Patent Publication Number: US-2022218565-A1

Title: Adaptive primary packaging for therapeutic solutions

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the benefit of and priority to U.S. Provisional Application Ser. No. 62/849,215, filed on May 17, 2019; the content of which is incorporated herein by reference in its entirety. 
    
    
     BACKGROUND 
     Various embodiments disclosed herein are directed to container assemblies. More specifically, the various embodiments are directed to container assemblies that are flexible and easily adaptable to various uses as primary packaging for therapeutic solutions. 
     The design of the primary container for holding therapeutic medicines in liquid form encounters several challenges. For example, the volume of medicine delivered and tested to clinical patients during early stage development may need be either increased or decreased during the development and/or approval process during the later stages of development. As a result, the form of the primary container used to hold and/or deliver the medicine may need to be re-designed. This may not only affect the design of the delivery device that carries the primary container, but also the filling equipment used to fill the primary container. 
     Thus, there is a need for improved primary packaging for therapeutic solutions that may be easily adaptable to various environments during the drug development process, as well as manufacturing processes when the drug is ultimately approved for use. 
     SUMMARY 
     In one aspect, a container assembly for a therapeutic liquid comprises a frame, a collar, and a collapsible film. The frame may have a proximal end and a distal end and comprise a plurality of axially extending legs. The collar may be attached to the plurality of axially extending legs at the proximal end of the frame. The collapsible film may cover the frame and attach to the distal end of the frame and at least a portion of the collar. 
     In another aspect, a container assembly for a therapeutic liquid comprises a collar and a collapsible film. The collar may comprise a plurality of hingedly connected segments configured to switch from an open configuration to a closed configuration. The collapsible film may be configured as a pouch having an open end attached to one end of the collar. 
     These and other aspects of the various embodiments disclosed herein will be apparent in view of the following description. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
       Various aspects and embodiments of the present concepts disclosed herein will be described with reference to the following figures. It should be appreciated that the figures are not necessarily drawn to scale. The figures depict one or more implementations in accord with the present concepts, by way of example only, not by way of limitations. In the figures, like reference numerals refer to the same or similar elements. 
         FIG. 1  is a top perspective exploded view of a container assembly according to a first embodiment. 
         FIG. 2A  is a top perspective view of the first embodiment in an assembled condition. 
         FIG. 2B  is a front view of the first embodiment in the assembled condition. 
         FIG. 2C  is a side view of the first embodiment in the assembled condition. 
         FIG. 2D  is a side view of the first embodiment, wherein the film-formed container is in a collapsed condition. 
         FIG. 2E  is top perspective view of the first embodiment in combination with a needle guard. 
         FIG. 2F  is a partial top perspective view of proximal end of a stopper collar of the first embodiment. 
         FIG. 3A  is a side view of a container assembly according to a second embodiment. 
         FIG. 3B  is a front view of the second embodiment. 
         FIG. 4  is a top perspective view of a container assembly according to a third embodiment. 
         FIG. 5A  is a partial cross-sectional side view of a proximal end of a container assembly according to a fourth embodiment. 
         FIG. 5B  is a partial cross-sectional side view of a proximal end of a container assembly according to a fifth embodiment. 
         FIG. 5C  is a top perspective view of a closure that may be included in a container assembly. 
         FIG. 5D  is a partial top perspective view of a proximal end of a container assembly with the closure of  FIG. 5C . 
         FIG. 6A  is a top perspective view of a container assembly according to a sixth embodiment having a collar in an open configuration. 
         FIG. 6B  is a top perspective view of the sixth embodiment in a closed configuration. 
         FIG. 6C  is a top perspective view of a seal portion of the sixth embodiment. 
         FIG. 6D  is a partial top perspective view of the proximal end of the sixth embodiment illustrating the position of the seal portion within a collar. 
         FIG. 6E  is a partial top perspective view of the proximal end of the sixth embodiment, wherein the collar is in the open configuration. 
