ACTUATIONS Field of the Invention

The invention relates to liquid drug transfer devices for mixing, reconstitution and administration purposes.

Background of the Invention

Commonly owned PCT International Application No.

PCT/IL2012/000354 entitled Valve Assembly for Use with Liquid Container and Vial and published under PCT International Publication No. WO 2013/054323 discloses valve assemblies for use with an infusion liquid container and a drug vial. The valve assemblies include a conventional male drug vial adapter having a male connector in flow communication with a puncturing member for puncturing a drug vial stopper. The valve assemblies also include an access port adapter for attachment to an access port of an infusion liquid container and a female connector for sealingly mounting on the male connector. The use of the valve assemblies includes several user actions including inter alia attaching a valve assembly to an access port, telescopic clamping the valve assembly on a drug vial, and opening the valve assembly for enabling flow of infusion liquid to the drug vial for mixing or reconstitution purposes and subsequent transfer of liquid contents from the drug vial to the infusion liquid container for subsequent administration.

Commonly owned US Patent No. 6,558,365 to Zinger et al. entitled

Fluid Transfer Device discloses liquid drug transfer devices for aseptic reconstitution of a drug medicament for administration purposes. The liquid drug transfer devices include a so-called female drug vial adapter and a so- called male liquid vial adapter pre-mounted on the female drug vial adapter. The female drug vial adapter is intended to be telescopically clamped on a drug vial containing a drug medicament typically under negative pressure. The male liquid vial adapter is intended to be telescopically clamped on a liquid vial containing diluent only or an active liquid component to be drawn into the drug vial by its negative pressure. The use of the liquid drug transfer devices involves several user actions including inter alia a user telescopically clamping the liquid vial adapter on a liquid vial, inverting the liquid drug transfer device together with the liquid vial, and telescopically clamping the drug vial adapter on a drug vial.

The aforesaid liquid drug transfer devices require several user actions which can be time consuming and prone to error, for example, inaccurate telescopic clamping a drug vial adapter on a drug vial can lead to the drug vial being unusable. There is a need for improved liquid drug transfer devices requiring less user actions for actuation purposes, thereby facilitating user convenience and reducing wastage of drug vials. Summary of the Invention

The present invention is directed toward liquid drug transfer devices employing manual rotation for dual flow communication step actuations for establishing flow communication between a liquid container containing liquid contents and an initially intact, namely, non-punctured, drug vial containing a drug medicament. The liquid container can be either an infusion liquid container or a liquid vial. Infusion liquid containers include inter alia a bottle, an IV bag, and the like. Liquid vials can contain diluent only or an active liquid component. Drug vials can include a powder drug medicament or a liquid drug medicament. Some drug vials are under negative pressure.

The liquid drug transfer devices have a longitudinal device axis and include a liquid container adapter for attachment to a liquid container, a dual ended liquid transfer member, and a drug vial adapter for telescopic clamping on a drug vial. The dual ended liquid transfer member has a trailing liquid transfer member end terminating in a puncturing tip co-directional with the longitudinal device axis and initially spaced apart from an uppermost drug vial surface of an initially intact drug vial. The liquid drug transfer devices are designed such that a manual rotation about a longitudinal device axis linearly compacts a liquid drug transfer device therealong for urging the puncturing tip along a linear displacement to puncture through a drug vial stopper during a drug vial flow communication step for flow communication with a drug vial interior.

Liquid drug transfer devices can be designed such that a drug vial flow communication step is a first flow communication step or a second flow communication step of a two flow communication step actuation depending on a clinical application at hand. Two flow communication step actuations including an initial drug vial flow communication step and a subsequent liquid container flow communication step afford the advantage that liquid contents can immediately flow from a liquid container to a drug vial. Two flow communication step actuations including an initial liquid container flow communication step and a subsequent drug vial flow communication step are mandatory in the case of a drug vial's negative pressure is employed for drawing liquid contents from a liquid vial into a drug vial for mixing or reconstitution purposes in a similar manner to hitherto mentioned US Patent No. 6,558,365 to Zinger et al.

The liquid drug transfer devices can employ different mechanical arrangements for converting manual rotation into a linear displacement for drug vial puncturing purposes. Suitable mechanical arrangements include inter alia a screw thread arrangement, a pin and track arrangement, and the like. Some liquid drug transfer devices employ the same mechanical arrangement for both their drug vial flow communication step and their liquid container flow communication step. Other liquid drug transfer devices employ one mechanical arrangement for their drug vial flow communication step and another mechanical arrangement for their liquid container flow communication step. Selection of mechanical arrangements is a function of different design features to balance between the number of rotations required and the torque to be applied by a user to effect the manual rotation. The higher the number of rotations the less the torque required and vice versa. The liquid drug transfer devices of the present invention can be classified into one of two types depending on an intended liquid container as follows: Infusion liquid container type and liquid vial type.

In the infusion liquid container type, a liquid container adapter is constituted by an access port adapter typically in the form of an injection port adapter. A dual ended liquid transfer member can terminate in an access port flow member co-directional with the longitudinal device axis and initially spaced apart from an access port of an infusion liquid container for subsequent urging along the longitudinal device axis during a liquid container flow communication step for sliding insertion into the access port. Alternatively, an access port adapter can include an access port flow member for insertion into an access port on attachment of the access port adapter onto an infusion liquid container, and a dual ended liquid transfer device can terminate in an infusion liquid container stopcock arrangement for selective opening and closing flow communication with the access port flow member.

