Packaging systems for aseptic filling of small volume bottles

Abstract

A packaging system for aseptically packaging, filling and sealing a drug container includes a container tray (100) having a container unit (120) for accommodating and stabilizing the drug container. The system also includes a plug holder (300) having a plug unit (320), the plug unit (320) forming a closed body having a distal opening, an interior space, a proximal wall opposite to the distal opening, and a proximal outer surface (330). When pressure is applied to the proximal outer surface of the plug unit (320), the plug unit (320) is configured to releasably fix the plug unit and release the plug unit into the filling opening of the drug container.

Description

[0001] The present invention is a divisional application with application date of December 24, 2018, application number 201880087765X, and invention name “Packaging system for aseptic filling of small volume bottles”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional Application No. 62 / 609,758 filed on December 22, 2017, and No. 62 / 712,635 filed on July 31, 2018. The contents of these two provisional applications are hereby incorporated into this application by reference. Technical Field

[0004] The present application relates to the field of filling of pharmaceutical containers, and more particularly to small volume, aseptic filling of pharmaceutical containers. Background Art

[0005] There is an increasing need for small-volume sterile drug filling containers, partly due to the growth of biopharmaceuticals and personalized medicines, which are often produced in small batches. In this context, drug filling applications often require systems that have a high level of component quality but are suitable for use on a relatively small scale, where a relatively small number of drug containers are filled in a particular batch while maintaining sterility.

[0006] In a small volume medication filling operation, one option is for an operator to individually handle, fill and stopper medication containers such as vials. Another option is for an operator to perform an "assisted manual filling operation" in which medication containers are filled in small batches with the assistance of a device, tool or other element that increases the efficiency and ease of operation compared to repeating a separate filling operation. The devices and systems disclosed herein can be advantageously used in assisted manual filling operations. Summary of the invention

[0007] Briefly, a packaging system for filling and sealing at least one drug container having a filling opening using a stopper is disclosed. The packaging system includes a container tray having a container unit for accommodating and stabilizing the drug container. A stopper holder having a stopper unit, the stopper unit forming a closed body having a distal opening, an interior space, a proximal wall opposite to the distal opening, and a proximal outer surface. The stopper unit is configured to releasably fix the stopper. When pressure is applied to the proximal outer surface of the stopper unit, the stopper unit is adapted to release the stopper into the filling opening of the drug container.

[0008] Another packaging system for filling and sealing at least one drug container having a filling opening with a plug is provided. The packaging system includes a container tray, the container tray having a container unit, and the container unit is used to accommodate and stabilize the drug container. The packaging system also includes a shuttle, the shuttle having an outer surface and an inner surface. The inner surface is configured to releasably fix the plug. The shuttle is configured to release the plug into the filling opening when a release force is applied to the outer surface of the shuttle. The shuttle tray has the shuttle unit, and the shuttle unit forms a closed body, the closed body having a proximal opening, an internal space, a bottom inner surface opposite to the proximal opening, and a side inner surface. The shuttle releasably fixes the shuttle.

[0009] Another packaging system for filling and sealing at least one drug container having a filling opening using a stopper is provided. The packaging system includes a container tray having a container unit for accommodating and stabilizing the drug container. The packaging system also includes a stopper clamp having a stopper unit. The stopper unit includes an articulated base having a first articulated base leg and a second articulated base leg. The first articulated base leg has a first proximal articulated base leg end and a first distal articulated base leg end. The second articulated base leg has a second proximal articulated base leg end and a second distal articulated base leg end. The first proximal articulated base leg end and the second proximal articulated base leg end are connected to each other by a hinge. The hinge is biased to push the first distal articulated base leg end and the second distal articulated base leg end toward each other to a first position. The first articulated base leg has a first rod extending proximally from the first articulated base leg, and the second articulated base leg has a second rod extending proximally from the second articulated base leg. The first rod has a first inner rod surface and a first outer rod surface, the first inner rod surface facing the second rod, the first outer rod surface opposing the first inner rod surface. The second rod has a second inner rod surface and a second outer rod surface, the second inner rod surface facing the first rod, the second outer rod surface opposing the second inner rod surface. The first rod and the second rod are in a spaced relationship such that when a first pressure is applied by the first outer rod surface and the second outer rod surface, the first base leg and the second base leg are urged to a second position, wherein the first articulated base leg and the second articulated base leg are spaced apart to allow the plug to be inserted between the first articulated base leg and the second articulated base leg to be releasably fixed between the first articulated base leg and the second articulated base leg. Upon removal of the first pressure, the first hinged base leg and the second hinged base leg are urged to a third position to releasably secure the plug between the first hinged base leg and the second hinged base leg.

[0010] A system for manipulating stoppers of a drug container is claimed, the system comprising a plurality of stoppers. A manipulation tray is also claimed, the manipulation tray comprising a base on which a plurality of stopper holders are disposed, the plurality of stopper holders being used to releasably secure the plurality of stoppers to the base. The stopper holders are disposed such that the stoppers are in spaced relation to one another. A cover is releasably and sealingly connected to the base for covering the stoppers. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The foregoing summary of the invention as well as the following detailed description of the invention will be better understood when read in conjunction with the accompanying drawings. For the purpose of illustrating the invention, presently preferred embodiments are shown in the accompanying drawings. However, it should be understood that the invention is not limited to the precise arrangements and instrumentalities shown. In the accompanying drawings:

[0012] Figure 1 is a top upper right partial perspective view of a first embodiment of a packaging system according to the present invention with the drug container omitted;

[0013] Figure 2 is a top left rear perspective view of a container tray for use in the packaging system disclosed herein;

[0014] Figure 3 yes Figure 2 A top view of a container tray;

[0015] Figure 4 is used in Figure 1 A top front perspective view of a plug holder used in a system of FIG.