         FIG. 6F  is a partial top perspective view of the proximal end of the sixth embodiment, wherein the collar is in the closed configuration. 
         FIG. 6G  is a magnified partial view of  FIG. 6F . 
         FIG. 7A  is a top perspective front view of a seventh embodiment, wherein the collar is in the open configuration. 
         FIG. 7B  is a top perspective front view of the seventh embodiment, wherein the collar is absent. 
         FIG. 7C  is a top perspective front view of a seal portion of the seventh embodiment. 
         FIG. 7D  is a top perspective front view of the collar of the seventh embodiment. 
         FIG. 7E  is a top perspective rear view of the collar of the seventh embodiment. 
         FIG. 7F  is a top perspective side view of the collar of the seventh embodiment. 
         FIG. 8A  is a top perspective view of a container assembly according to an eighth embodiment. 
         FIG. 8B  is a top perspective view of a closure included in the container assembly of the eighth embodiment. 
         FIG. 8C  is a top perspective view of the eighth embodiment excluding the closure. 
         FIG. 9A  is a top perspective view of a container assembly according to a ninth embodiment. 
         FIG. 9B  is a side view of the ninth embodiment. 
         FIG. 10A  is a front plan view of a container assembly according to a tenth embodiment. 
         FIG. 10B  is a front plan view of the collar and frame of the tenth embodiment. 
         FIG. 10C  is a side view of  FIG. 10B . 
         FIG. 10D  is a bottom perspective view of the  FIG. 10B . 
     
    
    
     DETAILED DESCRIPTION 
     Certain terminology is used in the following description for convenience only and is not limiting. The words “lower,” “bottom,” “upper” and “top” designate directions in the drawings to which reference is made. The words “inwardly,” “outwardly,” “upwardly” and “downwardly” refer to directions toward and away from, respectively, the geometric center of the liquid transfer device, and designated parts thereof, in accordance with the present disclosure. 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.” The terminology includes the words noted above, derivatives thereof and words of similar import. 
     It should also be understood that the terms “about,” “approximately,” “generally,” “substantially” and like terms, used herein when referring to a dimension or characteristic of a component of the disclosure, indicate that the described dimension/characteristic is not a strict boundary or parameter and does not exclude minor variations therefrom that are functionally similar. At a minimum, such references that include a numerical parameter would include variations that, using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.), would not vary the least significant digit. 
     It will also be appreciated by those skilled in the art that modifications may be made to the exemplary embodiments described herein without departing from the invention. Structural features of systems and apparatuses described herein may be replaced with functionally equivalent parts. Moreover, it will be appreciated that features from the embodiments may be combined with each other without departing from the disclosure. 
     Designs are disclosed for an adaptive primary container for therapeutic solutions suitable for high-volume manufacturing. The container may incorporate means for using traditional elastomeric closure materials and flexible-tube construction. A substantially rigid stopper collar serves a purpose similar to a flange of a syringe, allowing the container to be disposed within a traditional tub-and-nest format for introduction into fill-finish equipment. An element, such as a structural protrusion or frame, may extend from the stopper collar to the di stat end of the container. The protrusion may impart structural stability to the container that would not otherwise exist, A film may be sealed and attached to the stopper collar to establish a cavity in which the therapeutic solution is stored. An elastomer placed within the stopper collar provides for container closure integrity and in certain embodiments may be applied with traditional stoppering equipment. 
     Embodiments of the presently disclosed devices may achieve one or more of the following main aspects:
         1. Introducing a primary container for pharmaceutical agents that is appropriate for long-term drug contact and permits a greater range of fill volumes while minimizing residual volume not delivered to the patient,   2. Allowing for delivery devices that accept a wider range of deliverable volumes while minimizing the size of the delivery device;   3. Permitting the same primary container to be utilized for early stage drug development and seamlessly incorporated into existing installed fill-finish equipment; and   4. Providing for a means of establishing structural integrity of the container without substantially reducing the advantages of the flexible cavity.       

