APPARATUS AND SYSTEM FOR DRUG RECONSTITUTION BY LIQUID TRANSFER

Abstract

An apparatus for combining a first liquid component 90 stored in a container 125 and a second component stored in a vial 7 by means of negative pressure is disclosed. A tray 1 has a vial cavity 11 and a container cavity 12. A dual-ended transfer needle 131 is fixedly held at the tray 1 at an intermediate needle holding portion 13 between the vial cavity 11 and the container cavity 12 for establishing a fluid communication between the vial 7 and the container 125 by piercing a rubber stopper of the vial and a bottom of the container, respectively. The vial cavity 11 guides the vial 7 along an axial direction AD from an intermediate position towards the transfer position for fluid communication. And the container cavity 12 guides the container 125 along the axial direction AD from an intermediate position towards the transfer position for fluid communication.

Claims

1. An apparatus for combining a first liquid component (90) stored in a container (125) and a second solid or liquid component stored in a vial (7) by means of negative pressure, comprising a tray (1) having a vial cavity (11) for accommodating at least a portion of the vial (7) and a container cavity (12) for accommodating at least a portion of the container (125), and a transfer needle (131) having a first needle tip (131a), a second needle tip (131b) and a lumen (131) for establishing a fluid communication between the vial (7) and the container (125) in a transfer position, in which the first needle tip (131a) is engaged with the vial (7) and the second needle tip (131b) is engaged with the container (125); wherein the transfer needle (131) is fixedly held at the tray (1) at an intermediate needle holding portion (13) of the tray (1) between the vial cavity (11) and the container cavity (12), wherein the vial cavity (11) is configured for guiding a movement of the vial (7) along an axial direction (AD) from an intermediate position, in which the first needle tip (131a) is not engaged with the vial (7), towards the transfer position, and the container cavity (12) is configured for guiding a movement of the container (125) along the axial direction (AD) from an intermediate position, in which the second needle tip (131b) is not engaged with the container (125), towards the transfer position.

2. The apparatus as claimed in claim 1, wherein the vial cavity (11) or the vial cavity (11) and the container cavity (12) each comprises retaining members (35a-35c, 36a, 36b; 128, 129), which are configured to position the vial (7) and the container (125), respectively, in the intermediate position and in parallel with the axial direction (AD).

3. The apparatus as claimed in claim 2, wherein the retaining members (36a, 36b; 129) are further configured to guide an axial movement of at least one of the vial (7) and container (125) from the intermediate position to the transfer position while maintaining an axial alignment of at least one of the vial (7) and container (125) with the needle (131).

4. The apparatus as claimed in claim 3, wherein the retaining members comprise pairs of protrusions (36a, 36b; 129) formed on opposite side-walls (18, 121) of the vial cavity (11) and container cavity (12), respectively, which are configured for contacting side-surfaces of the vial (7) and container (125), respectively, for positioning the vial (7) and the container (125), respectively, and guiding the axial movement of the vial (7) and container (125), respectively, along the axial direction.

5. The apparatus as claimed in claim 4, wherein a height (h2) of contact regions (80) of the protrusions (36a, 36b; 129) with the side-surfaces of the vial (7) and container (125), respectively, above a bottom (17, 120) of the vial cavity (11) and container cavity (12), respectively, is larger than the height of a center line (CL) of the vial (7) and container (125) above the bottom (17, 120) of the vial cavity (11) and container cavity (12), respectively.

6. The apparatus as claimed in claim 4, wherein the opposite side-walls (18, 121) on which the protrusions (36a, 36b; 129) are formed are each upright and planar side-walls.

7. The apparatus as claimed in claim 4, wherein the vial cavity (11) comprises at least two pairs of protrusions (36a, 36b) formed on opposite side-walls (18) of the vial cavity (11), and at least one pair of protrusions (36b) is still in contact with side-surfaces of the vial (7) in the transfer position.

8. The apparatus as claimed in claim 4, wherein a bottom (17) of the vial cavity (11) is curved with a radius of curvature corresponding to an outer radius of a vial body (70) of at least one of the vial (7) and wherein the profile of a bottom (120) of the container cavity (13) corresponds to an outer profile of the container (125).

9. The apparatus as claimed in claim 1, wherein the vial cavity (11) further comprises axial position limiting members (35a, 35b) configured for delimiting an axial movement of the vial (7) inside the vial cavity (11) in a storage position.

10. The apparatus as claimed in claim 9, wherein the axial position limiting members (35a, 35b) are more flexible than the retaining members (36a, 36b) of the vial cavity (11).

11. The apparatus as claimed in claim 1, wherein the vial cavity (11) and the container cavity (12) each comprises a stop surface (19, 122a) for delimiting an axial displacement of the vial (7) and of the container (125) towards the transfer needle (131) by abutment with a front end (77) of the vial (7) and a surface (127) of the container (125), respectively.

12. The apparatus as claimed in claim 1, wherein the vial cavity (11) further comprises a portion (15) that is sufficiently wide to enable access to a vial body (70) of the vial (7) by means of fingers of a user or grippers of a robot in the intermediate position for at least one of driving the axial displacement of the vial (7) towards the transfer position and removal of the vial (7) in the intermediate position from the tray (1).

13. The apparatus as claimed in claim 1, wherein the vial cavity (11) further comprises a rear end cavity (14), where a bottom (71) of the vial (7) is sufficiently exposed to enable access to the bottom (71) for a finger of a user or a manipulation member of a robot for driving the axial movement of the vial (7) from the intermediate position to the transfer position.

14. The apparatus as claimed in claim 1, wherein the tray (1) comprises a tray member (10) having a planar upper surface (10a) and wherein the retaining members (35a-35c, 36a, 36b; 128, 129) of the cavities (11, 125) are formed integrally with the tray member (10).