[0016] Figure 5 yes Figure 4 A top view of a plug holder;

[0017] Figure 6 yes Figure 2 A right side elevation view of a container tray;

[0018] Figure 7 yes Figure 1 A plug holder having a plug fixed therein along with Figure 1 A partial enlarged cross-sectional view taken along line 7-7;

[0019] Figure 8 yes Figure 7 The plug has no stopper fixed therein along with the stopper holder Figure 1 A partial enlarged cross-sectional view taken along line 7-7;

[0020] Fig. 9 yes Figure 2 A partial enlarged perspective view of a container unit of a container tray;

[0021] Fig.10 is along Figure 1 The line 10-10 in Figure 1 A cross-sectional view of a packaging system;

[0022] Fig.11 and 12 It shows that from Figure 1 A partial cross-sectional schematic diagram of a stopper unit in a packaging system of inserting a stopper into a vial;

[0023] Fig.13is a top view of an exemplary stopper for use in a packaging system according to the present invention;

[0024] Fig.14 yes Fig.13 A side view of the stopper;

[0025] Fig.15 yes Fig.13 A bottom view of the stopper;

[0026] Fig.16 is along Fig.13 A cross-sectional view of the plug system 13 taken along line 16-16 in FIG.

[0027] Fig.17 is a perspective view of an exemplary vial for use in the packaging system disclosed herein;

[0028] Fig.18 is an upper right perspective view of a second embodiment of a packaging system according to the present invention;

[0029] Fig.19 yes Fig.18 The upper right partial exploded view of the packaging system;

[0030] Fig. 20 yes Fig.18 A greatly enlarged partial perspective view of the packaging system;

[0031] Fig.21 is used in Fig.18 Bottom plan view of a reciprocating member pallet used in a packaging system;

[0032] Fig. 22 is used in Fig.18 An enlarged, exploded, partial perspective view of a reciprocating member and a plug used in a packaging system;

[0033] Fig.23 is used in Fig.18 A top perspective view of a reciprocating moving member used in a packaging system;

[0034] Fig.24 yes Fig.23 A side view of a reciprocating moving part;

[0035] Fig.25 is along Fig.23 The line 25-25 is intercepted, Fig.23 A cross-sectional view of a reciprocating moving part;

[0036] Fig.26 is included that can be removably fixed to Fig.18 A perspective schematic diagram of a reciprocating moving part of a stopper in a tray;

[0037] Fig. 27 is from Fig.26 A perspective schematic diagram of a reciprocating moving part released by a reciprocating moving part tray;

[0038] Fig.28 is through Fig.26 A perspective schematic diagram of a tool and a reciprocating member for inserting a stopper into a vial;

[0039] Fig.29 yes Fig.28 A perspective schematic diagram of a stopper in a vial, wherein the stopper is released from a reciprocating member by a tool;

[0040] Fig.30 is a perspective view of a sterilization bag disclosed herein for use in a packaging system;

[0041] Fig.31 is used for Fig.18 A top perspective view of a first embodiment of a reciprocating member operating tool for use with a packaging system;

[0042] Fig.31A yes Fig.31 An enlarged partial view of the reciprocating member operating tool, showing its Fig.31 A portion of the shown;

[0043] Fig.32 is an enlarged partial perspective view of a stopper handling tool for use with the packaging system disclosed herein;

[0044] Fig.33 is an inverted bottom perspective view of a plug clip according to an embodiment of the present invention;

[0045] Fig.33A is a bottom perspective view of a plug clip according to an embodiment of the present invention.

[0046] Fig.34 yes Fig.33 A top view of the plug clamp;

[0047] Fig.35A and 35B is a schematic cross-sectional view showing the use of a plug clip according to a second embodiment of the present invention;

[0048] Fig.36 is a right rear perspective view of a second embodiment of a plug holder for use in the packaging system disclosed herein;

[0049] Fig.37 is along Fig.36 The line 37-37 is intercepted Fig.36 A cross-sectional view of a plug holder;

[0050] Fig.38 is a front perspective view of a third embodiment of a plug handling system according to the present invention;

[0051] Fig.39 yes Fig.38 A top view of the plug manipulation system; and

[0052] Fig.40 yes Fig.38 A side view of the plug manipulation system;

[0053] Fig.41 is a perspective view of a filling system according to the present invention;

[0054] Fig.42 yes Fig.41 A detailed perspective view of the filling system; and

[0055] Fig.43 is used for Fig.41 A perspective view of a lid used with the filling system. DETAILED DESCRIPTION

[0056] Reference Figure 1-17 The first embodiment of the packaging system 10 includes a drug container, which in the illustrated embodiment is a conventional vial 20 having a filling opening 22 and a vial flange 23 (see Fig.17 The packaging system further comprises a stopper 200 for sealing the filling opening of the vial 20 ( Figure 13-16 ). The example of the stopper 200 shown herein includes a larger portion 202 having a larger diameter 204 and a smaller portion 206 having a smaller diameter 208. The smaller portion 206 has a hole 210 and a tapered lower end portion 212. Many types of stoppers are compatible with the vial 20 and the packaging system 10, including but not limited to stoppers lacking clearly defined larger and smaller portions of the stopper 200 shown herein. As described in more detail below, the packaging system 10 preferably includes a second vial 20 and a second stopper 200, and more preferably includes a plurality of vials 20 and a plurality of stoppers 200 for sealing the plurality of vials 20.

