Pressure adjustment vial adapter

Abstract

A vial adapter configured to mate with a sealed vial is provided. In some embodiments, the vial adapter includes a housing configured to couple the adapter with a vial, an access channel, a regulator channel, and a regulator assembly. The access channel is configured to facilitate drawing fluid from the vial when the adapter is coupled to the vial. The regulator channel is configured to facilitate flow of conditioning fluid from the regulator assembly to compensate for changes in the volume of drug fluid in the vial. In some embodiments, the regulator assembly includes a flexible member configured to expand and contract in response to changes in the volume of drug fluid in the vial. In some embodiments, the flexible member is substantially free to expand and contract. In some embodiments, the flexible member is not partially or completely disposed within a rigid enclosure.

Description

Technical Field

[0001] Related Applications This application claims the benefit of U.S. Provisional Application No. 61 / 525,126, filed Aug. 18, 2011, entitled "PRESSURE-REGULATING VIAL ADAPTORS" and U.S. Provisional Application No. 61 / 614,250, filed Mar. 22, 2012, entitled "PRESSURE-REGULATING VIAL ADAPTORS". The entire contents of each of the above patent applications are hereby incorporated by reference.

[0002] Some embodiments disclosed herein relate to an adaptor for coupling to a drug vial, and components thereof, and methods for containing vapor and / or assisting in regulating the pressure within a drug vial.

Background Art

[0003] Storing drugs or other medical-related fluids in vials or other containers is commonly done. In some cases, drugs or fluids so stored have a therapeutic effect when injected into the bloodstream, but are harmful when inhaled or when contacting skin exposure sites. Some known systems for extracting potentially harmful drugs from vials have various drawbacks.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

SUMMARY OF THE INVENTION

MEANS FOR SOLVING THE PROBLEM

[0005] In some embodiments, the adapter is configured to couple with a sealed vial and includes a storage device. In some cases, the storage device includes a distal extractor aperture configured to enable fluid to be drawn from the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the extractor flow path and at least a portion of the regulator flow path extend through the storage device. The adapter can also include an enclosure, such as a regulator enclosure, that is in fluid communication with the regulator flow path. In some configurations, the adapter is configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which the regulator enclosure is at least partially unexpanded or folded when fluid is drawn from the sealed vial through the extractor flow path. Further, the adapter can include a volume component, such as a packing material, disposed within the regulator enclosure. The packing material need not fill the entire enclosure. In some embodiments, the volume occupied or encompassed by the packing material can be less than, or at least a majority of, or substantially all of the internal volume of the enclosure. In some cases, the packing material is configured to secure an initial volume of regulator fluid within the regulator enclosure such that, when fluid is drawn from the sealed vial through the extractor aperture, the adapter can supply the regulator fluid from the regulator enclosure to the sealed vial.

[0006] In some configurations, the adapter is configured such that when the adapter is coupled to a sealed vial, the regulator enclosure is outside the sealed vial. In some cases, at least a majority of the volume of the regulator enclosure is not within the rigid housing, or at least a substantial portion of the regulator enclosure is not within the rigid housing.

[0007] In some cases, the storage device is configured to couple with a syringe configured to hold a defined volume of fluid within the barrel and having a medical connector interface that is in fluid communication with the extractor flow path. In some such cases, the fill material is configured to ensure that the initial volume of the regulator fluid is greater than or equal to the defined volume of the fluid. In some of such cases, the initial volume of the regulator fluid within the regulator enclosure is at least about 60 mL. In some embodiments, the regulator enclosure is configured to hold the maximum volume of the regulator fluid when the regulator enclosure is fully expanded or deployed, and the maximum volume is at least about 180 mL.

[0008] In some embodiments, the regulator enclosure is made from a material system that includes a film, such as a polyethylene terephthalate film. In some cases, the film includes a metallized coating or a metal component. For example, in some cases, the metallized coating includes aluminum.

[0009] In some embodiments, the pressure regulating vial adapter comprises a piercing member connected to a storage device, and the enclosure is at least partially disposed within the piercing member. In some configurations, the pressure within the sealed vial is regulated by causing the regulator enclosure to contract or fold when the pharmaceutical fluid is withdrawn from the sealed vial, thereby substantially equalizing the pressure on the opposite side of the regulator enclosure. In some instances, the regulator enclosure comprises a layer substantially impermeable to the pharmaceutical fluid disposed within the vial, thereby preventing passage of the pharmaceutical fluid between the outer and inner surfaces of the regulator enclosure.

