ADAPTIVE PRIMARY PACKAGING FOR THERAPEUTIC SOLUTIONS

Various container assemblies for containing a therapeutic liquid are provided. A first container assembly comprises a frame having a proximal end and a distal end and includes a plurality of axially extending legs, a collar attached to the plurality of axially extending legs at the proximal end of the frame, and a collapsible film covering the frame and attached to the distal end of the frame and at least a portion of the collar. A second 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.

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.

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 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; and4. 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 toFIGS. 1 to 2F, an example of a container assembly10according to a first embodiment is illustrated. InFIG. 1, which is an exploded view, the container assembly10includes a stopper20. The stopper20is preferably elastomeric and may include one or more securing features, for example, the radial ridges and captivating ridge discussed below with respect toFIGS. 5A and 5B, to prevent displacement of the stopper20after insertion into an opening within a stopper collar30of the container assembly, as illustrated in the assembled view inFIG. 2A. The stopper collar30preferably is attached to a generally rigid frame40. In the embodiment ofFIG. 1, the frame40is generally rectangular having two parallel legs41a,41b. The proximal end40aof the legs41a,41bare attached to the stopper collar30while the distal end40bof the legs41a,41bare joined to an end portion40cof the frame40. The end portion40cis preferably perpendicular to the parallel legs41a,41b. 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 assembly10further comprises a film50that is preferably attached to at least a portion of the stopper collar30and/or the frame410, preferably the end portion43of the frame. The film50is preferably transparent to allow manual or automated inspection of the contents of the container assembly10after filling. Upon inserting the stopper20into the stopper collar30, the container assembly10is preferably sealed to prevent the escape of any liquids contained therein.

The stopper collar30, the frame40, and the stopper20may be formed of polymer materials known in the art. For example, the stopper collar30and frame40may 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 stopper20is preferably elastomeric and may be made from one or more of butyl rubbers, thermoplastic elastomers, thermoplastic urethanes, or other suitable materials.

The stopper collar30optionally includes a flange32located at a proximal end of the main portion34of the stopper collar30and extends radially to a distance greater than the outer diameter of the main portion34. The flange32may help to adapt the container10for use in tub-and-nest arrangements used in fill operations. The distal end portion40cof the generally rectangular frame40optionally includes a needle huh42for accommodating a needle70. The container assembly10may also optionally include a needle guard71, as illustrated inFIG. 2E, for preventing needle sticks. The needle70and needle hub42preferably extend coaxially with the longitudinal axis of the container assembly10. As previously noted, the film50is attached, preferably fused, to the main portion34of the stopper collar30and may be fused to a distal portion of the generally, rectangular frame40, such as the distal end portion40cthereof.

When the rectangular frame40, the needle70, and the film50are assembled, the assembled container10, as seen inFIG. 2A, forms a closable cavity for holding a medicine or therapeutic solution. When the container assembly10is in the assembled condition and filled with a therapeutic solution, the film50may comprise a generally cylindrical proximal portion52and a tapered distal portion34. The tapered distal portion54may help to reduce the amount of residual therapeutic solution or mixture that remains in the container assembly10when the contents are emptied or after injection into a patient due to imperfect emptying of the container10. After filling the container, the stopper20is secured within the stopped collar30to 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 assembly10ofFIG. 2Ais in a filled condition, wherein the container has a therapeutic liquid stored therein. In the filled condition, the film50may 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 container10is empty after use, the film50may 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 toFIGS. 3A and 3B, another embodiment of the container assembly is illustrated. The container assembly may include a collar30′ in which a stopper20′ is inserted, as well as a flexible film50′ in the shape of a container having a proximal end attached to a portion of the collar30′ 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 film50′ 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 toFIGS. 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 assembly10″ ofFIG. 4, the assembly may include a stopper20″, stopper collar30″, and flexible film50″ 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 assembly10″ ofFIG. 4, a syringe or pump having a sufficiently long needle capable of penetrating through the thickness of the stopper20″ 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 toFIG. 5A, the proximal end of the stopper120may include a top flange portion121. The diameter of the top flange portion121is preferably greater that than the inner diameter of the opening in the stopper collar, such that the bottom surface of the top flange portion121will abut the top surface of the stopper collar130when the stopper120is fully inserted into the opening of the stopper collar130. The stopper120may also be provided with a wedge-like flange124at the distal end of the stopper120. The wedge-like flange124may have an inclined leading edge that allows for insertion of the stopper120into the opening of the stopper collar130, as well as a top edge that is parallel with the bottom surface of the stopper collar130. The height of the stopper120may be selected, such that the top edge of the wedge-like flange124abuts against the bottom surface of the collar130when the top flange portion121contacts the top surface of the collar130, thereby captivating the stopper120within the collar130. The stopper120may further include one or more annular ridges122about the main portion of the stopper120between the top flange121and bottom wedge-like flange124. The ridges122may have a diameter that is slightly greater than the opening of the collar130in order to form a seal between the ridges122and inner circumferential surface of the collar130.

