Patent Publication Number: US-2023137976-A1

Title: Injection device with end of dose indicator

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of and claims priority to U.S. patent application Ser. No. 16/434,887, filed Jun. 7, 2019, which claims priority to U.S. Provisional Patent Application No. 62/682,592, filed Jun. 8, 2018, the disclosures of which are incorporated herein by reference in their entirety. 
    
    
     TECHNICAL FIELD 
     The present disclosure relates to an injection device for injecting a drug product, such as a therapeutic agent, into a patient. 
     BACKGROUND 
     One of the most common routes of administration for drug products is by injection, such as intravenous, subcutaneous, or intramuscular injection. A syringe containing a drug product is often used for the injection, which is often carried out by trained medical personnel. In certain instances, a patient is trained in the use of the syringe to allow for self-injection. Moreover, certain drug products are formulated in pre-filled syringes for patient use, to avoid the need for the patient to fill the syringe. Some patients, however, may be averse to carrying out self-injection with a manual syringe, particularly if the patient lacks the dexterity to manipulate the syringe to fill the syringe and inject the drug product from the syringe. Automatic injection devices offer an alternative to a manual syringes for delivering a drug product, as automatic injection devices are easier to use. 
     SUMMARY 
     The present disclosure provides injection devices with an end of dose indicator assembly that is simultaneously viewable from at least two different directions. The end of dose indicator assembly may be a binary indicator. 
     In an embodiment, the present disclosure provides an injection device including a housing having an internal volume and a viewing portion. A movable seal is disposed in the internal volume and is movable from an initial position to an injection end position to urge a drug product out of the housing. An indicator assembly is disposed in the internal volume and includes a dose end indicator. The indicator assembly is biased from a dose remaining position toward a dose end position where the dose end indicator is visible through the viewing portion. A release mechanism releasably holds the indicator assembly in the dose remaining position and is linked to the movable seal such that the movable seal reaching the injection end position causes the release mechanism to release the indicator assembly to the dose end position. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
       The foregoing and other objects, features and advantages of the exemplary embodiments will be more fully understood from the following description when read together with the accompanying drawings, in which: 
         FIG.  1 A  illustrates an exemplary injection device including an indicator assembly in a dose remaining position according to an example embodiment. 
         FIG.  1 B  is a perspective view of the injection device illustrated in  FIG.  1 A  when a dose end indicator of the indicator assembly is visible through a viewing portion of a housing of the injection device. 
         FIG.  2 A  is a cross-sectional view of the injection device illustrated in  FIG.  1 A  taken along line  2 A- 2 A while a release mechanism releasably holds an indicator assembly in a dose remaining position. 
         FIG.  2 B  is a cross-sectional view of the injection device illustrated in  FIG.  1 B  taken along line  2 B- 2 B as a movable seal moves to an injection end position such that the release mechanism releases the indicator assembly to a dose end position. 
         FIG.  3 A  illustrates another exemplary injection device that incorporates a firing button according to an example embodiment. 
         FIG.  3 B  is a cross-sectional view of the injection device illustrated in  FIG.  3 A  taken along line  3 B- 3 B. 
         FIG.  3 C  is a perspective view of the injection device illustrated in  FIGS.  3 A and  3 B  when the indicator assembly has reached a dose end position. 
         FIG.  4 A  illustrates another exemplary injection device that incorporates a firing button and an indicator assembly with a visual indicator that is a different color than a dose end indicator. 
         FIG.  4 B  is a perspective view of the injection device of  FIG.  4 A  after the indicator assembly has been released to a dose end position such that the dose end indicator is visible. 
         FIG.  5 A  illustrates another exemplary injection device including an indicator assembly in a dose remaining position according to an example embodiment. 
         FIG.  5 B  is a cross-sectional view of the injection device illustrated in  FIG.  5 A  taken along line  5 B- 5 B. 
         FIG.  5 C  is a perspective view of the injection device illustrated in  FIGS.  5 A and  5 B  after the indicator assembly has been released to a dose end position such that a dose end indicator is visible. 
         FIG.  6 A  illustrates another exemplary injection device that has an indicator assembly with a visual indicator that is a different color than a dose end indicator. 
         FIG.  6 B  is a perspective view of the injection device of  FIG.  6 A  after the indicator assembly has been released to a dose end position such that the dose end indicator is visible. 
         FIG.  7    illustrates an exemplary anchor for linking a movable seal to a tensioner according to an example embodiment. 
         FIG.  8 A  illustrates yet another exemplary injection device that includes an indicator assembly and utilizes pressurized fluid to drive an injection according to an example embodiment. 
         FIG.  8 B  is a perspective view of an exemplary septum that may be incorporated in the injection device illustrated in  FIG.  8 A  to fluidly isolate two fluid spaces within the injection device according to an example embodiment. 
         FIG.  8 C  is a perspective view of another exemplary septum that may be incorporated in the injection device illustrated in  FIG.  8 A  to fluidly isolate two fluid spaces within the injection device according to an example embodiment. 