In the liquid vial type, a liquid container adapter is constituted by a liquid vial adapter similar to a drug vial adapter. A leading liquid transfer member end also terminates in a puncturing tip co-directional with the longitudinal device axis and initially spaced apart from an uppermost liquid vial surface of an initially intact liquid vial for subsequent urging along the longitudinal device axis during a liquid vial flow communication step for puncturing a liquid vial stopper for flow communication with a liquid vial interior. Also, the dual ended liquid transfer member preferably has a dual component construction including a drug vial component and a liquid vial component. The drug vial component preferably terminates in a connector for subsequent aspiration of liquid drug contents from a drug vial. The connector is preferably a female connector. Pursuant to flow communication between a liquid vial and a drug vial, a liquid vial component of a liquid transfer member is intended to be detached from its counterpart drug vial component such that the two components remain attached to their respective vial adapters. The liquid drug transfer devices are preferably supplied as so-called "ready to use" medical devices insofar as they are supplied with at least a pre- attached intact drug vial. The liquid drug transfer devices can also additionally be supplied with a pre-attached liquid container be it either a pre-attached infusion liquid container or a pre-attached intact liquid vial. Each pre- attachment is instead of a user attachment and therefore facilitates user convenience and in particular precludes incorrect telescopic clamping of a vial adapter on a drug vial. Moreover, ready to use medical devices reduce drug waste because they facilitate patient bedside preparation immediately prior to use as opposed to be remote preparation in a compound pharmacy remote from a patient bedside which can lead to unused drugs.

Pre-attached intact drug vials can be clamped in drug vial adapters intended for enabling detachment by a release tool still in their intact state, for example, in the case that a patient no longer requires a drug medicament. The released intact drug vial can be placed in a controlled environment for storage purposes and re-attachment to a liquid drug transfer device for subsequent administration. Alternatively, pre-attached drug vials can be clamped in drug vial adapters precluding their detachment. Still again, liquid drug transfer devices can be supplied without a pre-attached drug vial and/or a pre-attached liquid container thereby requiring a user to attach a liquid drug transfer device to a drug vial and a liquid container.

Some liquid drug transfer devices can include a conventional drug vial adapter for telescopic clamping on a single size of a drug vial, namely, a small drug vial or a large drug vial. Alternatively, liquid drug transfer devices can optionally include a universal drug vial adapter designed for telescopic clamping equally on a drug vial of a single drug vial and a large drug vial. Suitable universal drug vial adapters are illustrated and described in commonly owned PCT International Application No. PCT/IL2013/050706 filed August 20, 2013 and entitled Liquid Drug Transfer Devices. The liquid drug transfer devices can similarly include either a conventional liquid vial adapter for telescopic clamping on a single size of a liquid vial or a universal liquid vial adapter.

Some liquid drug transfer devices can be preferably provided with a user indication for indicating establishment of flow communication between a liquid container and a drug vial. User indications can be in the form of visual indications and/or audible indications, for example, a click.

Brief Description of Drawings

In order to understand the invention and to see how it can be carried out in practice, preferred embodiments will now be described, by way of non- limiting examples only, with reference to the accompanying drawings in which similar parts are likewise numbered, and in which:

Fig. 1 is a front perspective view of a first preferred embodiment of a liquid drug transfer device in accordance of the present invention in an initial pre-actuated state, a small drug vial, a large drug vial, and an IV bag;

Fig. 2 is an exploded view of Figure 1 's liquid drug transfer device; Fig. 3 A is a front elevation view of Figure l 's liquid drug transfer device in a pre-actuated state prior to manual rotation;

Fig. 3B is a longitudinal cross section of Figure l 's liquid drug transfer device along line A-A in Figure 3A;

Fig. 4A is a front elevation view of Figure l 's liquid drug transfer device in an intermediate actuated state pursuant to execution of a drug vial flow communication step of a manual rotation;

Fig. 4B is a longitudinal cross sectional of Figure l 's liquid drug transfer device along line B-B in Figure 4 A;

Fig. 5 A is a front elevation view of Figure l 's liquid drug transfer device in its post-actuated state pursuant to subsequent execution of its liquid container flow communication step of a manual rotation;

Fig. 5B is a longitudinal cross sectional of the liquid drug transfer device along line C-C in Figure 5A; Figs. 6A to 6E show the use of Figure l 's liquid drug transfer device with a pre-attached small drug vial for introducing a drug vial medicament to an IV bag and administration of infusion liquid contents;

Fig. 6C is a longitudinal cross section of Figure 6B along line D-D thereon;

Fig. 7 A is a front perspective view of a second preferred embodiment of a liquid drug transfer device in a pre-actuated state in accordance with the present invention;

Fig. 7B is a longitudinal cross section of Figure 7A's liquid drug transfer device along line E-E thereon;

Fig. 8 is a front perspective view of a third preferred embodiment of a liquid drug transfer device in accordance with the present invention in a pre- actuated state;

Fig. 9 is an exploded view of Figure 8's liquid drug transfer device; Fig. 1 OA is a right side elevation view of Figure 8's liquid drug transfer device in its pre-actuated state including a closed stopcock position;

Fig. 10B is a longitudinal cross sectional of Figure 8's liquid drug transfer device along line F-F in Figure 10A;

Fig. 11A is a front elevation view of Figure 8's liquid drug transfer device in an intermediate actuated state including an open stopcock position pursuant to execution of a liquid container flow communication step of a manual rotation;

Fig. 1 IB is a longitudinal cross section of Figure 8's liquid drug transfer device along line G-G in Figure 11 A;

Fig. 12A is a front elevation view of Figure 8's liquid drug transfer device in its post-actuated state pursuant to execution of a drug vial flow communication step of a manual rotation;

Fig. 12B is a longitudinal cross section of Figure 8's liquid drug transfer device along line H-H in Figure 12 A;

Fig. 13 A is a front elevation view of Figure 8's liquid drug transfer device in a locking step of a manual rotation; Fig. 13B is a longitudinal cross section of Figure 8's liquid drug transfer device along line I-I in Figure 13 A;

Fig. 14A is a front elevation view of Figure 8's liquid drug transfer device in a closed stopcock position pursuant to a manual counter-rotation;

Fig. 14B is a longitudinal cross section of Figure 8's liquid drug transfer device along line J- J in Figure 14 A;

Fig. 15 is a front perspective view of a fourth preferred embodiment of a liquid drug transfer device in a pre-actuated state in accordance with the present invention;

