Patent Publication Number: US-2020289757-A1

Title: Injection Device Having Variable Dosing

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 15/545,358 filed Jul. 21, 2017, which is a U.S. National Stage of International Patent Application No. PCT/US2016/014217, filed Jan. 21, 2016, which claims the benefit of U.S. Provisional Patent Application No. 62/105,897 filed Jan. 21, 2015, U.S. Provisional Patent Application No. 62/116,836 filed Feb. 16, 2015, and U.S. Provisional Patent Application No. 62/140,023 filed Mar. 30, 2015, which are all entitled “Injection Device Having Variable Dosing” and each is incorporated by reference herein in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention generally relates to an injection device having variable dosing, and in some embodiments, to an auto-injection device having variable dosing. 
     BACKGROUND OF THE INVENTION 
     Injection devices for injection of medicaments into a patient are generally known. Such devices include, for example, traditional hypodermic needle syringes that contain a stock of medicament therein. Upon insertion of the needle under the patient&#39;s skin at an injection location, the medicament is forced out of the syringe and through the needle by depression of a plunger mechanism. 
     Self-injectors or auto-injectors like the ones disclosed in U.S. Pat. Nos. 4,553,962 and 4,378,015, and PCT Patent Application Publications WO 95/29720 and WO 97/14455 are configured to inject medicament at a rate and in a manner similar to hand-operated hypodermic syringes. 
     These injectors often are made for a single use, or alternatively to be refilled after each injection. Some refillable injectors can be refilled with a desired dosage to be injected. Upon injection, the entire loaded dosage is injected. 
     BRIEF SUMMARY OF THE INVENTION 
     In one embodiment there is an injection device for injecting medicament in a patient comprising: a housing configured to house a fluid reservoir having one of a plurality of volumes of medicament; an injection conduit fluidly coupled to the fluid reservoir configured to define a fluid pathway from the fluid reservoir to the patient; a firing mechanism coupled to the fluid reservoir and configured to expel the medicament from the fluid reservoir through the injection conduit; a volume setting mechanism coupled to the firing mechanism and configured to be adjusted to select the one of the plurality of volumes of medicament for the firing mechanism to expel; and a dose setting mechanism configured to be adjusted to select a fraction of the one of the plurality of volumes of medicament that is injected from the injection conduit when the firing mechanism is actuated. 
     In one embodiment, the volume setting mechanism includes a nut and the firing mechanism includes a ram and a biasing member, the nut being threadably coupled to the ram, the nut being releaseably retained against a force of the biasing member in an initial position by a latch. In one embodiment, the nut includes a plurality of indentations each configured to engage with a projection of the latch. In one embodiment, each of the plurality of indentations includes a ring shaped groove extending circumferentially around the nut. In a further embodiment, the injection device comprises a guard that is slideably coupled to the housing, wherein the guard is configured to release the latch from the nut. In a further embodiment, the injection device comprises a biasing member coupled to the guard and configured to bias the guard toward a distal end of the injection device, the guard configured to extend axially past the injection conduit. 
     In one embodiment, the guard extends further distally in a locked position than in an initial position. In one embodiment, the nut is rotatable relative to the latch. In one embodiment, the nut is configured to couple to the latch in one of a plurality of positions along an axial length of the nut, each of the plurality of positions along the axial length of the nut corresponding to one of the plurality of volumes of medicament for the firing mechanism to expel. In one embodiment, the volume setting mechanism includes a ram extension threadably coupled to the ram, the ram extension configured to extend the length of the ram to one of a plurality of positions corresponding to one of the plurality of volumes of medicament for the firing mechanism to expel. In one embodiment, the ram is rotatably fixed and axially moveable relative to the dose setting mechanism. 
     In one embodiment, the latch includes a latch arm releaseably retaining the nut in the initial position and a stop engaging the nut in a fired position, a distance between the latch arm and the stop being fixed. In one embodiment, the volume setting mechanism includes a retainer and a latch and the firing mechanism includes a ram and a biasing member, the latch being coupled between the biasing member and the ram, the latch being retained against a force of the biasing member in an initial position by the retainer. In a further embodiment, the injection device comprises a stop having a plurality of axially extending and radially projecting slots each extending a different axial depth, wherein the ram includes a wing extending radially from the ram and configured to engage one of the plurality of slots in a fired position. 
     In one embodiment, the stop and the retainer are integrally connected. In one embodiment, the dose setting mechanism is rotatably coupled to the ram to radially align the wing with one of the plurality of slots in the initial position. In one embodiment, the ram includes a prime screw threadably coupled to the end of the ram, the prime screw configured to couple the ram to a piston. In one embodiment, the ram remains in contact with the piston independent of the position of the dose setting mechanism. In one embodiment, the latch includes a plurality of axially spaced indentations each configured to engage with a projection of the retainer. In a further embodiment, the injection device comprises a guard that is slideably coupled to the housing, wherein the guard includes a sidewall configured to prevent radial motion of the retainer in the initial position and an aperture in the sidewall configured to allow radial motion of the retainer in a retracted position. 
     In one embodiment, the ram is rotatably fixed and axially moveable relative to the dose setting mechanism. In one embodiment, the dose setting mechanism includes a shaft extending partially into and radially keyed with an inner shaft of the ram in the initial position and a fired position. In one embodiment, the latch is axially fixed and rotatably moveable relative to the ram. In one embodiment, the firing mechanism includes a spring and the position of the spring being independent from the position of the dose setting mechanism. In one embodiment, the dose setting mechanism includes a knob rotatably coupled to the housing. In a further embodiment, the injection device comprises a guard slideably coupled to the housing and configured to extend axially past the injection conduit and lock relative to the housing after removing the injection conduit from the patient. 
     In one embodiment, the injection conduit comprises a needle. In a further embodiment, the injection device comprises a syringe containing the fluid reservoir, wherein the needle is fixed to the syringe. In one embodiment, the injection device is configured to prevent resetting after the firing mechanism is actuated so as to prevent a subsequent injection of the medicament by the injection device, thereby configuring the injection device as a single-use injector. In a further embodiment, the injection device comprises a safety cap coupled to a distal end of the housing, the safety cap being coupled to the firing mechanism such that decoupling the safety cap from the housing allows the firing mechanism to advance a predetermined distance relative to the fluid reservoir to prime the fluid reservoir. In one embodiment, actuating the dose setting mechanism advances the firing mechanism a predetermined distance relative to the fluid reservoir to prime the fluid reservoir. In one embodiment, the firing mechanism is configured to deliver each of the selected fraction of the one of the plurality of volumes of medicament over a generally equal amount of time as compared to one another. In one embodiment, the fraction is only greater than or equal to 0.5. In one embodiment, the selected fraction results in a residual volume remaining in the fluid reservoir after delivery of 0.18 ml or less. 
     In another embodiment, there is an injection device for injecting medicament in a patient comprising: a firing mechanism having an actuator and configured to be selectively preset during assembly to one of a plurality of positions based on a maximum volume of medicament to be delivered to the patient; and a dose setting mechanism configured to be selectably adjusted upon use, independent of the preset of the firing mechanism, to select a fraction of the maximum volume of medicament to be delivered to the patient. 
     In another embodiment there is an injection device for injecting medicament in a patient comprising: a housing configured to house a fluid container having a piston and a fluid reservoir having one of a plurality of volumes of medicament, the fluid container including an injection conduit fluidly coupled to the fluid reservoir defining a fluid pathway from the fluid reservoir to the patient; a ram coupled to the piston and configured to expel the medicament from the fluid reservoir through the injection conduit; a spring biasing the ram toward the fluid container in an initial position; a nut threadably coupled to the ram, the nut having a plurality of ring shaped grooves or projections; a latch fixed relative to the housing and engaging a predetermined one of the plurality of ring shaped grooves or projections to retain the ram in one of a plurality of axial positions against a force of the spring in the initial position, the nut being rotatable relative to the latch in the initial position; and a dose setting knob rotatably coupled to the housing and rotatably fixed and axially moveable relative to the ram in the initial position. 
     In another embodiment there is an injection device for injecting medicament in a patient comprising: a housing configured to house a fluid container having a piston and a fluid reservoir having one of a plurality of volumes of medicament, the fluid container including an injection conduit fluidly coupled to the fluid reservoir defining a fluid pathway from the fluid reservoir to the patient; a ram coupled to the piston and configured to expel the medicament from the fluid reservoir through the injection conduit, the ram having a radially extending wing; a latch axially fixed and rotatably moveable relative to the ram, the ram having a plurality of radial features; a spring biasing the latch toward the fluid container in an initial position; a retainer fixed relative to the housing and engaging a predetermined one of the plurality of radial features to retain the ram in one of a plurality of axial positions against a force of the spring in the initial position; a stop having a plurality of axially extending and radially projecting slots each extending a different axial depth, the ram being rotatable to align the wing with one of the plurality of slots in the initial position and the wing configured to engage the one of the plurality of slots in a fired position; and a dose setting knob rotatably coupled to the housing, the ram being rotatably fixed and axially moveable relative to the dose setting knob. 
     In another embodiment there is a method for assembling an injection device comprising: inserting a fluid container having a fluid reservoir including one of a plurality of volumes of medicament into a housing, the fluid container including an injection conduit fluidly coupled to the fluid reservoir defining a fluid pathway from the fluid reservoir to the patient; setting a volume setting mechanism based on a size of the one of the plurality of volumes of the medicament; coupling the volume setting mechanism to a firing mechanism; and coupling the firing mechanism to the fluid reservoir, the firing mechanism configured to expel the medicament from the fluid reservoir through the injection conduit, the firing mechanism being coupled to a dose setting mechanism configured to select all or a fraction of the one of the plurality of volumes of medicament that is injected from the injection conduit when the firing mechanism is actuated. 