         FIG.  8 D  is a cross-sectional view of an exemplary seal that may be incorporated in the injection device illustrated in  FIG.  8 A  to fluidly isolate two fluid spaces within the injection device according to an example embodiment. 
         FIG.  9 A  is a cross-sectional view of an exemplary pin that allows progressive movement of an indicator assembly to a dose end position. 
         FIG.  9 B  is a cross-sectional view of an exemplary stepped pin that allows step-wise movement of an indicator assembly to a dose end position. 
     
    
    
     DETAILED DESCRIPTION 
     The present disclosure provides injection devices with an indicator assembly including a dose end indicator viewable from at least both a side and a top of the injection device for indicating when an injection is completed. The indicator assembly is disposed in a housing of the injection device and is biased from a dose remaining position toward a dose end position where the dose end indicator is simultaneously visible from two or more different viewing positions through a viewing portion of the housing. A release mechanism releasably holds the indicator assembly in the dose remaining position. A movable seal that is linked to the release mechanism moves to an injection end position to release the indicator assembly into the dose end position. 
     The devices presented herein can be used for injecting a variety of drug products into a patient. In one embodiment, the injection device can be configured in the form of an automatic injection device. In some embodiments, the automatic injection device is configured in the form of a pen, i.e., a portable autoinjector that enables an individual to administer a dosage of a drug product. In other embodiments, the injection device can be configured as a traditional syringe or other type of injection device for injecting drug products. 
     As used herein, an “automatic injection device” (or “autoinjector”) is intended to refer to a device that enables an individual (also referred to herein as a user or a patient) to self-administer a dosage of a drug product. The automatic injection device differs from a standard syringe by the inclusion of a mechanism for automatically inserting the needle at an injection site, automatically delivering the drug product to the individual by injection, and automatically retracting the needle from the injection site when the mechanism is engaged. 
     As used herein, the term “drug product” refers to a composition intended for use in medical diagnosis, cure, treatment, or prevention of disease. A drug product may be a therapeutic agent or a combination of therapeutic agents. A drug product may include a therapeutic protein, for example, a peptide or antibody, or antigen-binding portion thereof. A drug product may include an anesthetic, steroid, and/or any other therapeutic agent(s). In one embodiment, a drug product represents a mixture of two or even more pharmacologically active agents. In some embodiments, the drug product is a liquid therapeutic agent which includes one or more biological agents, such as a protein, or antibody. For example, the liquid therapeutic agent can be a monoclonal antibody targeting interleukin  23 A, such as risankizumab. In yet another example embodiment, the liquid therapeutic agent may comprise an antibody drug conjugate (ADC). Additional details regarding possible therapeutic agents, including are provided in U.S. Pat. No. 8,679,061, the contents of which are incorporated by reference herein in its entirety. The drug product may have any suitable volume, for example between about 0.5 ml and about 4 ml, e.g. about 2.25 ml. 
     As used herein, the term “proximal” refers to the portion or end of an injection device or component in the injection device furthest from an injection site of the user when the device is held against the person for an injection. 
     As used herein, the term “distal” refers to the portion or end of an injection device or a component of the injection device closest to an injection site of the user during an injection. 
     As used herein, the term “dose end” or “end of dose” refers to a movable seal, for example, a bung or a piston reaching a termination point within the barrel of a syringe following compression of a drug product through an aperture of the syringe to deliver a volume of the drug product for treatment of a patient for which the drug product is indicated. 
     The present disclosure provides injection devices with a binary end-of-dose (“EOD”) indicator that does not deploy until the injection is complete. In some embodiments, the indicator is incorporated in a single-use automatic injection device to alert a user that the injection is complete, and that the injection device may be discarded. In some embodiments, the indicator is incorporated in a re-usable injection device, such as an infusion pump, to indicate that a complete dose has been delivered and the user may, for example, replace a drug product container holding the dose. 
     Referring now to the drawings, and more particularly to  FIGS.  1 A- 2 B , an exemplary embodiment of an injection device  100  is illustrated that includes a housing  110  having a viewing portion  111  and an internal volume V. In some embodiments, the housing  110  has a generally cylindrical shape with a proximal end  112  and a distal end  113  opposite the proximal end  112 . The viewing portion  111  may comprise a transparent portion of the housing  110  to allow a user to view an indicator assembly  120  that is disposed inside the housing  110  and is aligned with the viewing portion  111 . In some embodiments, the viewing portion  111  may be formed adjacent to the proximal end  112  in a cap  114  of the housing  110  through at least three viewing surfaces  114 A,  114 B,  114 C of the cap  114  to allow a user to view the indicator assembly  120  while holding the injection device  110  in hand. As illustrated, each of the viewing surfaces  114 A,  114 B,  114 C may define a separate viewing plane such that the viewing portion  111 , when formed through the viewing surfaces  114 A,  114 B,  114 C, may be visible from a variety of different angles and orientations. 