Fig. 16 is an exploded view Figure 15's liquid drug transfer device including its dual ended liquid transfer member;

Fig. 17 is a longitudinal cross section of Figure 15's liquid drug transfer device along line K2-K2 thereon;

Fig. 18 is a close-up view of Figure 16s' liquid transfer member;

Fig. 19A is a close-up cross section along line Kl-Kl in Figure 15 showing the drug vial adapter stem with a pair of minor stops for retaining the liquid transfer member in its pre-actuated state;

Fig. 19A is a close-up cross section along line K2-K2 in Figure 15 showing the drug vial adapter stem with a pair of major stops for retaining the liquid transfer member in its pre-actuated state;

Fig. 20A is a front elevation view of Figure 15's liquid drug transfer device in a pre-actuated state attached to an injection port and a large drug vial;

Fig. 20B is a longitudinal cross section of Figure 20A's liquid drug transfer device along line L-L thereon;

Fig. 21 A is a front elevation view of Figure 20 A' s assemblage in an intermediate actuated pursuant to a liquid container flow communication step;

Fig. 21B is a longitudinal cross section of Figure 21A's assemblage along line M-M thereon;

Fig. 22A is a front elevation view of Figure 20A's assemblage in a post- actuated state; Fig. 22B is a longitudinal cross section of Figure 22A's assemblage along line N-N thereon;

Fig. 23 is a front perspective view of a fifth preferred embodiment of a liquid drug transfer device in a pre-actuated state in accordance with the present invention, a large drug vial, a large liquid vial, and a needleless syringe;

Fig. 24 is a longitudinal cross section of Figure 23 's liquid drug transfer device along line P-P thereon;

Fig. 25 is an exploded view Figure 23 's liquid drug transfer device;

Fig. 26A is a front elevation view of Figure 23 's liquid drug transfer device in a pre-actuated state attached to a large drug vial and a large drug vial;

Fig. 26 is a longitudinal cross section of Figure 26A's assemblage along line Q-Q thereon;

Fig. 27 A is a front elevation view of Figure 26A's assemblage in an intermediate actuated state pursuant to a liquid container flow communication step;

Fig. 27B is a longitudinal cross section of Figure 27 A' s liquid drug transfer device along line R-R thereon;

Fig. 28A is a front elevation view of Figure 26A's assemblage in a post- actuated state pursuant to a drug vial flow communication step;

Fig. 28B is a longitudinal cross section of Figure 28 A' s assemblage along line S-S thereon;

Fig. 29 A is a front elevation view showing detachment of the liquid vial adapter and the drug vial adapter;

Fig. 29B is a longitudinal cross section of Figure 29A's liquid vial adapter and drug vial adapter along line T-T thereon;

Fig. 30A is a front elevation view of syringe aspiration of liquid drug contents from the drug vial; and

Fig. 30B is a longitudinal cross section of Figure 30A's assemblage along line U-U thereon. Detailed Description of Preferred Embodiments of the Invention

Figures 1 to 14 show three liquid drug transfer devices 100, 200 and 300 for use with a drug vial 20 of a small drug vial 20A and a large drug vial 20B and a liquid container constituted by an infusion liquid container depicted as an IV bag 40. The liquid drug transfer devices 100, 200 and 300 are similar insofar as each has a longitudinal device axis 101 and includes a liquid container adapter 102 constituted by an access port adapter, a liquid transfer member 103 and a drug vial adapter 104 constituted by a universal drug vial adapter. Their access port adapters 102 each has a leading access port adapter end 102 A and a trailing access port adapter end 102B. Their liquid transfer members 103 each has a leading liquid transfer member end 103 A disposed toward an access port adapter 102 for engaging same and a trailing liquid transfer member end 103B disposed toward a drug vial adapter 104 for engaging same.

The drug vials 20 have a longitudinal drug vial axis 21 and include a drug vial bottle 22 having a drug vial base 23, a drug vial head 24 defining a drug vial opening 26, and a narrow diameter drug vial neck 27 between the drug vial bottle 22 and the drug vial head 24. The drug vials 20 have a drug vial interior 28 for storing a powder or liquid medicament 29. The drug vials 20 are sealed by a drug vial stopper 31 inserted into the drug vial opening 26. The drug vials 20 have an uppermost drug vial surface 32. The drug vial heads 24 are typically sealed by a drug vial closure 33, for example, an aluminum band, and the like.

Large drug vials have the same shape as small drug vials but proportionally larger dimensions. In particular, large drug vials have a drug vial closure and a drug vial neck with wider diameters than their counterpart small drug vials. Widely commercially available small drug vials 20A have a drug vial closure 33 with an external diameter Dl of between 13 mm and 14 mm and widely commercially available large drug vials 20B have a drug vial closure 33 with an external diameter D2 > Dl and typically between 20 mm and 21 mm. The present invention is equally applicable to larger so-called small drug vials and so-called large drug vials containing larger liquid volumes, for example, a 28 mm diameter drug vial closure and a 32 mm diameter drug vial closure, respectively.

The IV bag 40 includes two types of access ports, namely, an injection port 41 and an administration port 42, and contains liquid contents 43. The IV bag ports 41 and 42 are in the form of plastic tubing. The injection port 41 terminates in an injection port tip 44 containing a self-sealing plug 46 with an exposed plug surface 47 intended for needle injection of syringe contents into the IV bag 40. The injection port tip 44 has a trailing injection port tip rim 48. The administration port 42 is typically sealed by a twist off cap 49 for insertion of an IV spike for administration purposes.

The liquid drug transfer devices 100, 200 and 300 are illustrated and described for attachment to an injection port 41 and can be equally implemented for attachment to an administration port 42.

