Patent Publication Number: US-8979791-B2

Title: Medicated module with needle guard

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/EP2010/057583 filed Jun. 1, 2010, which claims priority to U.S. Provisional Patent Application No. 61/183,457 filed on Jun. 2, 2009 and European Patent Application No. 09009663.7 filed on Jul. 25, 2009. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
    
    
     FIELD OF THE INVENTION 
     According to a preferred embodiment, the present disclosure relates to medical devices and methods of delivering at least two drug agents from separate reservoirs using devices having only a single dose setting mechanism and a single dispense interface. A single delivery procedure initiated by the user causes a non-user settable dose of a second drug agent and a variable set dose of a first drug agent to be delivered to the patient. The drug agents may be available in two or more reservoirs, containers, or packages, each containing independent (single drug compound) or pre-mixed (co-formulated multiple drug compounds) drug agents. One aspect of our present application is of particular benefit where the therapeutic response can be optimized for a specific target patient group, through control and definition of the therapeutic profile. 
     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. This invention may be 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 person suffering from diabetes with a long acting insulin and with a glucagon-like peptide-1 (GLP-1), which 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 or more active medicaments or “agents” simultaneously. The two or more active agents may interact with each other during the long-term, shelf life storage of the formulation. Therefore, there are certain advantages to storing the active components separately and only combine them at the point of delivery, e.g. injection, need-less injection, pumps, or inhalation. However, the process for combining the two agents needs to be simple and convenient for the user to perform reliably, repeatedly and safely. 
     A further concern 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 is varied in response to a patient&#39;s symptoms or physical condition. This problem means that pre-mixed formulations of multiple 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 concerns arise where a multi-drug compound therapy is required, because certain users cannot cope with having to use more than one drug delivery system or make the necessary accurate calculation of the required dose combination. This is especially true for users with dexterity or computational difficulties. 
     Other problems arise where a user may attempt to re-use a non-sterile needle after a certain dose combination has been delivered. Using such a non-sterile needle could lead to the transmission of certain diseases (septicaemia) and therefore there exists a need for a medicated module that prevents needle re-use. There is a further concern of inadvertent needle sticks with certain needle assemblies where the injection needle is not concealed or covered, especially after use when a needle may be contaminated with blood. As such, there is also a general need to reduce certain patient&#39;s needle anxiety that may heighten a patient&#39;s fear or phobia of exposed needles. 
     Accordingly, there exists a strong need to provide devices and methods for the delivery of two or more medicaments in a single injection or delivery step that is simple and safe for the user to perform and that also tends to reduce a patient&#39;s anxiety towards injections or needles. The present application discloses specific embodiments of methods, devices and drug delivery kits that overcome the above-mentioned concerns by providing separate storage containers for two or more active drug agents that are then only combined and/or delivered to the patient during a single delivery procedure. According to a preferred embodiment of the invention, such devices may be provided in separate storage containers or provided in a kit form comprising at least one medicated module and at least one non-medicated module. 
     According to the disclosure the term medicated module is preferably used to characterize a needle sub-assembly comprising a containment or reservoir of a (secondary) drug compound. Consequently, a non-medicated module is preferably characterized as a needle sub-assembly, however without having a containment or reservoir of a (secondary) drug compound. As such the medicated module and/or the non-medicated module may comprise at least one double ended needle. Furthermore the medicated module and/or the non-medicated module may comprise a needle guard. The medicated module and/or the non-medicated module may be configured to be attachable to a drug delivery device, e.g. a pen-type drug delivery device. 
     According to a specific embodiment described in the following, setting a dose of one medicament automatically fixes or determines the dose of the second medicament (i.e., a non-user settable dose). The present application may also give the opportunity for varying the quantity of one or both medicaments. For example, one fluid quantity can be varied by changing the properties of the injection device (e.g., dialing a user variable dose or changing the device&#39;s “fixed” dose). The second fluid quantity can be changed by manufacturing a variety of secondary drug containing packages or kits with each variant containing a different volume and/or concentration of the second active agent. The user or healthcare professional would then select or prescribe the most appropriate secondary package or series or combination of series of different packages or kits for a particular treatment regime. 
     These and other advantages will become evident from the following more detailed description of the invention. 
     SUMMARY 
     The general problem to be solved by the present invention is to provide a medicated module, a drug delivery kit and drug delivery system where the administration of a medicament is improved. 
     According to some specific embodiments, the present application discloses modules, systems, methods, and drug delivery kits that allow for the complex combination of multiple drug compounds within a single drug delivery system. Preferably, such a system includes a needle guard that functions to prevent needle reuse and that can also function to reduce needle phobia while also reducing potential inadvertent needle sticks. 
