the drug delivery device may also comprise a sounder or a sound control. For example, the device may have a sounder that generates a range of tones. Such tones could be provided so as to indicate when a button is pressed, when certain key events occur (e.g., after a dose is set, after the completion of a dose delivery, etc.), warnings that the device is not working correctly or if an incorrect cartridge has been inserted, if the device experiences certain operational errors, or if an alarm condition is triggered. The volume of the sounder may be set or configured by using a menu system controlled by the human interface elements or alternatively through a dedicated volume control button. 
     The main housing portion is preferably coupled to a proximal end of the cartridge holder  40 . Preferably, this cartridge holder  40  comprises at least two separate cartridge retainers that are configured to hold two reservoirs of medicament. Depending on the reservoirs, these two retainers may or may not be similarly sized. For example,  FIG. 3  illustrates a back side of the drug delivery  10  illustrated in  FIGS. 1   a  and  1   b  and illustrates one of the cartridge retainers  52 .  FIG. 6  illustrates a distal end of the cartridge holder of the drug delivery device illustrated in  FIGS. 1   a  and  1   b  and illustrates both the first and the second cartridge retainers  50 ,  52 . In one preferred arrangement, the first cartridge retainer  50  is configured for receiving a first cartridge  90  containing a primary medicament  92  and the second cartridge retainer  52  is configured for receiving a second cartridge  100  containing a secondary medicament  102 . The first and second cartridges  90 ,  100  may or may not be of similar size and/or dimensions. 
     As illustrated in  FIG. 6 , the cartridge housing  40  comprises a first window  46  residing along a first side portion of the cartridge housing. Similarly, the cartridge housing  40  comprises a second window  47  residing along a second side portion of the cartridge housing  40 . This cartridge housing  40  comprises two cartridge retainers  50 ,  52  and these retainers are positioned essentially side-by-side one another. Once the cap  18  is removed from the drug delivery device  10 , the windows  46 ,  47  enable a user to view the medicaments contained within the cartridges and monitor the amount of medicament remaining in each reservoir. For example, as may be seen from  FIG. 6 , the first window  46  allows the user to monitor the primary medicament  92  contained within the first cartridge  90  while the second window  47  allows the user to monitor the second medicament  102  contained within the second cartridge  100 . The visible cartridge contents could be confirmed by what is displayed on the digital display  80 . 
     In this illustrated arrangement, the first cartridge  90  contains a primary medicament  92  and the second cartridge  100  may contain a secondary medicament  102 . Preferably, both the first and the second cartridges contain multiple doses of each medicament  92 ,  102 , respectively. Each cartridge is self-contained and provided as a sealed and sterile cartridge. These cartridges can be of different volumes and replaceable when empty or they can be fixed (non-removable) in the cartridge holder  40 . They can also have a pierceable seal or septa at a distal end of the cartridge and configured to accept needle cannula. 
     Various cartridge holder arrangements may be used with the drug delivery device illustrated in  FIGS. 1-6 . As just one example, the cartridge holder  40  may comprise separately shaped cartridge retainers  50 ,  52 . As just one example, the first cartridge retainer  50  may be shaped to receive a cartridge having a first volume while the second cartridge retainer  52  may be shaped to receive a cartridge having a second volume. As just one example, in one preferred arrangement, the primary medicament  92  contained in the first cartridge  90  may comprise a long acting insulin whereas the second medicament  102  contained within the secondary cartridge  100  may comprise a GLP1 or like analog. 
     As such, in one preferred arrangement, the volume of the first cartridge  90  may be a standard 300 Unit cartridge and therefore the first cartridge retainer  50  must be geometrically configured for such a volume. In contrast, the volume of the second cartridge  100  may be a smaller volume (e.g., in the order of 20 Units) and therefore must be geometrically configured to receive such a smaller volume cartridge. As those of ordinary skill in the art with recognize, other cartridge and cartridge retainer arrangements and geometries are possible as well. 
     In one preferred arrangement, the first and a second cartridge retainers  50 ,  52  comprise hinged cartridge retainers. These hinged retainers allow user access to the cartridges. For example,  FIG. 9  illustrates a perspective view of the cartridge holder  40  illustrated in  FIG. 2  with the first hinged cartridge retainer  50  in an open position.  FIG. 9  illustrates how a user might access the first cartridge  90  by opening up the first retainer  50  and thereby having access to the first cartridge  90 . A user might access the second cartridge  100  contained in the second hinged retainer  52  in a similar manner. Of course, if different sized cartridges are used, a user might access the second cartridge  100  in a different manner. 
     As illustrated in at least  FIGS. 9 and 10 , the drug delivery device  10  may comprise a cartridge detection system. Such a system may be used so as to confirm that the cartridge  90  has been properly inserted into the first cartridge retainer  50 . In this illustrated arrangement, the cartridge detection device  70  is provided along an inner portion of the cartridge holder  40 . An alternative location of the detection device may also be used. 
     In one preferred arrangement, the first or primary cartridge  90  containing first medicament and the second or secondary cartridge  100  containing the second medicament are of similar dimensions. In a more preferred arrangement, the first cartridge  90  is a different size than the second cartridge. As just one example, the first medicament (e.g., a long acting insulin) could be provided within a 3 ml cartridge and this cartridge loaded into the first cavity. In addition, the second medicament (e.g., a GLP1) may be provided within a shortened 1.7 ml cartridge and could be loaded into the second cavity. Because the second hinged retainer contains a smaller sized cartridge, the second retainer would be sized differently than the first retainer. In a most preferred arrangement, the primary cartridge holder is designed so as to accept a 3 ml cartridge of insulin and the secondary holder is designed so as to accept a 1.7 ml cartridge of a GLP1. However, those of skill in the art will readily recognize, alternative cartridge holder structures and cartridge configurations could also be used. 
     In one arrangement, the cartridge holder  40  includes a cartridge dedication or coding system, such as a mechanical or an electronic cartridge dedication or coding system. Such a system would help to ensure that only a correctly coded cartridge and therefore the correct medicament could be loaded into each cartridge retainer. An electronic coding system that is able to detect a drug type, expiry date or other similar information would be a preferred arrangement. In such an electronic system, the microprocessor control unit could be programmed so that only a properly coded cartridge (and therefore the proper medicaments) would be acceptable in such a system. In such a coded system, the control unit could be programmed with an electronic lock-out so as to lock out or disable the operator interface if an improperly coded cartridge was detected. Preferably, if such an incorrect cartridge were loaded, an error message would be displayed on the digital display  80  so as to notify the user that an incorrect cartridge (and therefore perhaps an incorrect medicament) had been loaded. Most preferably, if such an incorrect cartridge were loaded, the drug delivery device  10  could be programmed so as to lockout the user interface keys and prevent the user from setting a dose. 
       FIG. 10  illustrates one type of cartridge identification system  110  that may be used with the cartridge housing of drug delivery device  10 . For example,  FIG. 10  illustrates a cartridge  120  (similar to either the first or the second cartridge  90 ,  100 ) residing in a cartridge retainer  116  of a cartridge holder  118 . Cartridge retainer  116  may be similar to the cartridge retainers  50 ,  52  illustrated in  FIGS. 3 and 6 . A cartridge  120  is illustrated as being nested within an internal cavity of the cartridge retainer  116 . A label  122  is provided along an outer surface of the cartridge  120  and a bar code  124  is provided along a portion of this label  122 . 
     In  FIG. 10 , the cartridge identification system  110  comprises a one dimensional (“1D”) bar code reading system. In such a cartridge identification system  110 , the barcode is provided along the cartridge surface and this bar code is an optical machine-readable representation of certain information. Alternatively, a two dimensional bar code reader could also be used. In such an arrangement, patterns of squares, dots, hexagons and other geometric patterns within images may be provided either on the cartridge outer surface itself or on a cartridge label. In addition, a cartridge detection device  70  may be provided along an inner surface wall of the system  110 . 
     As just one example, the cartridge holder  118  may comprise a bar code reader  126 . In one arrangement, this reader could comprise a 1D bar code reader comprising a light source  128  and a photo diode  130  and these two elements could be provided along an inner surface of the cartridge housing  118  adjacent the cartridge retainer  116 . As illustrated, the light source  128  and a photo diode  130  may placed next to each other and directed towards the barcode on the cartridge. To read the bar code  124  provided on the label  122  of the cartridge  120 , the light source  128  illuminates various lines provided on the label  122  as the cartridge is inserted into the cartridge housing  118 . This light is then reflected and the photo diode  130  measures the intensity of the light reflected back from the light source  128  and a waveform is generated. The micro-processor coupled to this cartridge identification system  110  uses this generated waveform to measure the widths of the bars and spaces of the bar code  124 . For example, dark bars in the bar code absorb the illuminated light while the white spaces reflect light. 
     As such, the voltage waveform generated by the photo diode will represent a duplicate of the bar and space pattern in the bar code. This waveform is then decoded by an algorithm provided in the micro-processor. Alternatively, a 2D barcode reader could also be used. One advantage of such a reader is that relative motion between the cartridge and the cartridge holder would not be required. 
     Utilizing such cartridge identification in Applicants&#39; proposed drug delivery device  10  results in certain advantages. For example, such a cartridge identification arrangement can provide a method of retrieving information from the cartridges to determine the manufacturer or supplier of the cartridge. Such a system could also determine the type of medicament contained within the cartridge and then may also determine information relating to the drug contained within the cartridge. For example, the cartridge identification system could determine whether the cartridge that was inserted into the first retainer that is supposed to contain the primary medicament actually comprises a cartridge containing such a primary medicament. Such an identification scheme could comprise either a passive or active type of identification scheme. For example, it could comprise a passively (typically mechanical) or active (typically electrical) identification scheme. Such cartridge identification schemes may comprise identification through a microchip interface or through a radio frequency identification (RF-ID) interface. The cartridge may then comprise a readable memory comprising information about the cartridge. The memory may also be writeable, for example to store information on the used number of units, or information on an estimated remaining content in the cartridge and the date first used. The remaining content may be given in number of units, mg, ml and/or the like. The information on the remaining content may be updated when content has been expelled from the cartridge. 
     In an alternative arrangement, the cartridge holder  40  may be provided as a disposable cartridge holder. For example, in such an arrangement, a medical device supplier or a medicament supplier could supply the cartridge holder containing the two medicaments and these would not be replaceable by the end user. Therefore, once either the primary or secondary medicament of such a cartridge holder has been expended, the entire cartridge holder is removed from the drug dispensing portion of the drug delivery device and is discarded. Thereafter, the user or patient could then attach a new cartridge holder containing two fresh cartridges to the drug dispensing portion of the drug delivery device. 
     The disposable nature of such a cartridge holder would provide a number of advantages. For example, such a cartridge holder would help to prevent inadvertent medicament cross use: that is, using an incorrect primary or secondary medicament within the cartridge housing. Such an arrangement could also help prevent tampering of the medicaments and could also help eliminate counterfeit products from being used with the drug delivery device. In addition, the cartridge holder may be connected to the device main body where the device main body comprise a one dimensional (“1D”) bar code reading system. Such a coding system could comprise a system similar to the coding system  110  discussed above. 
     As mentioned above when discussing  FIGS. 2 and 3 , a dispense interface  200  is coupled to the distal end of the cartridge holder  40 .  FIG. 11  illustrates a flat view of the dispense interface  200  unconnected to the distal end of the cartridge holder  40 . A dose dispenser or needle assembly that may be used with the interface  200  is also illustrated and is provided in a protective outer cap  420 . 
     In  FIG. 12 , the dispense interface  200  illustrated in  FIG. 11  is shown coupled to the cartridge holder  40 . The axial attachment means between the dispense interface  200  and the cartridge holder  40  can be any known axial attachment means to those skilled in the art, including snap locks, snap fits, snap rings, keyed slots, and combinations of such connections. The connection or attachment between the dispense interface and the cartridge holder may also contain additional features (not shown), such as connectors, stops, splines, ribs, grooves, pips, clips and the like design features, that ensure that specific hubs are attachable only to matching drug delivery devices. Such additional features would prevent the insertion of a non-appropriate secondary cartridge to a non-matching injection device. 
       FIG. 12  also illustrates the needle assembly  400  and protective cover  420  coupled to the distal end of the dispense interface  200  that may be screwed onto the needle hub of the interface  200 .  FIG. 13  illustrates a cross sectional view of the double ended needle assembly  402  mounted on the dispense interface  200  in  FIG. 12 . 
     The needle assembly  400  illustrated in  FIG. 13  comprises a double ended needle  406  and a hub  401 . The double ended needle or cannula  406  is fixedly mounted in a needle hub  401 . This needle hub  401  comprises a circular disk shaped element which has along its periphery a circumferential depending sleeve  403 . Along an inner wall of this hub member  401 , a thread  404  is provided. This thread  404  allows the needle hub  401  to be screwed onto the dispense interface  200  which, in one preferred arrangement, is provided with a corresponding outer thread along a distal hub. At a center portion of the hub element  401  there is provided a protrusion  402 . This protrusion  402  projects from the hub in an opposite direction of the sleeve member. A double ended needle  406  is mounted centrally through the protrusion  402  and the needle hub  401 . This double ended needle  406  is mounted such that a first or distal piercing end  405  of the double ended needle forms an injecting part for piercing an injection site (e.g., the skin of a user). 
     Similarly, a second or proximal piercing end  406  of the needle assembly  400  protrudes from an opposite side of the circular disc so that it is concentrically surrounded by the sleeve  403 . In one needle assembly arrangement, the second or proximal piercing end  406  may be shorter than the sleeve  403  so that this sleeve to some extent protects the pointed end of the back sleeve. The needle cover cap  420  illustrated in  FIGS. 11 and 12  provides a form fit around the outer surface  403  of the hub  401 . 
     The needle assembly of  FIG. 11  may be removably coupled to the distal end of the dispense interface  200 . Referring now to  FIGS. 11-12  and  14 - 19 , one preferred arrangement of this interface  200  will now be discussed. In this one preferred arrangement, this interface  200  comprises:
         a. a main outer body  210 ,   b. an first inner body  220 ,   c. a second inner body  230 ,   d. a first piercing needle  240 ,   e. a second piercing needle  250 ,   f. a valve seal  260 , and   g. a septum  270 .       