In greater particularity, Figures 1 to 7 show the liquid drug transfer device 100 includes an injection port adapter 102 engaging the leading liquid transfer member end 103 A by means of a screw thread mechanical arrangement and the trailing liquid transfer member end 103B engaging the universal drug vial adapter 104 by means of a pin and track mechanical arrangement. The liquid drug transfer device 100 employs a manual rotation for executing an initial drug vial flow communication step for establishing flow communication between the liquid transfer member 103 and a drug vial 20 and a subsequent liquid container flow communication step for establishing flow communication between the liquid transfer member 103 and the IV bag 40, thereby establishing flow communication between the drug vial 20 and the IV bag 40.

The injection port adapter 102 has a tubular housing 106 formed with a leading injection port recess 107 with a transverse injection port recess wall 108 with an inner injection port recess wall rim 108 A defining a throughgoing injection port recess wall aperture 109. The leading injection port recess 107 is preferably provided with a universal injection port connector 111 for attachment on the injection port 41 as also illustrated and described in hitherto mentioned commonly owned PCT International Application No. PCT/IL2013/050706 filed August 20, 2013 and entitled Liquid Drug Transfer Devices.

The housing 106 has an internal surface 112 provided with a leading transverse inward directed annular abutment rib 113 A and a trailing transverse inward directed annular abutment rib 113B for controlling displacement of the liquid transfer member 103. The internal surface 112 is formed with guide ribs 114 towards the trailing injector port adapter end 102B for guiding purposes during linear compaction of the universal drug vial adapter 104 towards the injection port adapter 102. The housing 106 is formed with a throughgoing slot 116 towards the leading injection port adapter end 102 A for enabling a visual user indication regarding establishment of flow communication between an IV bag and a drug vial.

The leading liquid transfer member end 103 A is provided with a liquid transfer member head 117 with an access port flow member 118 constituted by a needle for needle insertion into the injection port 41. The liquid transfer member head 117 is disposed on the abutment rib 113 A in a pre-actuated state of the liquid drug transfer device 100. The liquid transfer member 103 includes a sleeve 119 for initially covering the needle 118 for ensuring the needle 118 remains sterile until it punctures the injection port 41. The liquid transfer member head 117 has an exterior brightly colored surface for providing a visual user indication through the throughgoing slot 116 on execution of a manual rotation to establish flow communication between an IV bag 40 and a drug vial 20.

The trailing liquid transfer member end 103B terminates in a puncturing tip 119 for puncturing a drug vial stopper 31. The liquid transfer member 103 includes a sleeve 121 for initially covering the puncturing tip 119 for ensuring the puncturing tip 119 remains sterile until it punctures a drug vial stopper 31. The sleeve 121 includes a circular base 122 shaped and dimensioned for placing on the uppermost drug vial surface 32. The liquid transfer member 103 is formed with an axial lumen 123 for flow communication between the needle 118 and the puncturing tip 119.

The leading liquid transfer member end 103 A has a liquid transfer member head drill bit like section 124 for screw thread engaging the abutment rib 113 A on manual rotation of the drug vial adapter 104 in a clockwise tightening direction around the longitudinal device axis 101 for needle insertion of the needle 118 into the injection port 41. The drill bit like section 124 includes a trailing stop member 126 for stopping against the abutment rib 113B for stopping linear displacement of the liquid transfer member 103 towards the injection port adapter 102. The trailing liquid transfer member end 103B is formed with a pair of outward directed radial pins 128 for enabling rotation of the liquid transfer member 103 relative to the injection port adapter 102 by means of the universal drug vial adapter 104.

The universal drug vial adapter 104 includes a transverse vial adapter top wall 129 with an inner top wall rim 129 A defining a throughgoing top wall aperture 130 along the longitudinal device axis 101. The universal drug vial adapter 104 includes a downward depending vial adapter skirt 131 for telescopically clamping on a drug vial closure 33 such that the throughgoing top wall aperture 130 overlies an uppermost drug vial surface 32. The vial adapter skirt 131 includes four equispaced downward depending supports 132 supporting a trailing circular member 133. The circular member 133 is formed with resiliently flexible upward depending grip members 134 arranged in a first pair of opposite grip members 134 A and 134B and an orthogonal second pair of opposite grip members 134C and 134D. The grip members 134 are each formed with an internal directed gripper 136 for gripping a drug vial closure 33.

The vial adapter top wall 129 is formed with an axial directed upright tubular drug vial adapter stem 137 encircling the throughgoing top wall aperture 130 and opposite the downward depending vial adapter skirt 131. The drug vial adapter stem 137 has a pair of opposite generally helical tracks 138 for corresponding engagement by the pair of outward directed radial pins 128. The tracks 138 each have a start track end 139 A remote from the vial adapter top wall 129 and a final track end 139B adjacent the vial adapter top wall 129.

The liquid transfer member 103 is disposed in the drug vial adapter stem 137 such that its puncturing tip 119 is spaced apart from an uppermost drug vial surface 32 of an initially intact non-punctured drug vial 20 clamped in the downward depending vial adapter skirt 131 in the pre-actuated state of the liquid drug transfer device 100. The pair of outward directed radial pins 128 are typically deployed at the start track ends 139A. The puncturing tip 119 passes through the throughgoing top wall aperture 130 on displacement of the liquid transfer member 103 from the start track ends 139 A to the final track ends 139B for puncturing through a drug vial stopper 31 for establishing flow communication with a drug vial interior 28.

Figures 3 A and 3B show the liquid drug transfer device 100 in its pre- actuated state with the drug vial adapter 104 is at its most remote location from the injection port adapter 102. The liquid drug transfer device 100 has a pre- actuated height HI. The liquid transfer member 103 is deployed at the abutment rib 113 A and the needle 118 is disposed at the throughgoing injection port recess wall aperture 109 ready to be urged into the leading injection port recess 107. The outward directed radial pins 128 are deployed at the start track ends 136A and the puncturing tip 119 is disposed above the downward depending vial adapter skirt 131 and preferably above the throughgoing top wall aperture 130.