     In another embodiment there is an injection device for injecting medicament in a patient comprising: a housing configured to house a fluid reservoir; an injection conduit fluidly coupled to the fluid reservoir defining a fluid pathway from the fluid reservoir to the patient; a firing mechanism coupled to the fluid reservoir and configured to expel the medicament from the fluid reservoir through the injection conduit; and a safety cap coupled to a distal end of the housing, the safety cap being coupled to the firing mechanism such that decoupling the safety cap from the housing allows the firing mechanism to advance a predetermined distance relative to the fluid reservoir to prime the fluid reservoir. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
       The following detailed description of embodiments of the injection device having variable dosing will be better understood when read in conjunction with the appended drawings of exemplary embodiments. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities shown. 
       In the drawings: 
         FIG. 1  is a side view of an injection device in accordance with an exemplary embodiment of the present invention; 
         FIG. 2  is an exploded perspective view of the injection device of  FIG. 1 ; 
         FIG. 3A  is a first side view of the injection device of  FIG. 1 ; 
         FIG. 3B  is a cross sectional side view of the injection device shown in  FIG. 3A  taken along a plane indicated by line A-A; 
         FIG. 3C  is a second side view of the injection device of  FIG. 1  turned 90 degrees from the view shown in  FIG. 3A ; 
         FIG. 3D  is a cross sectional side view of the injection device shown in  FIG. 3C  taken along a plane indicated by line B-B; 
         FIG. 3E  is a cross sectional top view of the injection device shown in  FIG. 3C  taken along a plane indicated by line  3 E- 3 E; 
         FIG. 4A  is a second side view of the injection device of  FIG. 1 ; 
         FIG. 4B  is a cross sectional side view of the injection device shown in  FIG. 4A  taken along a plane indicated by line B-B; 
         FIG. 4C  is an enlarged cross sectional side view of a portion of the injection device shown in  FIG. 4B  within the circled area; 
         FIG. 4D  is an enlarged cross sectional side view of a portion of the injection device shown in  FIG. 4C  within the circled area; 
         FIG. 5A  is a first side view of the injection device of  FIG. 1  shown with the housing removed and in the un-primed position; 
         FIG. 5B  is a second side view of the injection device of  FIG. 1  shown with the housing removed, turned 90 degrees from the first side view shown in  FIG. 5A  and shown in the un-primed position; 
         FIG. 5C  is a cross sectional side view of the injection device shown in  FIG. 5B  taken along a plane indicated by line B-B; 
         FIG. 5D  is a second side view of the injection device of  FIG. 1  shown in the primed position; 
         FIG. 5E  is a cross sectional side view of the injection device shown in  FIG. 5D  taken along a plane indicated by line C-C; 
         FIG. 5F  is a top view of the injection device shown in  FIG. 5D ; 
         FIG. 6A  is a side view of the injection device of  FIG. 1  shown in the initial position; 
         FIG. 6B  is a cross sectional side view of the injection device shown in  FIG. 6A  taken along a plane indicated by line I-I; 
         FIG. 7A  is a side view of the injection device of  FIG. 1  shown in the minimum dose position; 
         FIG. 7B  is a cross sectional side view of the injection device shown in  FIG. 7A  taken along a plane indicated by line A-A; 
         FIG. 8A  is a side view of the injection device of  FIG. 1  shown in the insertion position; 
         FIG. 8B  is a cross sectional side view of the injection device shown in  FIG. 8A  taken along a plane indicated by line J-J; 
         FIG. 9A  is a side view of the injection device of  FIG. 1  shown in the released position; 
         FIG. 9B  is a cross sectional side view of the injection device shown in  FIG. 9A  taken along a plane indicated by line K-K; 
         FIG. 10A  is a side view of the injection device of  FIG. 1  shown in the fired position; 
         FIG. 10B  is a cross sectional side view of the injection device shown in  FIG. 10A  taken along a plane indicated by line L-L; 
         FIG. 11A  is a side view of the injection device of  FIG. 1  turned 90 degrees from the side view of  FIG. 10A ; 
         FIG. 11B  is a cross sectional side view of the injection device shown in  FIG. 11A  taken along a plane indicated by line M-M; 
         FIG. 12A  is a side view of the injection device of  FIG. 1  shown in the locked out position; 
         FIG. 12B  is a cross sectional side view of the injection device shown in  FIG. 12A  taken along a plane indicated by line N-N; 
         FIGS. 13A-13C  are views of the injection device of  FIG. 1  shown in the initial position with the housing removed; 
         FIGS. 14A-14C  are views of the injection device of  FIG. 1  shown in the insertion position with the housing removed; 
         FIGS. 15A-15C  are views of the injection device of  FIG. 1  shown in the released position with the housing removed; 
         FIGS. 16A-16C  are views of the injection device of  FIG. 1  in the fired position with the housing removed; 
         FIG. 17  is an illustration of the mechanical advantage of the latch of the injection device of  FIG. 1 ; 
         FIGS. 18A-18D  are various views of a ram of the injection device of  FIG. 1 ; 
         FIGS. 19A and 19B  are side views of an injection device in accordance with an exemplary embodiment of the present invention; 
         FIGS. 19C and 19D  are side cross sectional views of the injection device of  FIGS. 19A and 19B  respectively; 
         FIG. 20A  is a first exploded perspective view of the injection device of  FIG. 19A ; 
         FIG. 20B  is a second exploded perspective view of the injection device of  FIG. 19A ; 
         FIGS. 21A-21C  are various side views of the latch, ram and slot stop of the injection device of  FIG. 19A ; 
         FIGS. 22A-22F  are various views of the slot stop of the injection device of  FIG. 19A ; 
         FIGS. 23A-231  includes various views of the ram and the ram and dose knob assembly of the injection device of  FIG. 19A ; 
         FIGS. 24A-24E  are various side and perspective views of the injection device of  FIG. 19A  with the housing and other components removed in the initial, untriggered position; 
         FIGS. 25A-25E  are various side and perspective views of the injection device of  FIG. 19A  with the housing and other components removed in the insertion or retraction position; 
         FIGS. 26A-26D  are various side and perspective views of the injection device of  FIG. 19A  with the housing and other components removed in the triggered position; 
         FIGS. 27A-27D  are various side and perspective views of the injection device of  FIG. 19A  with the housing and other components removed in the locked out position; 
         FIGS. 28A-28C  are various views of the ram and slot stop of the injection device of  FIG. 19A  shown in the minimum dose setting before the dose is delivered; 
         FIG. 29  is a perspective view of the ram and slot stop of  FIGS. 28-28C  shown after the dose is delivered; 
         FIGS. 30A-30C  are various views of the ram and slot stop of the injection device of  FIG. 19A  shown in the maximum dose setting before the dose is delivered; 
         FIGS. 31A-31B  are side and side cross-sectional views respectively of the ram and slot stop of  FIGS. 30A-30C  shown after the dose is delivered; 
         FIG. 32  is a perspective view of a safety cap having a spacer for use with the injection device of  FIG. 19A ; 
         FIGS. 33A-33D  are cross sectional side views of the injection device of  FIG. 19A  having the safety cap shown in  FIG. 32 ; 
         FIGS. 34A and 34B  are cross sectional side views of on the injection device of  FIG. 19A  having a priming release pin; 
         FIGS. 35 a  and 35 b    are cross sectional sketches of the latch, slot stop and guard of the injection device of  FIG. 19A  illustrating a priming configuration; 
         FIG. 36  is a side cross sectional sketch of the injection device of  FIG. 19A  having an expandable ram for priming; 
         FIG. 37  is a perspective view of a latch for an injection device in accordance with an exemplary embodiment of the present invention; 
         FIGS. 38A and 38B  are side views of a lock-out system for an injection device in accordance with an exemplary embodiment of the present invention with the outer housing removed and shown in an initial position; 
         FIGS. 39A, 39B and 39C  are various views of a guard of the injection device of  FIGS. 38A and 38B ; 
         FIG. 40  is an enlarged side view of the front retainer retaining the guard shown within circle A of  FIG. 38A ; 
         FIGS. 41A and 41B  are side views of a sleeve of the injection device of  FIGS. 38A and 38B ; 
         FIG. 42  is a side view of the front retainer and guard of  FIG. 40  shown in a release position after the dose has been delivered; and 
         FIGS. 43A and 43B  are side views of the guard, sleeve and front retainer and the guard and the sleeve respectively of the injection device of  FIGS. 38A and 38B  rotated 90 degrees from the view shown in  FIG. 42  and with the guard extended and in the locked out position. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring to the drawings in detail, wherein like reference numerals indicate like elements throughout, there is shown in  FIGS. 1-18D  an injection device, generally designated  110 , a first exemplary embodiment of the present invention. Various embodiments of the injection device  110  are described in further detail below in reference to the exemplary embodiment shown in the figures. 
     The injection device  110  is configured to deliver a selected amount of one of a plurality of predetermined volumes of medicament to a patient. The injection device  110  is assembled using one of a plurality of fluid reservoirs and the dose that is ultimately delivered to the patient is equal to or less than the full amount contained in the injection device  110 . This allows for the injection device  110  to accept fluid cartridges, prefilled syringes or similar containers being filled to different volumes and/or multiples sizes of fluid containers and then allows for the user to select how much of the fluid in the fluid container to deliver. Such flexibility allows for one device to be adapted for multiple medicament volumes and ultimately reduces the amount of wasted medicament. 
     For example, a typical injection device may have a volume of 1.0 ml to encompass the range of potential dosages needed. A patient who is provided a 1.0 ml device but only needs a dosage of 0.5 ml, would leave a residual volume of 0.5 ml in the discarded device. Instead, the patient, requiring a dosage of 0.5 ml, can be provided a 1.0 ml injection device  110  containing 0.6 ml of fluid, resulting in a residual volume of only 0.1 ml in the discarded device. By allowing adjustment of the volume, the manufacturer can easily set the injection device  110  to one of a plurality of volumes to divide up the range of dosages selectable by a patient and reduce the amount of residual fluid left in the discarded device. 
     The injection device  110  includes an actuator for driving fluid from the injection device  110  into the patient. In some embodiments, the actuator is automatically actuated as a result of positioning the injection device  110  relative to the skin surface, also referred to as an auto-injection device. The injection device  110  may include a needle. In other embodiments, the injection device does not include a needle and the injection port of the fluid chamber preferably defines a fluid pathway in fluid communication with the fluid chamber for injecting medicament as a jet from the chamber through the port to the injection location. An example of a suitable needle-free jet nozzle arrangement is disclosed in U.S. Pat. No. 6,309,371, which is incorporated by reference in its entirety. 