[0057] The container tray 100 preferably includes a plurality of container units 120 for accommodating and stabilizing a corresponding plurality of vials 20. Figure 2 and 3 As best shown in FIG. 1 , the container tray 100 is preferably constructed of a molded polymeric material, wherein the container units 120 are formed by a molding process. The container tray 100 can assist the user in performing an assisted manual filling operation by stably holding the vials 20 so that the user can conveniently insert the stopper 200 into the opening 22 of each vial 20. Fig. 9As best shown in FIG. 1 , each container unit 120 includes a snap mechanism formed by two side wall flexible legs 124 and a flexible latch 122 attached to the container unit 120 for releasably securing the vial 20 in the container unit 120. Each container unit 120 is generally in the form of a truncated trough with an open end 120a. Each of the two side wall legs 124 includes a chamfered latch 124a extending radially inwardly relative to the container unit 120 at its top end. The latch 122 is located just inside the open end 120a. The side wall legs 124 and the latch 122 are positioned triangularly so as to releasably, slidably and securely accommodate the vial 20. When the vial 20 is positioned in the container unit 120, the chamfered latch 124a extends onto the shoulder 21 of the vial 20 in a snap fit manner.

[0058] Go to Figure 1 , 4 5, the packaging system 10 also preferably includes a plug holder 300, which in the illustrated embodiment includes a central panel 310 and two side panels 312 connected thereto by living hinges 314. Each living hinge described herein (including but not limited to living hinges 314) is preferably a thinned portion of the same material as the two components connected by the living hinge (in this case, the side panels 312). The living hinge 314 is disposed between the two side panels 312 to allow rotational movement therebetween. Alternatively, the plug holder 300' can have a row of plug units 320' arranged linearly in a single generally flat strip, such as Fig.36 and 37 As shown. The plug unit 320' may be sealed by an adhesive sheet 330'. The plug unit 320' may have minimal side walls, or the side walls may even be eliminated entirely. The plug holder 300, 300' is preferably constructed of a molded polymeric material.

[0059] Refer again Figure 1-17 , at least one plug unit 320, and preferably a plurality of plug units 320 are arranged on the side panel 312, and these plug units 320 can be conveniently positioned at regularly spaced intervals. The plug holder 320 is preferably aligned with the container unit 120 of the container tray 100. In the plug holder 300, each plug unit 320 can form a generally cylindrical closed body having a distal opening 322, an internal space 324, a proximal inner surface 326 opposite to the distal opening 322, a side wall 328, a proximal outer surface 330 and a side outer surface space 332. The proximal wall 325 is formed between the proximal inner surface 326 and the proximal outer surface 330. Note that the side wall 328 can be formed to have a minimum height or be completely eliminated, leaving a substantially dome-shaped (i.e., the proximal outer surface 330 will interface with the side panel 312) plug unit 320' (see Fig.36 and37 ). The stopper unit 320 releasably fixes the stopper 200 therein and is adapted to release the stopper 200 into the filling opening 22 of the vial 20 when pressure is applied to the proximal outer surface 330 of the stopper unit 300. The fixation of the stopper 200 is preferably achieved by an interference friction fit between the stopper 200 and the side inner surface 328 of the stopper unit 320, preferably a slight interference fit. The proximal outer surface 330 of the stopper unit 320 is preferably curved outwardly relative to the interior space 324.

[0060] The plug unit 320 is preferably constructed by thermoforming of a flexible polymer, such as polyethylene or PETG (modified polyethylene terephthalate), etc., from which at least a portion of the plug unit 320 (e.g., the proximal wall 325 and the side wall 328, etc.) and the plug holder 300 can be formed. Alternatively, in an embodiment not shown, the plug unit 320 can be constructed of a rigid material and have a living hinge along the interface between the plug unit 320 and the side panel 312 or between the proximal wall 330 and the side wall 328. Specific reference Fig.11 and 12 In the illustrated embodiment, when pressure is applied on the stopper unit (e.g., pressure that may be applied by a fingertip 331, etc.), the proximal outer surface 330 of the stopper unit 300 bends inwardly, and the proximal wall 325 bends toward the stopper 200 and applies pressure on the stopper 200 to push the stopper 200 from the stopper unit 320 into the filling opening 22 of the vial 20. The container unit 120 may be configured to releasably secure the vial 20 at an outward angle relative to the container tray 100. This configuration presents the filling opening 22 to the user at an advantageous angle to insert the stopper 200 into the filling opening 22.

[0061] Reference Figure 18-31 The second embodiment of the packaging system 410 includes one or more drug containers in the form of vials 20, a container tray 100, and a corresponding number of stoppers 200 as described above. Figure 22-25 ) has an outer surface 502 and an inner surface 504. The inner surface 504 is configured to releasably grip the stopper 200. The shuttle 500 is configured to release the stopper 200 into the filling opening 22 of the vial 20 when a release force is applied to the outer surface 502 of the shuttle 500 in a manner described below (i.e., the user manipulates the shuttle 500 rather than directly manipulating the stopper 200).

[0062] The packaging system 410 also includes a shuttle tray 600 having shuttle units 620. More particularly, the shuttle tray 600 preferably has a plurality of shuttle units 620, which are preferably arranged at regularly spaced intervals. The shuttle tray 600 is preferably made of a molded polymer material and can be stacked on the container tray 100 (as described above), and the shuttle tray 600 and the container tray 100 accommodate a matching number of shuttles 500 and vials 20 or other drug containers.

[0063] Reference Figure 20-21 Each reciprocating motion unit 620 forms a generally cylindrical closed body having a proximal opening 622, an interior space 624, a bottom inner surface 626 and a side inner surface 628 opposite the proximal opening 622. The reciprocating motion unit 620 releasably fixes the reciprocating motion member 500 therein. One of the bottom inner surface 626 and the side inner surface 628 of the reciprocating motion unit 620 has a locking opening 630 for engaging a portion of the reciprocating motion member 500 (see below) to fix the reciprocating motion member 500 in the reciprocating motion unit 620.