Figures 4 A and 4B show the liquid drug transfer device 100 pursuant to execution of a drug vial flow communication step of a manual rotation of the universal drug vial adapter 104 with respect to the injection port adapter 102 around the longitudinal device axis 101 in a clockwise tightening direction. The manual rotation urges the universal drug vial adapter 104 to travel to the final track ends 139B whilst the liquid transfer member 103 remains stationary with respect to the injection port adapter 102. This relative linear displacement between the injection port adapter 102 and the universal drug vial adapter 104 leads to the puncturing tip 119 puncturing a drug vial stopper 31 for establishing flow communication between the liquid transfer member 103 and a drug vial 20. The liquid drug transfer device 100 has an intermediate actuated height H3 where H3<H1.

Figures 5 A and 5B show the liquid drug transfer device 100 pursuant to execution of a liquid container communication step of continued manual rotation of the universal drug vial adapter 104 relative to the injection port adapter 102. The liquid drug transfer device 100 has a post-actuated height H2 where H2<H3 and therefore H2<H1. The continued manual rotation urges the liquid transfer member 103 to travel along the abutment rib 113 A until the trailing stop member 126 stops against the abutment rib 113B such that the universal drug vial adapter 104 is adjacent the injection port adapter 102. The needle 118 is urged into the leading injection port recess 107 for needle insertion into an injection port 41 for establishing flow communication between the liquid transfer member 103 and an IV bag 40 and therefore a drug vial 20. The liquid transfer member head 117 is visible through the throughgoing slot 116 such that the user is aware the liquid drug transfer device 100 is now in its actuated state.

Figures 6 A to 6E show the use of the liquid drug transfer device 100 with a pre-attached drug vial 20A. The use of the liquid drug transfer device 100 with a pre-attached drug vial 20B is the same for the liquid drug transfer device 100 with a pre-attached drug vial 20 A.

Figure 6 A shows attaching a liquid drug transfer device 100 to the IV bag 40 as denoted by arrow A for insertion of the injection port 41 into the leading injection port recess for attachment to the injection port connector.

Figure 6B shows manual rotation of the universal drug vial adapter 104 relative to the injection port adapter 102 in a clockwise tightening direction around the longitudinal device axis 101 as denoted by arrow B to urge the liquid drug transfer device 100 to establish flow communication between the IV bag 40 and the drug vial 20A. The liquid transfer member head 117 is visible through the slot 116 to indicate flow communication. The user squeezes the IV bag 40 as denoted by arrows C for transferring liquid contents from the IV bag 40 to the drug vial 20A for reconstitution or dilution purposes. The user may gently agitate the assemblage to ensure full reconstitution of powder contents.

Figure 6C shows the flow communication between the IV bag 40 and the drug vial 20 A via the needle 118, the axial lumen 123 and the puncturing tip 119.

Figure 6D shows inverting the IV bag 40, the liquid drug transfer device 100 and the drug vial 20 A and squeezing air from the IV bag 40 into the drug vial 20A as denoted by arrows D for draining liquid drug contents from the drug vial 20A into the IV bag 40.

Figure 6E shows inverting the IV bag 40, the liquid drug transfer device

100 and the now empty drug vial 20 A ready for administration of the IV bag liquid contents via an infusion set (not shown).

Figures 7A and 7B show a liquid drug transfer device 200 similar in construction and operation as the liquid drug transfer device 100 and therefore similar parts are likewise numbered. The former 200 differs from the latter 100 insofar as the former 200 includes a drug vial adapter 104 with a pre-attached non-detachable drug vial 20A.

Figures 8 to 14 show a liquid drug transfer device 300 for use with a drug vial 20 of a drug vial 20A and a drug vial 20B and an IV bag 40 similar to the liquid drug transfer device 100. The former 300 has a general similar construction as the latter 100 and therefore similar parts are likewise numbered as follows: The liquid drug transfer device 300 has a longitudinal device axis

101 and includes an injection port adapter 102, a liquid transfer member 103 and a universal drug vial adapter 104.

The former 300 differs from the latter 100 insofar that the former 300 employs a manual rotation for executing an initial liquid container flow communication step for establishing flow communication between the liquid transfer member 103 and an infusion liquid container and a subsequent drug vial flow communication step for establishing flow communication between the liquid transfer member 103 and a drug vial, thereby establishing flow communication between the infusion liquid container and the drug vial. Moreover, the former 300 differs from the latter 100 insofar that the former 300 employs the manual rotation for executing a linear compaction of the drug vial adapter 104 towards the injection port adapter 102 for drug vial puncturing and operation of an infusion liquid container stopcock arrangement 140 for selective flow communication between the injector port adapter 102 and an infusion liquid container.

The liquid drug transfer device 300 has a different construction from the liquid drug transfer device 100 in three main respects as follows:

First, the infusion liquid container stopcock arrangement 140 includes the leading injection port recess 107 of the injection port adapter 102 being provisioned with the needle 118 instead of the liquid transfer member 103. The needle 118 is mounted in an axial lumen 141 formed in the injection port recess wall 108. The liquid transfer member 103 and the drug vial adapter 104 have a rotation axis 142 offset from the longitudinal device axis 101. The leading liquid transfer member end 103 A terminates in a leading cone 143 formed with a port 144 in flow communication with the axial lumen 123. The cone 143 includes a key 146 for rotational movement along a keyway 147 formed on the inside surface 148 of a cone recess 149 forming part of the injection port recess wall 108 for selective alignment of the port 144 with the axial lumen 141 for enabling flow communication with the needle 118.

The infusion liquid container stopcock arrangement 140 has a closed flow position in which the key 146 is at a first extreme position along the keyway 147 for misaligning the port 144 with the lumen 141, thereby disabling flow communication between the needle 118 and the liquid transfer member 103. The infusion liquid container stopcock arrangement 140 has an open flow position in which the key 146 is at a second extreme position along the keyway 147 opposite to the first extreme position for aligning the port 144 with the axial lumen 141 for establishing flow communication between the needle 118 and the liquid transfer member 103's axial lumen 123. Second, the trailing liquid transfer member end 103B is formed with an opposite pair of inverted generally L-shaped tracks 151 instead of the helical tracks 138. The tracks 151 each include an upright spiral leg 152 and a horizontal leg 153 meeting at a juncture 154. The spiral legs 152 each have a sealed leg end 156 opposite their corresponding junctures 154. The horizontal legs 153 each have a sealed leg end 157 opposite their corresponding junctures 154. The sealed leg ends 157 are each formed with a lock feature 158 for locking their corresponding outward radial pin 128.