     In certain embodiments, a container assembly according to the present disclosure may lend itself to current syringe-style filling practices. For example, a container assembly according to the present disclosure may not require significant changes to an existing installed base of automated equipment on a liquid filling line. In certain embodiments, a container assembly according to the present disclosure would support or would allow filling according to current high-volume practices. 
     In certain embodiments, a container assembly according to the present disclosure is adapted for incorporation and acceptability to current high-volume fill-finish equipment. Embodiments of the devices disclosed herein are compatible with syringe-style filling while maintaining the benefits of flexible-walled packaging. 
     In certain embodiments, a container assembly according to the present disclosure permits traditional, syringe-style fill-finish. For example, a container assembly according to the present disclosure may receive a stopper in similar fashion to a prefilled syringe. The container assembly may have structural stability provided by way of a substantially rigid frame. In certain embodiments, a container assembly according to the present disclosure can be rotated at high revolutions per minute consistent with standard procedures for particle inspection, in some embodiments, the container assembly may also be provided with a means to establish container closure integrity by a collapsing mechanism or portion, thus reducing or minimizing the size of the field container. In certain embodiments, a container according to the present disclosure incorporates an integrated needle for delivery in a manner similar to a prefilled syringe. Incorporating an integrated needle may reduce the number of steps that must be performed by the user in using the device. 
     In certain embodiments, a container assembly according to the present disclosure provides an increased range of fill volumes considering the size of the container, compared to alternative containers. This may enable flexibility during development of the medication as the dose size is determined through clinical trials. In certain embodiments, a container assembly according to the present disclosure provides greater flexibility, permitting incorporation into a variety of injection modalities without changing the primary packaging. For example, the container assemblies according to the present disclosure may have a smaller size for a given volume of injection than alternative containers. Container assemblies according to the present disclosure may also permit on-body-type injections without requiring transferring contents between containers at or prior to the time of use. 
     The container assemblies according to the present disclosure may be used for the storage of therapeutic solutions from tilling to patient administration. The process of filling may be substantially similar to that of a prefilled syringe. The containers may be supplied equipment in a tub-and-nest format to a site with appropriate fill-finish equipment. Once extracted from the secondary packaging, the containers may be filled by peristaltic or rotary motion pumps. Following filling of the container, container closure may be established using an elastomeric closure, such as a stopper, or using a collapsible collar described in greater detail below. 
     Referring now to  FIGS. 1 to 2F , an example of a container assembly  10  according to a first embodiment is illustrated. In  FIG. 1 , which is an exploded view, the container assembly  10  includes a stopper  20 . The stopper  20  is preferably elastomeric and may include one or more securing features, for example, the radial ridges and captivating ridge discussed below with respect to  FIGS. 5A and 5B , to prevent displacement of the stopper  20  after insertion into an opening within a stopper collar  30  of the container assembly, as illustrated in the assembled view in  FIG. 2A . The stopper collar  30  preferably is attached to a generally rigid frame  40 . In the embodiment of  FIG. 1 , the frame  40  is generally rectangular having two parallel legs  41   a ,  41   b . The proximal end  40   a  of the legs  41   a ,  41   b  are attached to the stopper collar  30  while the distal end  40   b  of the legs  41   a ,  41   b  are joined to an end portion  40   c  of the frame  40 . The end portion  40   c  is preferably perpendicular to the parallel legs  41   a ,  41   b . In some embodiments the stopper collar and frame may be formed as a unitary piece. In other embodiments, the stopper collar and frame may be separate pieces that are joined either mechanically with a snap fit, for example, or fused together. 