[0064] The outer surface 502 extends over various outer contours and features of the shuttle 500, and the inner surface 504 similarly extends over various inner contours and features of the shuttle 500. The shuttle 500 has a generally cylindrical body 501 having a proximal end 508, a distal end 510, a first distally extending leg and a second distally extending leg 512 attached to the body 501, and a distally extending rib 501a. The first distally extending leg and the second distally extending leg 512 include a laterally extending locking mechanism 514. Notches 506 are located on the outer and inner surfaces 504 extending into the first distally extending leg and the second distally extending leg 512. The notches 506 on the first and second legs 512 provide a flex point for the legs 512, thereby allowing the legs 512 to be more easily moved to secure and release the plug 200. The first and second legs 512 also include proximally facing first and second plug supports 512a that engage the larger portion 202 of the plug 200 to secure the larger portion between the plug support 512a and the rib 501a. First and second tool accessories in the form of tool openings 518 are formed for releasably engaging a tool (preferably a bending tool 800 ( Fig.31)) in each of the first and second legs 512 (and more specifically in the locking protrusion 514) of the tool 800, so that movement of the tool 800 causes deformation of the legs 512, thereby bending the legs 512 outwardly and thus disengaging the notched stopper support 512a from the stopper 200, thereby releasing the stopper 200 from the shuttle 500. In addition, the first and second legs 512 have a bent portion 512b for contacting the vial flange 23 of the vial 20. The distal movement of the shuttle 500 causes the vial flange 23 to press against the bent portion 512b, thereby facilitating the outward bending of the legs 512 and thus facilitating the release of the stopper 200 from the shuttle 500. The form and operation of the bending tool 800 will be discussed in more detail below.

[0065] The locking projections 514 extend radially outward and are configured to engage the locking openings 630 of the shuttle unit 620 to releasably secure the shuttle 500 in the shuttle unit 620. In the illustrated embodiment, the shuttle unit 620 is configured such that the shuttle 500 can be placed in the shuttle unit 620 and rotated to engage and disengage the locking projections 514 from the locking openings 630, thereby securing and releasing the shuttle 500 from the shuttle unit 620.

[0066] As discussed in more detail below, the shuttle 500 enables a user to manipulate and release the stopper 200 by employing a tool, such as the tools 700, 800, etc., to contact only the outer surface 502 of the shuttle 500, such that any tool employed by the user does not contact the stopper 200 and, therefore, does not potentially soil or contaminate the stopper 200. The shuttle 500 is configured to release the stopper 200 into the filling opening 22 of the vial 20 when a release force is applied to the outer surface 502 of the shuttle.

[0067] The tools 700, 800 may be used with one or more packaging systems disclosed herein. Fig.32, a straight tool 700 can be used with the packaging system 410, and generally with the packaging system disclosed herein, for engaging the plug 200. The straight tool 700 includes a first arm 702 having a first proximal end 704 and a first distal end 706, and a second arm 708 having a second proximal end 710 and a second distal end 712. The first proximal end 704 and the second proximal end 710 are connected to each other at a proximal joint, which can be a hinge, but as shown, the proximal joint is shown as a unitary structure 714 of the first and second proximal ends 704, 710, so that the function of the tool 700 is similar to that of forceps. The first arm 702 has a first arm inner surface 716 facing the second arm 708, a first clamping surface 718 facing the second arm 708, and a first abutment surface 720 perpendicular to the first clamping surface. The second arm has a second arm inner surface 722 facing the first arm 702, and a second clamping surface and a second abutment surface (not numbered) that are mirror images of the first clamping surface 718 and the first abutment surface 720. The first gripping surface 718 of the first arm 702 and its mirror image on the second arm 708 help grip the stopper 200 by the larger portion 202 to avoid contaminating the smaller portion 204. The gripping surface 718 is preferably curved to match the larger portion 202 of the stopper 200. The first abutment surface 720 of the first arm 702 and its mirror image on the second arm 708 help press the stopper 200 into the filling opening 22 of the vial 20.

[0068] Reference Fig.31, a bending tool 800 can be used with the packaging system 410, and generally with the packaging systems disclosed herein, for engaging the tool opening 518 and, if applicable, the plug 200. The bending tool 800 includes a first arm 802 having a first proximal portion 804. A second arm 806 has a second proximal portion 808. The first proximal portion 804 and the second proximal portion 808 are connected to each other at a proximal joint, which in the illustrated embodiment is an integral structure 810 of the first and second arms 802, 806. The first arm 802 has a first distal end 812 and a first distal portion 814 extending proximally from the first distal end 812, a first inner surface 815 facing the second arm 806, and an opposing first outer surface 816, and the first inner surface 814 has a first curved portion 818 extending convexly toward the second arm 806. The second arm 806 has a second distal end 820 and a second distal portion 822 extending proximally from the second distal end 820, a second inner surface 821 facing the first arm 802 and an opposite second outer surface 824, and the second inner surface 821 has a second curved portion 826 extending convexly toward the first arm 802, which faces the front curved portion 818 but is spaced apart therefrom. The operation of the first curved portion 818 and the second curved portion 826 of the tool 800 is expected to generate fewer particles than other devices used for this purpose. In addition, the tool 800 can be formed with a single mold, which is an advantage in manufacturing.