     According to a specific embodiment, a user can set and dispense a multi-drug compound device through one single dose setting mechanism and a single drug dispense interface. Preferably, the single drug dispense interface may then be locked out so as to prevent reuse of a medicated module (i.e., re-use of the injection needle). Preferably, the single dose setter controls the mechanism of the device such that a predefined combination of the individual drug compounds is delivered when a single dose of one of the medicaments is set and dispensed through the single drug dispense interface. The term drug dispense interface preferably is, in the context of this disclosure, any type of outlet that allows the two or more medicaments to exit the drug delivery system and be delivered to the patient. In a preferred embodiment the single drug dispense interface comprises a hollow needle cannula. 
     By defining the therapeutic relationship between the individual drug compounds some embodiments of the presently disclosed delivery devices and systems would help ensure that a patient/user receives the optimum therapeutic combination dose from a multi-drug compound device without the inherent risks associated with multiple inputs where the user has to calculate and set the correct dose combination every time they use the device. The combination of the individual medicaments comprises preferably at least two different drug agents, wherein each medicament comprises at least one drug agent. The medicaments can be fluids, defined herein as liquids or gases that are capable of flowing and that change shape at a steady rate when acted upon by a force tending to change its shape. Alternatively, one of the medicaments may be a solid that is carried, solubilized or otherwise dispensed with another fluid medicament. 
     According to one specific aspect, the present application is of particular benefit to patients with dexterity or computational difficulties as the single input and associated predefined therapeutic profile removes the need for them to calculate their prescribed dose every time they use the device and the single input allows considerably easier setting and dispensing of the combined compounds. This application may also be of particular benefit to patients experiencing needle phobia or who may experience a general fear of inadvertent needle sticks. 
     In a preferred embodiment a primary or master drug compound or medicament, such as insulin, contained within a multiple dose, user selectable device could be used with a single use, user replaceable, module that contains a single dose of a secondary medicament and the single dispense interface. When connected to the primary device the secondary medicament is activated/delivered on dispense of the primary medicament. Although our invention 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 our invention 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-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) 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-NH 2 ), 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-NH 2 ). 
     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 embodiment, the present patent application relates to a medicated module attachable to a drug delivery device. The medicated module comprises a connecting body configured for attachment to the drug delivery device. A first needle is fixed within the module or, according to a specific embodiment, within the connecting body. Furthermore, an outer body may operatively be coupled to the connecting body. A needle guard is operatively coupled to the module or, according to a specific embodiment, to the outer body. A biasing member or element is positioned to bias the needle guard. The biasing member may be positioned between the outer body and the needle guard. A second needle is fixed within the module or, according to a specific embodiment, within the outer body. A reservoir containing at least one dose of a medicament is provided. The reservoir may be defined by a recess within the connecting body. The reservoir may alternatively be defined by a capsule, i.e. a self-contained sealed reservoir of a secondary medicament. The reservoir is configured for fluid communication with the first and the second needle. 
     In another arrangement, a drug delivery kit for a drug delivery device comprises a medicated module configured for connection to the drug delivery device. A non-medicated module may also be provided and is configured for connection to the drug delivery device. In one arrangement, the drug delivery kit comprises a plurality of medicated modules configured for connection to said drug delivery device. In one arrangement comprising a plurality of modules, each module comprises a medicament having a different titration level than the next medicated module. In an alternative arrangement, the drug delivery kit comprises a plurality of non-medicated modules. 
     A drug delivery device preferably comprises a (primary) reservoir of medicament containing at least one drug agent, a dose setter, a dose button, and a delivery mechanism. The dose button is operably connected to the primary reservoir. The dose setter is operably connected to the primary reservoir. The delivery mechanism may be of any type utilizing a rotatable piston rod, preferably a rotatable piston rod with two distinct threads. 
     A particular benefit of our application is that the medicated module makes it is possible to tailor dose regimes when required, especially where a titration period is necessary for a particular drug. The medicated module could be supplied in a number of titration levels with differentiation features such as, but not limited to, aesthetic design of features or graphics, numbering etc, so that a patient could be instructed to use the supplied medicated module in a specific order to facilitate titration. Alternatively, the prescribing physician may provide the patient with a number of “level one” titration medicated modules or a kit of modules and then when these were finished, the physician could then prescribe the next level or the next drug delivery kit. One advantage of this titration program is that the primary device can remain constant. 