[0010] In various embodiments, the adapter further comprises a hydrophobic filter disposed between the regulator enclosure and the distal regulator opening. The hydrophobic filter can be configured to allow regulator fluid to flow between the regulator enclosure and the vial when the adapter is coupled to the vial. In some arrangements, the hydrophobic filter is disposed within the regulator flow path, which is itself disposed between the distal regulator opening and the regulator enclosure. The filter can be, for example, a foamed material. For example, in some configurations, the packing is made from a polyurethane ether foam.

[0011] In some embodiments, a method of withdrawing fluid from a sealed vial includes connecting a pressure regulating vial adapter to the sealed vial and withdrawing fluid from the sealed vial through the pressure regulating vial adapter. In some aspects, the pressure regulating vial adapter comprises a storage device having a distal extractor opening. In some cases, the distal extractor opening is configured to allow fluid to be withdrawn from the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the extractor flow path and at least a portion of the regulator flow path extend through the storage device.

[0012] In some configurations, the pressure regulating vial adapter also includes a regulator enclosure that is in fluid communication with the regulator flow path. In some cases, the regulator enclosure is configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when fluid is withdrawn from the sealed vial through the extractor flow path.

[0013] In some embodiments, the pressure regulating vial adapter further includes a packing material disposed within the regulator enclosure. The packing material is configured to provide an initial volume of regulator fluid within the regulator enclosure such that the adapter can supply regulator fluid from the regulator enclosure to the sealed vial when fluid is withdrawn from the sealed vial through the extractor opening.

[0014] In various embodiments, a method of manufacturing an adapter for coupling to a sealed vial includes providing a housing having a distal extractor opening. In some cases, the distal extractor opening is configured to enable the adapter to withdraw fluid from the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the extractor flow path and at least a portion of the regulator flow path extend through the housing.

[0015] The method can also include disposing a packing material within the regulator enclosure. The packing material is configured to secure an initial volume of regulator fluid within the regulator enclosure such that the adapter can supply regulator fluid from the regulator enclosure to the sealed vial when fluid is withdrawn from the sealed vial through the extractor opening.

[0016] In some configurations, the method further includes placing a regulator enclosure in fluid communication with the regulator flow path, wherein the regulator enclosure is configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is less expanded or substantially or entirely collapsed or folded when fluid is withdrawn from the sealed vial through the extractor flow path.

[0017] In some embodiments of the method, the step of disposing a packing material within the regulator enclosure includes forming or providing a filling opening within the regulator enclosure configured to allow the packing material to pass therethrough, filling the regulator enclosure with the packing material through the filling opening, and closing the filling opening. In some embodiments of the method, the step of placing a regulator enclosure in fluid communication with the regulator flow path includes aligning an enclosure opening within the regulator enclosure with a proximal regulator opening of the housing device and securing the regulator enclosure to the housing device.

[0018] In various embodiments, an adapter configured to couple to a sealed vial comprises a storage device having a distal extractor opening configured to allow fluid to be drawn from the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the extractor flow path and at least a portion of the regulator flow path extend through the storage device. The adapter can also comprise a regulator enclosure in fluid communication with the regulator flow path. In some cases, the regulator enclosure is configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or folded when fluid is drawn from the sealed vial through the extractor flow path. In some embodiments, the rigid housing does not include the substantial volume of the regulator enclosure.

[0019] In some embodiments, the regulator enclosure comprises a first side and a second side opposite the first side. In some cases, each of the first side and the second side is configured to expand, contract, fold, or deploy when regulator fluid flows between the regulator flow path and the regulator enclosure. In some cases, the second side is configured to move away from or toward the storage device as regulator fluid passes through the regulator flow path. In some cases, the first side comprises an inner surface forming a portion of the inside of the regulator enclosure and an outer surface forming a portion of the outside of the regulator enclosure. In some of such cases, the outer surface of the first side is oriented toward the storage device.