15. The apparatus as claimed in claim 14, wherein the tray member (10) is made of plastic material by vacuum thermoforming or pressure thermo-forming of a plastic sheet or by means of plastic injection molding.

16. The apparatus as claimed in claim 14, wherein the tray member (10) is made of paper or cardboard with a thin film of plastic or bioplastic arranged on inner surfaces of at least one of the vial cavity (11) and container cavity (125).

17. The apparatus as claimed in claim 14, wherein the tray (1) comprises a first tray member (10) comprising the vial cavity (11) and having a planar upper surface (10a) and a second tray member (10) comprising the container cavity (125) and having a planar upper surface (10a), and a film hinge (140) is provided between the first tray member (10) and the second tray member (10) so that the first tray member (10) and the second tray member (10) can be pivoted relative to each other via the film hinge (140).

18. The apparatus as claimed in claim 17, wherein the film hinge (140) is a bistable film-hinge, pretensioned into an open position, in which the planar upper surface (10a) of the second tray member (10) is substantially aligned with the planar upper surface (10a) of the first tray member (10) and the vial cavity (11) and the container cavity (12) is each aligned along the axial direction.

19. The apparatus as claimed in claim 1, wherein a central portion of the transfer needle (131) is accommodated in a needle packaging (130) that is fixedly held at the tray (1) at the intermediate needle holding portion (13), the needle tips (131a, 131b) are covered by cap members (133a, 133b) so that the needle (131) is packaged under sterile conditions, the needle tips (131a, 131b) covered by the cap members (133a, 133b) protrude into the vial cavity (11) and container cavity (12), respectively, when the vial cavity (11) and the container cavity (12) is each aligned along the axial direction, and the cap members (133a, 133b) can be removed from the needle packaging (130) or opened for access to the needle tips (131a, 131b) of the transfer needle (131) for fluid transfer.

20. The apparatus as claimed in claim 19, wherein the needle packaging (130) is fixedly held at the tray (1) at the intermediate needle holding portion (13) in a positive-fit manner.

21. The apparatus as claimed claim 1, wherein the vial (7) is accommodated in the vial cavity (11) of the tray (1) at the intermediate position, in which the first needle tip (131a) is not engaged with the vial (7), and the container (125) is accommodated in the container cavity (12) at the intermediate position, in which the second needle tip (131b) is not engaged with the container (125).

22. The apparatus as claimed in claim 21, wherein the transfer needle (131) is packaged under sterile conditions by a needle packaging (130).

23. (canceled)

24. (canceled)

25. A packaging unit (9) for packaging a vial (7) storing a second solid or liquid component together with a container (125) storing a first liquid component (90), comprising an apparatus for combining a first liquid component (90) stored in a container (125) and a second solid or liquid component stored in a vial (7) by means of negative pressure, comprising a tray (1) having a vial cavity (11) for accommodating at least a portion of the vial (7) and a container cavity (12) for accommodating at least a portion of the container (125), and a transfer needle (131) having a first needle tip (131a), a second needle tip (131b) and a lumen (131) for establishing a fluid communication between the vial (7) and the container (125) in a transfer position, in which the first needle tip (131a) is engaged with the vial (7) and the second needle tip (131b) is engaged with the container (125); wherein the transfer needle (131) is fixedly held at the tray (1) at an intermediate needle holding portion (13) of the tray (1) between the vial cavity (11) and the container cavity (12), wherein the vial cavity (11) is configured for guiding a movement of the vial (7) along an axial direction (AD) from an intermediate position, in which the first needle tip (131a) is not engaged with the vial (7), towards the transfer position, and the container cavity (12) is configured for guiding a movement of the container (125) along the axial direction (AD) from an intermediate position, in which the second needle tip (131b) is not engaged with the container (125), towards the transfer position; wherein the vial (7) is accommodated in the vial cavity (11) of the tray (1) at the intermediate position, in which the first needle tip (131a) is not engaged with the vial (7), the container (125) is accommodated in the container cavity (12) at the intermediate position, in which the second needle tip (131b) is not engaged with the container (125), and the transfer needle (131) is packaged under sterile conditions by a needle packaging (130).

26. The packaging unit (9) as claimed in claim 25, wherein the tray (1) comprises a planar upper surface (10a) and the packaging foil (8) is adhesively bonded to the upper surface of the tray (11).

Description

OVERVIEW ON DRAWINGS

[0045] The invention will now be described by way of example and with reference to the accompanying drawings, from which further features, advantages and problems to be solved will be-come apparent. In the drawings:

[0046] FIG. 1a shows an example of an apparatus for combining a first liquid component stored in a container and a second solid or liquid component stored in a vial by means of negative pressure according to the present invention in a perspective top view;

[0047] FIG. 1b shows a tray member vial portion of the apparatus of FIG. 1a in a top view;

[0048] FIG. 1c shows a tray member container portion of the apparatus of FIG. 1a in a top view;

[0049] FIG. 1d shows another example of a tray member container portion of the apparatus of FIG. 1a in a top view;

[0050] FIGS. 2a to 2d show the tray member vial portion of an apparatus according to the present invention in a perspective top view, in a perspective bottom view, in a plan view and in a side-view;

[0051] FIG. 2e shows the tray member vial portion of FIG. 2a in a perspective top view, with the vial accommodated in the vial cavity of the tray member vial portion in a storage position that coincides with the intermediate position;

[0052] FIG. 2f shows the tray member vial portion of FIG. 2e in a perspective top view, with the vial displaced in axial direction towards the needle, shortly before the first end of the transfer needle pierces the vial stopper;

[0053] FIG. 2g shows a schematic cross-section of the tray member vial portion with the vial accommodated in the vial cavity, viewed towards the bottom of the vial;

[0054] FIG. 3a shows a needle packaging assembly for packaging a dual-ended transfer needle according to the present invention;