     In some embodiments, the injection device  100  may not include a cap. In such embodiments the viewing portion  111  may be formed in the proximal end  112  of the housing  110  through at least three viewing surfaces  114 A,  114 B,  114 C to allow a user to view the indicator assembly  120  while holding the injection device  110  in hand. The same principles of the viewing portion  111  described with respect to the cap  114  are equally applicable to an embodiment of the injection device  100  formed without a cap. 
     The viewing portion  111  may be formed as an aperture or other opening in the housing  110  that is partially or fully covered by a viewing window  115 . In some embodiments, the viewing window  115  is a generally translucent material and substantially transparent to allow a user to clearly view the indicator assembly  120  through the viewing portion  111 . The viewing portion  111  may be formed, for example, about a longitudinal axis LA of the housing  110  extending through the proximal end  112  and the distal end  113 . In some embodiments, the viewing portion  111  has a viewing portion width VPW that extends on an arc that is defined between approximately 1° and approximately 180° about the longitudinal axis LA to allow visibility through the viewing portion  111  from a variety of angles. In some embodiments, the viewing portion  111  has a viewing portion length VPL that is equal to a radius R of the housing  110 , relative to the longitudinal axis LA. 
     A movable seal  250 , for example a piston or a bung in  FIGS.  2 A and  2 B , is disposed in a container, such as a barrel of a syringe or a cartridge disposed in the internal volume V of the housing  110 . While the movable seal  250  is illustrated as a rodless piston, in some embodiments the movable seal  250  is connected to a plunger rod or similar element that translates the movable seal  250  along the longitudinal axis LA of the housing  110 . In some embodiments, the movable seal  250  is a sealed end of a container that urges drug product out of the container during movement. It should thus be appreciated that the movable seal  250  may take many forms to urge drug product out of the housing  110  in accordance with the present disclosure. 
     The movable seal  250  is movable from an initial position, illustrated in  FIG.  2 A , to an injection end position, which is illustrated in  FIG.  2 B  and described further herein, to urge drug product out of the housing  110 . In some embodiments, the injection device  100  may include, for example, a biasing element  270 , such as a coil spring, elastomeric material, and/or pressurized liquid or gas containers. The biasing element  270  may be directly coupled or linked, or indirectly coupled or linked via a plunger rod or other element, to the movable seal  250  such that, when activated, the biasing element  270  forces the movable seal  250  from the initial position to the injection end position to urge drug product out of the housing  110 . In some embodiments, translation of the movable seal  250  along the longitudinal axis LA pressurizes drug product in the syringe barrel, or other container, to urge the drug product out of the syringe barrel. 
     With further reference to  FIGS.  1 A- 2 B , it is illustrated that the indicator assembly  120  is disposed inside the internal volume V, adjacent to the cap  114  and the proximal end  112  of the housing  110 , and biased from a dose remaining position, illustrated in  FIGS.  1 A and  2 A , toward a dose end position, illustrated in  FIGS.  1 B and  2 B , where a dose end indicator  221  is visible through the viewing portion  111  of the housing  110 . In some embodiments, the dose end indicator  221  is not a component of a plunger rod and/or provides end of dose indication independent of movement of any plunger rod. 
     In some embodiments, the indicator assembly  120  includes a dome  224  with a first portion  122  and a second portion  223 , with each portion  122 ,  223  being a respective half of the dome  224 . The first portion  122  is visible through the viewing portion  111  when the indicator assembly  120  is in the dose remaining position and the second portion  223 , which includes the dose end indicator  221 , is visible through the viewing portion  111  when the indicator assembly  120  is in the dose end position. In some embodiments, some of the first portion  122  may also be visible through the viewing portion  111  when the indicator assembly  120  is in the dose end position. The first portion  122  may include a visual indicator  124  that is visually distinct from the dose end indicator  221 . The visual indicator  124  may be a first color or other type of visual marking, such as a symbol, that is visually distinct from the dose end indicator  221 . The visual indicator  124  may be, for example, a light or white colored portion while the dose end indicator  221  is a dark color, such as black, red, etc., that is visually distinct from the visual indicator  124 . While the visual indicator  124  is illustrated as having a first color and the dose end indicator  221  is illustrated as having a second color that is different from the first color, in some embodiments the visual indicator  124  may be a symbol or text, such as an X or the phrase “dose remaining,” while the dose end indicator  221  is a different symbol or text that conveys that the dose has ended, such as a checkmark or the phrase “dose completed.” It should thus be appreciated that there are many different ways in which the visual indicator  124  may convey that there is at least some dose of drug product remaining and the dose end indicator  221  may convey to a user that the dose has been delivered. 