[0069] In use, the stopper 200 is preloaded into the shuttle 500 in the following manner: the larger portion 202 of the stopper 200 is located between the rib 501a of the shuttle 500 and the stopper support 512a. The preloading process is completed in the manufacturing plant by assembly equipment not related to the present disclosure. The shuttle 500 with the preloaded stopper 200 is then ready for installation using the bending tool 800 to place the stopper 200 in the filling opening 22 of the vial 20, as described in more detail below. In the initial position, the first arm 802 and the second arm 806 are aligned and biased such that when no external force is applied to the bending tool 800, the first distal portion 814 and the second distal portion 822 are aligned at a first distal portion distance 828 that is less than the diameter of the plug 200 (preferably less than the larger diameter 204 of the plug) and such that when a first pressure is applied to the first outer surface 816 and the second outer surface 824, the first curved portion 818 contacts only the second curved portion 826, which slightly reduces the first distal portion distance 828. The first curved portion 818 and the second curved portion 826 bend in a complementary manner (here as mirror images of each other) such that when a second pressure greater than the first pressure is applied to the first outer surface 816 and the second outer surface 824, the first arm 802 bends and deforms and the second arm 806 bends and deforms such that the first distal portion 814 and the second distal portion 822 move apart to a second distal portion distance 830 (indicated in phantom) greater than the first distal portion distance 828. The first arm 802 and the second arm 806 are configured and biased so that when a second pressure is applied to the first outer surface 816 and the second outer surface 824 via the tool opening 518, the first portion 818 and the second portion 826 bend to separate the first distal portion 814 and the second distal portion 822 to allow the reciprocating member 500 to be clamped therebetween. That is, once the first distal portion 812 and the second distal portion 822 are located in the tool opening 518, the second pressure is released, causing the first distal portion 812 and the second distal portion 822 to bend inwardly to clamp the radially inward surface of the tool opening 518, and thus clamp the reciprocating member 500 and the plug 200 between the first distal portion 812 and the second distal portion 822 to facilitate operation.

[0070] The stopper 200 can now be positioned in the filling opening 22 of the vial 20 using the bending tool 800. To release the stopper 200 from the shuttle 500, a fourth pressure is applied to the first outer surface 816 of the first arm 802 and the second outer surface 824 of the second arm 806, and the first distal portion 814 and the second distal portion 824 move apart to allow the first arm 802 and the second arm 806 to engage the radial outer surfaces of the first tool opening and the second tool opening 518 of the shuttle 500 to move the first leg and the second leg 512 of the shuttle 500 outwardly, thereby causing the first notch and the second notch 506 of the first leg and the second leg 512 of the shuttle 500 to release the stopper 200. The first distal portion 814 of the first arm 802 has a first step 832 facing outwardly, and the second distal portion 824 of the second arm 806 has a second step 834 facing outwardly for engaging the first tool opening and the second tool opening 518 of the shuttle 500. The shuttle 500 can then be removed from the bending tool 800 releasing the first arm 802 and the second arm 806 until the first distal portion 812 and the second distal portion 822 can be removed from the tool opening 518. At this point, the shuttle 500 can be returned to the manufacturing facility to be reloaded with the plug 200 or recycled, if desired.

[0071] Reference Figure 33-3 5. The third embodiment of the packaging system further comprises a drug container in the form of a vial 20 (and preferably a plurality of vials 20), and a stopper 200 as described above, and may comprise a container tray 100 as described above.

[0072] The plug clip 1200 includes an articulated base having a first articulated base leg 1204 and a second articulated base leg 1210, the first articulated base leg 1204 having a first proximal articulated base leg end 1206 and a first distal articulated base leg end 1208, and the second articulated base leg 1210 having a second proximal articulated base leg end 1212 and a second distal articulated base leg end 1214, the first proximal articulated base leg end 1208 and the second proximal articulated base leg end 1214 being connected to each other by a hinge 1216. In an alternative plug clip 1200', the articulated base leg ends 1208, 1214 may be connected by a live hinge 1216' disposed between the first articulated base leg 1204 and the second articulated base leg 1210 (see FIG. 35). Again referring to FIG. Figure 33-3 5, the hinges 1216, 1216' are biased to push the first distal hinged base leg end 1208 and the second distal hinged base leg end 1214 toward each other to a first position, which is the resting position of the plug clip 1200 when unloaded (without a plug 200 therein). Fig.33As shown in FIGS. 35 and 35 , the hinged base legs 1204 , 1210 are configured such that when in the first position, the legs 1204 , 1210 clamp the plug 200 .

[0073] The first articulated base leg 1204 has a first rod 1218 extending proximally therefrom, and the second articulated base leg 1210 has a second rod 1230 extending proximally therefrom. The first rod 1218 has a first interior rod surface 1220 facing the second rod 1230 and a first exterior rod surface 1222 opposite the first interior rod surface 1220. The second rod 1230 has a second interior rod surface 1232 facing the first rod 1218 and a second exterior rod surface 1234 facing the second interior rod surface 1232.

[0074] The first rod 1218 and the second rod 1230 are in a spaced relationship and operate in the manner of a clothespin or clip such that upon application of a first pressure by the first outer rod surface 1222 and the second outer rod surface 1234, the first articulated base leg 1204 and the second articulated base leg 1210 are urged to a second position wherein the first articulated base leg 1204 and the second articulated base leg 1210 are spaced apart to allow the plug 200 to be inserted between the first articulated base leg 1204 and the second articulated base leg 1210 to be releasably secured therebetween. Fig.35B .