     In a preferred embodiment, the primary 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 our invention is equally applicable to both scenarios. It is possible to have a suite of different medicated modules for various conditions that could be prescribed as one-off extra medication to patients already using a standard drug delivery device (or family of devices). Should the patient attempt to reuse a previously used medicated module, the presently disclosed medicated module provides a lockable needle guard feature that could alert the patient to this situation. Other means of alerting the user may include some (or all) of the following:
     1. Physical prevention of medicated module re-attachment to the primary drug delivery device once the module was used and removed.   2. Physical prevention of insertion of the used drug dispense interface into the patient (e.g., a single use needle-guard type arrangement).   3. Physical/hydraulic prevention of subsequent liquid flow through the drug dispense interface once it has been used.   4. Physical locking of the dose setter and/or dose button of the primary drug delivery device.   5. Visual warnings (e.g., change in color and/or warning text/indicia within an indication window on the module once needle insertion and/or fluid flow has occurred).   6. Tactile feedback (presence or absence of tactile features on the outer surface of the module hub following use).   

     A further feature of this embodiment is that both medicaments are delivered via one injection needle 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. 
     A further aspect of the invention relates to a method of delivering two medicaments stored in separate primary packages. The medicaments may both be liquid, or alternatively one or more of the medicaments may be a powder, suspension or slurry. In one embodiment the medicated module could be filled with a powdered medicament that is either dissolved or entrained in the primary medicament as it is injected through the medicated module. 
     In addition, a drug delivery system is provided to deliver two or more medicaments operable through a single dispense interface. The system comprises a primary reservoir of medicament containing at least one drug agent for example a liquid medicament such as insulin or an analog thereof as well as a dose button operably connected to the primary reservoir of medicament. Furthermore, the drug delivery system may comprise a housing having a single dose setter operably connected to the primary reservoir of medicament. Furthermore, a single drug dispense interface configured for fluid communication with the primary reservoir is provided. The system has a medicated module comprising a needle guard and a secondary reservoir of medicament containing at least one drug agent. The system is designed such that a single activation of the dose button causes medicament from the primary reservoir and the second medicament from the secondary reservoir to be expelled through the single drug dispense interface. Preferably, the primary reservoir contains a liquid medicament. According to a specific embodiment, the single activation of the dose button causes a non-user settable dose of the second medicament to be expelled. The medicated module may be primable and may, in addition, contain a sealed sterile capsule containing a single dose of at least one drug agent. I.e. the medicated module may comprise a reservoir comprising a capsule being the self-contained sealed reservoir of a (secondary) medicament. In this case a single activation of the dose button will cause to expel the single dose of the capsule. 
     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. 
     The scope of the invention is defined by the content of the claims. The invention is not limited to specific embodiments but comprises any combination of elements of different embodiments. Moreover, the invention comprises any combination of claims and any combination of features disclosed by the claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Exemplary embodiments are described herein with reference to the drawings, in which: 
         FIG. 1  illustrates a sectional view of one arrangement of a medicated module attached to a drug delivery device; 
         FIG. 2  illustrates a perspective view of the medicated module of  FIG. 1  having two needles connected to a reservoir attached to a drug delivery device; 
         FIG. 3  illustrates a front view of the medicated module of  FIG. 2 ; 
         FIG. 4  illustrates the medicated module illustrated in  FIG. 1  having a locked out needle guard; 
         FIG. 5  illustrates a non-medicated module that may be provided in a drug delivery kit that includes the medicated module illustrated in  FIG. 1 ; 
         FIG. 6  illustrates a partial view of a movable lockout member of the non-medicated module illustrated in  FIG. 5 ; 
         FIG. 7  illustrates a perspective view of the movable lockout member illustrated in  FIG. 6 ; 
         FIG. 8  illustrates a front view of the module illustrated in  FIG. 5  having a locked needle guard; and 
         FIG. 9  illustrates one possible drug delivery device that can be used with the medicated module illustrated in  FIG. 1 . 
     
    
    
     DETAILED DESCRIPTION 
     According to a specific embodiment, the present invention administers a fixed predetermined dose of a second medicament (secondary drug compound) and a potentially variable dose of a first medicament (primary drug compound) through a single output or drug dispense interface such as a double ended needle. Setting the dose of the primary medicament by the user may automatically determine the fixed dose of the second medicament. This fixed dose of the second medicament is preferably a single dose. In a preferred arrangement, the drug dispense interface comprises a needle cannula (hollow needle) and a needle guard that may be locked out after medicament injection. 
       FIG. 1  illustrates a preferred arrangement of a medicated module  10  where a first needle  40  pierces a septum  2  of a device cartridge  14 . A second injection needle  80  may be used to subcutaneously inject the first medicament contained in the cartridge along with a second medicament contained in the medicated module. Located between the two needles  40 ,  80  is a recess  37  defined by a connection body  24 . Preferably, this recess contains a reservoir of a second medicament  38 . Most preferably, this reservoir comprises a capsule  46  that has ends sealed with first and a second pierceable seals  48 ,  50 , respectively. 