[0055] FIG. 3b shows another examiner of a needle packaging assembly according to the present invention;

[0056] FIG. 4a shows how the needle packaging assembly of FIG. 3b is disposed at the intermediate needle holding portion between the vial cavity and the container cavity, before removal of end caps of the needle packaging assembly;

[0057] FIG. 4b the needle packaging assembly of FIG. 4a after removal of end caps of the needle packaging assembly for providing access to the ends of the dual-ended needle for fluid transfer;

[0058] FIG. 5a shows a packaging unit for packaging a vial storing a second solid or liquid component together with a container storing a first liquid component in a schematic top view;

[0059] FIG. 5b shows tray of the packaging unit of FIG. 5a after removal of the packaging foil, with the vial and container disposed at the intermediate position;

[0060] FIGS. 5c to 5g show the stages of a process for transferring a diluent stored in the container into the vial, for reconstituting a drug solution in the vial using an apparatus according to the present invention;

[0061] FIG. 5h shows the removal of the vial with the reconstituted drug solution after performing the steps of FIGS. 5c to 5g;

[0062] FIGS. 6a and 6b show the apparatus according to the present invention with the vial and the container in the transfer position for fluid transfer in a top view and schematic cross-sectional view, respectively;

[0063] FIG. 7 shows a needle packaging assembly for particular use in a second embodiment according to the present invention;

[0064] FIGS. 8a to 8c show a drug reconstitution tray according to a second embodiment of the present invention in three different stages to finally obtain a drug reconstitution tray in an extended or open position, ready for a fluid transfer between a vial and a diluent container;

[0065] FIGS. 9a to 9f show the stages of a process for transferring a diluent stored in the container into the vial, for reconstituting a drug solution in the vial using an apparatus according to the second embodiment;

[0066] FIGS. 10a and 10b show a plan view and a cross-sectional view, respectively, of a drug reconstitution tray according to the second embodiment in the transfer position.

[0067] In the drawings, the same reference numerals designate identical or substantially equivalent elements or groups of elements.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0068] FIG. 1a shows an example of a medical apparatus for reconstitution of a drug solution by combining a first liquid component (e.g., diluent) stored in a container and a second solid or liquid component stored in a vial by means of negative pressure according to the present invention in a perspective top view. FIGS. 1b to 1d show examples of a tray member vial portion 10 and of a tray member container portion 10 of such a medical apparatus.

[0069] The vial 7 can be made of glass or plastic material and is used to store a solid or liquid component under negative pressure. Preferably, the vial stores a lyophilized powder under negative pressure, which needs to be mixed with a diluent to reconstitute the substance into a form that is suitable for injection. The diluent container 125 can be made of any material suited to store a diluent required for reconstitution of the drug solution and may also be embodied as a pouch made of a flexible foil. Preferably, the diluent container 125 is of cylindrical or parallelepiped shape and is accommodated in a container cavity 12 of corresponding profile formed in the tray member 10, more specifically in the tray member container portion 10. In particular, such a diluent container 125 may be made of plastic material with rigid or semi-rigid side-walls.

[0070] The tray member vial portion 10 and the tray member container portion 10 are preferably each formed as a tray having a planar upper surface that can be sealed by adhesive bonding of a packaging foil, if required. The tray member vial portion 10 and the tray member container portion 10 are preferably formed integrally to a single tray 1 as shown in FIG. 1a, but may also be coupled together for liquid drug reconstitution, e.g., by means of positive-fit locking structures.

[0071] The tray member vial portion 10 comprises a vial cavity 11 that is open towards an upper surface of the tray member 10, will be described hereinafter in more detail and defines an axial direction AD. The vial cavity 11 is configured for accommodating a vial 7 and primarily serves as a jig, gauge or caliber for guiding an axial displacement of the vial 7 in the vial cavity 11 along the axial direction AD from an intermediate position, in which the first end 131a of the dual-ended transfer needle 131 does not pierce a rubber stopper of the vial 7, towards a transfer position, in which the first end 131a of the dual-ended transfer needle 131 pierces the rubber stopper of the vial 7 for fluid transfer. Of course, the vial cavity 13 may also be used for positioning the vial 7 in this intermediate position and preventing or at least reducing an axial displacement of the vial 7 from this intermediate position, in particular for reliably preventing the first end 131a of the dual-ended transfer needle 131 piercing the rubber stopper of the vial 7. Of course, the vial cavity 13 may also be used for storage of the vial 7 in the intermediate position over an extended period of time. For this purpose, the vial cavity 13 may also be sealed against the environment by a packaging foil, as outlined below in more detail.

[0072] Correspondingly, the tray member container portion 10 comprises a container cavity 12 that is open towards the upper surface of the tray member 10, will be described hereinafter in more detail and defines an axial direction AD that is in parallel with the axial direction AD of the tray member vial portion 10 in the tray 1 shown in FIG. 1a. The container cavity 12 is configured for accommodating a diluent container 125 and primarily serves as a jig, gauge or caliber for guiding an axial displacement of the diluent container 125 in the container cavity 12 along the axial direction AD from an intermediate position, in which the second end 131b of the dual-ended transfer needle 131 does not pierce a bottom 127 of the diluent container 125, towards a transfer position, in which the second end 131b of the dual-ended transfer needle 131 pierces the a side-wall, in particular the bottom 127, of the diluent container 125 for fluid transfer. Of course, the container cavity 12 may also be used for positioning the diluent container 125 in this intermediate position and preventing or at least reducing an axial displacement of the diluent container 125 from this intermediate position, in particular for reliably preventing the second end 131b of the dual-ended transfer needle 131 piercing the bottom of the diluent container 125. Of course, the container cavity 12 may also be used for storage of the diluent container 125 in the intermediate position over an extended period of time. For this purpose, the container cavity 12 may also be sterile sealed by a packaging foil, as outlined below in more detail.