[0075] The first hinged base leg 1204 has a first pushing surface 1240 adapted to contact the proximal surface 214 of the stopper 200 when the stopper 200 is fixed between the first hinged base leg 1204 and the second hinged base leg 1210, and the stopper 200 is aligned with the filling opening 22 of the vial 20, and the stopper clip 1200 is pushed distally to push the stopper 200 into the filling opening 22. Similarly, the second hinged base leg 1210 has a second pushing surface 1242 adapted to contact the proximal surface 214 of the stopper when the stopper 200 is fixed between the first hinged base leg 1204 and the second hinged base leg 1210, and the stopper 200 is aligned with the filling opening 22 of the vial 20, and the stopper clip 1200 is pushed distally to push the stopper 200 into the filling opening 22. The first articulated base leg 1204 has a first retaining arm 1244 that protrudes toward the second articulated base leg 1210, and the second articulated base leg 1210 has a second retaining arm 1246 that protrudes toward the first articulated base leg 1204. When the first pressure is removed, the first articulated base leg 1204 and the second articulated base leg 1210 are urged to a third position, which may be the same as or different from the first position, so that the first articulated base leg 1204 and the second articulated base leg 1210 meet to releasably secure the plug 200 between the first articulated base leg 1204 and the second articulated base leg 1210 ( Fig.33 , 35A ).

[0076] First retaining arm 1244, 1244' and second retaining arm 1246, 1246' are configured and aligned to form a retaining gap 1250, 1250' between first retaining arm 1244, 1244' and second retaining arm 1246, 1246' (see Fig.33A ), the size of the maintaining gap 1250, 1250' is smaller than the larger diameter 204 of the plug 200 and greater than or equal to the smaller diameter 208 of the plug 200. The first retaining arm 1244, 1244' and the second retaining arm 1246, 1246' together support the plug 200 to prevent the plug 200 from moving distally when the plug 200 is fixed between the first hinged base leg 1204 and the second hinged base leg 1210 in the second position.

[0077] Preferably, the plug clip 1200, 1200' is provided with a plurality of plugs similar to Figure 1-17 The use of the stopper clamp 1200 allows for simultaneous clamping and insertion of multiple stoppers 200 into corresponding multiple vials 20 by manipulating the first rod 1218 and the second rod 1230 toward each other during insertion to clamp and release the stoppers.

[0078] Reference Figure 38-40 A system for manipulating stoppers of drug containers includes a plurality of stoppers 200 as described above. The manipulation tray 1500 includes a base 1510, a plurality of stopper holders 1520 disposed on the base 1510, and the plurality of stopper holders 1520 are used to releasably fix the plurality of stoppers 200 to the base 1510. The base 1510 has an upper surface 1512 and a lower support surface 1514. The upper surface 1512 is spaced apart in a conical form relative to the lower support surface 1514 and is inclined upward to facilitate access to the stoppers 200.

[0079] A transparent cover 1550 is releasably and sealingly connected to the base 1510 for covering the stopper 200. The cover 1550 has a cover flange perimeter 1552 and a plurality of spaced and outwardly extending circumferential cover flanges 1554 extending therefrom. The cover 1510 may include a sterilant permeable plate 1556 for sterilizing the contents of the manipulation tray 1500. The base 1510 has a circumferential base flange 1516 extending outwardly therefrom, and the base flange 1516 in turn has a plurality of spaced and upwardly extending cover retaining walls 1518 extending therefrom. The cover retaining walls 1518 form a plurality of cover retaining gaps 1519 therebetween for removing the cover 1550. The lid retaining wall 1518 and the base flange 1516 of the base 1510 are spaced apart so that in a first position, the lid 1550 is supported on the base flange 1510 with the lid flange 1554 supported in the lid retaining gap 1519. In a second rotational position, the lid flange 1554 is aligned with and in contact with the lid retaining wall 1518 of the base 1510 to releasably secure the lid 1550 to the base 1510. In an alternative embodiment (not shown), the lid 1550 may be threadedly attached to the base 1510 or may be non-threaded and may be interference fit with the base 1510; in either case, the base flange 1516, lid retaining wall 1518, and lid retaining gap 1519 may be omitted.

[0080] The plug holder 1520 is arranged so that the plug 200 ( Figure 13-Figure 16) are spaced apart from each other. Each stopper holder 1520 includes a recess 1522 having a stopper holder opening 1524 in an upper surface 1512 that communicates with a stopper holder bottom surface 1526, the stopper holder opening 1524 being shaped so that a smaller portion 206 of the stopper 200 passes through the stopper holder opening 1524, while a larger portion 202 of the stopper 200 does not pass through the stopper holder opening 1524. The stopper holder opening 1524 also has a vent 1528 that communicates between the stopper-unit bottom surface 1526 and a space 1530 above the upper surface 1512 of the base 1510 for at least sterilization purposes. In addition, the vent 1528 may also allow air / gas to be displaced from the recess when the stopper 200 is inserted into the recess 1522. The post extends upward from the stopper holder bottom surface 1526 and is positioned in the hole 210 ( Figure 13-Figure 16 ) to help align the plug in the plug holder opening 1524.

[0081] Reference Figures 41-43, an alternative filling system 1010 includes a container tray 100 and a stopper tray 1300 having a lid 1400. The stopper tray 1300 and the lid 1400 are preferably constructed of molded polymeric material. At least one stopper bracket 1302 is arranged on the stopper tray 1300, and preferably a plurality of stopper brackets 1302, which can be conveniently placed at regularly spaced intervals. The stopper brackets 1302 preferably correspond in number to the container units 120 of the container tray 100 and can be aligned therewith. In the stopper tray 1300, each stopper bracket 1302 includes a generally cylindrical closed body having a proximal opening 1322, an interior space 1324, a distal inner surface 1326 opposite the proximal opening 1322, and a side wall 1328. The proximal opening 1322 can be arranged in a stopper bracket recess 1340 in a top surface 1342 of the stopper bracket 1302. The plug tray 1302 includes at least one plug positioning surface, which in the illustrated embodiment includes four free end surfaces 1330a of four plug support extensions 1330 extending radially inwardly from the sidewall 1328 and extending upwardly from the distal inner surface 1326. The free end surfaces 1330a can be configured to engage the smaller portion 206 of the plug 200, and the larger portion 204 of the plug 200 is supported on the plug support body 1330. The top surface 1342 of the plug tray 1300 has a downwardly extending hole 1332. The cover 1400 is secured to the plug tray 1300 to secure the plug 200 in the plug tray 1300 during transportation and prior to use. The cover 1400 has an upper surface 1401 and a downwardly extending boss feature 1402 for engaging and positioning within a downwardly extending hole 1332 of complementary size in the stopper tray 1300 to secure the cover 1400 to the stopper tray 1300 and a downwardly extending stopper tray cover 1404 which is aligned with and extends into the stopper tray 1302 to secure the stopper 200 to the stopper tray 1300.