     As disclosed in further detail below, in some embodiments, the injection device  110  includes a firing mechanism having an actuator, a volume setting mechanism configured to be selectively preset during assembly to one of a plurality of positions based on a maximum volume of medicament to be delivered to the patient (e.g., one of a 0.4 ml, 0.6 ml, 0.8 ml or 1.0 ml prefilled syringe) and a dose setting mechanism configured to be selectably adjusted upon use, independent of the preset of the volume setting mechanism, to select a fraction of the maximum volume of medicament to be delivered to the patient (e.g., a 0.2 ml to 0.4 ml dose for a 0.4 ml syringe). 
     Referring to  FIG. 1 , the injection device  110  may include a housing  112 . The housing  112  extends along a longitudinal axis A and is configured to be held in one hand of a patient or caregiver to deliver the dose of medicament to the patient. In one embodiment, the housing  112  is cylindrical. In other embodiments, the cross sectional shape of the housing  112  is elliptical, triangular, square or any other desired shape. The housing  112  may include one or more windows  112   a ,  112   b  for viewing components of the injection device  110  contained within the housing  112 . The windows  112   a ,  112   b  may be covered with a transparent material. Windows  112   a ,  112   b  may allow the viewing of the fluid reservoir  118  within the housing  112 . The window  112   a ,  112   b  may also allow viewing of the preset volume that has been chosen. In another embodiment, the window  112   a ,  112   b  allows viewing that the injection device  110  is ready for use. In another embodiment, the window  112   a ,  112   b  allows viewing that the injection is complete. Other uses of a window to allow viewing internal aspects of the injection device are anticipated. In an embodiment, the window  112   a ,  112   b  allows viewing of injection device internal components that assist in administering an injection. In one embodiment, the housing  112  is comprised partially or entirely of a transparent material. 
     Referring to  FIG. 3B , the housing  112  is configured to house a fluid reservoir  118  having one of a plurality of volumes of medicament. The desired volume of the fluid reservoir  118  is selected before assembling the injection device  110 . In one embodiment, the desired volume of the fluid reservoir  118  is based on the desired maximum dose that the patient will be able to inject. In one embodiment, the injection device  110  is configured to receive one sized container or syringe having a fluid reservoir  118  configured to accommodate a plurality (e.g., four) different maximum volumes for injection. In other embodiments, the injection device  110  is configured to receive a fluid reservoir configured to accommodate two, three, or five or more different maximum volumes for injection. In other embodiments, the injection device  110  is configured to receive one of four differently sized containers having a fluid reservoir  118 . In other embodiments, the injection device  110  is configured to receive one of two, three, five or more differently sized containers having fluid reservoirs  118 . In one embodiment, the fluid reservoir  118  contains one of 0.4 ml, 0.6 ml, 0.8 ml, or 1.0 ml of medicament. In other embodiments, the fluid reservoir  118  contains other amounts of medicament such as one or more of the following amounts: 0.04 ml, 0.05 ml, 0.06 ml, 0.07 ml, 0.08 ml, 0.09 ml, 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.5 ml, 0.6 ml, 0.7 ml, 0.8 ml 0.9 ml, 1.0 ml, 1.1 ml, 1.2 ml, 1.3 ml, 1.4 ml, 1.5 ml, 1.6 ml, 1.7 ml, 1.8 ml, 1.9 ml, 2.0 ml, greater than 2.0 ml, less than 0.010 ml and any amount between these numbers. In one embodiment, the fluid reservoir  118  includes a prefilled syringe having a piston  120  forming a sliding seal at a proximal end. An injection conduit  122  is fluidly coupled to the fluid reservoir defining a fluid pathway from the fluid reservoir to the patient. In one embodiment, the injection conduit  122  is a needle. The needle  122  may be staked to the prefilled syringe. 
     Referring to  FIG. 3B , the needle  122  may be covered by a needle cap  124  in the stowed or initial position. The needle cap  124  may include an elastomeric material for sealing and protecting the needle  122  in the initial position. Referring to  FIG. 1 , the injection device  110  may further or alternatively include a safety cap  114  that is releaseably coupled to a distal end  110   a  of the injection device  110 . The safety cap  114  covers the injection conduit  118  in the initial position to prevent contamination and accidental needle sticks or actuation of the actuator. The safety cap  114  may be coupled to the needle cap  124  such that removing the safety cap  114  from the housing  112  also strips the needle cap  124  from the needle  122  and exposes the needle  122 . 
     The injection device  110  may include a firing mechanism coupled to the fluid reservoir  118  and configured to expel the medicament from the fluid reservoir  118  through the injection conduit  122  (see  FIG. 3B ). The firing mechanism may include an actuator such as a biasing member  126 . In one embodiment, the biasing member  126  includes a compression spring. In another embodiment, the actuator is pneumatically driven. The biasing member  126  may be operatively associated with a ram  128  extending along the longitudinal axis A. The ram  128  may include a keyed proximal end  128   a  and one or more male or female threads  128   b . The ram  128  may include a pair of diametrically opposed threadless portions  128   e  extending along the length of the ram  128  (see  FIGS. 18A-18D ). In one embodiment the threadless portion  128   e  may serve as a keyed feature to transfer torque or provide location to an adjacent component. The threadless portions  128   e  may be recessed relative to the threads  128   b  to allow for a flash or other manufacturing artifact to exist on the threadless portion  128   e  without interfering with the use of the threads  128   b . The ram  128  may be coupled to the fluid reservoir  118  such that the biasing member  126  urges the ram  128  to compress the fluid reservoir  118  and deliver the medicament to the patient through the injection conduit  122 . In one embodiment, the ram  128  is coupled to the piston  120 . The ram  128  may include a projection  128   c  extending distally for supporting the engagement between the ram  128  and the piston  120  (see  FIG. 3B ). 
     Referring to  FIGS. 4A-4D , the volume setting mechanism may be set to provide the one of the plurality of volumes of medicament. The volume setting mechanism may include a nut  130  that is releaseably retained in the axial direction against a force of the biasing member  126  in an initial position by a latch  132  (see  FIG. 3B ). The latch  132  may include a projection  132   a  that engages a corresponding indent  130   a  in the nut  130  to prevent axial movement of the nut  130  in the initial position. 
     The nut  130  may include a plurality of indentations  130   a  each configured to engage with the projection  132   a  of the latch. Each of the plurality of indentations may be axially spaced from one another. Each of the plurality of indentations  130   a  of the nut  130  may include a ring shaped groove extending circumferentially around the nut  130 . The nut  130  may be rotatable relative to the latch  132 . In some embodiments, providing ring shaped grooves and allowing the nut  130  to rotate relative to the latch  132  allows for the dose setting mechanism  116  to rotate the ram  128  relative to the nut  130  and therefore axially move the ram  128  as discussed further below. During assembly of the injection device  110 , the nut  130  is configured to couple to the latch  132  in one of a plurality of positions along an axial length of the nut  130 , each of the plurality of positions along the axial length of the nut  130  corresponding to one of the plurality of volumes of medicament for the firing mechanism to expel. 
     The nut  130  may be configured to engage a stop fixed relative to the fluid delivery device  110  at the end of the delivery stroke as discussed below. As a result, the distance the ram  128  extends distally from the nut  130 , in some embodiments, is set to correspond to the volume of the fluid reservoir  118  (e.g., the axial distance between the piston  120  and the nut  130 ). For example, the position of the latch  132  relative to the nut  130  in the position illustrated in  FIGS. 4B-4D  corresponds to a volume of a 0.6 ml fluid reservoir  118 . If a 0.4 ml fluid reservoir  118  is used, then the nut  130  may be rotated distally down the ram  128  until the next higher indent  130   a  of the nut  130  aligns with the projection  132   a  of the latch  132 . If a 0.8 ml fluid reservoir  118  is used, then the nut  130  may be rotated proximally up the ram  128  until the next lower indent  130   a  of the nut  130  aligns with the projection  132   a  of the latch  132 . 
     The latch  132  may include a sleeve  132   d  surrounding the nut  130  and axially fixed relative to the fluid reservoir  118 . The latch  132  may include a pivot arm  132   c  that is pivotably connected to the sleeve  132   d  and configured to radially move the projection  132   a  out of the axial path of the nut  130  in the firing or released position (see  FIG. 9B ). In one embodiment, the pivot arm  132   c  is prevented from pivoting in an initial position by a radial stop  140   e  (see  FIG. 2 ). The latch  132  may include a slanted surface  132   b  that engages with a corresponding slanted surface  140   d  in the released position (see also  FIG. 17 ). Once the latch  132  is disengaged from the nut  130 , the nut  130  and the threadably engaged ram  128  are released axially and fired distally by the biasing member  126 . In other embodiments, the latch  132  and nut  130  have the reverse mating relationship described above such that the latch  132  includes a feature that engages with one of a plurality of projections from the nut  130 . 
     Referring to  FIG. 4B , the direct force of the biasing member  126  upon triggering may be borne by the latch  132 . In an embodiment, the latch  132  includes a stop  132   e  to attenuate the shock resulting from the stoppage of the firing mechanism at the termination of the injection stroke. The stop  132   e  may be a radially inwardly extending flange. At the end of delivery stroke (see  FIGS. 9B and 10B ) the nut  130  may engage the stop  132   e . In one embodiment, the stop  132   e  includes a resilient feature. In one embodiment, the resilient feature of the stop  132   e  includes a spring. In another embodiment, the resilient feature of the stop  132   e  includes an elastomeric washer. 
     In one embodiment, setting the volume by coupling the nut  130  to the latch  132  at one of a plurality of locations results in an adjustment of the spring force by biasing member  126 . By moving the nut  130  axially relative to the latch  132  to set the volume, the biasing member  126  may be more compressed for the larger volumes and less compressed for the smaller volumes. The rate of delivery for a larger dose may therefore be higher than the rate of delivery for a smaller dose resulting in a generally equal amount of time to deliver each dose. In some embodiments, the delivery time is not equal for each dose but closer to being equal than if the rate of delivery was instead constant. Referring to Table 1 below for example, a dose of 1.0 ml may be delivered in approximately 7-10 seconds and a dose of 0.6 ml may be delivered in approximately 6-9 seconds. Such a configuration, where the variability between delivery times for each dose is minimized, may be desirable for compliance. For example, a patient who starts a treatment at a lower volume may be accustomed to waiting a certain amount of time to deliver a dose and be inclined to wait the same amount of time even if the treatment is adjusted to a higher volume. An amount of spring decay may be selected such that any differences in injection time between volumes do not result in improper use of the device. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Range of delivery times 
               