     The main outer body  210  comprises a main body proximal end  212  and a main body distal end  214 . At the proximal end  212  of the outer body  210 , a connecting member is configured so as to allow the dispense interface  200  to be attached to the distal end of the cartridge holder  40 . Preferably, the connecting member is configured so as to allow the dispense interface  200  to be removably connected the cartridge holder  40 . In one preferred interface arrangement, the proximal end of the interface  200  is configured with an upwardly extending wall  218  having at least one recess. For example, as may be seen from  FIG. 15 , the upwardly extending wall  218  comprises at least a first recess  217  and a second recess  219 . 
     Preferably, the first and the second recesses  217 ,  219  are positioned within this main outer body wall so as to cooperate with an outwardly protruding member located near the distal end of the cartridge housing  40  of the drug delivery device  10 . For example, this outwardly protruding member  48  of the cartridge housing may be seen in  FIGS. 11 and 12 . A second similar protruding member is provided on the opposite side of the cartridge housing. As such, when the interface  200  is axially slid over the distal end of the cartridge housing  40 , the outwardly protruding members will cooperate with the first and second recess  217 ,  219  to form an interference fit, form fit, or snap lock. Alternatively, and as those of skill in the art will recognize, any other similar connection mechanism that allows for the dispense interface and the cartridge housing  40  to be axially coupled could be used as well. 
     The main outer body  210  and the distal end of the cartridge holder  40  act to form an axially engaging snap lock or snap fit arrangement that could be axially slid onto the distal end of the cartridge housing. In one alternative arrangement, the dispense interface  200  may be provided with a coding feature so as to prevent inadvertent dispense interface cross use. That is, the inner body of the hub could be geometrically configured so as to prevent an inadvertent cross use of one or more dispense interfaces. 
     A mounting hub is provided at a distal end of the main outer body  210  of the dispense interface  200 . Such a mounting hub can be configured to be releasably connected to a needle assembly. As just one example, this connecting means  216  may comprise an outer thread that engages an inner thread provided along an inner wall surface of a needle hub of a needle assembly, such as the needle assembly  400  illustrated in  FIG. 13 . Alternative releasable connectors may also be provided such as a snap lock, a snap lock released through threads, a bayonet lock, a form fit, or other similar connection arrangements. 
     The dispense interface  200  further comprises a first inner body  220 . Certain details of this inner body are illustrated in  FIGS. 15-19 . Preferably, this first inner body  220  is coupled to an inner surface  215  of the extending wall  218  of the main outer body  210 . More preferably, this first inner body  220  is coupled by way of a rib and groove form fit arrangement to an inner surface of the outer body  210 . For example, as can be seen from  FIG. 16 , the extending wall  218  of the main outer body  210  is provided with a first rib  213   a  and a second rib  213   b . This first rib  213   a  is also illustrated in  FIG. 17 . These ribs  213   a  and  213   b  are positioned along the inner surface  215  of the wall  218  of the outer body  210  and create a form fit or snap lock engagement with cooperating grooves  224   a  and  224   b  of the first inner body  220 . In a preferred arrangement, these cooperating grooves  224   a  and  224   b  are provided along an outer surface  222  of the first inner body  220 . 
     In addition, as can be seen in  FIGS. 15-18 , a proximal surface  226  near the proximal end of the first inner body  220  may be configured with at least a first proximally positioned piercing needle  240  comprising a proximal piercing end portion  244 . Similarly, the first inner body  220  is configured with a second proximally positioned piercing needle  250  comprising a proximally piercing end portion  254 . Both the first and second needles  240 ,  250  are rigidly mounted on the proximal surface  226  of the first inner body  220 . 
     Preferably, this dispense interface  200  further comprises a valve arrangement. Such a valve arrangement could be constructed so as to prevent cross contamination of the first and second medicaments contained in the first and second reservoirs, respectively. A preferred valve arrangement may also be configured so as to prevent back flow and cross contamination of the first and second medicaments. 
     In one preferred system, dispense interface  200  includes a valve arrangement in the form of a valve seal  260 . Such a valve seal  260  may be provided within a cavity  231  defined by the second inner body  230 , so as to form a holding chamber  280 . Preferably, cavity  231  resides along an upper surface of the second inner body  230 . This valve seal comprises an upper surface that defines both a first fluid groove  264  and second fluid groove  266 . For example,  FIG. 16  illustrates the position of the valve seal  260 , seated between the first inner body  220  and the second inner body  230 . During an injection step, this seal valve  260  helps to prevent the primary medicament in the first pathway from migrating to the secondary medicament in the second pathway while also preventing the secondary medicament in the second pathway from migrating to the primary medicament in the first pathway. Preferably, this seal valve  260  comprises a first non-return valve  262  and a second non-return valve  268 . As such, the first non-return valve  262  prevents fluid transferring along the first fluid pathway  264 , for example a groove in the seal valve  260 , from returning back into this pathway  264 . Similarly, the second non-return valve  268  prevents fluid transferring along the second fluid pathway  266  from returning back into this pathway  266 . 
     Together, the first and second grooves  264 ,  266  converge towards the non-return valves  262  and  268  respectively, to then provide for an output fluid path or a holding chamber  280 . This holding chamber  280  is defined by an inner chamber defined by a distal end of the second inner body both the first and the second non return valves  262 ,  268  along with a pierceable septum  270 . As illustrated, this pierceable septum  270  is positioned between a distal end portion of the second inner body  230  and an inner surface defined by the needle hub of the main outer body  210 . 
     The holding chamber  280  terminates at an outlet port of the interface  200 . This outlet port  290  is preferably centrally located in the needle hub of the interface  200  and assists in maintaining the pierceable seal  270  in a stationary position. As such, when a double ended needle assembly is attached to the needle hub of the interface (such as the double ended needle illustrated in  FIG. 13 ), the output fluid path allows both medicaments to be in fluid communication with the attached needle assembly. 
     The hub interface  200  further comprises a second inner body  230 . As can be seen from  FIG. 16 , this second inner body  230  has an upper surface that defines a recess, and the valve seal  260  is positioned within this recess. Therefore, when the interface  200  is assembled as shown in  FIG. 16 , the second inner body  230  will be positioned between a distal end of the outer body  210  and the first inner body  220 . Together, second inner body  230  and the main outer body hold the septum  270  in place. The distal end of the inner body  230  may also form a cavity or holding chamber that can be configured to be fluid communication with both the first groove  264  and the second groove  266  of the valve seal. 
     Although not shown, the dispense interface  200  could be supplied by a manufacturer as being contained in a protective and sterile capsule or container. As such, where the user would peel or tear open a seal or the container itself to gain access to the sterile single dispense interface. In some instances it might be desirable to provide two or more seals for each end of the interface. The seal may allow display of information required by regulatory labeling requirements. When a double ended needle assembly is used as a single dispense assembly to deliver the single dose of both medicaments, it is preferred that the interface is designed to be economical and safe for allowing the user to attach a new hub for each injection. 
     Axially sliding the main outer body  210  over the distal end of the drug delivery device attaches the dispense interface  200  to the multi-use device. In this manner, a fluid communication may be created between the first needle  240  and the second needle  250  with the primary medicament of the first cartridge and the secondary medicament of the second cartridge, respectively. 
       FIG. 19  illustrates the dispense interface  200  after it has been mounted onto the distal end  42  of the cartridge holder  40  of the drug delivery device  10  illustrated in  FIG. 1 . A double ended needle  400  is also mounted to the distal end of this interface. The cartridge holder  40  is illustrated as having a first cartridge containing a first medicament and a second cartridge containing a second medicament. 
     When the interface  200  is first mounted over the distal end of the cartridge holder  40 , the proximal piercing end  244  of the first piercing needle  240  pierces the septum of the first cartridge  90  and thereby resides in fluid communication with the primary medicament  92  of the first cartridge  90 . A distal end of the first piercing needle  240  will also be in fluid communication with a first fluid path groove  264  defined by the valve seal  260 . 
     Similarly, the proximal piercing end  254  of the second piercing needle  250  pierces the septum of the second cartridge  100  and thereby resides in fluid communication with the secondary medicament  102  of the second cartridge  100 . A distal end of this second piercing needle  250  will also be in fluid communication with a second fluid path groove  266  defined by the valve seal  260 . 
       FIG. 19  illustrates a preferred arrangement of such a dispense interface  200  that is coupled to a distal end  15  of the main body  14  of drug delivery device  10 . Preferably, such a dispense interface  200  is removably coupled to the cartridge holder  40  of the drug delivery device  10 . 
     As illustrated in  FIG. 19 , the dispense interface  200  is coupled to the distal end of a cartridge housing  40 . This cartridge holder  40  is illustrated as containing the first cartridge  90  containing the primary medicament  92  and the second cartridge  100  containing the secondary medicament  102 . Once coupled to the cartridge housing  40 , the dispense interface  200  essentially provides a mechanism for providing a fluid communication path from the first and second cartridges  90 ,  100  to the common holding chamber  280 . This holding chamber  280  is illustrated as being in fluid communication with a dose dispenser. Here, as illustrated, this dose dispenser comprises the double ended needle assembly  400 . As illustrated, the proximal end of the double ended needle assembly is in fluid communication with the chamber  280 . 
     In one preferred arrangement, the dispense interface is configured so that it attaches to the main body in only one orientation, that is it is fitted only one way round. As such as illustrated in  FIG. 19 , once the dispense interface  200  is attached to the cartridge holder  40 , the primary needle  240  can only be used for fluid communication with the primary medicament  92  of the first cartridge  90  and the interface  200  would be prevented from being reattached to the holder  40  so that the primary needle  240  could now be used for fluid communication with the secondary medicament  102  of the second cartridge  100 . Such a one way around connecting mechanism may help to reduce potential cross contamination between the two medicaments  92  and  102 . 
     In one arrangement, the drug delivery device  10  comprises a detection sensor so as to sense or confirm that the dispense interface  200  has been correctly mounted onto the cartridge housing  40 . Such a detection sensor may comprise either a mechanical, an electrical, a capacitive, an inductive or other similar type sensor. As illustrated, this sensor may be provided near the distal end of the cartridge housing. 
     In addition, the drug delivery device may comprise a similar detection sensor for detecting the presence of the dose dispenser. For example, such a sensor may be provided adjacent the needle hub of the interface  200 . Preferably, either or both of the detection sensors would be communicatively coupled to the micro-processor. Optionally, the micro-processor would be programmed so as prevent a user from setting a dose with the drug delivery device  10  unless the device has detected that both the dispense interface  200  has been properly mounted to the cartridge holder  40  and that a dose dispenser has been properly mounted onto the interface. If either the dispense interface or the dose dispenser has been detected as being incorrectly mounted, the user may be locked out of the device and a connection error may be shown on the digital display  80 . 
     Additionally, the dispense interface  200  could incorporate a safety shield device that would prevent accidental needle sticks and reduce the anxiety experienced by users who suffer from needle phobia. The exact design of the safety shield is not critical to the presently described drug delivery device and system. However, a preferred design is one that is operably connected to drug delivery device  10 . In such a design, the activation of the safety shield could unlock the drug delivery system or enable medicament to be dispensed via the dispense interface and dose dispenser. Another preferred design would physically prevent insertion of the used drug dispense interface into the patient (e.g., a single use needle-guard type arrangement). Preferably, the interface is configured to work with a conventional double ended needle assembly. Alternatively, the interface may be configured to work with a non-conventional needle assembly. One example of such a non-conventional-needle assembly may comprise a coded needle assembly. 
     In one preferred electro-mechanical drug delivery device, a single dispense assembly comprising a catheter may be coupled to the interface  200 . 
     In one preferred arrangement, the dispense interface  200  is a disposable interface and as such, the needle hub comprises a disposable element that is discarded when either the first or the second cartridge in the device is replaced (e.g., when such cartridge is empty). In one arrangement, the dispense interface  200  may be provided in a drug delivery kit. For example, in one drug delivery kit arrangement, a needle assembly interface can be provided with each replacement cartridge. In an alternative kit arrangement, a plurality of double ended needle assemblies are provided with a multi-use dispense interface. 
     In some situations, it may be beneficial for a dispense interface component to remain on the drug delivery device (i.e., attached to the drug delivery device), but not pierce the cartridges of the drug delivery device when the device is not being used for an injection. Generally, such a dispense interface component may include a main body, a first piercing portion, a second piercing portion, and a biasing element. The main body is configured for connection to the drug delivery device. The first piercing portion is for piercing a first cartridge (i.e., first drug reservoir) contained within the drug delivery device, and the first piercing portion is connected to the main body. The second piercing portion is for piercing a second cartridge (i.e., second drug reservoir) contained with the drug delivery device, and the second piercing portion is connected to the main body. 
     The at least one biasing element is operably coupled to the main body, wherein the at least one biasing element is configured to, when the load on the at least one biasing element is less than or equal to a threshold load, bias (i) the first piercing portion away from the first cartridge and (ii) the second piercing portion away from the second cartridge, thereby preventing the first piercing portion from piercing the first cartridge and the second piercing portion from piercing the second cartridge.  FIGS. 51 and 53  illustrate examples of such a dispense interface component. In addition,  FIGS. 54-56  illustrate examples of such dispense interface components having covers configured for improving potential sterility of the interface component. 
       FIG. 51  shows a sprung dispense interface component  1200 . The dispense interface component includes a main body  1202  configured for connection to drug delivery device  1204 . The distal end of drug delivery device  1204  (and in particular the distal end of cartridge holder  1206 ) is shown in  FIG. 51 . Dispense interface component  1200  includes first piercing portion  1208  for piercing a first cartridge  1210  contained within the drug delivery device  1204 . The dispense interface component  1200  also includes a second piercing portion  1212  for piercing a second cartridge  1214  contained in the drug delivery device  1204 . Note that while first and second cartridges  1210 ,  1214  are referred to as drug “cartridges,” herein the first and second cartridges  1210 ,  1214  comprise any type of drug reservoir. 