[0073] As shown in FIG. 1a, a dual-ended transfer needle 131 is fixedly held or fixed at the tray 1 at an intermediate needle holding portion 13 between the vial cavity 11 and the container cavity 12. For this purpose, the transfer needle 131 is preferably packaged in a needle packaging 130 that prevents an axial displacement of the transfer needle 131 inside the needle packaging 130 and that is fixed at an intermediate position between the vial cavity 11 and the container cavity 12. If the tray 1 is formed by two separate tray member portions 10, 10, which are coupled together for fluid transfer, the intermediate needle holding portion 13 is either provided at the front end of the vial cavity 11 or at the front end of the container cavity 12. Preferably, the transfer needle 131 is packaged in the needle packaging 130 under sterile conditions against the residual volume of the tray 1.

[0074] As shown in FIG. 1a, the transfer needle 131 is positioned at the center of the front wall 19 of the vial cavity 11 and at the center of the front wall 122a of the container cavity 12. The front wall 19 of the vial cavity 11 delimits the axial displacement of the vial 7 inside the vial cavity 11 towards the transfer position by abutment with the front end of the vial 7, in which the first end 131a of the transfer needle 131 pierces the rubber stopper of the vial 7, whereas the front wall 122a of the container cavity 12 delimits the axial displacement of the diluent container 125 towards the transfer position by abutment with the bottom 127 of the diluent container 125, in which the second end of the transfer needle 131 pierces the bottom 127 of the diluent container 125.

[0075] The general shape of a vial to be accommodated in the vial cavity 11 of a tray member vial portion 10 of the tray 1 is shown in FIGS. 1b and 6b. The vial 7 has a cylindrical vial body 70 with a closed bottom 71 and a conical shoulder 73 that is followed by a narrow neck 74 and a wider rolled edge 75 that defines a filling opening of the vial 7. This filling opening is sealed by an elastomeric stopper 76 that is held in place by a cylindrical metal cap 77 that is crimped over the rolled edge 75. A circular central opening is defined in the upper surface of the metal cap 77 and exposes a central portion of the stopper 76 that will be pierced or punctured by the first end 131a of the dual-ended transfer needle 131 in the transfer position shown in FIGS. 6a and 6b, when the front end of the vial 7 abuts against the front wall of the vial cavity 11. The cylindrical shape of such a vial 7 precisely defines a center line.

[0076] More details of the tray member vial portion 10 are shown in FIGS. 2a-2g and will be explained in the following. The tray member vial portion 10 comprises a vial cavity 11 for accommodating a vial 7 spaced apart from the first end 131a of the dual-ended transfer needle 131 and in axial alignment with the transfer needle 131 in the intermediate position. The vial cavity 11 may have an inner profile corresponding to the outer contour of the vial body 70 (cf. FIG. 6b) of the vial 7 to be accommodated in the vial cavity 11. More specifically, the vial cavity 11 may have a curved bottom 17 having a radius of curvature that corresponds to the outer radius of the vial body 70. As shown in FIGS. 2a and 2d, the two opposite upper side-walls 18 of the vial cavity 11 may be planar and extend perpendicular to the upper surface 10a of the tray member vial portion 10. As shown in FIGS. 2a and 2d, a pair of front vial retaining members 36b is formed on the opposite upper side-walls 18 of the vial cavity 11 to retain the vial in the vial cavity 11 in the intermediate position. The front vial retaining members 36b may also serve to prevent a displacement of the vial 7 in a direction perpendicular to the axial direction of the vial cavity 11 and even to push the vial body 70 downward toward the bottom 17 of the vial cavity 11 to define the height of the center line CL of the vial 7 in the intermediate position. Additionally, a second pair of rear vial retaining members 36a may be formed on the opposite upper side-walls 18 of the vial cavity 11 to retain the vial 7 in the vial cavity 11 in the intermediate position. The rear vial retaining members 36a may also serve to prevent a displacement of the vial 7 in a direction perpendicular to the axial direction of the vial cavity 11 and even to push the vial body 70 downward toward the bottom 17 of the vial cavity 11 to define the height of the center line CL of the vial 7 in the intermediate position.

[0077] As shown in FIG. 2g, the retaining members 36a, 36b are preferably formed integrally with the upper side-walls 18 of the vial cavity 11. More specifically, the retaining members 36a, 36b may be formed as convexly curved protrusions protruding from the upper side-walls 18 of the vial cavity 11 at a height h2 that is larger than the height h1 of a center line CL of the vial body 70 above the bottom 17 of the vial cavity 11. Thus, a certain force component may always prevail to push the vial body 70 towards the bottom 17 of the vial cavity 11 when accommodated therein in the intermediate position. When a vial 7 is inserted from above into a vial cavity 11 for storage or positioning, the vial 7 will be locked by the retaining members 36a, 36b in the vial cavity 11 at least in a direction perpendicular to the center line CL of the vial body 70, to thereby define an orientation of the vial 7 in parallel with the bottom 17 of the vial cavity 11 and in axial alignment with the dual-ended transfer needle 131. As shown in FIG. 2g, when the vial body 70 is accommodated in the vial cavity 11, it may not protrude beyond the upper surface 10a of the tray member vial portion 10 so that the vial cavity 11 may be sealed by a packaging foil bonded on the upper surface 10a of the tray member vial portion 10. Locking of the vial body 70 by the retaining members 36a, 36b in the vial cavity 11 may also be sufficient to define the position of the vial in axial direction.

[0078] As will become apparent to the skilled person, the bottom 17 and upper side-walls 18 of the vial cavity 11 may also embrace the vial body 70 by a little more than 180 degrees and thus serve directly as retaining members to position the vial 7 in the intermediate position and in parallel with the axial direction AD. For insertion of the vial 7 into the vial cavity 11 it would thus be necessary to flex the tray 1 a little about the central axis of the vial cavity 11 to open the vial cavity 11 a little bit more.