For the purpose of execution of a drug vial flow communication step for drug vial puncturing purposes, the sealed leg ends 156 correspond with the start track ends 139A and the junctures 154 correspond with the final track ends 139B.

Third, the universal drug vial adapter 104 has a downward depending skirt 131 for telescopic clamping on a drug vial 20. The vial adapter skirt 131 includes an inner vial grip 161 for snap fitting onto a small drug vial 20 A and an outer vial grip 162 for snap fitting onto a large drug vial 20B. The inner vial grip 161 includes two opposite flex members 163 each formed with an inner directed rim 164 for snap fitting on a small drug vial 20's drug vial closure 33. The outer vial grip 162 encircles the inner vial grip 161 and includes a first pair of adjacent flex members 166 A and 166B and a second pair of adjacent major flex members 167 A and 167B opposite the first pair of major flex members 166 A and 166B. The major flex members 166 and 167 are each formed with an inner directed rim 168 for snap fitting on a large drug vial 20B's drug vial closure 33.

The flex members 166 A and 166B are adjacent. The flex members

167 A and 167B are adjacent. The flex members 166A and 167 A are spaced apart to leave a separation therebetween 169 A. The flex members 166B and 167B are spaced apart to leave a separation therebetween 169B. The flex members 163 A and 163B are correspondingly aligned with the separations 169 A and 169B thereby enabling their outward flexing to be unhindered by the flex members 166 and 167 on snap fitting the universal drug vial adapter 104 onto a drug vial 20 A.

Figures 10 to 14 show the use of the liquid drug transfer device 300 as follows:

Figures 10A and 10B show the liquid drug transfer device 300 in its pre- actuated state with a pre-actuated height HI. The infusion liquid container stopcock arrangement 140 is in a closed flow position with the key 146 deployed at its first extreme position along the keyway 147 such that the port 144 is not in flow communication with the axial lumen 141. The outward directed radial pins 128 are deployed at the sealed leg ends 156 such that the puncturing tip 119 is disposed so as to be spaced apart from an uppermost drug vial surface 32 of a drug vial 20 clamped in the downward depending skirt 131.

Figures 11A and 11B show the liquid drug transfer device 300 with its infusion liquid container stopcock arrangement 140 in its open flow position pursuant to a liquid container flow communication step of a manual rotation of the universal drug vial adapter 104 relative to the injection port adapter 102 in a clockwise tightening direction round the rotation axis 142 as denoted by arrow E. The liquid container flow communication step causes the liquid transfer member 103 to rotate together with the universal drug vial adapter 104 relative to the injection port adapter 102 until the key 146 stops at the opposite extreme end of the keyway 147. In this position, the port 144 is aligned with the axial lumen 141 to establish flow communication between the needle 118 and the axial lumen 123. The pins 128 remain in their initial position at the sealed leg ends 156. The liquid drug transfer device 300 remains at its pre-actuated height HI.

Figures 12A and 12B show the liquid drug transfer device 300 remaining with the infusion liquid container stopcock arrangement 140 in its open flow position and subsequent to a drug vial flow communication step of a continuing manual rotation of the universal drug vial adapter 104 in a clockwise tightening direction round the rotation axis 142 relative to the injection port adapter 102 as denoted by arrow F. Due to further rotation of the liquid transfer member 103 being stopped by the keyway 147, the continuing manual rotation urges the universal drug vial adapter 104 along the upright spiral legs 152 towards the injection port adapter 102. This relative movement causes the puncturing tip 119 to traverse through the throughgoing top wall aperture 130 into the downward depending skirt 131. The continuing manual rotation stops when the pair of outward directed radial pins 128 reach the junctures 154. The port 144 remains aligned with the axial lumen 141 such thereby establishing flow communication between the needle 118 and the puncturing tip 119. The liquid drug transfer device 300 is at its post- actuated height H2 where H2 < HI.

Figures 13 A and 13B show the liquid drug transfer device 300 subsequent to manual rotation of the universal drug vial adapter 104 relative to the injection port adapter 102 in a counter clockwise loosening direction round the rotation axis 142 as denoted by arrow G. The manual rotation stops when the pins 128 reach the leg ends 157 and are locked by the lock features 158. The infusion liquid container stopcock arrangement 140 remains in its open flow position with the port 144 aligned with the axial lumen 141 for flow communication between the needle 118 and the puncturing tip 119.

Figures 14A and 14B show the liquid drug transfer device 300 in an actuated state subsequent to continuing manual rotation of the universal drug vial adapter 103 relative to the injection port adapter 101 in a counter clockwise loosening direction round the rotation axis 142 as denoted by arrow H. Due to further rotation of the universal drug vial adapter 104 relative to the liquid transfer member 103 being stopped by the lock features 158, the continuing manual rotation urges the liquid transfer member 103 to rotate together with the universal drug vial adapter 104 relative to the injection port adapter 102 to return the key 146 to its initial first extreme end of the keyway 147 to close the infusion liquid container stopcock arrangement 140. In this position, the port 144 is not in alignment with the axial lumen 141 thereby disabling flow communication between the needle 118 and the liquid transfer member 103. Figures 15 to 22 show a liquid drug transfer device 400 and Figures 23 to 30 show a liquid drug transfer device 500 which are similar to the liquid drug transfer devices 100, 200 and 300 insofar as the former 400 and 500 each has a longitudinal device axis 101, a liquid container adapter 102, a liquid transfer member 103 and a drug vial adapter 104, and therefore similar parts are likewise numbered. The former 400 and 500 differ from the latter 100, 200 and 300 insofar as the former 400 and 500 have a liquid container adapter 102 with an axial directed upright tubular liquid container adapter stem 171 for directly engaging an axial directed upright tubular drug vial adapter stem 137. Also their liquid transfer members 103 are slidingly disposed in their drug vial adapter stems 137 for being urged during the manual rotation of the drug vial adapter 104 relative to the liquid container adapter 102 for puncturing a drug vial stopper 31 for flow communication with a drug vial interior 28.