            
           
           
               
               
               
            
               
                   
                 Delivered Vol. 
                 Injection time range 
               
               
                   
                 (ml) 
                 (sec) 
               
               
                   
                   
               
               
                   
                 1.0 
                  7-10 
               
               
                   
                 0.8 
                 7-9 
               
               
                   
                 0.6 
                 6-8 
               
               
                   
                 0.4 
                 5-8 
               
               
                   
                 0.2 
                 4-7 
               
               
                   
                   
               
            
           
         
       
     
     It may be desirable to provide a spring with a spring force decay curve where such that the difference in injection time between the volumes is such that the user does not perceive a significant difference. 
     In another embodiment, rather than or in addition to the nut  130  having a plurality of predetermined positions, the volume setting mechanism includes a ram extension (not shown) threadably coupled to the ram  128 . The ram extension may be configured to extend the length of the ram  128  to a plurality of axial positions during assembly corresponding to one of the plurality of volumes of medicament for the firing mechanism to expel. 
     Referring to  FIG. 2 , the injection device  110  may include a dose setting mechanism  116  configured to select a fraction of the one of the plurality of volumes of medicament that is injected from the injection conduit  122  when the firing mechanism is actuated. The dose setting mechanism  116  may include a knob rotatably coupled to the housing. In one embodiment, the dose setting mechanism  116  caps the proximal end of the housing  112 . The dose setting mechanism  116  may include a grip portion  116   a  for grasping by the patient. The grip portion  116   a  may include one or more features such as axially extending ribs  116   a  for increasing the frictional force between the dose setting mechanism  116  and a user&#39;s hand during use. The dose setting mechanism  116  may include a dosage level portion  116   b  having a plurality of dosage indicia  116   e . The dose setting mechanism  116  may include a shaft  116   c  for coupling to the ram  128 . 
     Referring to  FIGS. 3A-3D , the dose setting mechanism  116  is rotatably moveable relative to the housing  112 . In one embodiment, the dose setting mechanism  116  is fixed axially relative to the housing  112 . The dose setting mechanism  116  may be rotatably fixed and axially moveable relative to the ram  128 . The proximal end  128   a  of the ram  128  may have a keyed shape that corresponds to the shape of the inside surface  116   d  of shaft  116   c  of the dose setting mechanism  116  such that rotating the dose setting mechanism  116  rotates the ram  128 , and due to the threaded connection between the ram  128  and the axially retained nut  130 , moves the ram  128  distally and proximally depending on the direction of rotation. When the dose setting mechanism  116  is rotated, indicia  116   e  corresponding to the position of the ram  128  may align with the window  112   a  in the housing  112  to display the selected dosage to the patient. In one embodiment, rotating the dose setting mechanism  116  to move the ram  128  does not impact the position and force on the biasing member  126 . In some embodiments, the dose setting mechanism  116  includes a resistance and/or an audible click between selected dosages. 
     Referring to  FIG. 6B , the biasing member  126  such as a spring may be uniform and configured to not buckle. In one embodiment, there is no direct spring load on the ram  128  from the biasing member  126  in the initial position. This allows for the ram  128  to be axially positioned during dose setting without impacting the spring force allowing for the spring force to be the same for each different volume of medicament. 
     Referring to  FIG. 2 , the injection device  110  may configured to prevent resetting after the firing mechanism is actuated so as to prevent a subsequent injection of the medicament by the injector, thereby configuring the injection device  110  as a single-use injector. In one embodiment, the injection device  110  includes a guard  140  that is slideably coupled to the housing  112 . The injection device  110  may include a biasing member  138  coupled to the guard and configured to bias the guard  140  toward a distal end  110   a  of the injection device  110 . The guard  140  may be configured to extend axially past the injection conduit  122 . In one embodiment, the guard  140  is configured to extend axially past the injection conduit  122  and lock axially relative to the housing  112  after removing the injection conduit  122  from the patient. 
     A sleeve  134  may be coupled to the fluid reservoir  118 . The sleeve  134  may include a pair of diametrically opposed tabs  134   a  extending outwardly in the radial direction. The housing  112  may include a front retainer  136  coupled to the distal end of the housing  112 . The front retainer  136  may include a pair of axially extending slots configured to receive the tabs  134   a  of the sleeve  134 . The safety cap  114  may releaseably couple to the front retainer  136 . The biasing member  138  may be positioned within the front retainer  136  and engage the distal end of the sleeve  134 . The other end of the biasing member  138  may be configured to engage a flange proximate the distal end of the guard  140 . The guard  140  may include a pair of diametrically opposed and axially extending slots  140   c  for receiving the tabs  134   a . The axial range of motion of the guard  140  may be dictated by the ends of the slots  140   c  of the guard  140  engaging the tabs  134   a  of the sleeve  134 . The guard  140  and the sleeve  134  may include one or more openings  140   b ,  134   b  respectively for aligning with a window  112   a  of the housing  112  to reveal the level of medicament in the fluid reservoir  118 . The fluid reservoir  118  may include indicia that are visible through the window  112   a  so that the patient can verify that the appropriate volume of medicament is included in the injection device  110 . 
     Referring to  FIG. 8B , the firing mechanism may be automatically released based on the position of the injection conduit  122  relative to the patient. In one embodiment, retracting the guard  140  relative to the injection conduit  122  releases the firing mechanism. In other embodiments, the patient must actuate a button or another feature before or after retracting the guard  140 , or in an embodiment not including a guard  140 , in order to release the firing mechanism. 
     The injection device  110  may accommodate two injection volume adjustments. This may help to minimize the amount of unused drug. The first adjustment is set during assembly and sets the range of volume to be delivered (e.g., the dosing range). The dosing range may vary depending on the fill volume in the fluid reservoir  118 . This amount may be set as part of the assembly process. In one embodiment, there are four configurations or SKUs. Each SKU will represent a maximum volume of fill to allow delivery of the maximum dose within that SKU (e.g., 0.8 to 1.0 ml volume delivery to the patient; 0.6 to 0.8 ml volume delivery to the patient; 0.4 to 0.6 ml volume delivery to the patient; and 0.2 to 0.4 ml volume delivery to the patient). The second adjustment is set by the user prior to injecting the medicament. The second volume adjustment sets the dose, a fraction of the volume in the fluid reservoir  118 , and this dose to be delivered within the range allowed by the injection device  110 . In one embodiment, the user may adjust the dose, up and down, until the injection is delivered. 
     Referring to  FIGS. 5C-5F , the injection device  110  may be pre-primed for the user. In one embodiment, priming the injection device  110  allows for placing the ram  128  in a known position relative to the piston  120 . Priming may be used to reduce an initial gap between the ram  128  and the piston  120  and/or compression in the piston  120  to allow for tight control of the dose expelled during triggering. Since the ram  128  moves a fixed (controlled based on the dose selected) displacement, minimizing the variability associated with the starting position of the ram  128  and controlling the end position of the ram  128  allows for greater accuracy of the delivered dose. Also, by providing a device that is already primed, there may be greater assurance that the patient will get the correct dosing by eliminating a step that the user might have to do and therefore eliminate an opportunity for the user to get this wrong. 
     The injection device  110  may be designed for assembly that eliminates the priming step. A filling process may be utilized to minimize air bubble in the fluid reservoir  118 . Once the fluid reservoir  118  is inserted into a front assembly, including the safety cap  114 , the front retainer  136 , the guard  140  and the sleeve  134 , is coupled with a middle assembly including the ram  128 , the nut  130  and the latch  132 . The connection between the distal end  128   c  of the ram and the piston  120  may be fully secured by rotating the nut  130  relative to the ram  128 . The nut  130  may include one or more keyed features  130   b  (see  FIG. 103 b   ) such as a radially extending slot for coupling to a tool. Once the ram  128  and stopper  120  are sufficiently coupled, a rear assembly including the housing  114  may be positioned over the middle assembly and coupled to the front assembly and the dose mechanism  116  and biasing member  126  may be coupled to the middle assembly and the housing. 
     In some embodiments, the injection device  110  is primed by the user. Syringes are commonly supplied to autoinjector manufacturers in a ‘drug-prefilled’ state. The prefilling process fills the syringe with drug, and may use various methods including a vacuum process that attempts to remove as much air as possible inside the syringe chamber before a plug/stopper is placed, sealing the syringe. Bubble priming, whereby all or most of the air is expelled from the syringe chamber through the needle prior to injection, is extremely common in manual injections: a bubble in an intravenous injection can cause an air embolism in a patient. Unfortunately, bubble priming is not as simple in an autoinjector and the presence of an air bubble is detrimental to the accuracy &amp; precision of an autoinjector&#39;s drug delivery mechanism, which commonly relies upon advancing a ram abutted to the piston a tightly controlled travel distance. The bubble cannot be removed (primed) from the syringe without removing the needle cap resulting in a breach of the sterile barrier. 
     When an appreciable force is applied to a syringe piston during an injection, any bubbles remaining trapped within the syringe will compress, or displace ejected fluid decreasing the injected volume. This is due to pressure induced by the ram, the incompressible nature of liquids, and compressibility of gas. A steady-state pressure equilibrium is then reached while the liquid drug is ejected until the ram reaches the end of its stroke. At the end of the ram stroke, any previously compressed gasses will expand to equilibrium with the ambient. The rate upon which the gas expands is variable and dependent upon the ram force, the viscosity of the liquid, bubble size, needle lumen size and length, and the ambient pressure. As the bubble pressure approaches ambient, the rate of fluid expulsion decays, increasing injection time (e.g., preferably less than 10 seconds) for injectors with combined viscous drug liquid and small needle lumens. As delivered volume is related to the travel of the syringe plunger, the amount of liquid drug that is encompassed within this travel distance is required to be constant to allow accurate dispensing of drug. 