[0079] The vial body 70 may be clamped a little by the bottom 17 and upper side-walls 18 of the vial cavity 11 to define the position of the vial 7 in axial direction. As shown in FIG. 2d, movement limiting protrusions 35a, 35b may be provided in the vial cavity 11 near the rear end of the vial cavity 11 and near the position of the transition between the vial body 70 and the vial shoulder 73 (see FIG. 6b), for defining the position of the vial 7 in axial direction even more precisely by abutment of protrusions in the vial cavity 11 with the bottom 71 and shoulder 73 of the vial 7, respectively. Moreover, additional movement limiting protrusions 35c may be provided on the side surfaces of the vial cavity 11, in particular at the front end thereof.

[0080] The vial body 70 may be accommodated in the vial cavity 11 in the intermediate position with a certain play in axial direction, but the vial body 70 may also be accommodated in the vial cavity 11 in the intermediate position without play in axial direction. The movement limiting protrusions 35a, 35b and 35c may be formed integrally with the bottom or side-walls of the vial cavity 11, and are preferably formed in the bottom 17 of the vial cavity 11, as shown in FIG. 2d. The movement limiting protrusions 35a, 35b, 35c may be formed as convex bulges protruding a little into the vial cavity 11. The rear movement limiting protrusion 35a may be U-shaped to extend along the entire rear end of the vial cavity 11, as shown in FIG. 2a. As the vial body 70 will slide over the front movement limiting protrusion 35b on its way towards the transfer position, the front movement limiting protrusion 35b may be relatively shallow and thin so that it can be pressed down easily by the vial body 70. As shown in FIGS. 2a, 2d and 2e, the front movement limiting protrusion 35b may be disposed in the region of an intermediate cavity 16, which received the metal cap 77/front end of the vial 7 in the intermediate position and through which the front end of the vial 7 when being displaced from the intermediate position toward the transfer position.

[0081] As shown in FIGS. 1a and 1c, the tray member container portion 10 comprises a container cavity 12 for accommodating a diluent container 125 spaced apart from the second end 131b of the dual-ended transfer needle 131 and preferably in axial alignment with the transfer needle 131 in the intermediate position. The container cavity 12 may have an inner profile corresponding to the outer contour of the diluent container 125 to be accommodated in the container cavity 12. More specifically, the container cavity 12 may be formed by a planar bottom 120 and two opposite side-walls 121 which may be planar and extend perpendicular to the bottom 120 of the container cavity 12. As shown in FIG. 1c, the diluent container 125, at its end facing the rear wall 122b of the container cavity 12, may be closed by a closure 126 that seals a filling opening for filling the container 125 with a diluent. The closure 126 is received in a recess 124 of a pusher 123 that is slidably received in the container cavity 12 and serves for pushing the container 125 from the intermediate position shown in FIGS. 1a and 1c toward the transfer position. Such a pusher is, however, not necessary. Instead a free space 124 may be provided at the end of the container cavity 12.

[0082] As shown in FIG. 1d, a pair of container retaining members 129 of similar configuration as outlined above for the vial retaining protrusions, may be formed on the opposite side-walls 121 of the container cavity 12 to retain the diluent container 125 in the container cavity 12 in the intermediate position. The container retaining members 129 may also serve to prevent a displacement of the container 125 in a direction perpendicular to the axial direction AD of the container cavity 12 and even to push the container 125 downward toward the bottom 120 of the container cavity 12 to define the height of the center line CL of the container 12 in the intermediate position.

[0083] As will become apparent to the skilled person, the bottom 120 and upper side-walls 121 of the container cavity 12 may also embrace the container 125 by a little more than 180 degrees and thus serve directly as retaining members to position the container 125 in the intermediate position and in parallel with the axial direction AD. For insertion of the container 125 into the container cavity 12 it would thus be necessary to flex the tray 1 a little about the central axis of the container cavity 12 to open the container cavity 12 a little bit more.

[0084] As shown in FIG. 1d, a movement limiting protrusion 128 may be provided in the container cavity 12 in front of the diluent container 125 in the intermediate position, for defining the position of the diluent container 12 in axial direction even more precisely by abutment of protrusion 128 in the container cavity 12 with the bottom 127 of the diluent container 125. Moreover, additional movement limiting protrusions may be provided on the side-walls 121 of the container cavity 12, in particular at the front end thereof.

[0085] The diluent container 125 may be accommodated in the container cavity 12 in the intermediate position with a certain play in axial direction, but the diluent container 125 may also be accommodated in the container cavity 12 in the intermediate position without play in axial direction. The movement limiting protrusion 128 may be formed integrally with the bottom 120 or side-walls 121 of the container cavity 12. The movement limiting protrusion 128 and the container retaining protrusions 129 may be formed as convex bulges protruding a little into the container cavity 12.

[0086] The tray 1 is preferably made of plastic material, in particular by vacuum thermoforming or pressure thermo-forming of a thin plastic sheet or by means of plastic injection molding, and preferably all of the retaining and movement limiting members 35a, 35b, 35c, 36a, 36b, 128 and 129 are formed integrally with the tray 1. Any other materials may be used as well, however. In particular, the tray 1 may also be made of paper or cardboard. A thin film of plastic or bioplastic may be arranged on inner surfaces of the diluent container cavity 12 and vial cavity 11 to enable even the storage of the diluent container and vial in the cavities 11, 12 under sterile conditions. DE 102011122211 A1 discloses an example of such a compound packaging material including a substrate made of paper or cardboard that is coated by a thin film of plastic or bioplastic, and the whole contents of DE 102011122211 A1 is hereby incorporated by reference. Preferably, the tray 1 may be a little flexible, so that it can be flexed a little about the middle axis of the cavities 11, 12, e.g., to ease insertion of the vial 7 and diluent container 125 into the cavities 11, 12, as outlined above.