     In addition, the dispense interface component  1200  includes at least one biasing element operably coupled to the main body  1202 . For instance, dispense interface component  1200  includes biasing elements  1216  and  1218 . The biasing elements are configured to, when the load on the at least one biasing element is less than or equal to a threshold load, bias (i) the first piercing portion away from the first cartridge and (ii) the second piercing portion away from the second cartridge, thereby preventing the first piercing portion from piercing the first cartridge and the second piercing portion from piercing the second cartridge. The first piercing portion and the second piecing portion are sometimes herein be referred to as “septum needles,” as the portions are configured for piercing the septa of the drug cartridges in drug delivery device  1204 . Further, in this example of  FIG. 51 , biasing elements  1216  and  1218  are compression springs. However, other biasing elements are possible as well. 
     A user may attach the dispense interface component  1200  to the cartridge holder  1206  by passing the dispense interface component  1200  over the threaded boss  1220 . A user may push the dispense interface component  1200  upward in proximal direction  1222  such that the two septum needles  1208 ,  1212  pierce the respective septa  1224 ,  1226  (see  FIG. 52   a ) of the drug cartridges  1210 ,  1214 . The action of pushing the sprung dispense interface component  1200  upwards may also be achieved by using the vertical force provided by threading the needle assembly  1230  onto the threaded boss  1220 . The needle assembly  1230  may be a standard needle assembly, such as a standard needle assembly commonly used in the art. 
     It should be noted that in this example the threaded boss  1220  is part of the cartridge holder  1206 . However, in other examples, the dispense interface component and the drug delivery device may be modified such that the threaded boss is part of the cartridge holder. 
     Returning to  FIG. 51 , the dispense interface component  1200  is secured in place by attaching a standard needle assembly  1230  to the threaded boss  1220 . The standard needle assembly  1230  may include the outlet needle  1232  and threaded hub  1234 . As shown in  FIG. 51 , the biasing elements  1216 ,  1218  linking the dispense interface component  1200  to the cartridge holder  1206  bias the septum needles  1208 ,  1212  away from the cartridges  1210 ,  1214 . As such, the spring force must be overcome on attachment of the standard needle assembly  1230 . The spring force is such that on removal of the standard needle assembly  1230 , the dispense interface component  1200  moves downwards in distal direction  1236 , thus retracting the two septum needles  1208 ,  1212  from their respective cartridges  1210 ,  1214 . This ensures that the needles  1208 ,  1212  do not remain in fluidic communication with the drug cartridges  1210 ,  1214  when the drug delivery device  1204  is not in use. Therefore, the septum needles are only in fluid communication with the drug cartridges when the dispense interface component is fully attached (i.e., the drug delivery device is ready for use). 
     As mentioned above, the biasing elements  1216 ,  1218  are configured to bias (i) the first piercing portion (i.e., septum needle  1208 ) away from the first cartridge and (ii) the second piercing portion (i.e., septum needle  1212 ) away from the second cartridge, thereby preventing the first piercing portion from piercing the first cartridge and the second piercing portion from piercing the second cartridge when the load on the at least one biasing element is less than or equal to a threshold load. In an example, the threshold load may be no load or a minimal load. For instance, in some situations, when the needle assembly  1230  is not attached, the septum needles may be biased in distal direction  1236  to the point where there is no load or minimal load on the biasing elements. For example, the compression springs  1216 ,  1218  may return to an unloaded, uncompressed state (i.e., an equilibrium or relaxed state). However, in other situations, the biasing elements may bias the septum needles, but the biasing elements may still have a threshold load even when a needle assembly is not attached to the drug delivery device. For instance, the compression springs  1216 ,  1218  may still be slightly compressed (i.e., they have a residual load as their movement is constrained before they reach a fully relaxed state), but the load is not enough to cause the septum needles to pierce the respective septum of the drug cartridges. 
     The biasing elements  1216 ,  1218  may bias the septum needles  1208 ,  1212  in the distal direction  1236  in numerous ways. For example, when biasing the septum needles in the distal direction, the biasing elements may bias the entire dispense interface component  1200  in the distal direction  1236  (e.g., as shown in  FIG. 51 ). However, in another example, the dispense interface component outer body may remain attached to the drug delivery device, and the needles may be biased without the outer body of the dispense interface component being biased in the distal direction. For instance, the septum needles may be attached to a moveable sprung platform that may move relative to the main outer body of the dispense interface component. 
       FIG. 52   a  shows an example cross section through the dispense interface component  1200 , where the needle assembly  1230  is attached to the dispense interface component. In other words, the dispense interface component  1200  is in the upward, engaged position. As the needle hub assembly  1230  is threaded onto the cartridge holder  1206 , the needle assembly  1230  forces the dispense interface component  1200 , U-shaped needle  1217  and seal  1219  upward against the action of the springs  1216 ,  1218 . Generally, a U-shaped needle is a needle that is generally in the shape of a “u”. The upwards movement of the dispense interface component forces both the first and second piercing ends of the U-shaped needle  1217  to pierce the septa  1224 ,  1226  of the cartridges  1210 ,  1214  and forces the outlet needle  1232  to pierce the seal  1219 . At this point, a sealed fluidic path has been established between both cartridges  1210 ,  1214  and the outlet needle  1232 . At this stage, the first medicament from the first cartridge and the second medicament from the second cartridge may be dispensed. 
     As shown in  FIG. 52   c , it should be noted that the cartridge holder  1206  may have axial slots  1238  along the threaded portion  1220  to allow the U-shaped needle  1217  to be assembled into position and move upwards under the action of the sprung dispense interface component  1200 . 
     The relative position between the U-shaped needle  1217 , the seal  1219 , and the outlet needle  1232  is shown in  FIG. 52   b . A hole  1240  may be added to the U-shaped tube to allow fluid to flow from the U-shaped needle cannula  1217  into the outlet needle  1232 . When the needle hub assembly  1230  is removed, the springs  1216 ,  1218  force the sprung dispense interface component  1200  downwards, causing (i) the U-shaped needle  1217  to be retracted from the septa  1224 ,  1226  and (ii) as the needle hub is completely detached from the device, the outlet needle  1232  to be retracted from the seal  1219 . 
     With reference to  FIGS. 51 and 52   a , it is noted that the septum needles  1208 ,  1212  are shown constructed from a single piece of U-shaped tubing with a hole  1240  in the center. The septum needles, however, could be constructed from two separate L-shaped pieces which are separated by a small gap allowing the drug compounds to flow into the outlet needle  1232 . Generally, an L-shaped needle is a needle that is generally in the shape of an “L”. Additional means by which the two needles (or three needles, in the case of two L-shaped needles) meet are possible as well. Further,  FIG. 51  shows two compression springs; however, fewer or more biasing elements could be used in other examples. 
       FIG. 53  shows a second example sprung dispense interface component  1250  configured for attaching to drug delivery device  1253 . In particular,  FIG. 53  shows a cross section through the sprung dispense interface component  1250 . The sprung dispense interface component  1250  is shown in the upward, engaged position. As the needle hub assembly  1280  is threaded onto the cartridge holder  1256 , the needle assembly forces the main body  1251  and L-shaped needles  1265 ,  1267  upward in distal direction  1222  against the action of the biasing element (spring  1270 ). The upwards movement of the sprung dispense interface component  1250  (i) forces the ends of the L-shaped needles  1265 ,  1267  to pierce the septa  1274 ,  1276  of cartridges  1260 ,  1264  and (ii) aligns the exit points  1290 ,  1292  of the septum needles  1265 ,  1267  with the cross hole  1294 . At this point a sealed fluidic path has been established between both cartridges  1260 ,  1264  and the outlet needle  1282 . Sliding seals  1296  are employed along the surfaces marked  1298 . These sliding seals may comprise any material known in art that is compativle with device drgu compounds including, but not limited to TPW&#39;s, LSR, rubbers, PTFE, PU, Nylon, PEEK, POM and other similar materials and compositions. The cross hole  1294  allows fluid exiting both septum needles  1265 ,  1267  to be channeled to the entrance of the outlet needle  1282 . 
     When the needle hub assembly  1280  is removed, the spring  1270  forces L-shaped needles  1265 ,  1267  downwards, thereby causing the L-shaped needles  1265 ,  1267  to be retracted from the septa  1274 ,  1276 . This prevents fluid flow from the exit of the septum needles  1265 ,  1267 , as the entrance to the cross hole  1294  is sealed by the sliding seals  1296 .  FIG. 53  shows two compression springs; however, fewer or more biasing elements could be used. 
     The needle hub assembly provides a means of connecting and registering this dispense interface component to the drug delivery device. Once attached, a fluidic connection can be simultaneously established between both cartridges and the common outlet needle. On dispense of each medicament, the medicaments flow through the respective septum needle and then through the common outlet needle to a single injection site. 
     The system in accordance with Applicants&#39; disclosure could be designed such that the dispense interface component, two septum needles and biasing element(s) are all integrated into the cartridge holder and are considered part of the overall drug delivery device. This potentially means that a device can have an integral 2 into 1 needle system that utilizes standard commercially available needles. 
     In other examples, the drug delivery device and dispense interface component may be separate, but the drug delivery device could include the biasing element (rather than the dispense interface component including the biasing element). That is, the biasing element may be provided on the distal end of the cartridge holder, and the dispense interface component may be provided without the at least one biasing element. 
     As mentioned above, one advantage of a dispense interface component such as the dispense interface components illustrated in  FIGS. 51 and 53  is that the septum needles are only in fluid communication with the drug cartridges when the dispense interface component is fully attached. This is beneficial from a sterility perspective, as when the septum needles are withdrawn from the cartridges, the medicament is maintained within a sterile environment which is not connected to a needle system (and hence potentially to the external environment). In this way, the integrity of each drug cartridge is maintained in the same way as with a standard single therapy device as is known in the art. 
     In addition to sterility of the drug cartridges, the prevention of potential exposure or ingress of foreign contaminant is also important for the needle elements of a drug delivery device. Generally, standard single needles are sterile upon attachment (e.g., per current commercial practice, needle assemblies are typically individually packaged and sterile). However the septum needle cleanliness on the sprung dispense interface component may also be an issue. For instance, the septum needle cleanliness on the sprung dispense interface component may need to be considered in two example scenarios discussed below. 
     When the sprung dispense interface component is integrated to a single-use device, the needles would typically remain sterile within the dispense interface component packaging until use. Once removed from the packaging, attachment of a standard single needle assembly would result in the sprung dispense interface component moving in the proximal direction, causing the two embedded needles to pierce their respective cartridges. In this instance, the sprung dispense interface component is providing a means of delivering two medicaments from two separate cartridges, and prevention of contamination is achieved through packaging and the inherency of a single-use device. 
     However, in a multi-use device, the sprung dispense interface component has the additional functionality of repeatedly making sure that the cartridges are not pierced unless a dispense interface (e.g., single needle assembly) is attached. That is, in between doses and where the standard single needle assembly has been removed, the sprung dispense interface component disengages the septum needles from their respective cartridges. Multiple attachments and detachments of standard single needle assemblies will cause multiple penetrations of the sprung dispense interface needles into their associated cartridges. Accordingly, although the needles may be sterile for the first penetration, once disengaged there is a potential risk of exposure to contaminants and therefore a risk of potentially compromising the cartridge contents each time the cartridge is re-pierced. 
     As a result, the dispense interface component in accordance with Applicants&#39; disclosure may further comprise a cover that is configured for preventing contamination.  FIGS. 54-56  depict example covers. However, it should be understood that other examples covers are also possible. 
     For example, as shown in  FIG. 54 , the cover could be a full flexible or rigid cover. The full cover could be a sliding cover  1300  that retracts over the cartridge holder  1302  as a standard needle assembly is attached. Alternatively, the full cover could be a flexible skin (e.g., TPE-type material) such that upon attachment of the standard needle assembly, the flexi cover is forced backwards to reveal the threaded interface  1304 . The sliding cover  1300  may beneficially seal the dispense interface component at primary sealing points  1306   a - d . These points are points where contaminants could potentially enter the dispense interface component and potentially contaminant the medicament; however, the seal  1300  may beneficially prevent such contaminants from contaminating the dispense interface. 
     As another example, the cover could be a bellows-type cover, such as the covers illustrated in  FIGS. 55-56 . In the example of  FIG. 55 , the sprung dispense interface component  1320  forms a sliding seal on the connection interface  1322 . A flexible bellows-type enclosure  1324  may collapse as the dispense interface component  1320  is pushed in the proximal direction as a standard needle assembly is attached. This bellows-type cover beneficially provides a level of protection from potential contamination of septum needles. The bellows-type enclosure  1324  may seal the dispense interface component at primary sealing points  1326   a - d , and the sliding seal  1328  seals the dispense interface component at primary sealing points  1330   a - b . These points are points where contaminants could potentially enter the dispense interface component and potentially contaminant the medicament; however, the seals  1324  and  1328  may beneficially prevent such contaminants from contaminating the dispense interface. 
     In the example of  FIG. 56 , the sprung dispense interface component  1340  forms a sliding seal  1342  on a central boss  1344 . The sliding seal  1342  allows for a complete seal around the connection interface. In particular, the sliding seal  1342  seals at the primary sealing points  1346   a - d . Combined with the flexible bellows-type enclosure  1348 , which collapses as the dispense interface component  1340  is pushed upwards upon attachment of needle assembly  1350 , this system provides protection from contaminants. The bellows-type enclosure provides sealing at primary sealing points  1352   a - d.    
       FIG. 20  illustrates a functional block diagram of a control unit to operate and control the drug delivery device illustrated in  FIG. 1 .  FIG. 21  illustrates one arrangement of a printed circuit board (PCB) or printed circuit board assembly (PCBA)  350  that may comprise certain portions of the control unit illustrated in  FIG. 20 . 
     Referring now to both  FIGS. 20 and 21 , it may be seen that the control unit  300  comprises a microcontroller  302 . Such a microcontroller may comprise a Freescale MCF51JM microcontroller. The microcontroller is used to control the electronic system for the drug delivery device  10 . It includes internal analogue to digital converters and general purpose digital I/O lines. It can output digital Pulse Width Modulated (PWM) signals. It includes an internal USB module. In one arrangement, a USB protection circuit such as ON-Semi NUP3115 may be implemented. In such an implementation, the actual USB communications may be provided on board the microcontroller  302 . 
     The control unit further comprises a power management module  304  coupled to the microcontroller  302  and other circuit elements. The power management module  304  receives a supply voltage from a main power source such as the battery  306  and regulates this supply voltage to a plurality of voltages required by other circuit components of the control unit  300 . In one preferred control unit arrangement, switched mode regulation (by means of a National Semiconductor LM2731) is used to step up the battery voltage to 5V, with subsequent linear regulation to generate other supply voltages required by the control unit  300 . 