The liquid drug transfer devices 400 and 500 are similar to the liquid drug transfer devices 100 and 200 insofar the former 400 and 500 include a second linear displacement along the longitudinal device axis 101 for executing a liquid container flow communication step.

The liquid drug transfer devices 400 and 500 are similar to the liquid drug transfer device 300 insofar the former 400 and 500 execute an initial liquid container flow communication step and a subsequent drug vial flow communication step.

The liquid drug transfer device 400 is similar to the liquid drug transfer devices 100, 200 and 300 insofar as the former 400 is intended for use with a drug vial 20 and an infusion liquid container 40. Accordingly, the liquid drug transfer device 400 can be optionally implemented such that a manual rotation executes an initial drug vial flow communication step and a subsequent liquid container flow communication step similar to the liquid drug transfer devices 100 and 200. Additionally, the liquid drug transfer device 400 can be optionally implemented with an infusion liquid container stopcock arrangement similar to the infusion liquid container stopcock arrangement 140. The liquid drug transfer device 500 is different from the liquid drug transfer devices 100, 200, 300 and 400 insofar as the former 500 is intended for use a drug vial 50A and a liquid vial 50B for filling an initially empty syringe 10 with liquid drug contents as shown in Figure 23 for administration to a patient. The liquid vial 50B is typically filled with diluent. Alternatively, the liquid vial 50B can include an active liquid component. The syringe 10 includes a barrel 11 with a plunger rod 12 and a male connector 13. The male connector 13 is preferably a male Luer lock connector. The syringe 10 can be formed with other types of male connectors, for example, a slip Luer connector, and the like.

In greater particularity, Figures 15 to 19 show the liquid drug transfer device 400 includes a liquid container adapter 102 constituted by an injection port adapter having the universal injection port connector 111 and the liquid container adapter stem 171. The liquid container adapter stem 171 includes a pair of opposite stem members 172 including a pair of inward directed radial pins 173 for sliding engagement along a pair of opposite generally helical tracks 174 formed in the drug vial adapter stem 137 in a similar manner to the pair of tracks 138. The tracks 174 each have a start track end 176 A remote from the vial adapter top wall 129 and a final track end 176B adjacent the vial adapter top wall 129.

The liquid transfer member 103 has a central liquid transfer member body 103C intermediate the leading liquid transfer member end 103A and the trailing liquid transfer member 103B. The liquid transfer member 103 includes a needle 118 at its leading liquid transfer member end 103 A for needle insertion into an injection port 41 and a puncturing tip 119 at its trailing liquid transfer member end 103B for puncturing a drug vial stopper 31. Sleeves 118 A and 121 correspondingly protect the needle 118 and the puncturing tip 119.

The liquid transfer member body 103C is formed with a set of four resiliently mounted axial directed retaining members 178 extending towards the needle 118 for snap fitting onto the injection port adapter 102 during the liquid container flow communication step of the manual rotation of the liquid drug transfer device 400. The retaining members 178 have retaining member tips 178 A with inclined leading retaining member tip surfaces 178B and radial directed trailing retaining member tip surfaces 178C. The retaining member tips 178 A are inward radial flexed at the central liquid transfer member body 103C towards the longitudinal device axis 101 as their inclined leading retaining member tip surfaces 178B slide along the inner injection port recess wall rim 108 A defining the throughgoing injection port recess wall aperture 109 as the needle 118 is urged therethrough. The retaining members 178 revert to their unflexed state as their retaining member tips 178A pass through the throughgoing injection port recess wall aperture 109 whereupon the radial directed trailing retaining member tip surfaces 178C abut the injection port recess wall 108.

Similarly, the liquid transfer member body 103C is formed with a set of four resiliently mounted axial directed retaining members 179 extending towards the puncturing tip 119 for snap fitting onto the drug vial adapter 104 during the drug vial flow communication step of the manual rotation of the liquid drug transfer device 400. The retaining members 179 have retaining member tips 179 A with inclined leading retaining member tip surfaces 179B and radial directed trailing retaining member tip surfaces 179C. The retaining member tips 179 A are inward radial flexed at the central liquid transfer member body 103C towards the longitudinal device axis 101 as their inclined leading retaining member tip surfaces 179B slide along an inner top wall rim 129 A defining the throughgoing top wall aperture 130 as the puncturing tip 119 is urged therethrough. The retaining members 179 revert to their unflexed state as their retaining member tips 179 A pass through the throughgoing top wall aperture 130 whereupon the radial directed trailing retaining member tip surfaces 179C snap fit on the inner top wall rim 129 A.

The drug vial adapter stem 137 has a leading end face 181 opposite the drug vial adapter skirt 131. The drug vial adapter stem 137 is formed with a pair of inward directed minor stops 182 adjacent the leading end face 181 and a pair of major stops 183 disposed inward from the pair of minor stops 182 by a separation to snugly receive the flange 177 therebetween in a pre-actuated state of the liquid drug transfer device 400. The pair of minor stops 182 and the pair of major stops 183 are orthogonal to one another and employed for ensuring the liquid transfer member 103 remains in place during transportation and for determining the sequence between a drug vial flow communication step and a liquid container flow communication step.