     The container assembly  10  further comprises a film  50  that is preferably attached to at least a portion of the stopper collar  30  and/or the frame  410 , preferably the end portion  43  of the frame. The film  50  is preferably transparent to allow manual or automated inspection of the contents of the container assembly  10  after filling. Upon inserting the stopper  20  into the stopper collar  30 , the container assembly  10  is preferably sealed to prevent the escape of any liquids contained therein. 
     The stopper collar  30 , the frame  40 , and the stopper  20  may be formed of polymer materials known in the art. For example, the stopper collar  30  and frame  40  may be made from cyclic olefin polymer, cyclic olefin copolymer, polypropylene, glass, or other suitable material, if of a rigid type, as well as combinations thereof. The stopper  20  is preferably elastomeric and may be made from one or more of butyl rubbers, thermoplastic elastomers, thermoplastic urethanes, or other suitable materials. 
     The stopper collar  30  optionally includes a flange  32  located at a proximal end of the main portion  34  of the stopper collar  30  and extends radially to a distance greater than the outer diameter of the main portion  34 . The flange  32  may help to adapt the container  10  for use in tub-and-nest arrangements used in fill operations. The distal end portion  40   c  of the generally rectangular frame  40  optionally includes a needle huh  42  for accommodating a needle  70 . The container assembly  10  may also optionally include a needle guard  71 , as illustrated in  FIG. 2E , for preventing needle sticks. The needle  70  and needle hub  42  preferably extend coaxially with the longitudinal axis of the container assembly  10 . As previously noted, the film  50  is attached, preferably fused, to the main portion  34  of the stopper collar  30  and may be fused to a distal portion of the generally, rectangular frame  40 , such as the distal end portion  40   c  thereof. 
     When the rectangular frame  40 , the needle  70 , and the film  50  are assembled, the assembled container  10 , as seen in  FIG. 2A , forms a closable cavity for holding a medicine or therapeutic solution. When the container assembly  10  is in the assembled condition and filled with a therapeutic solution, the film  50  may comprise a generally cylindrical proximal portion  52  and a tapered distal portion  34 . The tapered distal portion  54  may help to reduce the amount of residual therapeutic solution or mixture that remains in the container assembly  10  when the contents are emptied or after injection into a patient due to imperfect emptying of the container  10 . After filling the container, the stopper  20  is secured within the stopped collar  30  to form a sealed container that prevents leaking of any therapeutic liquid, and preferably prevents the ingress of any undesired contaminants into the container. 
     As previously noted, the container assembly  10  of  FIG. 2A  is in a filled condition, wherein the container has a therapeutic liquid stored therein. In the filled condition, the film  50  may form a generally cylindrical or other expanded form having a first volume. In order to expel the liquid within the container assembly, the flexible outer film may be manually or mechanically compressed causing the therapeutic liquid to exit the needle through the needle hub. When the container  10  is empty after use, the film  50  may flatten and conform to the shape of the internal frame, e.g. forming a rectangular shape of relatively small height or thickness, and having a second, lesser volume, ( FIG. 2D ). 
     Referring to  FIGS. 3A and 3B , another embodiment of the container assembly is illustrated. The container assembly may include a collar  30 ′ in which a stopper  20 ′ is inserted, as well as a flexible film  50 ′ in the shape of a container having a proximal end attached to a portion of the collar  30 ′ and a distal end that is welded or fused closed. The length of the weld may be selected to ensure closure integrity and prevent any leakages. The proximal end of the film  50 ′ may also be welded to a portion of an internal frame. For example, the container assembly may further comprise a V-shaped frame, such as the frame discussed in greater detail below with respect to  FIGS. 10A-10D . 
     As previously noted, the inclusion of a needle hub and needle in the container assembly is optional. In some embodiments, such as the container assembly  10 ″ of  FIG. 4 , the assembly may include a stopper  20 ″, stopper collar  30 ″, and flexible film  50 ″ attached to an internal frame (not shown), such as those previously described; but, the needle hub and needle may be excluded. In order to extract the liquid stored within the container assembly  10 ″ of  FIG. 4 , a syringe or pump having a sufficiently long needle capable of penetrating through the thickness of the stopper  20 ″ may be inserted to access the internal contents of the container, for example. 