     The battery  306  provides power to the control unit  300  and is preferably supplied by a single lithium-ion or lithium-polymer cell. This cell may be encapsulated in a battery pack that contains safety circuitry to protect against overheating, overcharging and excessive discharge. The battery pack may also optionally contain coulomb counting technology to obtain an improved estimate of remaining battery charge. 
     A battery charger  308  may be coupled to the battery  306 . One such battery charger may be based on Texas Instruments (TI) BQ24150 along with other supporting software and hardware modules. In one preferred arrangement, the battery charger  308  takes energy from the external wired connection to the drug delivery device  10  and uses it to charge the battery  306 . The battery charger  308  can also be used to monitor the battery voltage and charge current to control battery charging. The battery charger  308  can also be configured to have bidirectional communications with the microcontroller  302  over a serial bus. The charge status of the battery  306  may be communicated to the microcontroller  302  as well. The charge current of the battery charger may also be set by the microcontroller  302 . 
     The control unit may also comprise a USB connector  310 . A micro USB-AB connector may be used for wired communications and to supply power to the device. 
     The control unit may also comprise a USB interface  312 . This interface  312  may be external to the microcontroller  302 . The USB interface  312  may have USB master and/or USB device capability. The USB interface  312  may also provide USB on-the-go functionality. The USB interface  312  external to the microcontroller also provides transient voltage suppression on the data lines and VBUS line. 
     An external Bluetooth interface  314  may also be provided. The Bluetooth interface  314  is preferably external to the microcontroller  302  and communicates with this controller  302  using a data interface. 
     Preferably, the control unit further comprises a plurality of switches  316 . In the illustrated arrangement, the control unit  300  may comprise eight switches  316  and these switches may be distributed around the device. These switches  316  may be used to detect and or confirm at least the following:
         a. Whether the dispense interface  200  has been properly attached to the drug delivery device  10 ;   b. Whether the removable cap  18  has been properly attached to the main body  20  of the drug delivery device  10 ;   c. Whether the first cartridge retainer  50  of the cartridge holder  40  for the first cartridge  90  has been properly closed;   d. Whether the second cartridge retainer  52  of the cartridge holder  40  for the second cartridge  100  has been properly closed;   e. To detect the presence of the first cartridge  90 ;   f. To detect the presence of the second cartridge  100 ;   g. To determine the position of the stopper  94  in the first cartridge  90 ; and   h. To determine the position of the stopper  104  in the second cartridge  100 .       

     These switches  316  are connected to digital inputs, for example to general purpose digital inputs, on the microcontroller  302 . Preferably, these digital inputs may be multiplexed in order to reduce the number of input lines required. Interrupt lines may also be used appropriately on the microcontroller  302  so as to ensure timely response to changes in switch status. 
     In addition, and as described in greater detail above, the control unit may also be operatively coupled to a plurality of human interface elements or push buttons  318 . In one preferred arrangement, the control unit  300  comprises eight push buttons  318  and these are used on the device for user input for the following functions:
         a. Dose dial up;   b. Dose dial down;   c. Sound level;   d. Dose;   e. Eject;   f. Prime;   g. Dose set; and   h. OK.       

     These buttons  318  are connected to digital inputs, for example to general purpose digital inputs, on the microcontroller. Again, these digital inputs may be multiplexed so as to reduce the number of input lines required. Interrupt lines will be used appropriately on the microcontroller to ensure timely response to changes in switch status. In an example embodiment, the function of one or more buttons may be replaced by a touch screen. 
     In addition, the control unit  300  comprises a real time clock  320 . Such a real time clock may comprise an Epson RX4045 SA. The real-time clock  320  may communicate with the microcontroller  302  using a serial peripheral interface or similar. 
     A digital display module  322  in the device preferably uses LCD or OLED technology and provides a visual signal to the user. The display module incorporates the display itself and a display driver integrated circuit. This circuit communicates with the microcontroller  302  using a serial peripheral interface or parallel bus. 
     The control unit  300  also comprises a memory device, for example volatile and non-volatile memory. Volatile memory may be random access memory (RAM), for example static RAM or dynamic RAM and/or the like, as working memory of microcontroller  302 . Non-volatile memory may be read only memory (ROM), FLASH memory or electrically erasable programmable read-only memory (EEPROM), such as an EEPROM  324 . Such an EEPROM may comprise an Atmel AT25640. The EEPROM may be used to store system parameters and history data. This memory device  324  communicates with the processor  302  using a serial peripheral interface bus. 
     The control unit  300  further comprises a first and a second optical reader  326 ,  328 . Such optical readers may comprise Avago ADNS3550. These optical readers  326 ,  328  may be optional for the drug delivery device  10  and are, as described above, used to read information from a cartridge when such a cartridge is inserted into either the first or the second cartridge retainers  50 ,  52 . Preferably, a first optical reader is dedicated for the first cartridge and the second optical reader is dedicated for the second cartridge. An integrated circuit designed for use in optical computer mice may be used to illuminate a static 2D barcode on the drug cartridge, positioned using a mechanical feature on the drug cartridge, and read the data it contains. This integrated circuit may communicate with the microcontroller  302  using a serial peripheral interface bus. Such a circuit may be activated and deactivated by the microcontroller  302  e.g., to reduce power consumption when the circuit is not needed, for example by extinguishing the cartridge illumination when data is not being read. 
     As previously mentioned, a sounder  330  may also be provided in the drug delivery device  10 . Such a sounder may comprise a Star Micronics MZTO3A. Applicants&#39; proposed sounder may be used to provide an audible signal to the user. The sounder  330  may be driven by a pulse-width modulation (PWM) output from the microcontroller  302 . In an alternative configuration, the sounder may play polyphonic tones or jingles and play stored voice commands and prompts to assist the user in operating or retrieving information from the device. 
     The control unit  300  further comprises a first motor driver  332  and a second motor driver  334 . The motor drive circuitry may comprise Freescale MPC17C724 and is controlled by the microcontroller  302 . For example, where the motor drive comprises a stepper motor drive, the drive may be controlled using general purpose digital outputs. Alternatively, where the motor drive comprises a brushless DC motor drive, the drive may be controlled using a Pulse Width Modulated (PWM) digital output. These signals control a power stage, which switches current through the motor windings. The power stage requires continuous electrical commutation. This may for example increase device safety, decreasing the probability of erroneous drug delivery. 
     The power stage may consist of a dual H-bridge per stepper motor, or three half-bridges per brushless DC motor. These may be implemented using either discrete semiconductor parts or monolithic integrated circuits. 
     The control unit  300  further comprises a first and a second motor  336 ,  338 , respectively. As explained in greater detail below, the first motor  336  may be used to move the stopper  94  in the first cartridge  90 . Similarly, the second motor  338  may be used to move the stopper  104  in the second cartridge. The motors can be stepper motors, brushless DC motors, or any other type of electric motor. The type of motor may determine the type of motor drive circuit used. The electronics for the device may be implemented with one main, rigid printed circuit board assembly, potentially with additional smaller flexible sections as required, e.g., for connection to motor windings and switches. 
     The micro-processor provided on the PCBA  350  will be programmed to provide a number of features and carry out a number of calculations. For example, and perhaps most importantly, the micro-processor will be programmed with an algorithm for using a certain therapeutic dose profile to calculate at least a dose of the secondary medicament based at least in part on the selected dose of the primary medicament. 
     For such a calculation, the controller may also analyze other variables or dosing characteristics in calculating the amount of second medicament to administer. For example, other considerations could include at least one or more of the following characteristics or factors:
         a. Time since last dose;   b. Size of last dose;   c. Size of current dose;   d. Current blood glucose level;   e. Blood glucose history;   f. Maximum and/or minimum permissible dose size;   g. Time of day;   h. Patient&#39;s state of health;   i. Exercise taken; and   j. Food intake.       

     These parameters may also be used to calculate the size of both the first and the second dose size 
     In one arrangement, and as will be described in greater detail below, a plurality of different therapeutic dose profiles may be stored in the memory device or devices operatively coupled to the micro-processor. In an alternative arrangement, only a single therapeutic dose profile is stored in the memory device operatively coupled to the micro-processor. 
     The presently proposed electromechanical drug delivery device is of particular benefit to patients with dexterity or computational difficulties. With such a programmable device, the single input and associated stored predefined therapeutic profile removes the need for the user or patient to calculate their prescribed dose every time they use the device. In addition, the single input allows easier dose setting and dispensing of the combined compounds. 
     In addition to computing the dose of the second medicament, the micro-processor can be programmed to achieve a number of other device control operations. For example, the micro-processor may be programmed so as to monitor the device and shut down the various elements of the system to save electrical energy when the device is not in use. In addition, the controller can be programmed to monitor the amount of electrical energy remaining in the battery  306 . In one preferred arrangement, an amount of charge remaining in the battery can be indicated on the digital display  80  and a warning may be given to the user when the amount of remaining battery charge reaches a predetermined threshold level. In addition, the device may include a mechanism for determining whether there is sufficient power available in the battery  306  to deliver the next dose, or it will automatically prevent that dose from being dispensed. For example, such a monitoring circuit may check the battery voltage under different load conditions to predict the likelihood of the dose being completed. In a preferred configuration the motor in an energized (but not moving) condition and a not energized condition may be used to determine or estimate the charge of the battery. 
     Preferably, the drug delivery device  10  is configured to communicate via a data link (i.e., either wirelessly or hard wired) with various computing devices, such as a desktop or laptop computer. For example, the device may comprise a Universal Serial Bus (USB) for communicating with a PC or other devices. Such a data link may provide a number of advantages. For example, such a data link may be used to allow certain dose history information to be interrogated by a user. Such a data link could also be used by a health care professional to modify certain key dose setting parameters such as maximum and minimum doses, a certain therapeutic profile, etc. The device may also comprise a wireless data link, for example an IRDA data link or a Bluetooth data link. A preferred Bluetooth module comprises a Cambridge Silicon Radio (CSR) Blue core 6. 
     In an example embodiment, the device has USB On-The-Go (USB OTG) capability. USB OTG may allow the drug delivery device  10  to generally fulfill the role of being slave to a USB host (e.g., to a desktop or notebook computer) and to become the host themselves when paired with another slave device (e.g. a BGM). 
     For example, standard USB uses a master/slave architecture. A USB Host acts as the protocol master, and a USB ‘Device’ acts as the slave. Only the Host can schedule the configuration and data transfers over the link. The Devices cannot initiate data transfers, they only respond to requests given by a host. Use of OTG in Applicants&#39; drug delivery device  10  introduces the concept that the drug delivery device can switch between the master and slave roles. With USB OTG, Applicants&#39; device  10  at one time be a ‘Host’ (acting as the link master) and a ‘Peripheral’ (acting as the link slave) at another time. 
       FIG. 22  illustrates various internal components of the drug delivery device  10  illustrated in  FIGS. 1   a  and  1   b  including one preferred arrangement of a drive train  500 . As illustrated,  FIG. 22  illustrates the digital display  80 , a printed circuit board assembly (PCBA)  520  (such as the PCB  350  illustrated in  FIG. 21 ), along with a power source or battery  510 . The PCBA  520  may be positioned between the digital display  80  and a drive train  500  with the battery or power source  510  positioned beneath this drive train. The battery or power source  510  is electronically connected to provide power to the digital display  80 , the PCBA  520  and the drive train  500 . As illustrated, both the first and second cartridges  90 ,  100  are shown in an expended state. That is, the first and second cartridges are illustrated in an empty state having a stopper at a most distal position. For example, the first cartridge  90  (which ordinarily contains the first medicament  92 ) is illustrated as having its stopper  94  in the distal position. The stopper  104  of the second cartridge  100  (ordinarily containing the second medicament  102 ) is illustrated in a similar position. 
     With reference to  FIG. 22 , it may be seen that there is provided a first region defining a suitable location for a power source  510  such as a replaceable battery or batteries. The power source  510  may comprise a rechargeable power source and may be recharged while the power source  510  remains in the device. Alternatively, the power source  510  may be removed from the drug delivery device  10  and recharged externally, for example, by way of a remote battery charger. This power source may comprise a Lithium-Ion or Lithium-polymer power source. In this preferred arrangement, the battery  510  comprises a generally flat and rectangular shaped power source. 
       FIG. 23  illustrates the first arrangement of the electro-mechanical system illustrated in  FIG. 22  with both the digital display  80  and the PCBA  520  omitted. As illustrated in  FIG. 23 , the electro-mechanical system  500  operates to expel a dose from the first cartridge  90  containing the primary medicament  92  and the second cartridge  100  containing the secondary medicament  102 . Again, as illustrated in  FIG. 23 , the first and second cartridges  90 ,  100  are illustrated in an empty state having stoppers at a most distal position. 
     In this preferred electro-mechanical system  500 , the system comprises an independent mechanical driver for each cartridge  90 ,  100 . That is, an independent mechanical driver  502  operates to expel a dose from the first cartridge  90  and an independent mechanical driver  506  operates to expel a dose from the second cartridge  100 . In an alternative electro-mechanical system  500  operating on three different medicaments, three independent mechanical drivers could be provided. The independent mechanical drivers act under control of the motor drivers  332 ,  334  of the control unit  300  (see, e.g.,  FIG. 20 ). 
     The first independent mechanical driver  502  operates to expel a dose from the first cartridge  90 . This first driver  502  comprises a first motor  530  that is operatively coupled to a first gearing arrangement  540 . To energize this motor  530 , a connector  532  is provided as a means of electrically connecting to the motor driver  332 . This first gearing arrangement  540  is mechanically linked to a proximal portion of the first telescoping piston rod  514 . The first telescoping piston rod  514  is illustrated in a fully extended position having a distal end  521  acting on the stopper  94  of the first cartridge  90 . 
     As this gearing arrangement  540  is driven by the output shaft of the first motor  530 , this arrangement  540  rotates the proximal portion  518  of the first telescoping piston rod  514 . As this proximal portion  518  of the piston rod  514  is rotated, the second or distal portion  519  of the piston rod  514  is driven in a distal direction. 