     In some embodiments, the first portion  122  and the second portion  223  of the dome  224  may be integral or otherwise connected with one another to move together, i.e., static relative to one another, so movement of the dome  224  causes movement of both of the portions  122 ,  223 . In some embodiments, the indicator assembly  120  may be disposed on one side of a partition  225  disposed in the internal volume V to separate the indicator assembly  120  from a cavity  226  in the housing  110  that houses the movable seal  250  and other components of the injection device  100 . 
     In some embodiments, an indicator assembly biaser  231 , for example, illustrated as a torsion spring, bears on the indicator assembly  120  to bias the indicator assembly  120  from the dose remaining position toward the dose end position. In some embodiments, the biaser  231  is placed in an indicator assembly biaser cavity  232  formed adjacent to the partition  225 . The biaser  231  may store, for example, rotational energy in a constrained position that, when released, pivots a portion or all of the indicator assembly  120  about the longitudinal axis LA, which thus defines a pivoting axis of the indicator assembly  120 . While the exemplary embodiment illustrated in  FIGS.  1 A- 2 B  includes the biaser  231  to pivotably bias the indicator assembly  120  from the dose remaining position toward the dose end position, it should be appreciated that the indicator assembly  120  may be naturally biased toward the dose end position without the need of a separate element. For example, the dome  224  may comprise an elastic material, such as a rubber element, that is twisted to the dose remaining position and naturally biased to untwist from the dose remaining position to the dose end position unless held in the twisted position. 
     Referring specifically now to  FIGS.  2 A and  2 B , a release mechanism  240  is illustrated that releasably holds the indicator assembly  120  in the dose remaining position and is linked to the movable seal  250 . In some embodiments, the release mechanism  240  is in the form of a pin, catch, or other element that extends through a release mechanism opening  241  formed in the partition  225  so the release mechanism  240  extends into the cavity  226  while also contacting some or all of the indicator assembly  120  to hold the indicator assembly  120  in the dose remaining position. To hold the indicator assembly  120  in the dose remaining position, the release mechanism  240  may abut against a contact surface  227  of the dome  224  and prevent free pivoting of the dome  224 . In some embodiments, the release mechanism  240  is pressed into sides of the release mechanism opening  241  by the natural bias of the dome  224  and the contact surface  227  toward the dose end position. While the release mechanism  240  is illustrated and described as a pin that abuts against a surface  227  of the indicator assembly  120  to hold the indicator assembly  120  in the dose remaining position, in some embodiments the release mechanism  240  is formed as, for example, a hook or other type of similar element having a portion placed in an opening of the indicator assembly  120 , or otherwise coupled to the indicator assembly  120 , to releasably hold the indicator assembly  120  in the dose remaining position. 
     The release mechanism  240  may be coupled or linked directly or indirectly to the movable seal  250  by, for example, a tensioner  242 , illustrated as a monofilament fiber or wire. In some embodiments, the tensioner  242  is slacked when the movable seal  250  is in the initial position, as illustrated in  FIG.  2 A , such that little, if any, tension applies to the release mechanism  240  through the tensioner  242 . When the movable seal  250  translates along the longitudinal axis LA, as illustrated in  FIG.  2 B , the tensioner  242  becomes taut such that movement of the movable seal  250  pulls the release mechanism  240  along the longitudinal axis LA. In some embodiments, the tensioner  242  extends through a guide opening, or has another element associated therewith, and prevents the tensioner  242  from becoming tangled during operation. 
     In some embodiments, a needle shroud or other element may also be directly or indirectly coupled to or linked to the movable seal  250 , independently of or dependently on linkage of the indicator assembly  120  to the movable seal  250 , and deploys when the movable seal  250  reaches the injection end position. In this manner, the needle shroud may be deployed in temporal sequence with the dose end position of indicator assembly. Many types of needle shrouds are conventional and may be readily incorporated in the injection device  100 . Similarly, the injection device  100  may include a syringe carrier holding a syringe that translates along the longitudinal axis LA with the movable seal  250  to urge drug product out of the housing  110 . Many types of syringe carriers are conventional and may be readily incorporated in the injection device  100 . 
     A stop  228 , illustrated as a surface, is positioned in the internal volume V adjacent to the indicator assembly  120  such that the stop  228  prevents the indicator assembly  120  from moving past the dose end position. For example, the stop  228  may be placed in a rotation path of the dome  224  such that the second portion  223  hits the stop  228  when the indicator assembly  120  reaches the dose end position, with the abutment of the second portion  223  against the stop  228  preventing the dome  224  from further rotating. 