[0020] In some embodiments, the pressure within the sealed vial is regulated by causing the regulator enclosure to contract or fold when the pharmaceutical fluid is withdrawn from the sealed vial, or by substantially equalizing the pressure on the opposite side of the regulator enclosure. In some embodiments, the regulator enclosure comprises a layer that is substantially impermeable to the pharmaceutical fluid disposed within the vial, thereby preventing passage of the pharmaceutical fluid between the outer and inner surfaces of the enclosure.

[0021] The adapter can further comprise a hydrophobic filter disposed between the regulator enclosure and the distal regulator opening. The hydrophobic filter can be configured to allow regulator fluid to flow between the regulator enclosure and the vial when the adapter is coupled to the vial.

[0022] Also, the adapter can comprise a packing material disposed within the regulator enclosure. The packing material is configured to secure an initial volume of regulator fluid within the regulator enclosure, whereby the adapter can supply regulator fluid from the regulator enclosure to the sealed vial when fluid is withdrawn from the sealed vial through the extractor opening.

[0023] In some embodiments, a vial adapter configured to couple with a sealed vial comprises a housing having a distal extraction opening configured to enable the extraction of fluid from the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the extractor flow path and at least a portion of the regulator flow path pass through the housing. In some embodiments, the vial adapter further comprises a regulator enclosure in fluid communication with the regulator flow path. In some cases, the regulator enclosure is configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when fluid is withdrawn from the sealed vial via the extractor flow path.

[0024] In some embodiments of the vial adapter, the regulator enclosure has a first side and a second side generally opposite the first side. The first side can comprise an inner surface forming a portion of the inside of the regulator enclosure and an outer surface forming a portion of the outside of the regulator enclosure. The outer surface of the first side can be oriented towards the housing. In some cases, each of the first side and the second side is configured to expand, contract, fold, or deploy when regulator fluid, such as air, gas, or vapor, passes through the regulator flow path. In some configurations, the second side is configured to move away from the housing or towards the housing when regulator fluid passes through the regulator flow path. In many cases, the regulator enclosure does not fit entirely within the rigid housing.

[0025] In some embodiments, a vial adapter configured to couple with a sealed vial comprises a storage device having a distal extractor opening configured to allow fluid to be drawn from the sealed vial when the adapter is coupled to the sealed vial. In various configurations, at least a portion of the extractor flow path and at least a portion of the regulator flow path extend through the storage device. In some embodiments, the vial adapter comprises a regulator enclosure configured to be in fluid communication with the regulator flow path and to receive a volume of regulator fluid. The regulator enclosure can be configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when fluid is drawn from the sealed vial through the extractor flow path.

[0026] In some embodiments, the regulator enclosure has a first layer connected to a second layer that faces the first layer. The first layer and the second layer can be configured to receive a volume of regulator fluid therebetween. In some configurations, each of the first side and the second side is configured to expand, contract, fold, or deploy as the regulator fluid passes through the regulator flow path. In some cases, the second side is configured to move away from or toward the storage device as the regulator fluid passes through the regulator flow path. In some cases, the regulator enclosure does not fully fit within a rigid housing.

[0027] In some configurations, the first layer is made from a first sheet of material and the second layer is made from a second sheet of material. In some cases, the first layer and the second layer are connected around the perimeter of the first layer and the second layer. In some cases, the first layer and the second layer each comprise a central portion, and the first layer and the second layer are not connected at the central portion.

[0028] In some embodiments, a modular vial adapter configured to couple with a sealed vial comprises a pressure regulating vial adapter module and a regulator fluid module. In some cases, the pressure regulating vial adapter module comprises a housing having a distal extractor opening configured to enable drawing fluid from the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the extractor flow path and at least a portion of the regulator flow path pass through the housing.

[0029] The pressure regulating vial adapter module can comprise a proximal regulator opening in fluid communication with the regulator flow path. In some configurations, the proximal regulator opening is configured such that when the vial adapter module is coupled to the sealed vial and fluid is drawn from the vial, regulator fluid can flow into or out of the proximal regulator opening.

[0030] In some cases, the regulator fluid module comprises a regulator enclosure configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed such that it is configured to couple with the proximal regulator opening, and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded such that regulator fluid passes through an enclosure opening in the regulator enclosure.