     Preferably, the proximal portion  518  of the telescope piston rod  514  comprises an external thread  517 . This thread  517  engages the distal portion  519  which has in integrated nut comprising a short threaded section at a proximal end of the distal portion  519 . This distal portion  519  is prevented from rotating via a key acting in a keyway. Such a keyway may pass through the middle of first telescope  514 . Therefore, when the first gearbox arrangement  540  causes rotation of the proximal section  518 , rotation of the proximal portion  518  acts upon the distal end  521  to thereby drive the distal portion of telescope piston rod to extend along the longitudinal axis. 
     Moving in this distal direction, the distal end  521  of the second portion  519  of the piston rod  514  exerts a force on a stopper  94  contained within the first cartridge  90 . With this distal end  521  of the piston rod  514  exerting a force on the stopper, the user selected dose of the first medicament  92  is forced out of the cartridge  90  and into an attached dispense interface  200  and consequently out an attached needle assembly  400  as previously discussed above. 
     A similar injection operation occurs with the second independent driver  506  when the controller first determines that a dose of the second medicament  102  is called for and determines the amount of this dose. As previously mentioned, in certain circumstances, the controller may determine that a dose of the second medicament  102  may not be called for and therefore this second dose would be “set” to a “0” dose. 
     Preferably, motors  530 ,  536  comprise motors suitable for electronic commutation. Most preferably, such motors may comprise either a stepper motor or a brushless DC motor. 
     To inject a dose of the primary and secondary medicaments  92 ,  102 , a user will first select a dose of the primary medicament by way of the human interface components on the display  80 . (see, e.g.,  FIGS. 1 and 4 ). After a dose of the drug from the primary medicament  92  has been selected, the microcontroller will utilize a previously stored algorithm for determining the dose size of a second drug  102  from a second medicament cartridge. This pre-defined algorithm may help to determine at least in part the dose of the second medicament  102  based on a pre-selected therapeutic profile. In one arrangement, these therapeutic profiles are user selectable. Alternatively, these therapeutic profiles may be password protected and selectable only by a person authorized with the password, such a physician or patient care giver. In yet another arrangement, the therapeutic profile may only be set by the manufacture or the supplier of the drug delivery device  10 . As such, the drug delivery device  10  may be provided with only one profile. 
     When the dose sizes of the first and second medicaments have been established, the user can press the injection button  74  (see e.g.,  FIG. 4 ). By pressing this button  74 , the motor drivers  332 ,  334  energize both the first and the second motors  530 ,  536  to begin the injection process described above. 
     The piston rods  514 ,  516  are preferably movable between a first fully withdrawn position (not shown) and a second fully extended portion (as shown in  FIGS. 22 and 23 ). With the piston rods  514 ,  516  in the withdrawn position, the user will be allowed to open up the respective cartridge retainer and remove an empty cartridge. In one preferred arrangement, an end stop switch may be provided in the main body  14  of the drug delivery device  10  so as to detect when either or both of the piston rods  514 ,  516  are in a fully withdrawn position. Tripping of the end stop switch may release a catch or other fastening device so as to allow access to the main body for replacement of either cartridge  90 ,  100 . 
     In one preferred arrangement, both the first and second motors  530 ,  536  operate simultaneously so as to dispense the user selected dose of the first medicament  92  and the subsequently calculated dose of the second medicament  102  simultaneously. That is, both the first and the second independent mechanical drivers  502 ,  506  are capable of driving the respective piston rods  514 ,  516  either at the same or a different time. In this manner, now referring to the dispense interface  200  previously discussed, the first medicament  92  enters the holding chamber  280  of the dispense interface  200  at essentially the same time as the second medicament. One advantage of such an injecting step is that a certain degree of mixing can occur between the first and second medicament  92 ,  102  prior to actual dose administration. 
     If after an injection, the patient determines that one or more of the cartridges  90 , 100  is spent and therefore needs to be exchanged, the patient can follow the following method of cartridge exchange:
         a. Remove the double ended needle from the dispense interface  200 ;   b. Remove the dispense interface  200  from the cartridge holder  40  of the device  10 ;   c. Enable a menu option on the digital display  80  to change the first cartridge  90  and/or the second cartridge  100 ;   d. Rewind the first and/or the second piston rods  514 ,  516 ;   e. The first and/or second cartridge retainer doors will pop open;   f. The user removes the spent cartridge and replaces this spent cartridge with a new cartridge;   g. The reservoir doors may manually be closed;   h. Once the doors are closed, the first and second piston rods  514 ,  516  advance so that a most distal portion of each rod will meet the stopper of the respective cartridge and will stop advancing when a bung detect mechanism coupled to the micro-processor is activated;   i. The user replaces the dispense interface  200  in the one way manner on the cartridge holder  40 ;   j. The user can, optionally, connect a new double ended needle to the dispense interface  200 ;   k. The user can, optionally, perform a test shot or a priming step with the device  10 ; and   l. The user can then set the next dose for a subsequent dose administration step.       

     One or more of the steps may be performed automatically, for example controlled by microcontroller  302 , such as the step of rewinding the first and/or second piston rod. 
     In an alternative arrangement, the controller may be programmed so that the first and the second independent mechanical drivers  502 ,  506  may be operated to dispense either the first medicament  92  or the second medicament  102  prior to the other medicament. Thereafter, the second or the primary medicament may then be dispensed. In one preferred arrangement, the secondary medicament  102  is dispensed before the primary medicament  92 . 
     Preferably, the first and second motors  530 ,  536  comprise electronic commutation. Such commutation may help to minimise the risk of a motor runaway condition. Such a motor runaway condition could occur with a system comprising a standard brushed motor experiencing a fault. In one embodiment of the motor drive system, a watchdog system may be provided. Such a system has the ability to remove power to either or both of the motors in the event of a software malfunction or a failure of the electronic hardware. To prevent the power from being removed, the correct input from a number of sections of the electronic hardware and/or the microcontroller software will need to be provided. In one of these input parameters is incorrect; power may be removed from the motor. 
     In addition, preferably both motors  530 ,  536  may be operated in a reverse direction. This feature may be required in order to allow the piston rods  514 ,  516  to be moved between a first and a second position. 
     Preferably, the first independent drive train  502  illustrated in  FIG. 23  comprises a first motion detection system  522 .  FIG. 24   a  illustrates a perspective view of the first motor  530  illustrated in  FIG. 23 .  FIG. 24   b  illustrates a preferred motion detection system  522  comprising the first motor  530  illustrated in  FIG. 24   a  in conjunction with a digital encoder  534 . 
     As illustrated in  FIGS. 24   a  and  24   b , such a motion detection system  522  may be beneficial as it can be utilized to provide operational and positional feedback from the first independent driver  502  to the control unit of the drug delivery device  10 . For example, with respect to the first independent driver  502 , a preferred motion detection system  522  may be achieved through the use of a first motor pinion  524 . This first pinion  524  operatively coupled to an output shaft  531  of the first motor  530 . The first pinion  524  comprises a rotating gearing portion  526  that drives a first gear of the first gearing arrangement  540  (see, e.g.,  FIG. 23 ). The first motor pinion  524  also comprises a plurality of flags  528   a - b . In this first motion detection system arrangement  522 , the first pinion  524  comprises a first flag  528   a  and a second flag  528   b . These two flags  528   a - b  are positioned on the motor pinion  524  so that they pass through a first optical encoder  534  as the motor output shaft  531  and hence the connected first pinion  524  rotate when the motor is driven. 
     Preferably, as the first and second flags  528   a - b  pass through the first optical encoder  534 , the encoder  534  can send certain electrical pulses to the microcontroller. Preferably, the optical encoder  534  sends two electrical pulses per motor output shaft revolution to the microcontroller. As such, the microcontroller can therefore monitor motor output shaft rotation. This may be advantageous to detect position errors or events that could occur during a dose administration step such as jamming of the drive train, incorrect mounting of a dispense interface or needle assembly, or where there is a blocked needle. 
     Preferably, the first pinion  524  comprises a plastic injection molded pinion. Such a plastic injection molded part may be attached to the output motor shaft  531 . The optical encoder  534  may be located and attached to a gearbox housing. Such a housing may contain both the first gearing arrangement  540  along with the optical encoder  534 . The encoder  534  is preferably in electrical communication with the control unit potentially via a flexible portion of the PCB. In a preferred arrangement, the second independent drive train  506  illustrated in  FIGS. 22 and 23  comprises a second motion detection system  544  that operates in a similar fashion as the first motion detection system  522  of the first drive train  502 . 
       FIG. 25  illustrates various internal components of the drug delivery device  10  illustrated in  FIGS. 1   a  and  1   b  including a preferred alternative drive train arrangement  600 . As illustrated,  FIG. 25  illustrates the digital display  80 , a printed circuit board assembly (PCBA)  620 , along with a power source or battery  610 . The PCBA  620  may be positioned between the digital display  80  and a drive train  600  with the battery or power source  610  positioned beneath this drive train. The battery or power source  610  is electronically connected to provide power to the digital display  80 , the PCBA  620  and the drive train  600 . The digital display  80  and the PCBA  620  of this alternative drive train arrangement  600  operate in a similar manner as previously described. 
     As illustrated, both the first and second cartridges  90 ,  100  are shown in an expended state. That is, the first and second cartridges are illustrated in an empty state having a stopper at a most distal position. For example, the first cartridge  90  (which ordinarily contains the first medicament  92 ) is illustrated as having its stopper  94  at the end or most distal position. The stopper  104  of the second cartridge  100  (ordinarily containing the second medicament) is illustrated in a similar end position. 
       FIG. 26  illustrates the electro-mechanical system illustrated in  FIG. 25  with both the digital display  80  and the PCBA  620  omitted. As illustrated, this alternative electro-mechanical system  600  operates to expel a dose from the first cartridge  90  containing a primary medicament  92  and the second cartridge  100  containing a secondary medicament  102 . In this preferred electro-mechanical system  600 , the system comprises an independent mechanical driver for both the first cartridge and the second cartridge. That is, an independent mechanical driver  602  operates to expel a dose from the first cartridge  90  and an independent mechanical driver  606  operates to expel a dose from the second cartridge  100 . If this preferred electro-mechanical system  600  were to be reconfigured to operate on three different medicaments contained within three separate cartridges, three independent mechanical drivers could be provided so as to administer a combined dose. The independent mechanical drivers act under control of the motor drivers  332 ,  334  of the control unit  300  (see, e.g.,  FIG. 20 ). 
     The first independent mechanical driver  602  operates to expel a dose from the first cartridge  90  and operates in a similar manner as the independent drivers  502 ,  506  described with reference to the drive train  500  illustrated in  FIGS. 22-23  above. That is, this first independent driver  602  comprises a first motor  630  that is operatively coupled to a first gearing arrangement  640 . To energize this motor  630 , a connector  632  is provided as a means of electrically connecting to the motor driver  332 . This first gearing arrangement  640  is mechanically linked to a proximal portion of the telescoping piston rod  614 . As this gearing arrangement  640  is driven by an output shaft of the first motor  632 , this arrangement  640  rotates the proximal portion  618  of the telescoping piston rod  614 . As this proximal portion  618  of the piston rod  614  is rotated, the second or distal portion  622  of the piston rod  614  is driven in a distal direction. Moving in this distal direction, a distal end  623  of the second portion  622  of the piston rod  614  exerts a force on the stopper  94  contained within the first cartridge  90 . With a distal end  623  of the piston rod  614  exerting a force on the stopper  94 , the user selected dose amount of the first medicament  92  is forced out of the cartridge  90  and into an attached dispense interface  200  and consequently out an attached needle assembly  400  as previously discussed. 
     Preferably, the first independent mechanical driver  602  comprises a bung or stopper detection system. Such a detection system may be used detect the position of the cartridge stopper  94  following a cartridge change event. For example, when a cartridge change event occurs, the piston rod is retracted in a proximal position so as to enable a user to open the cartridge retainer and thereby provide access to a spent cartridge. When the cartridge is replaced and the cartridge retainer door is shut, the piston rod will advance in a distal direction towards the stopper of new the cartridge. 
     In one preferred stopper detection system, a switch is provided at the distal end of the piston rod. Such a switch may comprise a mechanical, optical, capacitive, or inductive type switch. Such a switch would be in communication with the microcontroller and indicates when the piston rod is in contact with the stopper and hence may be used as a mechanism for stopping the drive system. 
     The second independent mechanical driver  606  operates to expel a dose from the second cartridge  100  in a different manner than the first independent driver  602 . That is, this second mechanical driver  606  comprises a second motor  636  that is operatively coupled to a second gearing arrangement  646 . To energize this motor  636 , a connector  638  is provided as a means of electrically connecting to the motor driver  334 . 
     This independent mechanical driver  606  comprises: 
     A motor  636 ; 
     A second gearing arrangement  646 ; and 
     A telescope piston rod  616 . 
     The second gearing arrangement  646  is mechanically linked to a proximal portion of a nested piston rod  660 . As this gearing arrangement  646  is driven by the output shaft of the second motor  636 , this arrangement  646  rotates the proximal portion  660  of the telescoping piston rod  616 . 
     The second gearing arrangement  646  comprises a motor pinion along with a plurality of compound gears (here four compound gears) along with a telescope input piston rod. Two of the compound gears are elongated to enable continuous mesh engagement with the input piston rod as the telescope extends in a distal direction to exert an axially pressure on the cartridge stopper  104  so as to expel a dose from the cartridge. The elongated gear may be referred to as a transfer shaft. The gearbox arrangement preferably has a ratio of 124:1. That is, for every revolution of the telescope input screw the output shaft of the second motor rotates 124 times. In the illustrated second gearing arrangement  646 , this gearing arrangement  646  is created by way of five stages. As those skill in the art will recognize, alternative gearing arrangements may also be used. 
     The second gearing arrangement  646  comprises three compound reduction gears  652 ,  654 , and  656 . These three compound reduction gears may be mounted on two parallel stainless steel pins. The remaining stages may be mounted on molded plastic bearing features. A motor pinion  643  is provided on an output shaft of the second motor  636  and is retained on this shaft  637 , preferably by way of an interference or friction fit connection. 
     As described above, the motor pinion  643  may be provided with two mounted “flag” features that interrupt the motion detect optical sensor. The flags are symmetrically spaced around the cylindrical axis of the pinion. 