     To use the injection device  100 , a user depresses or otherwise actuates an element, such as a firing button or plunger or a component at a distal end  113  of the injector (e.g. a distal end of a needle shroud), so the movable seal  250  translates along the longitudinal axis LA toward the distal end  113  to urge drug product out of the housing  110  through, for example, a needle  190 . As the movable seal  250  translates, or otherwise moves, the tensioner  242  linking the release mechanism  240  to the movable seal  250  becomes taut, if not already taut, and allows the movable seal  250  to pull the release mechanism  240  toward the distal end  113 . When the movable seal  250  reaches the injection end position in which the movable seal  250  has fully moved to urge drug product out of the housing  110 , the release mechanism  240  releases the indicator assembly  120  to the dose end position by, for example, pulling out of the release mechanism opening  241  and thus out of contact with the contact surface  227 . When the release mechanism  240  releases the indicator assembly  120 , the bias on the indicator assembly  120  is configured to move the indicator assembly  120  to the dose end position where the dose end indicator  221  is visible through the viewing portion  111  of the housing  110 , alerting a user that the dose has ended. The indicator assembly  120  contacting the stop  228 , or another element, upon reaching the dose end position may be configured to provide a vibration, or other type of tactile feedback, in the housing  110 . The indicator assembly  120  contacting the stop  228 , or another element, upon reaching the dose end position may also, or alternatively, may be configured to provide a “click” or other type of audible feedback. While the movement of the movable seal  250  is illustrated as pulling the release mechanism  240 , in some embodiments the movable seal  250  reaching the injection end position pushes, or causes pushing of, the release mechanism  240  to release the indicator assembly  120 . 
     Referring now to  FIGS.  3 A,  3 B, and  3 C , another embodiment of the injection device  100 , hereafter referred to as automatic injection device  300 , is illustrated that incorporates a firing button  380  to activate an automatic injection by the automatic injection device  300 . For elements of the automatic injection device  300  that are similar to elements of the automatic injection device  100 , similar reference numerals are used with a prime (′) designation, e.g., housing  110 ′. As illustrated in  FIG.  3 B , the automatic injection device  300  has a modified injection assembly  120 ′ with a firing button opening  381  formed therein to accommodate the firing button  380 , which extends through the firing button opening  381 . The firing button  380  includes a button rod  382  surrounded by a biaser  231 ′ and is connected to a trigger assembly  383  that holds a biasing element  270 ′ in a constrained position until activated by depressing the firing button  380 . The trigger assembly  383  releases the biasing element  270 ′ when the firing button  380  depresses, allowing the biasing element  270 ′ to deploy and start the automatic injection. In some embodiments, the trigger assembly  383  includes a lock or other element to prevent inadvertent triggering of an injection. 
     During the injection, a movable seal  250 ′ translates along the longitudinal axis LA to urge drug product out of the housing  110 ′. When the movable seal  250 ′ translates along the longitudinal axis LA to the injection end position, the release mechanism  240 ′ releases the injection assembly  120 ′. After the release mechanism  240 ′ releases the injection assembly  120 ′, the injection assembly  120 ′ rotates about the firing button  380  from the dose remaining position to the dose end position where one or more dose end indicators  221 ′, rather than one or more visual indicators  124 ′, are visible through the viewing portion  111 ′. As illustrated in  FIGS.  3 A and  3 C , the visual indicators  124 ′ and the dose end indicators  221 ′ may be visually distinct symbols, illustrated as X&#39;s and check marks, respectively. In some embodiments, the number of visual indicators  124 ′ and dose end indicators  221 ′ may be at least equal to the number of viewing surfaces  114 A′,  114 B′,  114 C′ of a cap  114 ′ of the housing  110 ′ so at least one visual indicator  124 ′ and/or at least one dose end indicator  221 ′ is visible through each of the viewing surfaces  114 A′,  114 B′,  114 C′. Thus, the firing button  380  provides a relatively easy-to-use mechanism for automatically injecting drug product with the automatic injection device  300  and, once the injection is complete, causing the release mechanism  240 ′ to release the injection assembly  120 ′. In all other respects, the automatic injection device  300  may be similar to the injection device  100 . 
     In another exemplary embodiment illustrated in  FIGS.  4 A and  4 B , an automatic injection device  400  is provided that is similar to the automatic injection device  300 , with similar elements numbered similarly in  FIGS.  4 A and  4 B , but includes an indicator assembly  120 ″ with a visual indicator  124 ″ that is a different color from a dose end indicator  221 ″ of the indicator assembly  120 ″. In all other respects, the automatic injection device  400  is similar to the automatic injection device  300 . 