     In order to prevent displacement of the stopper and maintain a sealed container, the stopper may include one or more securing features. For example, referring to  FIG. 5A , the proximal end of the stopper  120  may include a top flange portion  121 . The diameter of the top flange portion  121  is preferably greater that than the inner diameter of the opening in the stopper collar, such that the bottom surface of the top flange portion  121  will abut the top surface of the stopper collar  130  when the stopper  120  is fully inserted into the opening of the stopper collar  130 . The stopper  120  may also be provided with a wedge-like flange  124  at the distal end of the stopper  120 . The wedge-like flange  124  may have an inclined leading edge that allows for insertion of the stopper  120  into the opening of the stopper collar  130 , as well as a top edge that is parallel with the bottom surface of the stopper collar  130 . The height of the stopper  120  may be selected, such that the top edge of the wedge-like flange  124  abuts against the bottom surface of the collar  130  when the top flange portion  121  contacts the top surface of the collar  130 , thereby captivating the stopper  120  within the collar  130 . The stopper  120  may further include one or more annular ridges  122  about the main portion of the stopper  120  between the top flange  121  and bottom wedge-like flange  124 . The ridges  122  may have a diameter that is slightly greater than the opening of the collar  130  in order to form a seal between the ridges  122  and inner circumferential surface of the collar  130 . 
     In another embodiment, a stopper  120 ′ as illustrated in  FIG. 5B  may again include a top stopper flange  121 ′ and one or more annular ridges  122 ′; however, instead of relying on a bottom wedge-like flange to captivate the stopper, the stopper collar  130  may be provided with annular grooves  123  in the inner circumferential surface of the collar  130 ′. The size, shape, and location of the grooves  123  may be selected to mate with the annular ridges  12 ′ of the stopper  120 ′ when the stopper  120 ′ is fully inserted and the top flange  121 ′ contacts the top surface of the collar  130 ′; thereby, captivating the stopper  120 ′ within the collar  130 ′. 
       FIG. 5C  depicts a stopper  220  for minimizing dead-space volume within the container, i.e. minimizing the volume within the container wherein therapeutic liquid will potentially remain within the container and may not be capable of being expelled. The stopper  220  comprises a tapered distal end  22  and may further include one or more optional radial ridges  222  for sealing against the inner circumferential surface of corresponding stopper collar; as previously described. Referring to  FIG. 5D , when the outer flexible film  250  is collapsed in order to expel the liquid contents of the container, the flexible film  250  is capable of conforming closely to the shape of the tapered distal end  221  of the stopper  220 , thereby reducing the potential of any dead-space volume. The result is a reduction in the potential volume of residual therapeutic liquid remaining in the container after use. 
     According to another embodiment, the stopper of the container assembly may be replaced, with a collapsible means that is configured to switch from an open condition to a sealed condition. For example, referring to  FIGS. 6A to 6G , in one embodiment, the container assembly  310  comprises a collar  330  having a plurality of connected segments, preferably in the form of panels  331   a ,  331   b ,  331   c ,  331   d . In an embodiment in which the segments comprise four panels, such as the embodiment illustrated in  FIGS. 6A to 6G , the opening within the collar  330  may, take the form of a rectangle, square, or parallelogram in the initial open configuration. The segments of the collar are preferably hingedly connected, as by a hinge or a living hinge, for example, and made of similar materials as the stopper collars of the previously described embodiments. The container assembly  310  may Maher comprise a flexible film  350 , made of similar materials and preferably transparent as previously described, that is attached to one of the open ends of the collar  330  and dosed at a distal end  351  of the film  350  to essentially form a tillable bag or pouch. A rigid frame as previously disclosed may be incorporated within the container assembly  310 ; however, the rigid frame is optional. 