In another embodiment, a stopper120′ as illustrated inFIG. 5Bmay again include a top stopper flange121′ and one or more annular ridges122′; however, instead of relying on a bottom wedge-like flange to captivate the stopper, the stopper collar130may be provided with annular grooves123in the inner circumferential surface of the collar130′. The size, shape, and location of the grooves123may be selected to mate with the annular ridges12′ of the stopper120′ when the stopper120′ is fully inserted and the top flange121′ contacts the top surface of the collar130′; thereby, captivating the stopper120′ within the collar130′.

FIG. 5Cdepicts a stopper220for 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 stopper220comprises a tapered distal end22and may further include one or more optional radial ridges222for sealing against the inner circumferential surface of corresponding stopper collar; as previously described. Referring toFIG. 5D, when the outer flexible film250is collapsed in order to expel the liquid contents of the container, the flexible film250is capable of conforming closely to the shape of the tapered distal end221of the stopper220, 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 toFIGS. 6A to 6G, in one embodiment, the container assembly310comprises a collar330having a plurality of connected segments, preferably in the form of panels331a,331b,331c,331d. In an embodiment in which the segments comprise four panels, such as the embodiment illustrated inFIGS. 6A to 6G, the opening within the collar330may, 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 assembly310may Maher comprise a flexible film350, made of similar materials and preferably transparent as previously described, that is attached to one of the open ends of the collar330and dosed at a distal end351of the film350to essentially form a tillable bag or pouch. A rigid frame as previously disclosed may be incorporated within the container assembly310; however, the rigid frame is optional.

While the collar330is in the open condition, the container assembly310may be filled with a therapeutic liquid and subsequently sealed by collapsing the collar330along pre-defined bending/deflection zones that effectively hinge the assembly collar330to permit movement into a relatively flat closed configuration, as illustrated inFIGS. 6B, 6F and 6G. When the collar330has been moved into the closed condition, a closure latch338alocated on panel331amay capture catch340alocated on panel331bto secure the collar in the dosed condition. Optionally, a second closure latch338blocated on panel331dand catch340hlocated on panel331cmay be located on the opposing side of the collar330in the closed condition.

The collar330may further comprise a seal portion332located on at least a portion of the inner surface of the panels331a-331d. When the collar330is in the dosed condition, the seal portion332may similarly be compressed into a at configuration. The seal portion332is preferably made of material that may be sealed under sufficient temperature and/or pressure to seal the container assembly310and thereby ensure container closure integrity during the entire product life of the therapeutic liquid within the container. For example, the material of the seal portion332may 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 panels331a-331d. Additionally, a port336(best viewed inFIG. 6G) may preferably be provided through a central portion of the collar330(when collapsed) and may preferably be formed by curved portions337a,337bof the respective panels331a-331dwhich are aligned when the collar330is collapsed. The port336may be provided as a guide for a needle that may be introduced through the sealing elastomer of the seal portion332for extraction of the therapeutic liquid from within the container.