[0082] Reference Fig.30 , a sterilization bag 900 can be provided to contain any or all components of any packaging system disclosed herein. The sterilization bag 900 can preferably be a material that is permeable to a sterilant (e.g., steam) but impermeable to contaminants. The sterilization bag 900 can be used to sterilize the packaging system after manufacture or before use, and can be used as a disposable package that can provide the packaging system to a user.

[0083] Those skilled in the art will appreciate that changes may be made to the above embodiments without departing from the broad inventive concept of the present invention. Therefore, it should be understood that the present invention is not limited to the specific embodiments disclosed, but is intended to cover modifications within the spirit and scope of the present invention as defined by the appended claims.

[0084] In addition, certain terms are used in the following description for convenience only, not for limitation. The words "low", "bottom", "upper", "top", "front", "back" and "back" represent directions in the referenced drawings. The words "inward" and "outward" refer to the directions toward and away from the geometric center of the components and designated parts thereof discussed in accordance with the present disclosure, respectively. Unless specifically set forth herein, the terms "one", "an" and "the" are not limited to one element, but should be understood as "at least one". For clarity or readability, "at least one" may sometimes be used, but such use does not change the interpretation of "one", "an" and "the". The terms include the above words, their derivatives, and words with similar meanings. And the singular includes the plural, and vice versa, unless the context clearly indicates otherwise. Various components are described in terms of a single component; however, the illustrated embodiment or other embodiments not shown may include two or more identical components, as shown in the drawings or described in the specification, or as understood by those skilled in the art. Various components are described as being fixed to prevent movement or bending; these references do not contemplate the absolute elimination of all movement or bending. Instead, these references include restrictions or movements of bending that are sufficient to change the function of a component or an operational relationship between components. Reference to a component extending, moving, or bending in a particular direction refers to a component that extends, moves, or bends at least partially in the particular direction; including extension, movement, or bending of any component of motion in the particular direction.

Claims

1. A packaging system for filling and sealing at least one drug container having a filling opening using a stopper, the packaging system comprising: a container tray having a container unit for accommodating and stabilizing the drug container; a shuttle having an outer surface and an inner surface, the inner surface being configured to releasably secure the plug, the shuttle being configured to release the plug into the fill opening upon application of a release force to the outer surface of the shuttle; as well as a reciprocating member tray having a reciprocating member unit, the reciprocating member unit forming a closed body having a proximal opening, an internal space, a bottom inner surface opposite to the proximal opening, and a side inner surface, the reciprocating member unit releasably fixing the reciprocating member; The reciprocating member has a main body having a proximal end, a distal end, and a first leg and a second leg attached to the main body and extending toward the distal end; The first leg has a first locking protrusion extending radially outward, the second leg has a second locking protrusion extending radially outward, and One of the bottom inner surface and the side inner surface of the reciprocating member unit has a locking opening for engaging the locking protrusion of the leg to releasably fix the reciprocating member in the reciprocating member unit.

2. The packaging system according to claim 1, wherein: The first leg is attached with a first plug accessory for releasably fixing the plug to the reciprocating member and a tool accessory for releasably engaging a tool so that movement of the tool causes a first deformation of the first leg, and the second leg is attached with a second plug accessory for releasably fixing the plug to the reciprocating member and a tool accessory for releasably engaging the tool so that movement of the tool causes a second deformation of the second leg, the first deformation and the second deformation causing the first plug accessory and the second plug accessory to release the plug.

3. The packaging system according to claim 2, further comprising: A tool for engaging the tool accessory, the tool comprising: a first arm and a second arm, the first arm having a first proximal portion, the second arm having a second proximal portion, the first proximal portion and the second proximal portion being connected to each other at a proximal joint, The first arm has a first distal end and a first distal portion extending proximally from the first distal end, a first inner surface facing the second arm, and an opposite first outer surface, wherein the first inner surface has a first curved portion, The second arm has a second distal end and a second distal portion extending proximally from the second distal end, a second inner surface facing the first arm, and an opposite second outer surface, wherein the second inner surface has a second curved portion, The first arm and the second arm are aligned and biased such that when no external force is applied to the tool, the first distal portion and the second distal portion are aligned at a first distal portion distance that is less than a diameter of the plug, and such that when a first pressure is applied to the first outer surface and the second outer surface, the first curved portion contacts the second curved portion, The first curved portion and the second curved portion are curved such that when a second pressure greater than the first pressure is applied to the first outer surface and the second outer surface, the first arm bends and deforms, and the second arm bends and deforms such that the first distal portion and the second distal portion move apart to a second distal portion distance greater than the first distal portion distance, and The first arm and the second arm are configured and biased so that when a second pressure is applied to the first outer surface and the second outer surface, the first distal portion and the second distal portion move apart to allow the reciprocating motion member to be clamped between the first distal portion and the second distal portion, and the first arm and the second arm are biased so that when a third pressure is applied to the first outer surface and the second outer surface, the first distal portion and the second distal portion engage with the outer surface of the reciprocating motion member to releasably secure the reciprocating motion member between the first arm and the second arm.