     The drive train telescoping piston rod  616  is illustrated in  FIG. 27  and comprises a telescope plunger  644  that is operatively coupled to an input screw  680 .  FIG. 28  illustrates a perspective view of the telescope piston rod  616  coupled to a latch barrel.  FIG. 29  illustrates a cross sectional view of the independent mechanical driver with the piston rod  616  in an extended position. 
     As illustrated, the outer elements (the telescope piston rod plunger  644  and telescope) create the telescopic piston rod  616  and react to the compressive axial forces that are developed. An inner element (telescope piston rod key  647  provides a means of reacting the rotational input force. This operates with a continuous motion and force since there will be no changes in drive sleeve diameter to generate varying levels of force. 
     The transfer shaft  670  is operatively linked to the gearing arrangement  646 . The transfer shaft  670  can rotate but it cannot move in an axial direction. The transfer shaft  670  interfaces with the second gearing arrangement  646  and transfers the torque generated by the second gearbox arrangement  646  to the telescope piston rod  616 . 
     Specifically, when the transfer shaft  670  is rotated by way of the gearing arrangement  646 , the transfer shaft  670  will act on an integrated geared part  681  on a proximal end of the input screw  680 . As such, rotation of the transfer shaft  670  causes the input screw  680  to rotate about its axis. 
     A proximal portion of the input screw  680  comprise a threaded section  682  and this threaded section is mated with a threaded section of the latch barrel  660 . As such, when the input screw  680  rotates, it winds or screws itself in and out of the latch barrel  660 . Consequently, as the input screw  680  moves in and out of the latch barrel, the screw  680  is allowed to slide along the transfer shaft  670  so that the transfer shaft and the gears remain mated. 
     The telescope plunger  644  is provided with a threaded section  645 . This threaded section  645  is threaded into short section in distal end of the input screw  680 . As the plunger  644  is constrained from rotating, it will wind itself in and out along the input screw  680 . 
     A key  647  is provided to prevent the plunger  644  from rotating. This key  647  may be provided internal to the input screw  680  of the piston rod  616 . During an injection step, this key  647  moves in the axial direction towards the stopper  104  of the cartridge  100  but does not rotate. The key  647  is provided with a proximal radial peg that runs in a longitudinal slot in the latch barrel  660 . Therefore, the key  647  is not able to rotate. The key may also be provided with a distal radial peg that engage a slot in the plunger  644 . 
     Preferably, the drug delivery device  10  comprises memory devices comprising enough memory storage capability so as to store a plurality of algorithms that are used to define a plurality of different therapeutic profiles. In one preferred arrangement, after a user sets a dose of the primary medicament, the drug delivery device will be preprogrammed so as to determine or calculate a dose of the secondary medicament and perhaps a third medicament based on one of the stored therapeutic profiles. In one arrangement, the healthcare provider or physician selects a therapeutic dose profile and this profile may not be user alterable and/or may be password protected. That is, only a password known by the user, for example a healthcare provider or physician, will be able to select an alternative profile. Alternatively, in one drug delivery device arrangement, the dose profile is user selectable. Essentially, the selection of the therapeutic dose profiles can be dependent upon the individualized targeted therapy of the patient. 
     As described above, certain known multi drug compound devices allow independent setting of the individual drug compounds. As such, the delivery of the combined dose in a combination is determined by a user. This is not ideal in all the therapeutic situations that a patient may face. For example,  FIG. 30  illustrates a potential deliverable therapy  700  of such a known two input and two compound combination device: that is, a device that requires a user to physically set the first dose of a first medicament and then physically set the second dose of the second medicament. In such a known device, a user could select a dose of the Compound A or the primary medicament  702  along the x-axis (i.e., between 0 units to a top dose). Similarly, the user could then select a dose of the secondary medicament—Compound B  704  along the y-axis (i.e., between 0 units to a top dose). As such, although these known devices can potentially deliver the combination of the two compounds as illustrated by area  706  shown in  FIG. 30 , there is an inherent risk that the user does not follow the correct, prescribed therapeutic profile, either intentionally or otherwise. For example, in such a device, the user must know, or be able to determine or calculate, the required relationship and then set the dose of both the first and second compounds  702 ,  704  independently. 
     One of the primary reasons for combining drug compounds is that generally all the pharmaceutical elements are required to ensure an increased therapeutic benefit to a patient. In addition, some compounds and some combinations of compounds need to be delivered in a specific relationship with each other in order to provide the optimum pharmacokinetic (“PK”) and pharmacodynamic (“PD”) response. Such complex relationships between one, two, or more (i.e., more than a plurality) of medicaments may not be achievable through a single formulation route and could potentially be too complex for the user to understand, or follow correctly, in all cases. 
     In an example embodiment of the invention, a multi drug compound device may be reliant upon the user input for each independent compound to control the delivered dose profile within predetermined thresholds. For example,  FIGS. 31   a  and  31   b  illustrate in diagrammatic form a potential delivered therapy  720  of a theoretical two input, two compound combination device. The area  710  illustrates the range of potential combination doses that are achievable. That is, a user can set the dose of the primary medicament or Compound A  724  anywhere from a minimum value  730  to a maximum value  732 . Similarly, the user can separately and independently set the dose of the secondary medicament or Compound B  726  anywhere from a minimum value  740  to an overall maximum value  744  within predetermined thresholds, for example between a lower limit  712  and an upper limit  714 . In this area  710 , the plurality of ‘X’ designations illustrate specific combination doses that a patient and/or user of such a device may elect to set and deliver. Essentially, the combined dose of Compound A  724  and Compound B  726  can be set anywhere within this area  710 . In the example embodiment, the user is limited to setting a combined dose only along a predefined profile, such as the predefined profile illustrated by area  710  in  FIGS. 31   a  and  31   b . For example, if an amount of Compound A is selected by a user to be the minimum value  730 , Compound B may be selected between the minimum value  740  and a maximum value  742  defined for this minimum value of Compound A. 
     The lower limit  712  and the upper limit  714  may be represented by a curve as in  FIG. 31   a . In an alternative embodiment, the lower limit and the upper limit may be represented by one or more lines, by a stepwise function, and/or the like. For example, in the diagram of  FIG. 31   b , the upper limit  714  is represented by a diagonal line and a horizontal line, the lower limit  712  is represented by a stepwise function of 3 steps. The upper limit  714  and the lower limit  712  define an area  710 , in which a user may select a combination of Compound A and Compound B, for example one of the combinations designated by the ‘X’-marks. 
     In further example embodiments, the presently proposed programmable electro-mechanical drug delivery device described in detail above uses only a single input in order to offer an innovative solution to these and other related problems. In further embodiments, the proposed programmable multi-drug compound device uses only a single dispense interface. As just one example, such a device is capable of delivering any of a plurality of predefined programmed therapeutic profiles for various drug combinations. As an alternative, such a device is capable of delivering only one predefined programmed therapeutic profile for various drug combinations. 
     By defining the ratio-metric relationship or relationships between the various individual drug compounds (2, 3, or more), the proposed device helps to ensure that a patient and/or user receives the optimum therapeutic combination dose from a multi drug compound device. This can be accomplished without the inherent risks associated with multiple inputs. This can be achieved since the patient and/or user is no longer called upon to set a first dose of medicament and then determine or calculate and then independently set a correct dose of a second and/or third medicament in order to arrive at the correct dose combination each time the device is used to administer a combination dose. 
     As just one example,  FIG. 32  illustrates a first arrangement of a predefined therapeutic profile  760  that may be programmed into Applicants&#39; programmable drug delivery device. In  FIG. 32 , a first therapeutic dose line represents an example of a predefined therapeutic profile  760  compared to the area  706  indicating all potential drug combinations that can be selected by way of currently known devices as illustrated in  FIG. 30 . As can be seen from this predefined profile  760  illustrated in  FIG. 32 , for every dose value of Compound A  764  (also herein referred to as the Master Drug or the Primary Drug or the Primary Medicament) selected by the user, Applicants&#39; drug delivery device  10  will rely on a previously stored therapeutic profile to calculate the dose value of Compound B  766  along this therapeutic profile  760 . 
     As such, the user merely needs to select a first dose of the first drug: Drug A or the primary medicament and Applicants&#39; drug delivery device  10  automatically calculates the dose of the secondary medicament or Drug B based on this preselected dosing profile  760 . For example, if the user selects a dose comprising “60 Units” for Compound A  764 , the drug delivery device  10  will recall the selected dosing profile  760  from its memory device and then automatically calculate the dose value of “30 Units” for Compound B  766 . 
     In an alternative drug delivery device arrangement, and as discussed in greater detail above, the drug delivery device may comprise a coding system. A coding system may be provided if coding means is provided on either the first or the second cartridge so that the drug delivery device could then identify the particular medicament contained within an inserted cartridge. After the drug delivery device undergoes a method or process for determining cartridge and/or medicament identification, the drug delivery device could then potentially automatically update the therapeutic profile or profiles. For example, a new or a revised/updated profile may be selected if required to reflect an updated or revised pharmaceutical philosophy so as to achieve an optimum medicament relationship. Alternatively, a new or a revised/updated profile may be selected if a health care provider has decided to alter a patient&#39;s therapy strategy. An updated or revised profile may be loaded into the device through a wired or wireless connection, for example from a memory comprised in the cartridge, from an external device, from the internet and/or the like. The updated or revised profile may be loaded automatically, for example after insertion of the cartridge, or only after user confirmation, for example after a user presses a button on the device to confirm a message shown in the display. 
     As another example of a therapeutic profile, the proposed drug delivery device  10  may be programmed to calculate a linear ratio profile for the delivered dose from the drug delivery device  10  that comprises two or more discrete medicament reservoirs. 
     For example, with such a programmed therapeutic profile, the constituent components of the dose would be delivered to a patient in a fixed, linear ratio. That is, increasing the dose of one element will increase the dose of the other constituent element(s) by an equal percentage. Similarly, reducing the dose of one element will reduce the dose of the other constituent element(s) by an equal percentage. 
       FIG. 32  illustrates one arrangement of a predefined ratio therapeutic profile  760  that may be programmed into the drug delivery device  10 . In the profile illustrated in  FIG. 32 , the user would select a dose of Drug A  764 . As previously described above, the user could be called upon to select this first dose by toggling or manipulating one of the buttons provided on the operator interface of the drug delivery device  10 . Once this initial dose of the primary Drug A  764  is selected by the user and then set by the drug delivery device, the control unit of the device  10  calculates and then sets the resultant dose of Drug B  766  based on the therapeutic profile  760 . For example, referring to  FIG. 32 , if the user selects a dose of 60 units for Drug A  764 , the control unit would recall the algorithm for this particular therapeutic profile  760  and would then use this algorithm to calculate the dose of Drug B or the secondary medicament  766 . According to this profile  760 , the control unit would calculate a 30 Units dose of Drug B or the secondary medicament. In an alternative embodiment, the profile is stored as a look-up table in a memory. For every value of drug A, a corresponding value of drug B is stored in the look-up table. In a further embodiment only some values of drug A are stored in the look-up table along with corresponding values of drug B. Missing values are then calculated by interpolation, for example by linear interpolation. 
     Therefore, when the device is then used to dispense the combination of medicaments, this combined dose comprising 60 Units of Drug A and 30 Units of Drug B would be administered. As those of skill in the art will recognize, the ratio of the two (or more) medications can be tailored according to the needs of the patient or therapy by a number of methods including changing the concentration of the medicaments contained within the primary or secondary reservoirs. 
     As just one example, the drug delivery device  10  may comprise three or more medicaments. For example, the device  10  may contain a first cartridge containing a long acting insulin, a second cartridge containing a short acting insulin, and a third cartridge containing a GLP-1. In such an arrangement, referring back to  FIGS. 6 and 9 , the cartridge holder  40  of the drug delivery device  10  would be re-configured with three cartridge retainers (rather than the two retainers  50 ,  52  illustrated in  FIGS. 6 and 9 ) and these three cartridge retainers would be used to house three compound or medicament cartridges. 
     As just one example,  FIG. 33  illustrates an alternative arrangement of a predefined fixed ratio therapeutic profile  780  that may be programmed into the proposed drug delivery device  10 .  FIG. 33  illustrates a linear dose profile  780  that may be used with a drug delivery device comprising three medicaments. For example, in this profile, the user would first select a dose of 60 Units of the primary medicament—Drug A  782 . Once this initial dose of Drug A  782  has been selected, the control unit of the device  10  would calculate, based on this selected therapeutic profile  780 , the resultant dose amount of Drug B (the secondary medicament)  784  as well as the resultant dose of Drug C (the tertiary medicament)  786 . When the device  10  is then used to dispense the combined dose of medicaments, the combination dose of 105 Units would comprise a combination dose of 60 Units of Drug A, a calculated dose of 30 Units of Drug B  784 , and a calculated dose 15 Units of Drug C  786 . In such an arrangement, the primary or master drug  782  could comprise an insulin or insulin analog, the secondary medicament  784  could comprise a GLP-1 or GLP-1 analog, and the tertiary medicament  786  could comprise a local anesthetic or anti-inflammatory. 
     Similarly,  FIG. 34  illustrates an alternative arrangement of a predefined fixed ratio therapeutic profile  800  that may be programmed into the drug delivery device  10  illustrated in  FIG. 1 .  FIG. 34  illustrates a linear profile for use with a drug delivery device comprising four different medicaments: Drug A  802 , Drug B  804 , Drug C  806 , and Drug D  808 . Again, in this situation, once the initial dose of the primary medicament (i.e., Drug A)  802  has been selected by the user, the control unit of the device  10  calculates, based on this linear profile  800 , the resultant dose amount of Drug B  804 , Drug C  806 , and Drug D  808 . For example, in this illustrated exemplary profile, a user has selected a 60 Unit dose of Drug A or the primary medicament  802 . With such a selected primary dose, when the device  10  is then used to dispense the calculated combined dose, the combination dose of 129 Units would comprise 60 Units of the selected Drug A  802 , 30 Units of Drug B  804 , 24 Units of Drug D  806 , and 15 Units of Drug C  808 . 