     In this preferred arrangement, the medicated module  10  as illustrated is attached to a drug delivery device  12 . Only a portion of such a drug delivery device is illustrated in  FIG. 1 . The drug delivery device  12  may comprise a cartridge holder containing a standard cartridge  14 . This standard cartridge  14  comprises a first medicament  16  such as insulin or the like. 
     In one arrangement, the medicated module  10  is preferably self-contained and may be provided as a sealed and sterile disposable module. Such a module comprises an attachment means compatible to the attachment means at a distal end of the drug delivery device  12 . Although not shown, the medicated module  10  could be supplied by a manufacturer contained in a protective and sterile container where the user would peel or rip open a seal or the container itself to gain access to the sterile medicated module. In some instances it might be desirable to provide two or more seals for each end of the medicated module. In addition, and as will be explained in detail below, in one arrangement, such medicated module  10  may be provided in a drug delivery kit along with at least one non-medicated module, such as the module illustrated in  FIG. 5 . 
     One example of a drug delivery device  12  is illustrated in  FIG. 9 . Any known attachment means can be used, including permanent and removable connection means. Threads, snap locks, snap fits, luer locks, bayonet, snap rings, keyed slots, and combinations of such connections can be used to attach module  10  to device  12 . As just one example,  FIG. 1  illustrates the attachment means comprising screw threads. The arrangement shown in  FIG. 1  has the benefit of the second medicament  38  as a single dose being contained entirely within the medicated module  10 . This can minimize the risk of material incompatibility between the second medicament and the materials used in the construction of the medicated module  10 . 
     Returning to  FIG. 1 , the medicated module  10  comprises a connecting body  24 , a first needle  40 , an outer body  52 , a second needle  80 , a biasing member  70 , and a needle guard  90 . 
     The connecting body  24  extends from a proximal end  26  to a distal end  28 . The proximal end of the connecting body is provided with a connector  30  so that the medicated module  10  may be connected to the drug delivery device  12 . Preferably, this connector is provided along an inner surface  22  of the connecting body  24  and provides a releasable connection to the drug delivery device  12 . Such a releasable connector may comprise a snap fit, form fit, snap lock, luer lock or other similar connection mechanism known to those of skill in the art. As can also be seen from  FIG. 1 , the connecting body  24  further comprises a first and second recess  32 ,  34 . These recesses are provided along a connector body external surface  33 . Although only two recesses  32 ,  34  are illustrated in the medicated module  10  arrangement illustrated in  FIG. 1 , alternative recess arrangements may comprise more or less than two recesses  32 ,  34 . As will be explained in greater detail below, as illustrated in  FIG. 1 , a male member  60  of an outer body  52  is releasably engaged to the first recess  32 . 
     The connecting body  24  defines a reservoir  36  and preferably this reservoir contains a second medicament  38 . Most preferably, this second medicament  38  comprises a single dose of a medicament, such as a single dose of GLP-1 or alternatively a pre-mix of medicaments. In one preferred arrangement, the reservoir comprises a capsule  46  comprising a first and a second end that is sealed with pierceable membranes  48 ,  50 . Such a construction provides a hermetically sealed reservoir for the second medicament  38 . 
     The connecting body  24  further comprises a first needle  40  rigidly affixed in an upper surface  35  of the connecting body. Preferably, this first needle  40  comprises a double ended needle having a first piercing end  42  (i.e., a distal end) and a second piercing end  44  (i.e., a proximal end). In this preferred arrangement, when the medicated module  10  is initially mounted to the drug delivery device  12  as illustrated in  FIG. 1 , the second piercing end  44  pierces the membrane  18  of the cartridge  14  but the first piercing end  42  does not yet pierce the first or proximal seal  48  of the capsule  46 . As such, the first medicament  16  of the cartridge  14  is not in fluid communication with the second medicament  38  contained in the capsule  46 . 
     The medicated module  10  further comprises an outer body  52  and preferably this outer body is slidably engaged with the connecting body  24 . More preferably, this outer body  52  is slidably engaged with the connecting body  24  and is slidable from an initial position (as illustrated in  FIG. 1 ) to a second or dose injecting position (as illustrated in  FIGS. 2 and 3 ). 
     The outer body  52  comprises a distal end  54  and a proximal end  56 . The outer body proximal end  56  is configured with a male member  60  that releasably engages the connecting body  24 . Preferably, when the medicated module is initially mounted onto the drug delivery device  12  as illustrated in  FIG. 1 , the male member  60  releasably engages the first recess  32  provided along the outer surface  33  of the connecting body  24 . In the second or dose injecting position (as illustrated in  FIGS. 2 and 3 ), the male member  60  is moved proximally so that this member engages the second recess  34 . 