     The injection devices  100 ,  300 ,  400  disclosed herein provide an indicator assembly  120 ,  120 ′,  120 ″ with a dose end indicator  221 ,  221 ′,  221 ″ that becomes visible through the viewing portion  111 ,  111 ′,  111 ″ when the movable seal  250 ,  250 ′ reaches the injection end position. In this sense, the indicator assembly  120 ,  120 ′,  120 ″ is a binary indicator that conveys that the movable seal  250 ,  250 ′ has reached the injection end position, which generally corresponds to the injection ending and the dose of drug product being urged out of the housing  110 ,  110 ′, via the release mechanism  240 ,  240 ′ releasing the indicator assembly  120 ,  120 ′,  120 ″ to the dose end position when the movable seal  250 ,  250 ′ reaches the injection end position. In some embodiments, such an indicator assembly  120 ,  120 ′,  120 ″ may forego so-called “dose progress indicators,” which indicate how much dose is remaining in the injection and may be confusing to users. The viewing portion  111 ,  111 ′ and the indicator assembly  120 ,  120 ′,  120 ″ may also be placed adjacent to the proximal end  112 ,  112 ′ of the injection device  100 ,  300 ,  400 , rather than a middle portion of the device  100 ,  300 ,  400 , so the indicator assembly  120 ,  120 ′,  120 ″ is simultaneously viewable from a variety of viewing directions and angles while performing the injection. In some embodiments, the indicator assembly  120 ,  120 ′,  120 ″ is viewable from at least two different viewing directions. Further, the release mechanism  240 ,  240 ′ releasably holding the indicator assembly  120 ,  120 ′,  120 ″ may be linked to the movable seal  250 ,  250 ′ such that the release mechanism  240 ,  240 ′ releases the indicator assembly  120 ,  120 ′,  120 ″ with little, if any, detrimental effect, such as friction sticking of the movable seal  250 ,  250 ′, on the movement of the movable seal  250 ,  250 ′ to the injection end position. 
     In some embodiments, the injection device  100 ,  300 ,  400  may include one or more other indicators in addition to the indicator assembly  120 ,  120 ′,  120 ″. For example, the injection device  100 ,  300 ,  400  may include an additional indicator that “clicks” or otherwise indicates when the injection has finished and the dose of drug product has been urged out of the housing  110 ,  110 ′. The additional indicator may be, for example, a button or other type of element that pops out of the housing  110 ,  110 ′ when the injection finishes. Thus, the additional indicator may provide a tactile and/or audible indication to alert a user that the injection has finished. 
     With reference now to  FIGS.  5 A,  5 B, and  5 C , another exemplary embodiment of an injection device  500  is illustrated that is similar to the injection device  100  but has an indicator assembly  520  that pivots to the dose end position about a pivoting pin  525  defining a pivot axis PA that is orthogonal relative to a longitudinal axis LA of the injection device  500 . While the pivot axis PA is illustrated as being orthogonal relative to the longitudinal axis LA, in some embodiments the pivot axis PA is transverse, but not necessarily orthogonal, to the longitudinal axis LA. As illustrated, the pivoting pin  525  may extend through an outer surface of a housing  510  of the injection device  500 , which may be generally cylindrical with a proximal end  512  and a distal end  513  opposite the proximal end  512 . The housing  510  includes a viewing portion  511  that may be formed with a viewing portion width VPW 2  that is relatively narrow compared to a viewing portion length VPL 2  of the viewing portion  511 . In other respects, the housing  510  may be similar to the previously described housing  110 . 
     In some embodiments, the indicator assembly  520  is biased by a biaser  531 , illustrated as a compression spring, from a dose remaining position, in which one or more visual indicators  524 , illustrated as X&#39;s, of a first portion  522  of the indicator assembly  520  are visible through the viewing portion  511  as illustrated in  FIG.  5 A , to a dose end position in which one or more dose end indicators  521 , illustrated as check marks, of a second portion  523  are visible through the viewing portion  511  as illustrated in  FIG.  5 C . As illustrated in  FIGS.  5 A and  5 C , the visual indicator  524  may be a visually distinct symbol from the dose end indicator  521 , as previously described. A release mechanism  540 , illustrated as a pin, releasably holds the indicator assembly  520  in the dose remaining position and is linked to a movable seal  550  such that the movable seal reaching an injection end position causes the release mechanism  540  to release the indicator assembly  520  to the dose end position. The release mechanism  540  may be linked to the movable seal  550 , for example, by a tensioner  570 , illustrated as a flat or round cable, that unfolds and becomes taut as the movable seal  550  advances toward the injection end position, pulling the release mechanism  540  out of contact with, and thus releasing, the indicator assembly  520 . When the release mechanism  540  releases the indicator assembly  520 , the biaser  531  is unconstrained and forces the first portion  522  and the second portion  523 , which may be static relative to one another, to pivot about the pivot axis PA so the dose end indicator  521  is visible through the viewing window  511 . In other respects, the injection device  500  may be similar to the previously described injection device  100 . 
     In another exemplary embodiment illustrated in  FIGS.  6 A and  6 B , an automatic injection device  600  is provided that is similar to the automatic injection device  500 , with similar elements numbered similarly in  FIGS.  6 A and  6 B , but includes an indicator assembly  520 ′ with a visual indicator  524 ′ that is a different color from a dose end indicator  521 ′ of the indicator assembly  520 ′. The visual indicator  524 ′ of  FIG.  6 A  may be, for example, a light or white colored portion while the dose end indicator  521 ′ of  FIG.  6 B  is a dark color, such as black, red, etc., that is visually distinct from the visual indicator  524 ′. The visual indicator  524 ′ may convey that there is at least some dose of drug product remaining and the dose end indicator  521 ′ may convey to a user that the dose has been delivered. In all other respects, the automatic injection device  600  is similar to the automatic injection device  500 . 