[0087] FIG. 3a shows further details of the needle packaging 130. The dual-ended transfer needle 131 provides a lumen 131 for fluid transfer and may be formed of plastic material, but may also be formed of a metal, such as stainless steel. The transfer needle 131 is firmly received in the needle packaging 130 so that it does not move in axial direction, when the first and second end 131a, 131b get in contact with the vial stopper and bottom 127 of the diluent container 125, respectively. The needle packaging 130 may be a plastic foil tightly sleeved around the transfer needle 131 or may be a block of plastic material which the transfer needle 131 extends through. The first and second end 131a, 131b is each covered by an end cap member 133a, 133b, which is preferably integrally formed with the needle packaging 130 and may be torn or sheared off from the needle packaging 130. To ease removal of the end cap members 133a, 133b for providing access to the needle ends 131a, 131b, weakening zones or frangible portions 134a, 134b may be provided between the needle packaging 130 and the end cap members 1331, 133b. In particular, these weakening zones or frangible portions 134a, 134b may be notch-shaped, as shown in FIG. 3a.

[0088] More preferably, the transfer needle 131 is received in the needle packaging 130 under sterile conditions against the residual volume of the cavities 11, 12 of the tray 1.

[0089] As shown in FIG. 1a, the needle packaging 130 is fixedly mounted to the tray 1 between the vial cavity 11 and the container cavity 12, so that the needle ends 131a, 131b protrude into the vial cavity 11 and container cavity 12, respectively. For this purpose, the needle packaging 130 may be held by friction at the tray 1, e.g., by clamping by means of deformable clamping brackets or by crimping. The needle packaging 130 may also be adhesively bonded to the tray 1 or may be bonded to the tray 1 by ultrasonic welding or applying heat to the needle packaging 130 and central part of the tray 1.

[0090] As shown in FIG. 3b, the needle packaging 130 may also be held by positive-fit at the tray 1. For this purpose, protrusions 135 may be formed at lateral side-walls of the needle packaging 130 that are received with positive-fit in corresponding recesses 136 formed on the tray 1, as shown in FIG. 5a. Or, recesses may be formed at lateral side-walls of the needle packaging 130 that engage with corresponding protrusions formed on the tray 1 in a positive-fit manner. Such protrusions or recesses may also be formed directly on the outer surface of the transfer needle 131 or on extensions fixed mounted on the outer surface of the transfer needle 131.

[0091] In the state shown in FIG. 4a, the end cap members 133a, 133b may seal the ends 131a, 131b of the transfer needle 131 sterile against the local environment. Once, the end cap members 133a, 133b are removed, as shown in FIG. 4b, access to the needle ends 131a, 131b is permitted.

[0092] A system for combining a first liquid component stored in a container and a second solid or liquid component stored in a vial by means of negative pressure according to the present invention comprises the tray 1 with the transfer needle 131 fixedly held or fixed at the tray 1 at an intermediate needle holding portion 13 between the vial cavity 11 and the container cavity 12, as shown in FIG. 1a, wherein the vial cavity 11 accommodates a vial 7 in an intermediate position, in which the first needle tip 131a is not engaged with the vial 7, and wherein the container cavity 12 accommodates a diluent container 12 in an intermediate position, in which the second needle tip 131b is not engaged with the container 125.

[0093] FIG. 5a shows a packaging unit 9 according to the present invention, consisting of such a system for combining a first liquid component stored in a container and a second solid or liquid component stored in a vial by means of negative pressure, which is sealed by a packaging foil 8. The packaging foil 8 may seal the whole tray 1 together with the vial 7 and diluent container 125 against the environment, and may seal the whole tray 1 in a sterile manner. For this purpose, the packaging foil 8 may be adhesively bonded onto the planar upper surface of the tray 1. As an alternative the tray 1 may be accommodated in a sealed pouch formed by the packaging foil 8. The packaging foil 8 may be gas-permeable, in particular a Tyvek-foil, to enable a steam sterilization of the tray 1, vial 7 and container 125 by a gas flowing through the packaging foil 8.

[0094] From the intermediate position shown in FIG. 5a, the transfer position shown in FIGS. 6a and 6b, in which the first needle end 131a pierces the rubber stopper 76 of the vial 7 and in which the second needle end 131b pierces the bottom 127 of the diluent container 125, may be established by an axial displacement of the vial 7 towards the front wall 19 of the vial cavity 11 and by an axial displacement of the container 125 towards the front wall 122a of the container cavity 12.

[0095] Starting with the packaging unit 9 shown in FIG. 5a, firstly the packaging foil 8 needs to be removed from the tray 1. Next, the steps shown in FIGS. 5b to 5h are performed for drug reconstitution, as described below. These steps are preferably performed with the tray 1 held horizontally.

[0096] FIG. 5b shows the packaging unit after removal of the packaging foil 8. In this intermediate position, the vial 7 is spaced apart from the first needle end 131a and the container 125 is spaced apart from the second needle end 131b. The vial 7 stores e.g., a lyophilized drug component under negative pressure, whereas the container 125 stores a diluent 90, which is required for drug reconstitution.

[0097] As a next step, by pushing the pusher 123, the container 125 is pushed in the direction of the needle packaging 130 until the second needle end 131b engages the container 125 and pierces the bottom 127 or a side-wall of the container 125. For this purpose, the end cap member 133b (cf. FIG. 4a) may be removed only shortly before performing this step for providing access to the second needle end 131b. The axial displacement of the container 125 is guided by the bottom 120 and lateral side-walls 121 of the container cavity 12. Finally, the bottom of the container 125 will abut against the front wall 122a of the container cavity. This position of the container 125 may be fixed by fixing the position of the pusher 123 in the container cavity 12 by friction or positive-fit. As an example, the pusher 123 may be formed as a resilient, U-shaped member which is clamped against the side-walls 121 of the container cavity 12. As an alternative, a positive-fit structure, such as protrusions on the side-walls 121 of the container cavity 12, may be provided for positive-fit with the pusher 123 in the position shown in FIG.