     The outer body  52  further comprises a first and a second inner cavity  61 ,  62  respectively. Preferably, the first inner cavity  61  is formed to contain the reservoir of the connecting body  24  whereas the second inner cavity  62  is formed to contain an elastic member  70 , such as a compression spring. As illustrated in  FIG. 1 , in the initial mounted position of the medicated module, the elastic member  70  is in an extended state. In this extended state, the elastic member resides within this second cavity  62  and between the outer body  52  and the needle guard  90 . 
     The outer body  52  further comprises a distal and a proximal groove  65 ,  66  provided on inner surface  63 . The distal groove  65  includes a movable locking mechanism  68 , preferably in the form of a movable circlip. As will be explained below, this movable locking mechanism  68  is used to lock out the needle guard  90  after injection that is, after the needle guard is first moved in a proximal direction and then returned in a distal direction. 
     The outer body  52  further comprises a second or injection needle  80  rigidly affixed in outer body hub element  64 . Preferably, this second needle  80  comprises a double ended needle having a first piercing end  82  (i.e., a distal end) and a second piercing end  84  (i.e., a proximal end). 
     In this preferred arrangement, when the medicated module  10  is initially mounted to the drug delivery device  12  as illustrated in  FIG. 1 , the second piercing end  84  does not yet pierce the distal seal  50  of the capsule  46 . In addition, in this preferred arrangement, the first piercing end  82  of the second needle  80  is illustrated as being substantially concealed from a user&#39;s view by way of the needle guard  90  so as to help reduce any needle anxiety that a patient may be experiencing. 
     Preferably, needle guard  90  comprises a tubular shaped element and in a relaxed position, as illustrated in  FIG. 1 , substantially conceals the second needle  80 . While substantially concealing the second needle, the needle guard also helps to prevent inadvertent needle sticks. In  FIG. 1 , this needle guard  90  is illustrated in an unlocked position. That is, during an injection step where a user initiates the injection, the needle guard  90  is free to be moved in a proximal direction or towards the drug delivery device (illustrated by arrow  110  in  FIG. 1 ). 
     Preferably, the needle guard  90  comprises a plurality of outwardly directed arms  96 ,  98 . These arms  96 ,  98  are in sliding engagement with an inner surface  63  of the inner cavity  62  of the outer body  52  and reside within the second cavity  62  defined by the outer body. These outwardly directed arms  96 ,  98  allow for the needle guard  90  to be placed and held in a locked out position after dose injection. In addition, these outwardly directed arms  96 ,  98  may also serve as a rotation preventor so as to prevent the needle guard from rotating either when it is connected to the drug delivery device or during the medicament injection step. 
     As illustrated in  FIG. 1 , the module  10  is shown in a first mounted position on the drug delivery device  12 . In this first position, the connecting body  24  is connected to a distal end of the drug delivery device  12 . As illustrated, the drug delivery device comprises threads  13  for engagement with the connecting body  24 . In one arrangement, the connecting body  24  may comprise a threaded connector to releasably engage these threads. However, in an alternative arrangement, the connecting body  24  may comprise a connector  30  comprising a form fit or snap fit connector arrangement or the like. In this manner, the module  10  may be connected to the drug delivery device  12  merely by sliding the module onto the distal end of the drug delivery device. 
     As shown in  FIG. 1 , in this first position, the outer body  52  comprises at a proximal end inwardly extending male members  60  that engage the first recess  32  provided near the proximal end of the connecting body. When the outer body  24  resides in this initial connected position, the inwardly extending male members  60  engage the first set of recesses  32  of the connecting body and both the first and the second needles  40 ,  80  are not in fluid communication with the medicated module reservoir  36 . 
     As discussed above, in the initial mounting position, both the first and the second needles  40 ,  80  are not in fluid communication with the medicated module reservoir  36 .  FIG. 3  illustrates a side view of attachment of the medicated module  10  to the drug delivery device  12  in a dose ready state. To achieve this dose ready state or second state, the outer body  52  is moved in the proximal direction. This outer body proximal movement causes the inwardly extending male members  60  of the outer body to move from the first recess  32  to the second recess  34  of the connecting body. 
     Importantly, proximal movement of the outer body also causes the distal end  42  of the first needle  40  to penetrate the first pierceable seal  48  of the capsule  46  while the proximal end  44  of the first needle  40  maintains its penetration of the septum of the cartridge  14  of the device  12 . Proximal movement of the outer body also causes the proximal end  84  of the second needle  80  to penetrate the second pierceable seal  50  of the capsule  46 . Piercing of membranes  48  and  50  opens fluid communication between the first and second medicaments  16 ,  38  allowing these two medicaments to be dispensed through operation of the dispense mechanism on the drug delivery device  12 . 