     While the collar  330  is in the open condition, the container assembly  310  may be filled with a therapeutic liquid and subsequently sealed by collapsing the collar  330  along pre-defined bending/deflection zones that effectively hinge the assembly collar  330  to permit movement into a relatively flat closed configuration, as illustrated in  FIGS. 6B, 6F and 6G . When the collar  330  has been moved into the closed condition, a closure latch  338   a  located on panel  331   a  may capture catch  340   a  located on panel  331   b  to secure the collar in the dosed condition. Optionally, a second closure latch  338   b  located on panel  331   d  and catch  340   h  located on panel  331   c  may be located on the opposing side of the collar  330  in the closed condition. 
     The collar  330  may further comprise a seal portion  332  located on at least a portion of the inner surface of the panels  331   a - 331   d . When the collar  330  is in the dosed condition, the seal portion  332  may similarly be compressed into a at configuration. The seal portion  332  is preferably made of material that may be sealed under sufficient temperature and/or pressure to seal the container assembly  310  and thereby ensure container closure integrity during the entire product life of the therapeutic liquid within the container. For example, the material of the seal portion  332  may be an elastomer, pressure sensitive adhesive, or other material that is pliable and capable of forming a seal by being compressed against itself with sufficient pressure by the panels  331   a - 331   d . Additionally, a port  336  (best viewed in  FIG. 6G ) may preferably be provided through a central portion of the collar  330  (when collapsed) and may preferably be formed by curved portions  337   a ,  337   b  of the respective panels  331   a - 331   d  which are aligned when the collar  330  is collapsed. The port  336  may be provided as a guide for a needle that may be introduced through the sealing elastomer of the seal portion  332  for extraction of the therapeutic liquid from within the container. 
     The embodiment depicted in  FIGS. 6A-6G  may be include one or more of the previously disclosed features, such as the frames and/or needle hubs depicted in  FIGS. 1-4 . In certain embodiments, a needle hub is not used; and once the container is filled and container closure is established, the fluid may be extracted by introducing a needle through a port (such as the port  336  in  FIGS. 6 f  and 6 g   ) and through the elastomer of the seal portion. Alternately, embodiments with an integrated needle may utilize the needle as an outlet to expel the contents of the container assembly. Pressure applied to the flexible film  350  may generate an internal pressure serving to expel the therapeutic liquid from the container assembly  310 . Embodiments including a structural frame may provide containers that may be more easily handled within filling equipment or loaded into nesting tubs, for example, as well as loading into injection devices comprising mechanical means for applying pressure to the flexible film. 
       FIGS. 7A to 7F  are views of another embodiment of a container assembly  410  having a flexible film  450 , preferably transparent film, attached to a collapsible collar  430  shown in an open configuration. Both the film  450  and collar  430  may be made of similar materials as previously described. The collar  430  comprises a plurality of segments, preferably in the form four rectangular panels,  431   a ,  431   b ,  431   c ,  431   d , with the panels being connected, preferably by hinges  434   a ,  434   b ,  436   a ,  436   b  (which may be living; hinges formed from a portion of the panel material) at adjacent panel edges such that the collar  430  may be collapsed into a closed configuration. Similar to the embodiment of  FIGS. 6A to 6G , the collar  430  includes latches  438   a ,  438   b  and catches  440   a ,  440   b  on opposing sides of the collar  430 . When collapsed to a closed state, hinges  436   a ,  436   b , which are located between the latches  438   a ,  438   b  and catches  440   a ,  440   b  are urged towards each other until the catches  440   a ,  440   b  pass through an aperture  441   a ,  441   b  of their respective latches  438   a ,  438   b  to maintain the collar  430  in a flat closed configuration. 