[0098] As a next step, the vial 7 is pushed towards the first needle end 131a. To provide access to the first needle end 131a, the end cap member 133a (cf. FIG. 4a) may be removed only shortly before performing this step. The vial 7 is pushed in the direction of the needle packaging 130 until the first needle end 131a engages the vial 7 and pierces the rubber stopper of the vial 7. The axial displacement of the vial 7 is guided by the bottom and lateral side-walls of the vial cavity 11, and may be additionally guided by the retaining members 36a, 36b of the vial cavity 11. For driving the axial displacement of the vial 7, a user's finger or a pusher member of a robot may push against the bottom 71 of the vial 7 via the rear end cavity 14 of the tray 1 and/or fingers of a user or grippers of a robot may clamp the vial body 70 of the vial 7 via the widened lateral cavity 15, as outlined above.

[0099] Finally, the metal cap at the front end of the vial 7, which retains the rubber stopper, will abut against the front wall 19 of the vial cavity 11, and the first needle end 131a engages the vial 7 by piercing the rubber stopper. This transfer position of the vial 7 may be fixed by friction or positive-fit. As an example, the front retaining protrusions 36b may fix the transfer position of the vial 7 shown in FIG. 5d.

[0100] In the transfer position of FIG. 5d a fluid communication between the container 125 and the vial 7 has been established. The negative pressure in the vial 7 will drive the diluent 90 out of the container 125 and into the vial 7, until a pressure equilibrium is accomplished and at least the main portion of the diluent 90 has been transferred into the vial 7, as shown in FIG. 5f.

[0101] As a next step, the vial 7 is withdrawn from the front wall 19 of the vial cavity 11, to stop engagement with the first needle end 131a. The axial displacement of the vial 7 in the opposite direction is again guided by the bottom and lateral side-walls of the vial cavity 11, and may be guided additionally by the retaining members 36a, 36b of the vial cavity 11. For driving the axial displacement of the vial 7 in the opposite direction, a user's finger or a pusher member of a robot may push against the bottom 71 of the vial 7 via the rear end cavity 14 of the tray 1 and/or fingers of a user or grippers of a robot may clamp the vial body 70 of the vial 7 via the widened lateral cavity 15, as outlined above. Finally, the vial 7 reaches again the intermediate position shown in FIG. 5g, or a position near this intermediate position, in which the first needle end 131 does not engage the vial 7 anymore.

[0102] As a next step, the vial 7 is removed from the vial cavity 11, as shown in FIG. 5h, which leaves behind the tray 1 with the container 125 still in engagement with the second needle end 131b as well as the vial 7 including the reconstituted drug solution 91, which is then ready for use. As a final step, the needle of a syringe (not shown) may pierce the rubber stopper of the vial 7 for extraction of the reconstituted drug solution 91 from the vial 7.

[0103] FIGS. 6a and 6b show the apparatus according to the present invention with the tray 1 and the vial 7 and the container 125 in the transfer position for fluid transfer in a top view and schematic cross-sectional view, respectively.

[0104] As will become apparent to the skilled person from the above description, the tray 1 is used as a jig, gauge or caliber to define the positional relationship between the vial and vial adapter in the intermediate position and to keep them in axial alignment during the axial displacement from the intermediate position to the transfer position. From the intermediate position the transfer position can be accomplished by a simple axial displacement of the vial and diluent container, i.e., a displacement only in axial direction. In the transfer position, the vial and container are in engagement with the ends of the transfer needle for enabling the transfer of the liquid diluent out of the container and into the vial via the lumen 131 of the transfer needle 131, e.g., for reconstitution of a liquid drug solution in the vial.

[0105] Of course, the tray 1 may also be used for long-time storage of the diluent container and vial, in particular under sterile conditions. For this purpose, a sterile packaging foil 8 may be adhesively bonded to the upper surface of the tray 1, as shown in FIG. 5a. Also, the needle ends 131a, 131b of the transfer needle may be sterile sealed against the inner volume of the tray 1 and in particular against the vial cavity 11 and container cavity 12, in particular by means of the end cap members 133a, 133b of the needle packaging 130, as shown in FIGS. 5a and 4a.

[0106] With reference to FIGS. 8a to 10b, a second embodiment of a drug reconstitution tray according to the present invention will be described. This tray consists of two tray member portions 10, 10 that are connected with each other via a hinge 140, that is preferably a film hinge integrally formed with the two tray members 10, 10. Thus, the two tray member portions 10, 10 can be pivoted relative to each other, as shown in the sequence of FIGS. 8a to 8c. The drug reconstitution tray may thus be folded or collapsed to a rather compact configuration as shown in FIG. 8a, in which the two tray members 10, 10 are generally stacked one above the other and the total length of the drug reconstitution tray is much shorter, by up to 50%, as compared to the total length in the transfer position shown in FIG. 8c. Preferably, both the vial 7 and the diluent container 125 is accommodated in the respective cavity of the two tray members 10, 10, shown in FIG. 8a.