     Where the drug delivery device  12  comprises a dose setter  8 , a dose of the drug delivery device  12  may then be set using a dose setter  8  (see  FIG. 9 ) in the normal manner (e.g., by dialing out the appropriate number of units). Dispense of the medicaments  16 ,  38  may then be achieved by subcutaneously injecting the medicaments via activation of a dose button on device  12 . The dose button  6  may be any triggering mechanism that causes the dose of the first medicament that was set by the dose setter to move distally towards the distal end of the device. In a preferred embodiment, the dose button is operably connected to a spindle that engages a piston in the primary reservoir of the first medicament. In a further embodiment the spindle preferably is a rotatable piston rod comprising two distinct threads. 
     During injection, the needle guard  90  is moved in a proximal direction  110  against a force created by the elastic member  70 . As the needle guard moves proximally, its outwardly directed arms  96 ,  98  slide internally within the second cavity  62  of the outer body  52  from the distal groove  65  to the proximal groove  66 . Once the outwardly directed arms  96  reach the proximal groove  66 , the outwardly directed arms  96  pick up the movable locking feature  68 . The first and second medicament  16 ,  38  may then be injected into an injection site by way of the second needle  80 . 
     After injection and the drug delivery device and the medicated module are removed from the injection site, the needle guard  90  under the force of the biasing element  70  is forced in the distal direction  120 . On being forced down or in the distal direction (represented by arrow  120  in  FIG. 3 ) by the force created by the element  70 , the needle guard  90  pulls the movable lockout member  68  into the distal groove  65  to thereby lock the needle guard  90  in the down position. 
     Locking the needle guard  90  in the down position in this manner provides a number of beneficial features. First, it prevents a user from re-using a non-sterile medicated module. Second, the locked needle guard protects and substantially conceals the second needle  80  and therefore reduces the risk of a potential inadvertent needle stick. And third, in substantially concealing the second needle  80 , the locked needle guard acts to reduce any potential needle fear, needle phobia or needle anxiety that a patient may experience. 
     In the arrangements described herein, the second medicament may be either in a powdered solid state, any fluid state contained within the secondary reservoir or capsule, or coated to the inside surface of the drug dispense interface. The greater concentration of the solid form of the medicament has the benefit of occupying a smaller volume than the liquid having lower concentration. This in turn reduces the ullage of the medicated module. An additional benefit is that the solid form of the second medicament is potentially more straightforward to seal in the secondary reservoir than a liquid form of the medicament. The device would be used in the same manner as the preferred embodiment with the second medicament being dissolved by the first medicament during dispense. 
     The connection or attachment between the medicated module as well as the non-medicated module of the described embodiments may contain additional features (not shown), such as connectors, stops, splines, ribs, grooves, and the like design features, that ensure that specific medicated module are attachable only to matching drug delivery devices. Such additional features would prevent the insertion of a non-appropriate medicated module to a non-matching injection device. 
     The shape of the medicated module may be a cylindrical body or any other geometric shape suitable for defining a fluid reservoir or for containing discrete self-contained reservoir of the secondary medicament and for attaching one or more needle cannula. The secondary reservoir or capsule can be manufactured from glass or other drug contact suitable material. The integrated injection needle can be any needle cannula suitable for subcutaneous or intramuscular injection. 
     Preferably the medicated module is provided by a manufacturer as a stand-alone and separate device that is sealed to preserve sterility. The sterile seal of the module is preferably designed to be opened automatically, e.g. by cutting, tearing or peeling, when the medicated module is advanced or attached to the drug delivery device by the user. This opening of the seal may be assisted by features such as angled surfaces on the end of the injection device or features inside the module. 
     Alternatively, the medicated module may be provided in a kit form along where such a kit comprises at least one non-medicated module or a safety needle assembly. There are a number of reasons to provide one or more non-medicated needle assemblies along with a medicated module (such as illustrated in  FIG. 1 ) in a kit form. 
     For example, there may be a situation where a patient may need to split a dose or top up a dose between two or more drug delivery devices. For example, there may be a situation where a user may need to administer a dose greater than the medicament remaining in the cartridge of the drug delivery device. As just one example, consider that a user might face a situation where they may need to administer a 50 Unit dose and only have only 30 Units remaining in the cartridge of their old (i.e. part-used) drug delivery device. In such a situation, the user would first mount the medicated module onto the drug delivery device, set the drug delivery device to administer 30 Units of the first medicament and then administer the first and the second medicament in a generally known way. Then, because the user would still need to deliver the remaining 20 Units of the first medicament, rather than use another medicated module containing a dose of the second medicament, the user would simply mount a non-medicated module to a new drug delivery device and then administer the remaining 20 Units of the first medicament. 