     In order to bubble prime the injection device  110 , the injection device  110  may be configured to be primed by the user by pointing the distal end  110   a  upward and advancing the ram  128  relative to the fluid reservoir  118 . By pointing the distal end  110   a  of the injection device  110  upward, buoyancy of the bubble positions it directly adjacent to the proximal end of the needle  122 . Depending upon the viscosity of the liquid, a slight tapping of the injection device  110  may be required. In some embodiments, the bubble may be observed through the window  112   b  in the housing  112 . 
     In one embodiment, the injection device  110  is configured such that removing the safety cap  114  causes the ram  128  to advance a nominal predetermined distance, expelling the bubble and potentially a small amount of liquid from the needle  122 . For example, a spacer may be provided between the latch  132  and the proximal flanged end of the fluid reservoir  118 . 
     Referring to  FIG. 36 , in some embodiments, the ram  128  is expanded to preload the piston  120 . In one embodiment, the ram  128  includes two or more nesting elements. In one embodiment, a torsional spring  142  is nested in an outer ram  144 . The torsional spring  142  may have a keyed rod  146  passing completely through the torsional spring, and rotationally constrained to the torsional spring. The keyed rod  146  may be locked by a removable release pin  148  extending from the distal end  110   b  of the injection device  110  and inserted into a keyed slot  150  of an inner ram  152  on the other end. The release pin may constrain the torsional spring until use. Upon removal, the torsional spring will rotate the inner ram relative to the outer ram, extending the inner ram to release the bubble (or provide a preload immediately prior to bubble expulsion). 
     Annular or partially annular teeth in the nested ram elements may interlock, (e.g., internal teeth on the outer cylinder/external teeth or slots on the inner cylinder) allowing only one way relative movement of the nested ram elements, inducing the ram  128  to extend and preload the piston  120 . In one embodiment, instead of teeth, the nested ram elements are internally/externally threaded, allowing preload from rotation of a device element. In one embodiment, the ram  128  includes a three part ram  128  comprised of both one way-tooth interaction and threaded interactions. 
     The spacer or ram  128  may be coupled to the safety cap  114  such that removing the safety cap  114  removes the spacer or expands the ram  128  and preloading a force onto the piston  120 . In other embodiments, the user actuates a trigger such as by pulling a pin, flipping a switch, pushing a button, that pulls the spacer out of the loading stack or device entirely or expands the ram  128 . In one embodiment, setting the dose setting mechanism  116  automatically preloads piston  120 . For example, instructions or indication to twist the dose setting mechanism  116  may be visible through window  112   a  even to set the injection device  110  to the maximum dose. This initial twist of the dose setting mechanism  116  may be used to extend the ram  128  to prime the injection device  110 . The dosage indicia  116   e  may be oriented (rotated 180 degrees from example shown in  FIG. 1 ) such that the number is readable when the distal end  110   a  of the injection device  110  is pointed up. 
     In one embodiment, removal of the safety cap  114  allows the guard  140 , under spring load, to extend a predetermined distance. This movement allows a second spring loaded assembly connected to the ram to advance a nominal distance to a predetermined set-point, inducing an axial preload on the piston  120  (see  FIGS. 32 a  and 32 b    as discussed further below). In one embodiment, the guard  140  is under a lower spring force than the firing mechanism such that coupling the priming of the injection device  110  to the guard  140  allows for the priming force to be controlled more precisely. 
     Once the safety cap  114  is removed, the fluid reservoir  118  may be bubble primed and ready for injection. A liquid receiver, such as a piece of absorbent material, may be positioned adjacent to the needle  122  toward the distal end  110   a  of the injection device  110  to capture any expelled liquid drug during priming. The liquid receiver may be in circumferential association with the needle  122  and may be attached to the housing  112 , safety cap  114  or both (e.g., 2 pieces of absorbent material). 
     Following assembly, the injection device  110  is ready for use. Referring to  FIG. 6B , during use of an exemplary embodiment, the user is aware what volume of medicament is provided in the injection device  110  and may verify by looking at the fluid reservoir  118  through the window  112   b  in the housing (see  FIG. 1 ). The user then selects the desired dose to be delivered, either all or a fraction of the volume of the fluid reservoir  118 , by rotating the dose setting mechanism  116  relative to the housing  112 . The user may verify that the appropriate dosage is selecting by viewing the dosage amount indicated by the indicia visible through window  112   a  in the housing (see  FIG. 1 ).  FIG. 7B  shows the injection device in a minimum dosage selection such that the ram  128  is pulled back from piston  120 . The distance between the piston  120  and the ram  128  is the distance that will remain between the piston  120  and the distal end of the fluid reservoir  118 . The medicament remaining in the fluid reservoir following the injection is not delivered and may be discarded. 
     Referring to  FIG. 8B , once the dosage is set, the user removes the safety cap  114  (see  FIG. 7B ) from the front retainer  136  by pulling or twisting the safety cap  114  relative to the front retainer  136 . Any priming is conducted if necessary, and the injection device  110  is ready for injection. The patient may then press the distal end of the guard  140  against their skin, retracting the guard  140  proximally until the needle  122  penetrates the skin surface and the proximal end  140   d  of the guard  140  contacts the slanted surface  132   b  of the latch  132 . 
     Referring to  FIG. 9B , once the proximal end  140   d  of the guard contacts the slanted surface  132   b  of the latch  132 , the guard is further retracted to its fully retracted position, moving the stop  140   e  off of the pivot arm  132   c  of the latch and the proximal end  140   d  of the guard forces against the slanted surface  132   b  to pivot the pivot arm  132   c  and release the projection  132   a  of the latch  132  from the indentation  130   a  of the nut  130 . 
     Referring to  FIG. 10B , with the latch  132  released from the nut  130 , the biasing member  126  is no longer restrained and the ram  128  and nut  130  are fired toward the distal end, urging the piston  120  distally and delivering the dose of medicament to the patient through the injection conduit  122 . 
     Referring to  FIGS. 12 a  and 12 b   , after the dose is delivered, the housing  112  is pulled away from the patient, pulling the needle  122  from the patient and allowing the biasing member  138  to urge the guard  140  distally past the end of the needle  122 . A retaining member retains the guard  122  to lock the guard  140  relative to the needle  122  preventing further use of the injection device  110 . The injection device  110  may then be safely discarded. 
     Referring to the drawings in detail, wherein like reference numerals indicate like elements throughout, there is shown in  FIGS. 19A-35B  an injection device, generally designated  210 , a second exemplary embodiment of the present invention. Various embodiments of the injection device  210  are described in further detail below in reference to the exemplary embodiment shown in the figures. One or more of the embodiments discussed in reference to the injection device  210  described below may be combined with one or more desirable features of the embodiments discussed in reference to the injection device  110  described above. 
     The injection device  210  is configured to deliver a selected amount of one of a plurality of predetermined volumes of medicament to a patient. The injection device  210  is assembled using one of a plurality of fluid reservoirs  218  and the dose that is ultimately delivered to the patient is equal to or less than the full amount contained in the injection device  210 . This allows for the injection device  210  to accept a fluid cartridge, prefilled syringe or similar container filled to different volumes and/or accept multiples sizes of containers and allow for the user to select how much of the fluid in the fluid container to deliver. Such flexibility allows for one device to be adapted for multiple medicament volumes and ultimately reduces the amount of wasted medicament. 
     For example, a typical injection device may have a volume of 1.0 ml to encompass the range of potential dosages needed. A patient who is provided a 1.0 ml device but only needs a dosage of 0.5 ml, would leave a residual volume of 0.5 ml in the discarded device. Instead, the patient, requiring a dosage of 0.5 ml, can be provided a 1.0 ml injection device  210  containing 0.6 ml of fluid, resulting in a residual volume of only 0.1 ml in the discarded device. By allowing adjustment of the volume, the manufacturer can easily set the injection device  210  to one of a plurality of volumes to divide up the range of dosages selectable by a patient and reduce the amount of residual fluid left in the discarded device. 
     The injection device  210  includes an actuator for driving fluid from the injection device  210  into the patient. In some embodiments, the actuator is automatically actuated as a result of positioning the injection device  210  relative to the skin surface, also referred to as an auto-injection device. The injection device  210  may include a needle. In other embodiments, the injection device does not include a needle and the injection port of the fluid chamber preferably defines a fluid pathway in fluid communication with the fluid chamber for injecting medicament as a jet from the chamber through the port to the injection location. An example of a suitable needle-free jet nozzle arrangement is disclosed in U.S. Pat. No. 6,309,371, which is incorporated by reference in its entirety. 
     As disclosed in further detail below, in some embodiments, the injection device  210  includes a firing mechanism having an actuator, a volume setting mechanism configured to be selectively preset during assembly to one of a plurality of positions based on a maximum volume of medicament to be delivered to the patient (e.g., one of a 0.4 ml, 0.6 ml, 0.8 ml or 1.0 ml prefilled syringe) and a dose setting mechanism configured to be selectably adjusted upon use, independent of the preset of the volume setting mechanism, to select a fraction of the maximum volume of medicament to be delivered to the patient (e.g., a 0.2 ml to 0.4 ml dose for a 0.4 ml syringe). 
     Referring to  FIGS. 19A-19B , the injection device  210  may include a housing  212 . The housing  212  extends along a longitudinal axis A and is configured to be held in one hand of a patient or caregiver to deliver the dose of medicament to the patient. In one embodiment, the housing  212  is cylindrical. In other embodiments, the cross sectional shape of the housing  212  is elliptical, triangular, square or any other desired shape. The housing  212  may include one or more windows  212   a ,  212   b  for viewing components of the injection device  210  contained within the housing  212 . The windows  212   a ,  212   b  may be covered with a transparent material. Windows  212   a ,  212   b  may allow the viewing of the fluid reservoir within the housing  212 . The window  212   a ,  212   b  may also allow viewing of the preset volume that has been chosen. In another embodiment, the window  212   a ,  212   b  allows viewing that the device is ready for use. In another embodiment, the window  212   a ,  212   b  allows the viewing the injection is complete. Other uses of a window to allow viewing internal aspects of the injection device are anticipated. In an embodiment, the window  212   a ,  212   b  allows viewing of injection device internal components that assist in administering an injection. In one embodiment, the housing  212  is comprised partially or entirely of a transparent material. 