     The collar  430  further comprises a seal portion  432  that is attached to the inner surfaces of the panels  431   a ,  431   b ,  431   c ,  431   d . Similar to the previously described seal portion, the seal portion  432  is preferably made of a material that is capable of being sealed under sufficient pressure and/or temperature. To ensure that sufficient compression is applied to the portions of the seal portion  432  adjacent to the hinges  436   a ,  436   b  between the latches  438   a ,  438   b  and catches  440   a ,  440   b , the hinges  436   a ,  436   b  may be provided with one or more longitudinal fins  439  that will contact and compress the central portions of the seal portion  432  in the flat closed configuration. 
     As best viewed in  FIG. 7B , the flexible film  450  may be attached to the collar  430  between the panels  431   a ,  431   b ,  431   c ,  431   d  and the seal portion  432 . The film  450  is preferably fused to the lower portion of the outer surface of the seal portion  432 . In order to affix the seal portion  432  to the inner surfaces of the panels  431   a ,  431   b ,  431   c ,  431   d , the seal portion may be provided with one or more rails  433  that may be inserted or molded into corresponding tracks  442  on the inner surfaces of the panels  431   a ,  431   b ,  431   c ,  431   d . The edges of the rails  433  may be flared in order to provide an interference fit, for example, between the rails  433  and the tracks  442 . 
       FIGS. 8A to 8C  are views of a container assembly  510  having a collar  530  with a rectangular radially outwardly extending flange  532  and a stopper  526  having radial ridges  522  for forming a seal with the inner surface of the collar  530 . The container assembly  510  further comprises a flexible film  550 . As illustrated, film  550  is collapsed; therefore, the container assembly  510  is shown in the empty condition, after use, A rigid frame may or may not be included in the container assembly  510 . The collar  530  is provided with a relatively large flange  532 , so that the container assembly  510  may be loaded into automated filling equipment and/or nest tubs, for example. 
     Referring to  FIGS. 9A and 9B , another embodiment of the container assembly  710  includes a collar  730  compatible with a tapered stopper  720 . The container assembly  710  is shown in a collapsed state, in which the film  750  and the container  710  is generally rectangular. The container  710  does not have a needle hub or needle attached, but may include an optional port  742  located within a distal end of the rectangular frame within the film  750 . Therefore, the liquid contents of the container assembly  710  may be accessed either through the stopper  720  or the port  742 . The container assembly  710  has a collar for receiving the stopper  720 , and the frame within the film  750  is attached to a distal end of the collar  730 . The collar  730  may also include a flange  712 . Unlike the previously described flanges that extend radially from a proximal end of the collar, the collar  730  may include an axially oriented flange  712  arranged generally perpendicular to a principal side of film  750  wherein the rectangular shape is formed when the container is collapsed after use. The axially oriented flange  712  provides two corners having an axial edge and a radial edge that may aid in aligning the container  710  within an injection device or other fluid-dispensing device. 
     Referring to  FIGS. 10A to 10D , another embodiment of a container assembly  810  includes a stopper collar  830 , a stopper  820 , a film  850 , and a Y-shaped internal frame  840  with a needle hub  860  and a needle  870  inserted therein. The Y-shaped internal frame  840  has a proximal end  840   a  connected to the stopper collar  830  and a distal end  840   b  connected to the needle nub  860 . The frame  840  has two outer legs  840   c ,  840   d  which taper from two outer-leg connection points on the bottom surface at the distal end of the collar  830  inwardly to join an intermediate portion  840   e  of the Y-shaped frame. In the embodiment depicted, the intermediate portion  840   e  has a smaller width than the diameter of the stopper collar  830 . The internal frame  840  also has a center leg  840   f  which connects to a transverse support member  840   g  of the stopper collar. An aperture  844  located towards the distal end  840   b  of the frame  840  may be in fluid communication with a via  848  and the needle  870  to provide a pathway for fluid to exit the container through the central lumen of the needle  870 . Note that in any of the embodiments, the support frames preferably may be generally planar so that when the container is empty, the film may collapse as much as possible. 
     It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that the scope of this disclosure is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope thereof