     A user may also be faced with administering a large dose of the first medicament and may, for one reason or another, want to split this large dose (i.e., a large volume of medicament) into two or more injections. For example, some users may face themselves administering large doses on the order of 100 Units or more of a single medicament for a single injection. Rather than administer such a large volume of medicament during a single injection, the user may first administer 60 Units while using the medicated module and then administer the remaining 40 Units using a non-medicated module. Splitting up the volume of the administered dose helps to reduce patient discomfort and may reduce potential medicament pooling under the skin. Splitting such a large dose may also be required where there is a mechanical restraint on the drug delivery device in that the device may not be mechanically capable of setting and administering such a large volume of medication. 
     Another reason that a user may need to split a dose between a medicated and a non-medicated module is that perhaps a physician has instructed a user to split a dose up into two or more injections. Two or more injections may be required if a user experiences certain negative reactions when administering a full dose of a first medicament simultaneously with a second medicated dose. Alternatively, the patient may be instructed to initially administer a first medicament during a specific time of day (e.g., a long acting insulin in the morning) and then later in the day instructed to administer a combination of a first and second medicament (e.g., a long acting insulin in combination with a short acting insulin later in the day). In such a scenario, the non-medicated module could be used to administer the first injection. 
       FIG. 5  illustrates a first arrangement of a non-medicated module and is somewhat similar in construction to the medicated module. For example, this module  210  comprises a connecting body  224 , a double ended needle  280 , a biasing member  270 , a movable locking member  268 , and a needle guard  290 . 
     The connecting body  224  of the module  210  extends from a proximal end  226  to a distal end  228 . The proximal end of the connecting body is provided with a connector  230  so that the connector body may be connected to the drug delivery device  212 . Preferably, this connector  230  is provided along an inner surface  222  of the connecting body  224  and provides a releasable connection to the drug delivery device  212 . Such a releasable connector may comprise a snap fit, form fit, snap lock, screw lock, bayonet fit, luer lock or other similar connection mechanism known to those of skill in the art. 
     The connecting body  224  further comprises an injection needle  280  rigidly affixed within a main stem  231  of a needle hub. Preferably, this needle  280  comprises a double ended needle having a first piercing end  282  (i.e., a distal end) and a second piercing end  284  (i.e., a proximal end). In this preferred arrangement, when the module  210  is initially mounted to the drug delivery device  212  as illustrated in  FIG. 5 , the second piercing end  284  pierces the membrane  218  of the cartridge  214 . 
     The connection body  224  further comprises a first inner cavity  261 . Preferably, the first inner cavity  261  is formed to contain a movable locking element  268  and a biasing member  270 , such as a compression spring. As illustrated in  FIG. 5 , in the initial mounted position of the needle assembly, the biasing member  270  is in an extended state. 
     Details of a preferred arrangement of a locking mechanism can be clearly seen from  FIGS. 6 and 7 .  FIG. 6  illustrates a cross sectional view of the movable locking mechanism  268  and  FIG. 7  illustrates a perspective view of the locking mechanism  268 . As illustrated, the movable locking mechanism  268  is preferably in the form of a cylindrical shaped member having an outer beveled edge  274 . Preferably, the locking mechanism  268  comprises plurality of annular spring fingers  272   a, b, c  within the cavity created by the locking mechanism. As illustrated in the first mounted position of  FIG. 5 , these spring fingers  272  a, b, c engage a recess  239  located on the proximal end  226  of a main stem  231  of the connecting body main hub. The engagement of the spring fingers  272   a, b, c  and the recess prevents the locking mechanism from moving in the distal direction prior to injection. This movable locking mechanism  268  is used to lock out the needle guard  290  after an injection has been made. That is, after the needle guard is first moved in a proximal direction and then returned in a distal direction under the force of the biasing member  270 . 
     In this preferred arrangement, when the needle assembly  210  is initially mounted to the drug delivery device  212 , the second piercing end  284  of the needle pierces the membrane  218  of the cartridge contained in the drug delivery device  212 . The first piercing end  282  of the first needle  280  is illustrated as being substantially concealed from a user&#39;s view by way of the needle guard  290 . Concealing the needle  280  helps to reduce needle anxiety that a patient may be experiencing while also reducing a potential inadvertent needle stick. 