     Referring to  FIGS. 19C-19D , the housing  212  is configured to house a fluid reservoir  218  having one of a plurality of volumes of medicament. The volume of the fluid reservoir  218  is selected before assembling the injection device  210 . In one embodiment, the volume of the selected fluid reservoir  218  is based on the desired maximum dose that the patient can inject. In one embodiment, the injection device  210  is configured to receive one sized container or syringe having a fluid reservoir  218  to accommodate a plurality (e.g., six) different maximum volumes for injection. In other embodiments, the injection device  210  is configured to receive a container having two, three, four, five, seven or more different maximum volumes for injection. In other embodiments, the injection device  210  is configured to receive six differently sized containers having fluid reservoirs  118 . In other embodiments, the injection device  210  is configured to receive two, three, four, five, six, seven or more differently sized containers having fluid reservoirs  218 . In one embodiment, the fluid reservoir  218  contains one of 0.4 ml, 0.6 ml, 0.8 ml, or 1.0 ml of medicament. In other embodiments, the fluid reservoir  218  contains other amounts of medicament such as one or more of the following amounts: 0.04 ml, 0.05 ml, 0.06 ml, 0.07 ml, 0.08 ml, 0.09 ml, 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.5 ml, 0.6 ml, 0.7 ml, 0.8 ml 0.9 ml, 1.0 ml, 1.1 ml, 1.2 ml, 1.3 ml, 1.4 ml, 1.5 ml, 1.6 ml, 1.7 ml, 1.8 ml, 1.9 ml, 2.0 ml, greater than 2.0 ml, less than 0.010 ml and any amount between these numbers. In one embodiment, the fluid reservoir  218  includes a prefilled syringe having a piston  220  forming a sliding seal at a proximal end. An injection conduit  222  is fluidly coupled to the fluid reservoir defining a fluid pathway from the fluid reservoir  218  to the patient. In one embodiment, the injection conduit  222  is a needle. The needle  222  may be staked to the prefilled syringe. 
     The needle  222  may be covered by a needle cap  224  in the stowed or initial position. The needle cap  224  may include an elastomeric material for sealing and protecting the needle  222  in the initial position. The injection device  210  may further or alternatively include a safety cap  214  that is releaseably coupled to a distal end  210   a  of the injection device  210 . The safety cap  214  covers the injection conduit  218  in the initial position to prevent contamination and accidental needle sticks or actuation of the actuator. The safety cap  214  may be coupled to the needle cap  224  such that removing the safety cap  214  from the housing  212  also strips the needle cap  224  from the needle  222  and exposes the needle  222 . 
     The injection device  210  may include a firing mechanism coupled to the fluid reservoir  218  and configured to expel the medicament from the fluid reservoir  218  through the injection conduit  222 . The injection device  210  may include an actuator such as a biasing member  226 . In one embodiment, the biasing member  226  includes a compression spring. In another embodiment, the actuator is pneumatically driven. The biasing member  226  may be operatively associated with a ram  228  extending along the longitudinal axis A. The ram  228  may include a keyed shaft  228   c  (see  FIG. 21B ). The ram  228  may be coupled to the fluid reservoir  218  such that the biasing member  226  urges the ram  228  to compress the fluid reservoir  218  and deliver the medicament to the patient through the injection conduit  222 . In one embodiment, the ram  228  is coupled to the piston  220 . The ram  228  may include a prime screw  242  extending distally from the end of the ram  228  at selectively adjustable distances to maintain contact between the ram  228  and the piston  220  for priming purposes as discussed in further detail below. 
     Referring to  FIGS. 21A-21C and 22A-22F , the volume setting mechanism may be set or configured during assembly of the injection device  210  to properly deliver the one of the plurality of volumes of medicament selected as the fluid reservoir  218 . The volume setting mechanism may include a latch  232 , a slot stop or stop  230  and a retainer  230   a . The retainer  230   a  may be configured to retain the latch  232  relative to the slot stop  230 . In one embodiment, the latch  232  is releaseably retained in the axial direction against a force of the biasing member  226  in an initial position by the retainer  230   a . The latch  232  may include a radial projection such as a flange  232   a  configured to engage the end of the biasing member  226  (see  FIG. 19C ). The latch  232  may be axially fixed and rotatably coupled to the ram  228 . The proximal end of the ram  228  may include a collar  228   d  that is rotatably received in a corresponding ring shaped groove in the latch  232 . The slot stop  230  may be axially and rotatably fixed relative to the fluid reservoir  218 . The ram  228  may include a radially extending wing  228   b  fixed to the ram  228 . In other embodiments, the ram  228  includes two or more radially extending wings. As discussed further below, the slot stop  230  may be configured to set the axial position of the ram  228  relative to the fluid reservoir  218  and limit how far the ram  228  is permitted to travel relative to the fluid reservoir  218 . 
     Referring to  FIGS. 21A-21C , the latch  232  may include a plurality of radially extending features  232   b , such as apertures, indents and/or projections, each configured to engage with the retainer  230   a . Each of the plurality of radially extending features  232   b  may be axially spaced from one another. In one embodiment, such a configuration positions the distal end of the ram  228  relative to the fluid reservoir  218 . During assembly of the injection device  210 , the retainer  230   a  is configured to couple to the latch  232  in one of a plurality of positions along an axial length of the latch  232 , each of the plurality of positions along the axial length of the latch  232  corresponding to one of the plurality of volumes of medicament of the fluid reservoir  218  for the firing mechanism to expel. In one embodiment, the latch  232  includes an additional set of radially extending features  232   b  closest to the proximal end to retain the latch  232  relative to the slot stop  230  at the end of delivery. 
     Referring to  FIG. 37 , another embodiment of the latch  332  is shown. The latch  332  may include a single, radially extending feature  332   b  configured to engage with the retainer  230   a . In one embodiment, the radially extending feature  332   b  is a window or cut-out. The axial depth or height of the radially extending feature  332   b  may be predetermined, and one of a plurality of latches  332  is selected based on the axial depth or height of its radially extending feature  332   b . The latch  332  that is selected will depend on the desired one of the plurality of volumes of medicament of the fluid reservoir  218  for the firing mechanism to expel. The latch  332  may include one or more alignment features  332   d  that engage a corresponding feature of the housing to prevent the latch  332  from rotating relative to the housing during firing. In one embodiment, the alignment features  332   d  include a plurality of opposed and axially spaced projections that are configured to engage a rib extending axially and projecting radially inward from the housing. 
     Referring to  FIGS. 21A-21C , the wing  228   b  of the ram  228  may be configured to engage a stop fixed relative to the fluid delivery device  210  at the end of the delivery stroke as discussed below. As a result, the distance the ram  228  extends distally from a bottom surface  230   h  of the slot stop  230 , in some embodiments, is set to correspond to the volume of the fluid reservoir  218  (e.g., the axial distance between the piston  220  and the bottom surface  230   h  of the slot stop  230 ). For example, the position of the latch  232  relative to the slot stop  230  in the maximum position illustrated in  FIGS. 21A-21C  corresponds to a volume of a 1.0 ml fluid reservoir  218 . If a 0.8 ml fluid reservoir  218  is used for example, then the slot stop  230  may be move proximally relative to the latch  232  to engage the projection  230   c  of the retainer  230   a  with the next proximal radially extending feature  232   b  of the latch  232  and extend the ram  228  further toward the distal end  210   a  of the injection device  210 . 
     Referring to  FIGS. 22A-22F , the retainer  230   a  may be integrally formed with the slot stop  230 . In other embodiments, the retainer  230   a  is a separate component from slot stop  230 . The retainer  230   a  may be a cantilever arm. In one embodiment the retainer  230   a  has one or more circumferentially extending protections to form an upside down capital letter T or Y shape. In one embodiment, two or more retainers  230   a  are provided. In one embodiment, two diametrically opposed retainers  230   a  are provided. The retainer  230   a  may be configured to radially deflect inward about an inflection point  230   e . In one embodiment, inflection point  230   e  includes a groove or recess to help facility bending of the material. The retainer  230   a  may include a projection  230   c  that engages a corresponding radially extending feature  232   b  (see  FIG. 21A ) to prevent axial movement of the latch  232  in the initial position. The projection  230   c  may include a sloped top surface  230   d  to help facilitate translating the axial force exerted on the retainer  230   a  into a radial deflection of the retainer  230   a  to move the projection  230   c  from interfering with axial motion of the latch  232  in the triggered or released position. 
     Once the latch retainer  230   a  is disengaged from the latch  232 , the latch  232  and ram  228  are released axially and fired distally by the biasing member  226 . In other embodiments, the latch  232  and retainer  230   a  have the reverse mating relationship to the configuration described above such that the radially extending features  232   b  are protrusions that are engageable by an indent or aperture in the retainer  230   a.    
     In one embodiment, setting the volume by coupling the slot stop  230  to the latch  232  at one of a plurality of locations results in an adjustment of the spring force by biasing member  226 . By moving the slot stop  230  axially relative to the latch  232  to set the volume, the biasing member  226  may be more compressed for the larger volumes and less compressed for the smaller volumes. The rate of delivery for a larger dose may therefore be higher than the rate of delivery for a smaller dose resulting in a generally equal amount of time to deliver each dose. In some embodiments, the delivery time is not equal for each dose but closer to being equal than if the rate of delivery was instead constant. Referring to  FIG. 2  for example, a dose of 1.0 ml may be delivered in approximately 7-10 seconds and a dose of 0.6 ml may be delivered in approximately 6-9 seconds. Such a configuration, where the variability between delivery times for each dose is minimized, may be desirable for compliance. For example, a patient who starts a treatment at a lower volume may be accustomed to waiting a certain amount of time to deliver a dose and be inclined to wait the same amount of time even if the treatment is adjusted to a higher volume. An amount of spring decay may be selected such that any differences in injection time between volumes do not result in improper use of the device. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Range of delivery times 
               