4. The packaging system according to claim 3, wherein: The tool accessory of the first leg includes a first body protruding outward from the first leg and having a first tool hole therein, and the tool accessory of the second leg includes a second body protruding outward from the second leg and having a second tool hole therein, The first arm and the second arm of the tool are configured and aligned so that when a fourth pressure is applied to the first outer surface of the first arm and the second outer surface of the second arm, the first distal portion and the second distal portion move apart to allow the first arm and the second arm to engage with the first tool hole and the second tool hole to move the first leg and the second leg of the reciprocating movable member outward, thereby causing the first plug fittings and the second plug fittings of the first leg and the second leg of the reciprocating movable member to release the plug.

5. The packaging system according to any one of claims 1 to 4, further comprising: A tool for engaging a tool accessory, the tool comprising a first arm and a second arm, the first arm having a first proximal end and a first distal end, the second arm having a second proximal end and a second distal end, the first proximal end and the second proximal end being connected to each other, wherein the first arm has a first arm inner surface facing the second arm, a first clamping surface facing the second arm, and a first abutting surface perpendicular to the first clamping surface, and the second arm has a second arm inner surface facing the first arm, a second clamping surface facing the first arm, and a second abutting surface perpendicular to the first clamping surface.

6. The packaging system according to claim 5, wherein: The first distal portion of the first arm has a first outwardly facing step for engaging the first tool hole, and the second distal portion of the second arm has a second outwardly facing step for engaging the second tool hole.

7. A packaging system for filling and sealing at least one drug container having a filling opening using a stopper, the packaging system comprising: a container tray having a container unit for accommodating and stabilizing the drug container; as well as a plug clamp having a plug unit, the plug unit including an articulated base, the articulated base having a first articulated base leg and a second articulated base leg, the first articulated base leg having a first proximal articulated base leg end and a first distal articulated base leg end, and the second articulated base leg having a second proximal articulated base leg end and a second distal articulated base leg end, the first proximal articulated base leg end and the second proximal articulated base leg end being connected to each other by a hinge, the hinge being biased to urge the first distal articulated base leg end and the second distal articulated base leg end toward each other to a first position; The first articulated base leg has a first lever extending proximally from the first articulated base leg; the second articulated base leg having a second lever extending proximally from the second articulated base leg; The first lever has a first inner lever surface and a first outer lever surface, the first inner lever surface faces the second lever, and the first outer lever surface is opposite to the first inner lever surface; The second lever has a second inner lever surface and a second outer lever surface, the second inner lever surface faces the first lever, and the second outer lever surface is opposite to the second inner lever surface; The first lever and the second lever are in a spaced relationship such that when a first pressure is applied by the first outer lever surface and the second outer lever surface, the first articulated base leg and the second articulated base leg are pushed to a second position, wherein the first articulated base leg and the second articulated base leg are spaced to allow the plug to be inserted between the first articulated base leg and the second articulated base leg to be releasably secured between the first articulated base leg and the second articulated base leg, and when the first pressure is removed, the first articulated base leg and the second articulated base leg are pushed to a third position to releasably secure the plug between the first articulated base leg and the second articulated base leg.

8. The packaging system according to claim 7, wherein: The hinge includes a living hinge disposed between the first hinged base leg and the second hinged base leg.

9. The packaging system according to claim 7, wherein: The plug has a larger portion of larger diameter, a smaller portion of smaller diameter, and a proximal surface; the first hinged base leg having a first push surface adapted to contact a proximal surface of the bung when the bung is secured between the first hinged base leg and the second hinged base leg, the bung is aligned with a fill opening of the medicament container, and the bung clip is urged distally to push the bung into the fill opening; and the second hinged base leg having a second push surface adapted to contact the proximal surface of the bung when the bung is secured between the first hinged base leg and the second hinged base leg, the bung is aligned with the fill opening of the medicament container, and the bung clip is urged distally to push the bung into the fill opening; the first hinged base leg having a first retaining arm projecting toward the second hinged base leg; The second hinged base leg has a second retaining arm projecting toward the first hinged base leg; and The first retaining arm and the second retaining arm are configured and aligned to form a retaining gap therebetween, the retaining gap having a size smaller than a larger diameter of the plug and greater than or equal to a smaller diameter of the plug, such that when the plug is secured in a second position between the first articulated base leg and the second articulated base leg, the first retaining arm and the second arm together support the plug to prevent distal movement of the plug.

10. The packaging system according to claim 7, further comprising: A container tray, the container tray comprising a plurality of container units, the plurality of container units being used to releasably fix a plurality of drug containers; wherein the plug clamp comprises a plurality of plug units and the plug clamp is configured to align at least two of the plurality of plug units with at least two of the plurality of container units; the plug unit being aligned with the first hinged base legs aligned and attached to each other and the second hinged base legs aligned and attached to each other, the first levers of the plug unit aligned and attached to each other and the second levers of the plug unit aligned and attached to each other, the first proximal hinged base leg end and the second proximal hinged base leg end being connected to each other by a hinge, the hinge being biased to urge the attached first distal hinged base leg end and the second distal hinged base leg end toward each other to a first position; The first articulated base leg and the second articulated base leg are biased to move to the first position in unison, and when a first pressure is applied to the first lever and the second lever, the first articulated base leg and the second articulated base leg move to the second position in unison, and when the first pressure is removed, the first articulated base leg and the second articulated base leg move to the third position in unison.

11. The packaging system according to claim 10, wherein: The hinge is a living hinge.

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