     Preferably, the needle guard  290  comprises a tubular shaped element and in a relaxed position, as illustrated in  FIG. 5 , substantially conceals the needle  280 . While substantially concealing this needle, the needle guard also helps to prevent inadvertent needle sticks. In  FIG. 5 , this needle guard  290  is illustrated in an unlocked position. That is, during an injection step where a user initiates the injection, the needle guard  290  is free to be moved in a proximal direction or towards the drug delivery device. Preferably, the needle guard  290  comprises outwardly directed arms  296 ,  298  that are in sliding engagement with an inner surface  263  of the inner cavity  261  of the connecting body  224 . 
     As illustrated in  FIG. 5 , the module  210  is shown in a first mounted position on the drug delivery device  212 . In this first position, the connecting body  224  is connected to a distal end of the drug delivery device  212 . As illustrated, the drug delivery device comprises threads  213  for engagement with the connecting body  224 . In one arrangement, the connecting body  224  may comprise a threaded connector to releasably engage these threads. However, in an alternative arrangement, the connecting body  224  may comprise a connector  230  comprising a form fit or snap fit arrangement or the like. In this manner, the module  210  may be connected to the drug delivery device  212  merely by sliding the module onto the distal end of the drug delivery device. 
     In this initial mounting position, the needle  280  is in fluid communication with the medicament contained in the cartridge. Where the drug delivery device  212  comprises a dose setter, a dose of the drug delivery device  212  may then be set using a dose setter  212  (see  FIG. 9 ) in the normal manner (e.g., by dialing out the appropriate number of units). Dispense of the medicament  216  may be achieved by subcutaneously injecting the medicaments via activation of a dose button on device  212 . The dose button may be any triggering mechanism that causes the dose of the first medicament that was set by the dose setter to move distally towards the distal end of the device. In a preferred embodiment, the dose button is operably connected to a spindle that engages a piston in the primary reservoir of the first medicament. In a further embodiment the spindle preferably is a rotatable piston rod comprising two distinct threads. 
     During injection, the needle guard  290  is moved in a proximal direction  310  against a force created by the biasing member  270 . As the needle guard moves proximally, its arms  296 ,  298  slide internally within the cavity  261  of the connecting body  224 . Once the needle guard beveled edge  275  reaches the rib  274 , the beveled edge slips around the rib so that the needle guard  290  picks up the movable locking feature  268 . The medicament  216  may then be injected into an injection site by way of the needle  280 . 
     After the injection, the drug delivery device and the module  210  are moved away from the injection site. Then, under the force of the biasing member  270 , the needle guard  290  is forced in the distal direction  320 . On being forced down or in the distal direction  320  by the force created by the biasing member  270 , the needle guard  290  pulls the movable lockout member  268  distally. 
       FIG. 8  illustrates the module  210  with the needle guard  290  in a locked position. As illustrated, the annular ring fingers  272   a, b, c  of the locking member  268  flex inwardly to as to reside along a first recess  245  provided along the distal end of the main stem  231 . As such, the annular ring fingers  272  prevent the needle guard  290  from moving in the proximal direction and therefore prevents a user from re-using the module. 
     Locking the needle guard  290  in the down position in this manner provides a number of beneficial features. First, it prevents a user from re-using a non-sterile medicated module. Second, the locked needle guard protects and substantially conceals the needle  280  and therefore reduces the risk of a potential inadvertent needle stick. In addition, by substantially concealing the needle  280 , the locked needle guard  290  acts to reduce any potential needle fear, needle phobia or needle anxiety that a patient may experience. 
     The medicated module and the non-medicated module described herein should be designed to operate in conjunction with a multiple use injection device or family of devices, preferably a pen-type multi-dose injection device, similar to what is illustrated in  FIG. 9 . The injection device could be a reusable or disposable device. By disposable device it is meant an injection device that is obtained from the manufacturer preloaded with medicament and cannot be reloaded with new medicament after the initial medicament is exhausted. The device may be a fixed dose or a settable dose, but in either case it is a multi-dose device. 
     A typical injection device contains a cartridge or other reservoir of medication. This cartridge is typically cylindrical in shape and is usually manufactured in glass. The cartridge is sealed at one end with a rubber bung and at the other end by a rubber septum. The injection device is designed to deliver multiple injections. The delivery mechanism is typically powered by a manual action of the user, however, the injection mechanism may also be powered by other means such as a spring, compressed gas or electrical energy. In a preferred embodiment, the delivery mechanism comprises a spindle that engages a piston in the reservoir. In a further embodiment the spindle is a rotatable piston rod comprising two distinct threads. 
     In certain embodiments where the medicated module contains a single dose of a medicament, the module is attached to a drug delivery device in order to administer the single dose in the reservoir to a patient. In other words, the medicated module cannot be used as a stand-alone injection device. This is because the module does not have a dose delivery mechanism and instead relies on the dose delivery mechanism contained in the drug delivery device to which it is attached. 
     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.