            
           
           
               
               
               
            
               
                   
                 Delivered Vol. 
                 Injection time range 
               
               
                   
                 (ml) 
                 (sec) 
               
               
                   
                   
               
               
                   
                 1.0 
                  7-10 
               
               
                   
                 0.8 
                 7-9 
               
               
                   
                 0.6 
                 6-8 
               
               
                   
                 0.4 
                 5-8 
               
               
                   
                 0.2 
                 4-7 
               
               
                   
                   
               
            
           
         
       
     
     It may be desirable to provide a spring with a spring force decay curve where such that the difference in injection time between the volumes is such that the user does not perceive a significant difference. 
     Referring to  FIGS. 19C-20B , the injection device  210  may include a dose setting mechanism  216  configured to select a fraction of the one of the plurality of volumes of medicament that is injected from the injection conduit  222  when the firing mechanism is actuated. The dose setting mechanism  216  may include a knob rotatably coupled to the housing. In one embodiment, the dose setting mechanism  216  caps the proximal end of the housing  212 . The dose setting mechanism  216  may include a grip portion  216   a  for grasping by the patient. The grip portion  216   a  may include one or more features such as axially extending and radially projecting ribs  216   a  for increasing the frictional force between the dose setting mechanism  216  and a user&#39;s hand during use. The dose setting mechanism  216  may include a dosage level portion  216   b  having a plurality of dosage indicia  216   e . The dose setting mechanism  216  may include a shaft  216   d  for coupling to the ram  228 . 
     Referring to  FIGS. 19C-19D and 24A-24E , the dose setting mechanism  216  may be rotatably moveable relative to the housing  212 . In one embodiment, the dose setting mechanism  216  is fixed axially relative to the housing  212 . The dose setting mechanism  216  may be rotatably fixed and axially moveable relative to the ram  228 . The interior shaft  228   c  (see  FIGS. 21B and 23 ) of the ram  228  may have a keyed shape that corresponds to the shape (such as projections  216   f ) of the shaft  216   d  of the dose setting mechanism  216  such that rotating the dose setting mechanism  216  rotates the ram  228 , and rotates the wing  228   b  relative to the slot stop  230  (see  FIG. 28C ). When the dose setting mechanism  216  is rotated, indicia  216   e  corresponding to the radial position of the wing  228   b  may align with the window  212   a  in the housing  212  to display the selected dosage to the patient. In one embodiment, rotating the dose setting mechanism  216  to rotate the ram  228  does not impact the position and force on the biasing member  226 . In some embodiments, the dose setting mechanism  216  includes a resistance and/or an audible click between selected dosages. 
     Referring to  FIGS. 22A-22F , the slot stop  230  may include a body  230   f . The body  230   f  may be held stationary with respect to the fluid reservoir  218 . In one embodiment, the body  230   f  includes a hole  230   g  extending there through to allow the ram  228  to pass through the slot stop  230  (see  FIG. 21B ). The slot stop  230  may include a plurality of axially extending and radially projecting slots  230   b . In one embodiment, the slots  230   b  are open toward the hole  230   g . The slots  230   b  may be sized and configured to receive the wing  228   b  in the fired position. The slots  230   b  may have different axial depths such that the wing  228   b  is stopped different distances from a bottom surface  230   h  of the body  230   f  and therefore stops the distal end of the piston at different distances relative to the fluid reservoir  218 . The wing  228   b  may include a pointed bottom edge  228   c  and/or the slot stop  230  may include pointed spaces between each of the slots  230   b  to help ensure that the wing  228   b  is guided into the appropriate slot  230   b . In one embodiment, the slots  230   b  have an increasing axial depth from one slot  230   b  to an adjacent slot  230   b  moving around the hole  230   g . In other embodiments, every other slot  230   b  has an increasing axial depth if two diametrically opposed wings  228   b  are provided, for example. 
     Referring to  FIGS. 19C-21C , the injection device  210  may be pre-primed for the user. In one embodiment, priming the injection device  210  allows for placing the ram  228  in a known position relative to the piston  220 . Priming may be used to reduce an initial gap between the ram  228  and the piston  220  and/or compression in the piston  220  to allow for tight control of the dose expelled during triggering. Since the ram  228  moves a fixed (controlled based on the dose selected) displacement, minimizing the variability associated with the starting position of the ram  228  and controlling the end position of the ram  228  allows for greater accuracy of the delivered dose. Also, by providing a device that is already primed, there may be greater assurance that the patient will get the correct dosing by eliminating a step that the user might have to do and therefore eliminate an opportunity for the user to get this wrong. The injection device  210  may be designed for assembly that eliminates the priming step. A filling process may be utilized to minimize air bubble in the fluid reservoir  218 . Once the fluid reservoir  218  is inserted into a front assembly, including the safety cap  214 , the front retainer  236 , the guard  240  and the sleeve  234 , is coupled with a middle assembly including the ram  228 , the latch  232  and the slot stop  230  (selectively coupled to the desired axial position on the latch  232 ) which is then coupled with a rear assembly including the biasing member  226 , the housing  212  and the dose setting mechanism  216 . 
     After setting the volume setting mechanism and before attaching or sealing off the dose setting mechanism, the ram  228  may be primed. In one embodiment, the ram  228  is primed using a prime screw  242 . The prime screw  242  may be threadably attached to the ram  228  to adjust how far axially the prime screw  242  extends from the ram  228 . The prime screw  242  may include a keyed feature  242   b  such that a corresponding tool may be inserted through the shaft  228   c  of the ram  228  to rotate the prime screw  242  and adjust the position of the distal end  242   a  of the prime screw  242  relative to the piston  220 . In one embodiment, the distal end  242   a  is configured to be in contact with the piston  220  in the initial position independent of the position of the dose mechanism  216 . 
     In one embodiment, the distal end  242   a  of the prime screw  242  is in contact with the piston  220  in the initial position such that the ram  228  does not move relative to piston  220  during triggering. By eliminating an axial space between the piston  220  and the ram  228  in the initial position, the ram  228  may be prevented from dynamically impacting the piston  220  once the injection device  210  has been fired, referred to as “shock loading”. In some embodiments, the patient may feel or hear the impact between the ram  228  and the piston  220  if there is shock loading and/or the impact may potentially damage the syringe. In certain embodiments, a gap between the ram  228  and the piston  220  is provided if desired. 
     Referring to  FIGS. 32-35B , in some embodiments, the injection device  210  is primed by the user. Syringes are commonly supplied to autoinjector manufacturers in a ‘drug-prefilled’ state. The prefilling process fills the syringe with drug, and may use various methods including a vacuum process that attempts to remove as much air as possible inside the syringe chamber before a plug/stopper is placed, sealing the syringe. Bubble priming, whereby all or most of the air is expelled from the syringe chamber through the needle prior to injection, is extremely common in manual injections: a bubble in an intravenous injection can cause an air embolism in a patient. Unfortunately, bubble priming is not as simple in an autoinjector and the presence of an air bubble is detrimental to the accuracy and precision of an autoinjector&#39;s drug delivery mechanism, which commonly relies upon advancing a ram abutted to the piston a tightly controlled travel distance. The bubble cannot be removed (primed) from the syringe without removing the needle cap resulting in a breach of the sterile barrier. 
     When an appreciable force is applied to a syringe piston during an injection, any bubbles remaining trapped within the syringe will compress, or displace ejected fluid decreasing the injected volume. This is due to pressure induced by the ram, the incompressible nature of liquids, and compressibility of gas. A steady-state pressure equilibrium is then reached while the liquid drug is ejected until the ram reaches the end of its stroke. At the end of the ram stroke, any previously compressed gasses will expand to equilibrium with the ambient. The rate upon which the gas expands is variable and dependent upon the ram force, the viscosity of the liquid, bubble size, needle lumen size and length, and the ambient pressure. As the bubble pressure approaches ambient, the rate of fluid expulsion decays, increasing injection time (e.g., preferably less than 10 seconds) for injectors with combined viscous drug liquid and small needle lumens. As delivered volume is related to the travel of the syringe plunger, the amount of liquid drug that is encompassed within this travel distance is required to be constant to allow accurate dispensing of drug. 
     In order to bubble prime the injection device  210 , the injection device  210  may be configured to be primed by the user by pointing the distal end  210   a  upward and advancing the ram  228  relative to the fluid reservoir  218 . By pointing the distal end  210   a  of the injection device  210  upward, buoyancy of the bubble positions it directly adjacent to the proximal end of the needle  222 . Depending upon the viscosity of the liquid, a slight tapping of the injection device  210  may be required. In some embodiments, the bubble may be observed through the window  212   b  in the housing  212 . 
     Referring to  FIGS. 32-33D , in one embodiment, the injection device  210  is configured such that removing the safety cap  214  causes the ram  228  to advance a nominal predetermined distance, expelling the bubble from the fluid reservoir  218  and potentially a small amount of liquid from the needle  222 . For example, a spacer  214   a  may be provided between the latch  232  and the proximal flanged end of the fluid reservoir  218 . In one embodiment, the spacer  214   a  is a sleeve that extends proximally from the safety cap  214  to retain the slot stop  230  a distance G from a proximal end of the fluid reservoir  218 . Removing the spacer  214   a  allows the firing mechanism, including the ram  228 , to advance the distance G and have the slot stop  230  abut against the proximal end of the fluid reservoir  218  or whatever feature is coupled to the proximal end of the fluid reservoir  218  such as a bumper. 
     Referring to  FIG. 36 , in some embodiments, the ram  228  is expanded to preload the piston  220 . In one embodiment, the ram  228  includes two or more nesting elements. In one embodiment, a torsional spring  142  is nested in an outer ram  144 . The torsional spring  142  may have a keyed rod  146  passing completely through the torsional spring, and rotationally constrained to the torsional spring. The keyed rod  146  may be locked by a removable release pin  148  extending from the distal end  210   b  of the injection device  210  and inserted into a keyed slot  150  of an inner ram  152  on the other end. The release pin may constrain the torsional spring until use. Upon removal, the torsional spring will rotate the inner ram relative to the outer ram, extending the inner ram to release the bubble (or provide a preload immediately prior to bubble expulsion). 
     Annular or partially annular teeth in the nested ram elements may interlock, (e.g., internal teeth on the outer cylinder/external teeth or slots on the inner cylinder) allowing only one way relative movement of the nested ram elements, inducing the ram  228  to extend and preload the piston  220 . In one embodiment, instead of teeth, the nested ram elements are internally/externally threaded, allowing preload from rotation of a device element. In one embodiment, the ram  228  includes a three part ram  228  comprised of both one way-tooth interaction and threaded interactions. 
     The spacer or ram  228  may be coupled to the safety cap  214  such that removing the safety cap  214  removes the spacer or expands the ram  228  and preloads a force onto the piston  220 . In other embodiments, the user actuates a trigger such as by pulling a pin  244  (see  FIGS. 34 a   - 34 B), flipping a switch, pushing a button, that pulls the spacer out of the loading stack or device entirely or expands the ram  228 . In one embodiment, setting the dose setting mechanism  216  automatically preloads piston  220 . For example, instructions or indication to twist the dose setting mechanism  216  may be visible through window  212   a  even to set the injection device  210  to the maximum dose. This initial twist of the dose setting mechanism  216  may be used to extend the ram  228  to prime the injection device  210 . The dosage indicia  216   e  may be oriented (rotated 180 degrees from example shown in  FIG. 19B ) such that the number is readable when the distal end  210   a  of the injection device  210  is pointed up. 