     In some embodiments, and referring now to  FIGS.  5 B and  7   , an anchor  571  may be configured to directly or indirectly couple to the movable seal  550  and may be connected to the tensioner  570  to link the movable seal  550  to the release mechanism  540 . The anchor  571  may couple to the movable seal  550  by, for example, threading into threads  771  of the movable seal  550 . The anchor  571  may be bonded to the tensioner  570  by an adhesive or otherwise connected to the tensioner  570  so the anchor  571  can pull the tensioner  570  and connected release mechanism  540  as the movable seal  550  moves toward the injection end position to urge drug product out of the housing  410 . 
     In some embodiments a first portion of an indicator assembly is movable relative to a second portion of the indicator assembly. For example, one of the portions may be viewable through the viewing portion of the housing when the indicator assembly is in the dose remaining position. When the indicator assembly reaches the dose end position, one of the portions may move out of, or alternatively into, view through the viewing portion to indicate that the dose has been ejected from the housing. 
     From the foregoing, it should be appreciated that the injection devices  500 ,  600  provide a binary end of dose indicator assembly  520 ,  520 ′ that can convey to users that a dose of drug product has been injected without indicating progress of the injection. By having the indicator assembly  520 ,  520 ′ pivoted about the pivot axis PA extending orthogonally, or in some embodiments transversely, to the longitudinal axis LA, the indicator assembly  520 ,  520 ′ can be formed with a relatively small size. The relatively small size of the indicator assembly  520 ,  520 ′ may assist with, for example, assembly of the injection device  500 ,  600  and allow other components to fit within the injection devices  500 ,  600 . 
     Referring now to  FIG.  8 A , a portion of an injection device  800  is illustrated that utilizes fluid pressure to drive a movable seal  850 , such as a stopper, in a housing  810 , rather than a spring or other type of solid biasing element. As used herein, a “fluid” may be, but is not limited to, a liquid, a gas, or a combination of a liquid and a gas. The movable seal  850  is linked to a release mechanism  840 , such as a pin, that extends through a partition  825  that fluidly isolates a first fluid space S 1  of the housing  810  from a second fluid space S 2  of the housing  810 . As used herein, the first fluid space S 1  is “fluidly isolated” from the second fluid space S 2  in the sense that the fluid spaces S 1 , S 2  are not in fluid communication so respective fluid pressures in each fluid space S 1 , S 2  do not spontaneously equilibrate. In some embodiments, the first fluid space S 1  may be open to a surrounding environment and have a fluid pressure that is substantially similar to atmospheric pressure. The movable seal  850 , which may be a stopper disposed in a container holding one or more drug products, fluidly isolates a third fluid space S 3  from the second fluid space S 2 , the significance of which will be described further herein. 
     The release mechanism  840  may be disposed in a release mechanism opening  826  formed in the partition  825  and at least partially surrounded by, or embedded within, a plug  841  that seals the release mechanism opening  826  and maintains fluid isolation between the first fluid space S 1  and the second fluid space S 2 . In some embodiments, an indicator assembly  820 , which may be similar to any of the previously described indicator assemblies, is disposed in the first fluid space S 1  of the housing  810  and sealed off from the second fluid space S 2  of the housing  810  in which the movable seal  850  is disposed. The release mechanism  840  may be linked to the movable seal  850  by a tensioner  870 , which may be a monofilament wire or similar element, such that movement of the movable seal  850  to an injection end position causes the release mechanism  840  to release the indicator assembly  820 . The injection device  800  further includes a valve  890  that extends into the second fluid space S 2  of the housing  810  to, for example, selectively inject pressurized fluid into the second fluid space S 2  of the housing  810 , increasing the fluid pressure in the second fluid space S 2  and driving the movable seal  850  when the valve  890  is activated. 
     When the valve  890  activates, pressurized fluid enters the second fluid space S 2  of the housing  810  and urges the movable seal  850  toward the injection end position, As the movable seal  850  moves toward the injection end position, the movable seal  850  pressurizes the third fluid space S 3  to urge drug product from the housing  810  and pulls the release mechanism  840  via the tensioner  870 , Once the movable seal  850  reaches the injection end position, the release mechanism  840  releases the indicator assembly  820  to a dose end position so a user may see that the injection has ended, In some embodiments, the movable seal  850  fully pulls the release mechanism  840  through the release mechanism opening  826  upon reaching the injection end position, establishing a path for the fluid pressure in the second fluid space S 2  to vent and equalize with the pressure in the first fluid space S 1 . In some embodiments, the burst of fluid venting into the first fluid space S 1  may partially or fully drive the indicator assembly  820  to the dose end position. Alternatively, in some embodiments, at least a portion of the release mechanism  840  remains in the release mechanism opening  826  upon the movable seal  850  reaching the injection end position, maintaining the fluid separation between the first fluid space S 1  and the second fluid space S 2 . 