     A derivative therapeutic profile of the various profiles illustrated in  FIGS. 32-34  may be provided for the combination of compounds to be delivered in a fixed ratio, but for the dose setting process for the master drug compound (i.e., Drug A) to only allow doses of the secondary compound or medicament to be calculated in discrete amounts. This would mean that the dose of the dependent drug compound or compounds (e.g., Drug B, Drug C, etc.) or the secondary medicaments would also only be calculated in discrete amounts. 
     For example,  FIG. 35  illustrates an alternative arrangement of a predefined fixed ratio therapeutic profile  820  having discrete dose steps and that may be programmed into the drug delivery device  10 . For example, this profile  820  comprises a fixed ratio profile having five (5) discrete dose steps of Drug B  828  for varying amounts of Drug A  824 . While following the fixed ratio profile, Drug A  824  would be continuously variable between a maximum dose  825  and a minimum dose  826  while the calculated dose of the secondary medicament  828  would not be continuously variable. For example, if a user were to select a dose of either 0 or 20 Units of the master medicament Drug A  824 , the drug delivery device  10  would determine a zero (“0”) dose of Drug B  828 . Similarly, if a user were to select a dose of anywhere from 20-40 Units of the Drug A  824 , the drug delivery device  10  would compute a dose of 10 Units of Drug B  828 . Therefore, in this later case, a combination dose of 20 Units of Drug A  824  would result in a maximum dose of 10 Units of Drug B  828 . 
     Applicants&#39; proposed linear ratio profile discussed and described with respect to  FIGS. 32-34  provides a number of advantages. For example, these various proposed linear ratio profiles are analogous to a profile of a single formulation product that contains a combination of two or more therapeutic medicaments, where the concentration of the formulation is constant. This means that with the proposed drug device  10  programmed with such linear ratio profiles  760 ,  780 ,  800  and  820 , this would provide an alternative delivery platform for scenarios where it is not possible to formulate the individual elements together into a single formulation. This may be the case where mixing such medicaments may raise stability, compromised performance, toxicology issues and/or other related types of issues. 
     In addition, the proposed linear ratio therapy profiles  760 ,  780 ,  800  and  820  are robust to a split dosing requirement. That is, the desired dose can potentially be split into multiple, smaller injections without compromising the total amount of each constituent medicament that is ultimately administered. As just one example, returning to  FIG. 32 , if the patient were to split up a 60 Unit dose into a 30 Unit dose followed by two 15 Unit doses, the net result (in terms of the total amount of each of the constituent elements delivered) would be the same. Such a split dosing requirement might be advantageous in situations where the calculated combined dose is a large dose (e.g., where the injected dose is greater than 1 ml), where the delivery of such volumes to a single injection site might be painful for a particular patient or sub-optimal in terms of its absorption profile. 
     In addition, cognitively, the relationship between the various compounds or drugs is reasonably straightforward for a patient to understand. Moreover, with such profiles  760 ,  780 ,  800  and  820 , the patient and/or health care provider is not called upon to perform profile calculations themselves since it is the microcontroller of the device  10  that computes the value of the secondary medicament automatically once the initial dose of the primary medicament has been set. 
       FIG. 36  illustrates another proposed therapy profile  860  that might be programmed into the control unit of the drug delivery device  10 . This profile  860  comprises a non-linear ratio dose profile. With such a programmed profile, the constituent components of the dose would be delivered to a patient in a fixed, non-linear ratio. That is, the relationship between the size of the delivered dose of the primary medicament and that of the secondary medicament and perhaps a third medicament is fixed, but is non-linear in nature. With such profiles, the relationship between the primary and the secondary medicament might be cubic, quadratic, or other similar type of relationship. 
     As described above, the delivery of a combination of drug products (i.e., single doses that are made up from the combination of two or more individual drug formulations) in a format where the ratio-metric profile is predefined, offers a number of benefits for both a patient and the treatment of a particular condition. For certain combinations, the ideal profile might be for the various individual formulations to be delivered in a defined, non-linear ratio to one another. Therapeutic profiles of this type are not achievable from a combination drug or drugs that is co-formulated into a single drug reservoir, such as, but not limited to, a standard 3 ml glass cartridge. In such situations, the concentration of the various constituent parts within the glass cartridge is constant (i.e., xmg/ml), and would be particularly difficult for a patient to calculate on certain known devices for each dose. To calculate or determine such concentration would be reliant on the patient or health care provider being able to look up the correct dose on a table (or similar lookup document or prescription) and this may be less desirable as such a method would be more prone to error. 
       FIGS. 36-39  illustrate exemplary profiles  860 ,  880 ,  900  and  920  utilizing non-linear dose profiles. For example,  FIG. 36  illustrates an arrangement of a predefined non-linear fixed ratio therapeutic profile  860  having a decreasing rate of change. That is, as the amount of the primary medicament Drug A  864  increases, the amount of the secondary medicament Drug B  868  increases sharply, as, for example, the amount of Drug A increases from 0 Units to approximately 30 Units and quickly tapers off thereafter. As such,  FIG. 36  illustrates a sample dual formulation wherein the profile  860  is non-linear. 
       FIG. 37  illustrates a similar profile  880  but a profile that represents a sample triple formulation combination of three different medicaments: Drug A  884 , Drug B  886  and Drug C  888 . As just one example, with this profile  880 , if the user sets a dose of 50 Units of the master Drug A  884 , the control unit of the device  10  will compute a resulting combined dose comprising approximately a 37 Unit dose of Drug B  886  and an approximately 26 Unit dose of Drug C  888 . 
     Some of the advantages of using such a fixed, non-linear ratio of the constituent drug elements as illustrated include (but are not limited to) the fact that such profiles utilize a decreasing rate of change profile. These types of illustrated therapy profiles  860 ,  880  may be appropriate in situations where it is desirable to initially rapidly increase the dose of Compound B or the secondary medicament, relative to Compound A. However, once the desirable dose range has been reached to slow this rate of increase so that the dose does not then increase much further, even if the dose of Compound A doubles, for example. A profile of this type might be beneficial in therapeutic applications where there are a potentially wide range of doses of Compound A that patients might require (either as an individual, or across the therapy area as a whole), but where there is a much narrower therapeutically beneficial range of doses for Compound B. 
     The dose profiles  860 ,  880  illustrated in  FIGS. 36 and 37  provide a non-linear fixed ratio having a decreasing rate of change. Alternatively, a proposed non-linear fixed ratio dose profile may comprise a profile having an increasing rate of change. For example, one such profile  900  having such a non-linear increasing rate of change within a two medicament drug delivery device such as device  10  is illustrated in  FIG. 38 . 
       FIG. 39  illustrates a non-linear fixed ratio profile  920  having such an increasing rate of change within a three medicament drug delivery device. With this profile  920 , as the size of the user selected dose of Drug A  924 , the incremental increase in the computed dose of Drug B  926  and Drug C  928  increases. 
     Applicants&#39; therapeutic profiles  900  and  920  illustrated in  FIGS. 38 and 39  might be advantageous in situations where a patient receiving a low dose of Compound A (e.g., 0-40 Units of Drug A  904 ) may only require a relatively low dose of Compound B  906  for the desired pharmokenitic therapeutic response. However, as the size of the dose of Compound A  904  increases, the dose of Compound B  906  needs to provide the same therapeutic response increase at a much greater rate. 
     Alternatively, the drug delivery device  10  may be programmed with an algorithm for computing a dose of the secondary medicament based on a fixed, linear ratio followed by a fixed dose profile. As just one example, such a stored profile may initially follow a fixed ratio profile for certain low doses of the primary medicament or Compound A. Then, above a certain threshold dose level of the Drug A, the profile switches to a fixed dose of the secondary medicament or Compound B. That is, for higher doses of the primary medicament/Compound A, the secondary medicament will comprise essentially a fixed dose. 
     For certain therapies, the delivery of combination drug products (i.e., single doses that are made up from the combination of two or more individual drug formulations) might be beneficial for the dose of the secondary medicament to initially rise rapidly relative to the primary medicament. Then, once a pre-determined threshold value of the primary medicament has been reached, the profile will then flatten out. That is, the calculated dose of the secondary medicament will remain constant regardless of further increases in the set dose of the primary medicament. Such fixed ratio followed by fixed dose-low dose threshold therapeutic profiles are not achievable from a combination drug that is co-formulated into a single primary pack (such as, but not limited to, a standard 3 ml glass cartridge) where the concentration of the various constituent parts is constant (xmg/ml). Achieving such profiles would also be particularly difficult for a patient to calculate on current devices for every dose. 
       FIGS. 40-42  provide three illustrative examples of such fixed ratio followed by fixed dose-low dose threshold therapeutic profiles  940 ,  950 , and  960 . For example,  FIG. 40  illustrates an arrangement of a predefined fixed ratio-fixed dose therapeutic profile  940  having a low dose threshold and that may be programmed into the drug delivery device. As illustrated, this profile  940  initially follows a fixed ratio profile for a 0-10 Unit selected doses of the primary medicament or Compound A  944 . Then, once this 10 Unit threshold dose level of the Drug A has been surpassed, the profile  940  switches to a 30 Unit fixed dose of the secondary medicament or Compound B  948 . As such, for doses greater than 10 Units of the primary medicament/Compound A  944 , the secondary medicament  948  will comprise a fixed dose at 30 Units. 
       FIG. 41  illustrates an alternative arrangement of a predefined fixed ratio-fixed dose therapeutic profile  950  having a high dose threshold. As illustrated, this profile  950  initially follows a fixed ratio profile for a 0-50 Unit selected dose of the primary medicament or Compound A  952 . Then, above this 50 Unit threshold dose level of the Drug A  952 , the profile  950  switches to a 30 Unit fixed dose of the secondary medicament or Compound B  958 . As such, for doses greater than 50 Units of the primary medicament/Compound A  952 , the secondary medicament  958  will comprise essentially a fixed dose at 30 Units. 
       FIG. 42  illustrates an alternative arrangement of a predefined fixed ratio-fixed dose therapeutic profile having a low dose threshold and that may be programmed into the drug delivery device comprising three compounds or medicaments. As illustrated, this profile  960  initially follows a fixed ratio profile for both Drug B  966  and Drug C  968  for a 0-10 Unit selected dose of the primary medicament or Compound A  944 . Then, above this 10 Unit threshold dose level of the Drug A, the profile  960  switches to a 30 Unit fixed dose of the secondary medicament or Compound B  966  and a 10 Unit fixed dose of the tertiary medicament Compound C  968 . As such, for doses greater than 10 Units of the primary medicament/Compound A  944 , the secondary and tertiary medicaments  966 ,  968  will comprise essentially fixed doses at 30 Units and 10 Units, respectively. 
     Applicants&#39; profiles  940 ,  950 , and  960  delivering a fixed ratio up to a first point and thereafter delivering a fixed dose type of profile in a combination drug delivery device provide a number of advantages. For example, where priming of the drug delivery device may be required (either for initial first time use, or prior to each dose), these types of a predefined fixed ratio-fixed dose therapeutic profiles facilitate priming of both compounds with potentially minimal wastage. In this regard, these profiles have certain advantages over other programmable therapeutic profiles, such as the fixed dose profiles and the delayed fixed dose profiles described herein below. This may be especially true with regards to wastage of the secondary medicament or Compound B. 
     In addition, the various profiles described and illustrated in  FIGS. 40-42  may be appropriate in treatment situations where it is desirable to rapidly increase the dose of the secondary medicament, relative to the primary medicament initially. However, once a preset dose threshold has been reached, the secondary medicament may be kept constant regardless of further increases in the dose of the primary medicament. As such, this type of profile might be beneficial for drug delivery devices where an initial titration phase (of both drug compounds) is either required, or is deemed preferable for a patient. 
     An example of a particular combination therapy where profiles  940 ,  950  and  960  might be appropriate is for the combined delivery of a long acting insulin or insulin analog (i.e., Drug A or the primary medicament) in combination with an active agent, such as a GLP-1 or GLP-1 analog (i.e., Drug B or the secondary medicament). In this particular combination therapy, there is a reasonable variation in the size of the insulin dose across patient population, whereas the therapeutic dose of the GLP-1 may be considered as broadly constant (except during the titration phase) across the patient population. 
     Another preferred dose profile for use with the drug delivery device  10  comprises a fixed dose of the secondary medicament (i.e., Compound B) and a variable dose of the primary medicament (i.e., Compound A) profile. With such a therapeutic profile, the profile describes the delivery of a fixed dose of Compound B across the full range of potential doses of Compound A. 
     This fixed dose-variable dose therapeutic profile may be beneficial for the dose of Compound B to be constant for all potential doses of Compound A. One advantage of having the control unit programmed with such a profile is that fixed dose-variable dose therapeutic profiles are not achievable from a combination drug that is co-formulated into a single primary pack (such as, but not limited to, a standard 3 ml glass cartridge) where the concentration of the various constituent parts is constant (xmg/ml). 
     Two such fixed dose-variable dose profiles are illustrated in  FIGS. 43-44 .  FIG. 43  illustrates an arrangement of a predefined fixed dose-variable dose therapeutic profile  980  that may be programmed into the drug delivery device. More specifically,  FIG. 43  illustrates a sample formulation combination for a fixed dose of Compound B  986  and a variable dose of compound A  982 . As illustrated, for any selected dose of the primary medicament  982 , a fixed dose of 30 Units of Drug B  986  will be computed. 
       FIG. 44  illustrates an alternative arrangement of a predefined fixed dose-variable dose therapeutic profile  990  that may be programmed into the drug delivery device. As illustrated, profile  990  provides for a sample triple formulation combination of a fixed dose of Drug B  994  and Drug C  996  and a variable dose of Drug A  992 . As illustrated, for any selected dose of the primary medicament  992 , a fixed dose of 30 Units of Drug B  994  and a fixed dose of 18 Units of Drug C  996  will be computed by the drug delivery device  10 . 
     Such fixed dose-variable dose profiles  980  and  990  offer a number of advantages. For example, one of the benefits of these types of delivery profiles is in treatment situations where it is therapeutically desirable to ensure that patients receive a specific dose of one drug compound, irrespective of the size of the variable dose selected of the other compound. This particular profile has specific advantages over other predefined profiles (e.g., the fixed ratio then fixed dose profiles described above, the delayed fixed dose of compound B, variable dose of compound A profiles described below and the controlled thresholds profiles described below), there is not a predetermined minimum dose threshold of primary medicament required to ensure a complete dose of the secondary medicament. 