The embodiment depicted inFIGS. 6A-6Gmay be include one or more of the previously disclosed features, such as the frames and/or needle hubs depicted inFIGS. 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 port336inFIGS. 6fand 6g) 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 film350may generate an internal pressure serving to expel the therapeutic liquid from the container assembly310. 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 7Fare views of another embodiment of a container assembly410having a flexible film450, preferably transparent film, attached to a collapsible collar430shown in an open configuration. Both the film450and collar430may be made of similar materials as previously described. The collar430comprises a plurality of segments, preferably in the form four rectangular panels,431a,431b,431c,431d, with the panels being connected, preferably by hinges434a,434b,436a,436b(which may be living; hinges formed from a portion of the panel material) at adjacent panel edges such that the collar430may be collapsed into a closed configuration. Similar to the embodiment ofFIGS. 6A to 6G, the collar430includes latches438a,438band catches440a,440bon opposing sides of the collar430. When collapsed to a closed state, hinges436a,436b, which are located between the latches438a,438band catches440a,440bare urged towards each other until the catches440a,440bpass through an aperture441a,441bof their respective latches438a,438bto maintain the collar430in a flat closed configuration.

The collar430further comprises a seal portion432that is attached to the inner surfaces of the panels431a,431b,431c,431d. Similar to the previously described seal portion, the seal portion432is 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 portion432adjacent to the hinges436a,436bbetween the latches438a,438band catches440a,440b, the hinges436a,436bmay be provided with one or more longitudinal fins439that will contact and compress the central portions of the seal portion432in the flat closed configuration.

As best viewed inFIG. 7B, the flexible film450may be attached to the collar430between the panels431a,431b,431c,431dand the seal portion432. The film450is preferably fused to the lower portion of the outer surface of the seal portion432. In order to affix the seal portion432to the inner surfaces of the panels431a,431b,431c,431d, the seal portion may be provided with one or more rails433that may be inserted or molded into corresponding tracks442on the inner surfaces of the panels431a,431b,431c,431d. The edges of the rails433may be flared in order to provide an interference fit, for example, between the rails433and the tracks442.

FIGS. 8A to 8Care views of a container assembly510having a collar530with a rectangular radially outwardly extending flange532and a stopper526having radial ridges522for forming a seal with the inner surface of the collar530. The container assembly510further comprises a flexible film550. As illustrated, film550is collapsed; therefore, the container assembly510is shown in the empty condition, after use, A rigid frame may or may not be included in the container assembly510. The collar530is provided with a relatively large flange532, so that the container assembly510may be loaded into automated filling equipment and/or nest tubs, for example.

Referring toFIGS. 9A and 9B, another embodiment of the container assembly710includes a collar730compatible with a tapered stopper720. The container assembly710is shown in a collapsed state, in which the film750and the container710is generally rectangular. The container710does not have a needle hub or needle attached, but may include an optional port742located within a distal end of the rectangular frame within the film750. Therefore, the liquid contents of the container assembly710may be accessed either through the stopper720or the port742. The container assembly710has a collar for receiving the stopper720, and the frame within the film750is attached to a distal end of the collar730. The collar730may also include a flange712. Unlike the previously described flanges that extend radially from a proximal end of the collar, the collar730may include an axially oriented flange712arranged generally perpendicular to a principal side of film750wherein the rectangular shape is formed when the container is collapsed after use. The axially oriented flange712provides two corners having an axial edge and a radial edge that may aid in aligning the container710within an injection device or other fluid-dispensing device.

Referring toFIGS. 10A to 10D, another embodiment of a container assembly810includes a stopper collar830, a stopper820, a film850, and a Y-shaped internal frame840with a needle hub860and a needle870inserted therein. The Y-shaped internal frame840has a proximal end840aconnected to the stopper collar830and a distal end840bconnected to the needle nub860. The frame840has two outer legs840c,840dwhich taper from two outer-leg connection points on the bottom surface at the distal end of the collar830inwardly to join an intermediate portion840eof the Y-shaped frame. In the embodiment depicted, the intermediate portion840ehas a smaller width than the diameter of the stopper collar830. The internal frame840also has a center leg840fwhich connects to a transverse support member840gof the stopper collar. An aperture844located towards the distal end840bof the frame840may be in fluid communication with a via848and the needle870to provide a pathway for fluid to exit the container through the central lumen of the needle870. 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