     Referring now to  FIGS.  8 B- 8 D , exemplary embodiments of the partition  825  illustrated in  FIG.  8 A  for fluidly isolating the first fluid space S 1  and the second fluid space S 2  are illustrated. In one embodiment, illustrated in  FIG.  8 B , a partition  825 A is formed as a septum comprising a rubber or similar material with the tensioner  870 , which may be a monofilament wire, pierced through the septum  825 A by, for example, a needle or other sharp element carried by the tensioner  870  to form a tensioner opening  872  in the septum  825 A. The rubber material of the septum  825 A seals around the tensioner  870  in the tensioner opening  872  to seal and isolate the first fluid space S 1  from the second fluid space S 2 . 
     In another embodiment, illustrated in  FIG.  8 C , a partition  825 B is formed as a septum comprising a rubber or similar material with the tensioner  870  extending through a tensioner opening  871  formed in the septum  825 B and sealed with a sealant or other type of material. 
     In another embodiment, illustrated in  FIG.  8 D , a partition  825 C is formed as a rolling diaphragm seat that seals around the tensioner  870  to maintain the fluid isolation between the first fluid space S 1  and the second fluid space S 2 . 
     It should be appreciated from the foregoing that indicator assemblies disclosed herein may be used to indicate an injection has ended in injection devices that utilize pressurized fluid, rather than solid elements, to drive the injection. Thus, the indicator assemblies disclosed herein may be incorporated and function in many different types of injection devices, unlike many conventional indicators. 
     While the previously described injection devices  100 ,  300 ,  400 ,  500 ,  600 ,  800  are configured so their respective indicators are binary EOD indicators, in some embodiments the injection devices  100 ,  300 ,  400 ,  500 ,  600 ,  800  are configured so their respective indicators convey injection progress. 
     To convey progressive injection progress, and referring now to  FIG.  9 A , an injection device may include a release mechanism that allows progressive movement of an indicator assembly to the dose end position as the linked movable seat moves toward the injection end position, in one exemplary embodiment illustrated in  FIG.  9 A , the release mechanism includes a pin  940 A with a tapered surface  942 A held in a release mechanism opening  941 A. The tapered surface  942 A abuts against and interferes with movement of a portion  920 A of an indicator assembly, which includes one or more dose end indicators and is biased in a biasing direction B toward a dose end position. As the pin  940 A moves in a distal direction D, the portion  920 A progressively slides along the tapered surface  942 A until the portion  920 A clears an entirety of the pin  940 A to reach the dose end position. The one or more dose end indicators of the portion  920 A become progressively viewable as the portion  920 A progressively slides along the tapered surface  942 A, allowing a user to follow progress of the injection. 
     To convey step-wise injection progress, and referring now to  FIG.  9 B , an injection device may include a release mechanism that allows step-wise movement of an indicator assembly to the dose end position as the linked movable seal moves toward the injection end position. In one exemplary embodiment illustrated in  FIG.  9 B , the release mechanism includes a stepped pin  940 B with a series of steps  943 A,  943 B held in a release mechanism opening  941 B. One of the steps, such as step  943 A, initially abuts against and interferes with movement of a portion  920 B of an indicator assembly, which includes one or more dose end indicators and is biased in a biasing direction B toward a dose end position. As the stepped pin  940 B moves in a distal direction D, the steps  943 A,  943 B move in the distal direction D. When a step, such as step  943 A, travels in the distal direction D below a bottom  921 B of the portion  920 B, the portion  920 B clears the step  943 A and moves in the biasing direction B toward the dose end position until the portion  920 B contacts the next step  943 B, which inhibits further progress of the portion  920 B. This step-wise movement of the portion  920 B may repeat until the portion  920 B clears all of the steps of the stepped pin  940 B and releases to the dose end position. It should be appreciated that the number and shape of the steps  943 A,  943 B may be altered to provide the desired step-wise movement of the indicator assembly toward the dose end position. 
     In describing exemplary embodiments, specific terminology is used for the sake of clarity. For purposes of description, each specific term is intended to at least include all technical and functional equivalents that operate in a similar manner to accomplish a similar purpose. Additionally, in some instances where a particular exemplary embodiment includes a plurality of system elements or method steps, those elements or steps may be replaced with a single element or step. Likewise, a single element or step to may be replaced with a plurality of elements or steps that serve the same purpose. Further, where parameters for various properties are specified herein for exemplary embodiments, those parameters may be adjusted up or down by 1/20th, 1/10th, ⅕th, ½nd, and the like, or by rounded-off approximations thereof, unless otherwise specified. Moreover, while exemplary embodiments have been shown and described with references to particular embodiments thereof, those of ordinary skill in the art will understand that various substitutions and alterations in form and details may be made therein without departing from the scope of the invention, Further still, other aspects, functions and advantages are also within the scope of the invention.