     One example of a particular combination therapy where this type of fixed dose-variable dose profile might be particularly appropriate is for the combined delivery of a long acting insulin (i.e., the variable dose) with a GLP-1 (i.e., the fixed dose). In this particular combination, there is reasonable variation in the size of the insulin dose across the patient population, whereas the GLP-1 dose is broadly constant (except during the titration phase where it generally increases in stepped intervals) across the patient population. For this particular therapy regimen, titration of the GLP-1 dose may be needed during the early stages of treatment. This could be achieved with a combination device using different ‘strengths’ of drug within the GLP-1 primary pack (e.g., using 10, 15 or 20 g per 0.1 ml concentrations). 
     For certain therapies it might be beneficial for the dose of secondary medicament Compound B to be a constant dose once a minimum threshold dose of the primary medicament Compound A has been met and/or exceeded. Again, such profiles of this type are not achievable from a combination drug that is co-formulated into a single reservoir or cartridge (such as, but not limited to, a standard 3 ml glass cartridge). In such standard cartridges, the concentration of the various constituent parts is constant (xmg/ml). 
     In one arrangement, Applicants&#39; drug delivery device  10  may also be programmed with a therapeutic profile that calculates a delayed fixed dose of a secondary medicament Compound B and variable dose of a primary medicament Compound A. Such a profile provides for the delivery of a fixed dose of Compound B but provides this fixed dose only after a minimum threshold dose of Compound A has been met or exceeded. Illustrative examples of four predefined delayed fixed dose-variable dose therapeutic profiles  1000 ,  1020 ,  1040  and  1060  are illustrated in Applicants&#39;  FIGS. 45-48 . 
     For example,  FIG. 45  illustrates an arrangement of a predefined delayed fixed dose-variable dose therapeutic profile  1000  having a low threshold. More specifically,  FIG. 45  illustrates a sample dual formulation combination having a delayed fixed dose of the secondary medicament (i.e., Compound B) and a variable dose of the primary medicament (i.e., Compound A) with the primary medicament having a low dose threshold  1006 . 
     As illustrated in  FIG. 45 , the profile  1000  defines a variable dose of Drug A  1004  from a minimum dose of 0 Units to a maximum dose of 80 Units. In this illustrative profile  1000 , the low threshold  1006  for Drug A  1004  is 10 Units. Based on profile  1000 , if a user were to select a dose of Drug A  1004  anywhere from 0 to 10 Units, the control unit would calculate a dose of Drug B  1008  equal to “0” Units. Only after a minimum or threshold dose of 10 units were selected for the primary medicament  1004 , would a dose of Drug B  1008  be calculated above “0” Units. Moreover, this calculated dose of Drug B  1008  would be a constant 30 Units, irrespective of the amount of the selected dose set of Drug A  1004 , as long as this selected dose remains greater than 10 Units. 
       FIG. 46  illustrates an arrangement of a predefined delayed fixed dose-variable dose therapeutic profile  1020  having a high threshold of Drug A  1024 . More specifically,  FIG. 46  illustrates a profile  1020  for defining a dual formulation combination having a delayed fixed dose of Compound B  1028  and a variable dose of Compound A  1024 . In this illustrative profile  1020 , the high threshold  1026  for Drug A  1024  is 30 Units. This high initial threshold  1026  of Drug A  1024  is required before the profile  1020  allows a dose to be set from Drug B  1028 . In this illustrated profile  1020 , this high initial threshold  1026  equal to 30 Units of Drug A  1024  must be surpassed before the Applicant&#39;s delivery device  10  begins to calculate a 30 Unit dose of Drug B  1028 . 
       FIG. 47  illustrates an alternative arrangement of a predefined delayed fixed dose-variable dose therapeutic profile  1040  wherein the drug delivery device  10  comprises two compounds or medicaments. More particularly,  FIG. 47  illustrates a profile  1040  for defining a sample triple formulation combination having a delayed fixed dose of Drug B  1046  and Drug C  1048 , a variable dose of Drug A  1044  wherein this Drug A  1044  has a low threshold. In this illustrated profile  1040 , Drug A  1044  has a low threshold  1042  equal to 10 Units. That is, once a user equals or surpasses the low threshold  1042  of 10 Units of Drug A  1044 , the drug delivery device  10  will calculate a dose of 17.5 Units of Drug C  1048  and calculate a dose of 30 Units of Drug B  1046 . 
       FIG. 48  illustrates a profile  1060  that defines a sample triple formulation combination having a delayed fixed dose of Drug B  1066  and Drug C  1068 , and a variable dose of Drug A  1064 . In profile  1060 , the primary medicament Drug A has two offset thresholds  1062 ,  1063 . That is, once the user selects a dose that surpasses the low threshold  1062  of 20 Units of Drug A  1064 , the drug delivery device  10  will calculate a dose of 30 Units for Drug B  1066  and will calculate a dose of “0” Units for Drug C  1068 . 
     Similarly, if a user selects a dose of Drug A  1064  between 20 Units and 30 Units, again the drug delivery device  10  will calculate a dose of 30 Units for Drug B  1066  and calculate a dose of “0” Units for Drug C  1068 . Then, it is only after a user selects a dose greater than 30 Units for Drug A  1064  thereby surpassing the second threshold  1063 , the drug delivery device  10  will the calculate a dose of Drug C  1068 . In this illustrated profile  1060 , this dose of Drug C  1068  equals 19 Units. Although only two offset thresholds are illustrated in this profile  1060 , those of skill in the art will recognize alternative threshold arrangements may also be utilized. 
     Applicants&#39; preferred profiles  1000 ,  1020 ,  1040 , and  1060  illustrated in  FIGS. 45-48  offer a number of advantages. For example, these illustrated profiles could provide the basis for a single device solution where it is therapeutically desirable to ensure that a patient using the drug delivery device  10  receives a specific, calculated dose of one drug compound in conjunction with the dose they select of another drug compound. However, the patient would receive such specific, calculated doses of the second compound only once a minimum dose threshold (of a primary drug or Drug A) has been reached or surpassed. As such, these illustrated profiles  1000 ,  1020 ,  1040 , and  1060  could provide a cost-effective solution where a user&#39;s prescribed therapy requires that the primary medicament needs to be titrated up to a minimum value reasonably quickly before it should be taken in combination with a secondary medicament (and perhaps other medicaments), therefore rendering at least a two device option more costly and/or wasteful. Such a two device option may be more costly and/or wasteful as the device containing Drug A may be only part utilized at the point where the patient switches to the combination product. 
     An additional benefit stems from the situation that patients are sometimes required to carry out a priming step with their drug delivery device. Such a priming step may be required either prior to a first use of the drug delivery device or perhaps prior to each time a dose is to be administered by the drug delivery device. In the example of pen type drug delivery devices, one of the principle reasons for the set up prime is to remove clearances/backlash in the mechanism, thereby helping ensure that the first dose delivered is within the required dose accuracy range. The in-use prime (sometimes referred to in certain relevant art and/or literature as a “safety shot”) is recommended for some pen type drug delivery devices. For example, such a safety shot may be recommended so as to confirm that the dose setting mechanism within the device is functioning properly. Such a safety shot is also often recommended so as to confirm that the delivered dose is accurately controlled and also to ensure that the attached dose dispenser (e.g., double ended needle assembly) is not blocked. Certain safety shots also allow the user to remove air from the dose dispenser prior to a user setting and therefore administering a dose. For a multi primary pack device, a profile of this type would enable the ‘in use safety’ prime to be undertaken using primary medicament only, thereby minimizing potential wastage of the secondary medicament. 
     For example, a particular combination therapy where this type of profile might be particularly appropriate is for the combined delivery of a long acting insulin or insulin analog along with a GLP-1 or a GLP-1 analog for early-stage diabetics. For example, there is a reasonably large variation in the size of the insulin doses across patient population, whereas GLP1 doses are broadly constant (except during the titration phase where is generally increases in stepped intervals) across the patient population. For this particular type of combination therapy, titration of the GLP1 dose is needed during the early stages of treatment. This could be achieved with a combination device through the use different ‘strengths’ of drug within the GLP1 cartridge or reservoir (e.g., using 10, 15 or 20 g per 0.2 ml concentrations for instance). The proposed delivery profiles illustrated in  FIGS. 45-48  would enable the user to perform a safety shot of the long acting insulin only without wasting GLP1. In this example the accuracy of the insulin dose is the more important than the accuracy of the GLP1 dose which is why performing the safety shot with insulin only is preferred. 
     As previously described, the delivery of combination drug products (i.e., single doses that are made up from the combination of two or more individual drug formulations) in a format where the delivered dose profile is predefined, offers a number of key benefits for both a patient and the treatment of a particular condition. For certain therapies it might be beneficial for the dose of the secondary medicament to increase in fixed stepped increments as the corresponding dose of primary medicament increases, but for each of these stepped increases to only occur once a specific predefined threshold dose of primary medicament has been exceeded. The relative ‘spacing’ between these threshold values of the primary medicament may or may not be regular. Again, such profiles of this type are not achievable from a combination drug that is co-formulated into a single primary pack (such as, but not limited to, a standard 3 ml glass cartridge) where the concentration of the various constituent parts is constant. Two exemplary profiles  1080  and  1100  are illustrated in  FIGS. 49 and 50 , respectively. 
     For example,  FIG. 49  illustrates an arrangement of a predefined multi-level fixed dose-variable dose therapeutic profile  1080  that comprises a slow ramp up and that may be programmed into the drug delivery device  10 . Specifically,  FIG. 49  illustrates a sample dual formulation having a multi-level fixed dose of Drug B  1088  and having a variable dose of Drug A  1084  and a slow ramp up. 
     This particular delivery profile could provide the basis for a single device solution where it is therapeutically desirable for the dose of the secondary medicament to increase in a stepped (rather than linear) manner as the dose of primary medicament is increased. This may be related to the specific safety and efficacy characteristics of a prescribed therapy, or situations where titration of the secondary medicament is stepped, as is the case for the injection of GLP1 type drugs (for the treatment of early stage, Type II diabetes). 
       FIG. 50  illustrates an alternative profile  1100  for defining a predefined multi-level fixed dose-variable dose therapeutic and that may be programmed into the drug delivery device  10 . As illustrated, this particular predefined multi-level fixed dose-variable dose therapeutic profile comprises a quick ramp up. In this preferred profile  1100 , Applicants&#39; propose a multi-level fixed dose of Drug B  1108  and a variable dose of Drug A  1104  profile. In this case, the profile  1100  describes the delivery of stepped fixed doses of Drug B once corresponding threshold doses of Drug A have been exceeded. 
     The illustrated profiles in  FIGS. 49 and 50  have certain potential benefits in terms of splitting a set and calculated combined dose. In addition to the previously discussed advantages, it has been acknowledged that users of drug delivery devices (such as pen type drug delivery devices) may sometimes split their target dose into two, smaller doses. This may occur as a patient transitions from a device that is nearly empty to a replacement device, or because the delivery of a ‘large’ dose as a singular event is problematic (even painful). For single formulation devices, or combination device where the various constituent elements are delivered in a fixed ratio to each other, splitting a dose into smaller parts does not affect the dose that is ultimately received. However, for combination devices where a patient receives a fixed dose of one medicament irrespective of the selected dose of the primary medicament as previously described, splitting a dose could result in an overdose of one of the individual medicaments. The careful utilization of this type of multi-level profile, however, can provide a reasonably robust solution to this particular user scenario. 
     As just one example, consider a patient who generally takes between 50 and 80 units of Drug A (e.g., an insulin or insulin analog), and whose target dose of Drug B (e.g., a GLP-1 or GLP-1 analog) is 20 units. Assuming that the patient has been prescribed with a device utilizing the therapeutic profile detailed in  FIG. 49 , then their target prescription would be achieved if each dose is administered as a single injection. This would not be the case where the patient decides to split their target dose into two smaller doses. In an example embodiment, the device may determine that the two subsequent injections are split injections of a single target dose, for example by determining that a cartridge of one of the medicaments was changed, or by determining that only a small amount of time has passed since the last injection, for example less than 30 minutes. Referring to the profile of  FIG. 49 , a patient may want to administer a dose of 50 units of drug A. The device would determine that a dose of 10 units of drug B corresponds to a dose of 50 units of drug A. However, in a first injection, 25 units of drug A are selected, for example as the cartridge only contains a remainder of 25 units. The device determines according to the profile 10 units of drug B. 5 minutes later (for example after exchanging the cartridge) another 25 units of drug A are selected. As the time since the last injection is less than the threshold of 30 minutes, the device determines that the new selection of 25 units is a second dose of a split dose of drug A of 50 units. Therefore, the device determines the dose of drug B for the second injection to be 0 units, as 50 units of drug A will result in 10 units of drug B according to profile  1080 , and as 10 units of drug B have already been administered in the first injection of the split dose. 
     Applicants&#39; electro-mechanical dose setting mechanism is of particular benefit where a targeted therapeutic response can be optimized for a specific target patient group. This may be achieved by a microprocessor based drug delivery device that is programmed to control, define, and/or optimize at least one therapeutic dose profile. A plurality of potential dose profiles may be stored in a memory device operatively coupled to the microprocessor. For example, such stored therapeutic dose profiles may include, but are not limited to, a linear dose profile; a non-linear dose profile; a fixed ratio fixed dose profile; a fixed dose variable dose profile; a delayed fixed dose variable dose profile; or a multi-level, fixed dose variable dose profile as discussed and described in greater detail below. Alternatively, only one dose profile would be stored in a memory device operatively coupled to the microprocessor. In one dual medicament drug delivery device arrangement, the dose of the second medicament may be determined by way of a first therapeutic profile such as those identified above. In one drug delivery device comprising three medicaments, the dose of the second medicament may be determined by way of a first therapeutic profile while the dose of the third medicament may be determined by either the same first therapeutic profile or a second different therapeutic profile. As those of ordinary skill in the art will recognize, alternative therapeutic profile arrangements may also be used. 
     Exemplary embodiments of the present invention have been described. Those skilled in the art will understand, however, that changes and modifications may be made to these embodiments without departing from the true scope and spirit of the present invention, which is defined by the claims.