The pair of minor stops 182 are smaller than the pair of major stops 183 such that on manual rotation of the drug vial adapter 104 with respect to the injection port adapter 102, the liquid transfer member flange 177 initially snaps over the pair of minor stops 182 towards the injection port adapter 102 for needle insertion of the needle 118 into an injection port 41 to execute a liquid container flow communication step. On abutment of the leading liquid transfer member end 103 A against an injection port 41, the liquid transfer member flange 177 snaps over the pair of major stops 183 towards the drug vial adapter 104 for executing a drug vial flow communication step. The pair of minor stops 182 and the pair of major stops 183 can be reversed in position such that the liquid drug transfer device 400 initially executes a drug vial flow communication step and subsequently executes a liquid container flow communication step.

Figures 20 to 22 show the use of the liquid drug transfer device 400 as follows:

Figures 20A and 20B show the liquid drug transfer device 400 in a pre- actuated state with a pre-actuated height HI. The pair of minor stops 182 and the pair of major stops 183 retain the liquid transfer member 103 in the drug vial adapter stem 137. The pair of inward directed radial pins 173 are deployed at the start track ends 176 A.

Figures 21 A and 2 IB show the liquid drug transfer device 400 in an intermediate actuated state pursuant to a liquid container flow communication step. The liquid drug transfer device 400 has an intermediate actuated height H3 where H3<H1. The pair of inward directed radial pins 173 are midway along the pair of opposite tracks 174 between the start track ends 176 A and the finish track ends 176B. The retaining member tips 178A are snap fitted on the injection port adapter 102 thereby securing the liquid transfer member 103 thereto.

Figures 22A and 22B show the liquid drug transfer device 400 in a post- actuated state after a full linear compaction along the longitudinal device axis 101 following full manual rotation of the drug vial adapter 104 with respect to the infusion liquid adapter 102. The retaining member tips 179A are snap fitted on the inner top wall rim 129 A thereby securing the liquid transfer member 103 to the drug vial adapter 104. The liquid drug transfer device 400 has a post- actuated height H2 where H2<H3. Full compaction establishes flow communication between the injection port 41 and the drug vial 20 thereby enabling liquid flow from the IV bag to the drug vial 20.

In greater particularity, Figures 23 to 26 show the liquid drug transfer device 500 is similar in construction to the liquid drug transfer device 400 and therefore similar parts are likewise numbered. The former 500 differs from the latter 400 in three major respects as follows.

First, the liquid container adapter 102 is constituted by a liquid vial adapter 184 similar to the drug vial adapter 104. The liquid vial adapter 184 includes the liquid container adapter stem 171.

Second, the drug vial adapter stem 137 is provided with a pair of axial directed release grooves 186. The axial directed release grooves 186 are in sliding communication with the helical tracks 174 for enabling the pair of inward directed radial pins 173 to initial slide down the helical tracks 174 and then slide up the release grooves 186 for enabling detachment of the liquid container adapter stem 171 from the drug vial adapter stem 137 in a post- actuated state of the liquid drug transfer device 500.

And third, the liquid transfer member 103 has a dual component construction including a liquid vial component 187 and a drug vial component 188. The liquid vial component 187 includes the needle 118, an axial directed male connector 189 in flow communication with the needle 118, and the four axial directed retaining members 178. The drug vial component 188 includes the puncturing tip 119, an axial directed female connector 191 in flow communication with the puncturing tip 119 and the four axial directed retaining members 179. The male connector 189 is inserted in the female connector 191 in the pre-actuated state of the liquid drug transfer device 500. The male connector 189 and female connector 191 are preferably Luer connectors. The female connector 191 is also intended to receive the syringe's male connector 13 for syringe aspiration of liquid drug contents from the drug vial 50 A.

Figures 26 to 30 show the use of the liquid drug transfer device 500 as follows:

Figures 26 A and 26B show the liquid drug transfer device 500 in a pre- actuated state attached to a large drug vial 50A and a large liquid vial 50B. The pair of minor stops 182 and the pair of major stops 183 retain the liquid transfer member 103 in the drug vial adapter stem 137. The pair of inward directed radial pins 173 are deployed at the start track ends 176 A.

Figures 27 A and 27B show the liquid drug transfer device 500 in an intermediate actuated state pursuant to a liquid container flow communication step. The liquid drug transfer device 500 has an intermediate actuated height H3 where H3<H1. The pair of inward directed radial pins 173 are midway along the pair of opposite tracks 174 between the start track ends 176 A and the finish track ends 176B. The retaining member tips 178A are snap fitted on the liquid vial adapter 184 thereby securing the liquid vial component 187 thereto.

Figures 28A and 28B show the liquid drug transfer device 500 in a post- actuated state after a full linear compaction along the longitudinal device axis 101 following a full manual rotation of the drug vial adapter 104 with respect to the liquid vial adapter 184. The liquid drug transfer device 500 has a post- actuated height H2 where H2<H3. The retaining member tips 179 A are snap fitted on the drug vial adapter 104 thereby securing the drug vial component 188 thereto. Full compaction establishes flow communication between the liquid vial 50B and the drug vial 50A whereupon the negative pressure in the drug vial 50A draws liquid contents from the liquid vial 50B thereinto for mixing and/or reconstitution purposes, thereby leaving the liquid vial 50B empty.

Figures 29A and 29B show longitudinal detachment of the liquid vial adapter 184 from the drug vial adapter 104 along the longitudinal device axis 101 as depicted by the arrow I. Longitudinal detachment is achieved by aligning the pair of the inward directed radial pins 173 with the pair of axial directed release grooves 186. The liquid transfer member 103 separates into its liquid vial component 187 and drug vial component 188 such that the liquid vial adapter 184 detaches with its now empty liquid vial 50B and the liquid vial component 187 and the drug vial adapter 104 detaches with its drug vial 50 A now filled with liquid drug contents and the drug vial component 188.

Figures 30A and 30B show attachment of an initial empty syringe 10 to the female connector 191 and inversion of the assemblage for syringe aspiration of liquid drug contents from the drug vial 50A as denoted by arrow J to prepare the filled syringe 10 as shown in Figure 23.

While the invention has been described with respect to a limited number of embodiments, it will be appreciated that many variations, modifications, and other applications of the invention can be made within the scope of the appended claims.