     Referring to  FIGS. 35 a  and 35 b   , in one embodiment, removal of the safety cap  214  allows the guard  240 , under spring load, to extend a predetermined distance. This movement allows for one or more prime arms  230   i  to deflect radially inward and cause the second spring loaded assembly connected to the ram to advance a nominal distance to a predetermined set-point, inducing an axial preload on the piston  220 . In one embodiment, the guard  240  is under a lower spring force than the firing mechanism such that coupling the priming of the injection device  210  to the guard  240  allows for the priming force to be controlled more precisely. 
     Once the safety cap  214  is removed, the fluid reservoir  218  may be bubble primed and ready for injection. A liquid receiver, such as a piece of absorbent material, may be positioned adjacent to the needle  222  toward the distal end  210   a  of the injection device  210  to capture any expelled liquid drug during priming. The liquid receiver may be in circumferential association with the needle  222  and may be attached to the housing  212 , safety cap  214  or both (e.g., 2 pieces of absorbent material). 
     Referring to  FIGS. 19C and 27A-27D , the injection device  210  may configured to prevent resetting after the firing mechanism is actuated so as to prevent a subsequent injection of the medicament by the injector, thereby configuring the injection device  210  as a single-use injector. In one embodiment, the injection device  210  includes a guard  240  that is slideably coupled to the housing  212 . The injection device  210  may include a biasing member  238  coupled to the guard  240  and configured to bias the guard  240  toward a distal end  210   a  of the injection device  210 . The guard  240  may be configured to extend axially past the injection conduit  222 . In one embodiment, the guard  240  is configured to extend axially past the injection conduit  222  and lock axially relative to the housing  212  after removing the injection conduit  222  from the patient. 
     Referring to  FIGS. 20A-20B , a sleeve  234  may be coupled to the fluid reservoir  218 . The sleeve  234  may include a pair of diametrically opposed tabs  234   a  extending outwardly in the radial direction. The housing  212  may include a front retainer  236  coupled to the distal end of the housing  212 . The front retainer  236  may include a pair of axially extending slots  236   a  configured to receive the tabs  234   a  of the sleeve  234 . The safety cap  214  may releaseably couple to the front retainer  236 . The biasing member  238  may be positioned within the front retainer  236  and engage the distal end of the sleeve  234 . The other end of the biasing member  238  may be configured to engage a flange proximate the distal end of the guard  240 . The guard  240  may include a pair of diametrically opposed and axially extending slots  240   c  for receiving the tabs  234   a . The axial range of motion of the guard  240  may be dictated by the ends of the slots  240   c  of the guard  240  engaging the tabs  234   a  of the sleeve  234 . The guard  240  and the sleeve  234  may include one or more openings  240   b ,  234   b  respectively for aligning with a window  212   b  of the housing  212  to reveal the level of medicament in the fluid reservoir  218 . The fluid reservoir  218  may include indicia and/or the level of fluid contained therein that are visible through the window  212   b  so that the patient can verify that the appropriate volume of medicament is included in the injection device  210 . 
     Referring to  FIGS. 24A-27D , the firing mechanism may be automatically released based on the position of the injection conduit  222  relative to the patient. In one embodiment, retracting the guard  240  relative to the injection conduit  222  releases the firing mechanism. In other embodiment, the patient must actuate a button or another feature before or after retracting the guard  240 , or in an embodiment not including a guard  240 , in order to release the firing mechanism. 
     The injection device  210  may accommodate two injection volume adjustments. This may help to minimize the amount of unused drug. The first adjustment is set during assembly and sets the range of volume to be delivered (e.g., the dosing range). The dosing range may vary depending on the fill volume in the fluid reservoir  218 . This amount may be set as part of the assembly process. In one embodiment, there are four configurations or SKUs. Each SKU will represent a maximum volume of fill to allow delivery of the maximum dose within that SKU (e.g., 0.8 to 1.0 ml volume delivery to the patient; 0.6 to 0.8 ml volume delivery to the patient; 0.4 to 0.6 ml volume delivery to the patient; and 0.2 to 0.4 ml volume delivery to the patient). The second adjustment is set by the user prior to injecting the medicament. The second volume adjustment sets the dose, a fraction of the volume in the fluid reservoir  218 , and this dose to be delivered within the range allowed by the injection device  210 . In one embodiment, the user may adjust the dose, up and down, until the injection is delivered. 
     Referring to  FIGS. 24A-24E , during use of an exemplary embodiment, the user is aware what volume of medicament is provided in the injection device  210  and may verify by looking at the fluid reservoir  218  through the window  212   b  in the housing (see  FIGS. 20A-20B ). The user then selects the desired dose to be delivered, either all or a fraction of the volume of the fluid reservoir  218 , by rotating the dose setting mechanism  216  relative to the housing  212 . The user may verify that the appropriate dosage is selected by viewing the dosage amount indicated by the indicia visible through window  212   a  in the housing (see  FIGS. 20A-20B ).  FIGS. 28A-28C  show the injection device in a minimum dosage selection such that the ram  228  is rotated such that the wing  228   b  align with the shallowest slot  230   b . In one embodiment, the medicament remaining in the fluid reservoir  218  following the injection is not delivered and may be discarded. 
     Referring to  FIGS. 25A-25E , once the dosage is set by the user, the user removes the safety cap  214  from the front retainer  236  by pulling or twisting the safety cap  214  relative to the front retainer  236  (see  FIG. 19C ). Any priming is conducted if necessary, and the injection device  110  is ready for injection. The patient may then press the distal end of the guard  240  against their skin retracting the guard  240  proximally until the needle  222  penetrates the skin surface and the aperture  240   a  aligns with the retainer  230   a.    
     Referring to  FIGS. 25A-25E and 26A-26D , once the aperture  240   a  is aligned with the retainer  230   a , the retainer  230   a  is radially released and the axial force of the latch on the retainer  230   a  pivots the projection  230   c  inwardly and out of the axial path of the latch  232  allowing the biasing member  226  to distally extend the latch  232 , causing the ram  228  to urge the piston  220  distally and deliver the dose of medicament to the patient through the injection conduit  222 . The shaft  216   d  may extend a sufficient distance in the distal direction so that the dose setting mechanism  216  remains rotatably fixed relative to the ram  228 . Since the ram  228  is rotatably fixed by the wing&#39;s  228   b  engagement with the slot stop  230 , the dose setting mechanism  216  is prevented from rotating in the fired position and ensuring that the dosage displayed through the window  212   a  is the dosage that was delivered. If the dose setting mechanism  216  did not remain coupled to the ram  228  in the fired position, then the dose setting mechanism  216  may be able to rotate relative to the ram  228  and cause confusion as to what dosage was delivered. 
     Referring to  FIGS. 27A-27D , after the dose is delivered, the housing  212  is pulled away from the patient, pulling the needle  222  from the patient and allowing the biasing member  238  to urge the guard  240  distally past the end of the needle  222 . A retaining member retains the guard  240  to lock the guard  240  relative to the needle  222  preventing further use of the injection device  210 . The injection device  210  may then be safely discarded. An exemplary lock-out system is described below. 
     Referring to the drawings in detail, wherein like reference numerals indicate like elements throughout, there is shown in  FIGS. 38A-42B  a lock-out system for an injection device, generally designated  310 , a third exemplary embodiment of the present invention. Various embodiments of the lock-out system are described in further detail below in reference to the exemplary embodiment shown in the figures. One or more of the embodiments discussed in reference to the lock-out system described below may be combined with one or more desirable features of the embodiments discussed in reference to the injection devices  110  and  210  described above. 
     Referring to  FIGS. 38A and 40 , the front retainer  336 , which is axially fixed relative to a housing and the fluid reservoir (not shown), may initially prevent the biasing member  338  (see  FIGS. 43A and 43B ) from distally extending the guard  340 . The guard  340  however, may be free to retract relative to the front retainer  336  in the proximal direction. The front retainer  336  may include one or more arms  336   a  that engage with a corresponding stop  340   b  of the guard  340 . In one embodiment, the front retainer  336  includes two pairs of arms  336   a  (the front pair of arms  336   a  being visible in the drawings). 
     Referring to  FIGS. 38B, 39A, 41A and 41B , the injection device  310  may include a sleeve  334  fixed relative to the front retainer  336 . The sleeve  334  may include a radial projection  334   a . In one embodiment, the sleeve  334  includes a pair of diametrically opposed radial projections  334   a  (see  FIG. 41B ). In the initial position, the radial projection  334   a  may be positioned distally to the end of one or more arms  340   a  of the guard  340 . The radial projection  334   a  may extend through a slot  340   c  in the guard  340 . As the guard  340  is retracted during an injection, the slot  340   c  may be slid in a proximal direction relative to the radial projection  334   a.    
     Referring to  FIG. 42 , the latch may include one or more legs  332   c . In one embodiment, the latch includes a pair of diametrically opposed legs  332   c . The legs  332   c  may be tapered distally. Once the firing mechanism is actuated and the latch  332  is released, the latch  332  is fired distally by the biasing member  326  (see  FIGS. 38A-38B ). At the end of the delivery stroke, the legs  332   c  of the latch  332  engage with the arms  336   a  and flex the arms  335   a  out of the axial path of the stops  340   b  (see  FIG. 40 ) of the guard  340 . 
     Referring to  FIGS. 43A and 43B , once the arms  336   a  are disengaged from the stops  340   b , the biasing member  338  extends the guard  340  distally to cover the end of the needle. As the guard  340  extends, the slot  340   c  of the guard is slid proximally relative to the radial projection  334   a . As the guard  340  extends past the initial position of the guard  340 , the arms  340   a  of the guard  340  extend over the radial projection  334   a  of the sleeve  334 . As the arms  340   a  of the guard  340  extend over the radial projection  334   a , the ends of the arms  340   a  flex away from one another until they engage with corresponding grooves  334   b  (see  FIGS. 41A and 41B ) and move closer to one another. The grooves  334   b  of the radial projection  334   a  are shaped to retain the arms  340   a  in the locked position and prevent the guard  340  from being urged in the proximal direction. In the locked position, the guard  340  is kept from being retracted in the proximal direction, preventing additional exposure or use of the needle. The guard  340  may extend axially past the end of the needle to in both the initial and locked positions. In one embodiment, the guard  340  is retracted to expose and allow insertion of the needle and is then extended to cover the needle. In one embodiment, the guard  340  extends further distally in the locked position relative to the end of the needle than in the initial position. 
     It will be appreciated by those skilled in the art that changes could be made to the exemplary embodiments shown and described above without departing from the broad inventive concepts thereof. It is understood, therefore, that this invention is not limited to the exemplary embodiments shown and described, but it is intended to cover modifications within the spirit and scope of the present invention as defined by the claims. For example, specific features of the exemplary embodiments may or may not be part of the claimed invention and various features of the disclosed embodiments may be combined. Unless specifically set forth herein, the terms “a”, “an” and “the” are not limited to one element but instead should be read as meaning “at least one”. 
     It is to be understood that at least some of the figures and descriptions of the invention have been simplified to focus on elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that those of ordinary skill in the art will appreciate may also comprise a portion of the invention. However, because such elements are well known in the art, and because they do not necessarily facilitate a better understanding of the invention, a description of such elements is not provided herein. 
     Further, to the extent that the methods of the present invention do not rely on the particular order of steps set forth herein, the particular order of the steps should not be construed as limitation on the claims. Any claims directed to the methods of the present invention should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the steps may be varied and still remain within the spirit and scope of the present invention.