[0107] In such a tray, a needle packaging as shown in FIG. 7 is held at an intermediate needle holding portion formed by end walls of the cavities of the two tray members 10, 10. As shown in FIG. 8b, before pivoting the two tray member portions 10, 10 from the compact configuration of FIG. 8a to the extended or open configuration shown in FIG. 8c, first the end cap members 133a, 133b are removed from the needle packaging, to thereby expose the ends 131a, 131b of the transfer needle 131. In the extended or open position shown in FIG. 8c, the transfer needle 131 will then extend along the axial direction defined by the cavities 11, 12 of the two tray member portions 10, 10. In the extended or open configuration, the planar upper surface 10a of the tray member portion 10 is substantially aligned or flush with the planar upper surface 10a of the tray member portion 10, and the vial cavity 11 and the container cavity 12 is each aligned along the axial direction, and the two planer upper surfaces 10a, 10a will be aligned or flush with each other. As shown in FIG. 8c, the front end of the vial cavity 11 and container cavity 12 is each open so that the ends 131a, 131b of the transfer needle 131 can pierce the rubber stopper of the vial 7 and bottom 127 of the diluent container 125, respectively, unhindered, i.e. without the axial displacement of the vial 7 and diluent container 125, respectively, being impeded by a front end of the vial cavity 11 or container cavity 12.

[0108] Preferably, the film hinge 140 is a bistable plastic film hinge, which is pretensioned into the extended or open configuration of FIG. 8c by means of wing-shaped or bent tension members 143, 143. General examples for such a bistable plastic film hinge are described in detail e.g. in U.S. Pat. No. 5,257,708 B or U.S. Pat. No. 6,321,923 B1, the contents of which are hereby incorporated by reference so that a detailed disclosure of such a bistable plastic film hinge may be omitted. As will become apparent to the skilled person from FIG. 8c, in the unfolded position of FIG. 8c, the alignment of the vial cavity 11 and container cavity 12 with each other can be to automatically maintained, without the need that an operator needs to push down one (or both) of the tray members portions 10, 10 on a supporting plate or base (not shown in the drawings). This eases the reconstitution of a drug solution significantly, because the operator may better concentrate on a proper displacement of the vial 7 and diluent container 125 in order to establish the fluid transfer via the transfer needle 131.

[0109] The stages of a process for transferring a diluent stored in a diluent container 125 into a vial 7, for reconstituting a drug solution in the vial 7 using the drug reconstitution tray according to the second embodiment are summarized in FIGS. 9a to 9f, and it will become clear that this process is similar to the process shown in FIGS. 5c to 5g, so that a detailed description may be omitted.

[0110] As will become apparent to the skilled person when studying the above description, a tray according to the present invention may be used for the storage/positioning/guiding of any kind of vial and diluent container. As a preferred example, the vial may store a lyophilized drug component under negative pressure. Of course, the vial may also store other drug components, such as dry powders required for drug reconstitution.

[0111] As will become apparent to the skilled person, also the diluent container 125 may be vial made of glass or plastic material, having a pierceable member, such as a rubber stopper, that seals the diluent container 125 and will be pierced by the second end 131b of the transfer needle 131 in the afore-mentioned transfer position.

[0112] While the preferred embodiments of the present invention have been described so as to enable one skilled in the art to practice the device of the present invention, it is to be understood that variations and modifications may be employed without departing from the concept and intent of the present invention as defined in the appended claims. Accordingly, the preceding description is intended to be exemplary and should not be used to limit the scope of the invention. The scope of the invention should be determined only by reference to the appended claims.

LIST OF REFERENCE NUMERALS

[0113] 1 tray [0114] 7 vial [0115] 8 foil [0116] 9 combined packaging unit [0117] 10 tray member portion for vial [0118] 10a upper surface of tray member portion for vial 10 [0119] 10 tray member portion for diluent container [0120] 10a upper surface of tray member portion for diluent container 10 [0121] 11 vial cavity [0122] 12 diluent container cavity [0123] 13 needle holding portion [0124] 14 rear end cavity [0125] 15 lateral cavity [0126] 16 intermediate cavity [0127] 17 bottom of vial cavity 11 [0128] 18 upper side-wall of vial cavity 11 [0129] 19 front wall of vial cavity 11 [0130] 28 bottom of intermediate cavity 16 [0131] 29 side-wall of lateral cavity 15 [0132] 35a rear movement limiting protrusion [0133] 35b front movement limiting protrusion [0134] 35c front movement limiting protrusion [0135] 36a rear vial retaining protrusion [0136] 36b front vial retaining protrusion [0137] 70 vial body [0138] 71 vial bottom [0139] 73 shoulder [0140] 74 neck [0141] 75 rolled edge of vial [0142] 76 rubber stopper [0143] 77 metal cap [0144] 80 contact region [0145] 90 diluent [0146] 91 reconstituted drug [0147] 120 bottom of diluent container cavity 12 [0148] 121 side-wall of diluent container cavity 12 [0149] 122a front wall of diluent container cavity 12 [0150] 122b rear wall of diluent container cavity 12 [0151] 123 pusher [0152] 124 recess of pusher 123 or free space [0153] 125 diluent container [0154] 126 closure of diluent container 125 [0155] 127 bottom of diluent container 125 [0156] 128 movement limiting protrusion [0157] 129 container retaining protrusion [0158] 130 needle packaging [0159] 131 double-ended transfer needle [0160] 131 lumen of transfer needle 131 [0161] 131a first end of transfer needle 131 [0162] 131b second end of transfer needle 131 [0163] 132 packaging main body [0164] 133a first end cap member [0165] 133b second end cap member [0166] 134a first frangible portion [0167] 134b second frangible portion [0168] 135 protrusion [0169] 136 recess [0170] 137 hollow channel [0171] 140 film hinge [0172] 141 first side-wing of film hinge [0173] 141 second side-wing of film hinge [0174] 142 bridging portion [0175] 143 first tension member [0176] 143 second tension member [0177] 150 latching structure [0178] 151 first latching member [0179] 151 second latching member [0180] AD axial direction [0181] CL centre line [0182] h1 height of centre line CL over bottom of vial cavity 11 [0183] h2 height of contact region 80 over bottom of vial cavity 11