[0031] The regulator fluid module can comprise a fastener configured to couple the regulator enclosure to the proximal regulator opening. In some cases, the regulator enclosure does not fully fit within a rigid housing. In some cases, the fastener comprises an attachment member having a first surface and a second surface coated with an adhesive. In some such cases, the attachment member is made from a material system that includes an elastic material.

[0032] In some embodiments, a method of manufacturing a vial adapter configured to couple with a sealed vial includes providing a pressure regulating vial adapter module and providing a regulator fluid module. The pressure regulating vial adapter module can include a housing device. The housing device can include a distal extractor opening configured to enable fluid to be drawn from the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the extractor flow path and at least a portion of the regulator flow path pass through the housing device.

[0033] The pressure regulating vial adapter module can include a proximal regulator opening in fluid communication with the regulator flow path. The proximal regulator opening can be configured such that when the vial adapter module is coupled to the sealed vial and fluid is drawn from the vial, regulator fluid can flow into or out of the proximal regulator opening.

[0034] In some embodiments, the regulator fluid module includes a regulator enclosure. The regulator enclosure can be configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when regulator fluid passes through an enclosure opening in the regulator enclosure. The regulator fluid module can include a fixture configured to couple the regulator enclosure to the proximal regulator opening. In some cases, the regulator enclosure does not fit entirely within the rigid housing.

[0035] The method can further include aligning the enclosure opening of the regulator enclosure with the proximal regulator opening of the pressure regulating vial adapter module. In some embodiments, the method also includes attaching the regulator fluid module to the pressure regulating vial adapter module.

[0036] In some cases, the fastener includes a fastening member having a first surface and a second surface coated with an adhesive. In some such cases, the fastening member is made from a material system that includes an elastic material. In some cases, the fastening member has a thickness of about 0.01 inches or more and about 0.03 inches or less.

[0037] In some embodiments, the regulator fluid module is configured to be fastened to a pressure regulating vial adapter module to form a vial adapter for coupling with a sealed vial. The pressure regulating vial adapter module can include a housing having a distal extractor opening configured to allow fluid to be withdrawn from the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the extractor flow path and at least a portion of the regulator flow path pass through the housing. In some cases, the housing also includes a proximal regulator opening that is in fluid communication with the regulator flow path. The proximal regulator opening can be configured to allow regulator fluid to flow in or out therethrough when the vial adapter module is coupled to the sealed vial and fluid is being withdrawn from the vial.

[0038] The regulator fluid module can include a regulator enclosure configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when the regulator fluid passes through an enclosure opening in the regulator enclosure.

[0039] The regulator fluid module can include a filling material within the regulator enclosure. The filling material is configured to supply an initial volume of regulator fluid within the regulator enclosure such that when fluid is withdrawn from the sealed vial through the extractor opening, the adapter can supply regulator fluid from the regulator enclosure to the sealed vial.

[0040] In various embodiments, the regulator fluid module comprises a fastener configured to couple the regulator enclosure to the proximal regulator opening such that the regulator fluid module is allowed to move a small distance with respect to the pressure regulating vial adapter module without the fastener splitting, breaking, or otherwise being damaged during routine operation. In some cases, the regulator enclosure does not fully fit within the rigid housing. In some configurations, the fastener substantially couples the regulator enclosure and the proximal regulator opening and maintains an airtight state.

[0041] In some embodiments, a method of manufacturing a modular adapter for coupling to a sealed vial and regulating the pressure within the sealed vial includes forming a containment device having a distal access opening. The distal access opening can be configured to permit fluid transfer between the medical device and the sealed vial when the adapter is coupled to the sealed vial. In some cases, at least a portion of the access flow path and at least a portion of the regulator flow path extend through the containment device. The regulator flow path can be in fluid communication with the sealed vial when the adapter is coupled to the sealed vial.

[0042] The method can include connecting a coupling assembly such that the coupling assembly is in fluid communication with the regulator flow path. The coupling assembly can include a membrane and a cover, and the membrane and the cover can each have an opening. The coupling assembly can be configured to permit the flow of regulator fluid between the opening and the regulator flow path. In some cases, the flow of regulator fluid passes through the membrane.

[0043] In some embodiments, the method includes providing a regulator enclosure configured to be positioned in fluid communication with an aperture, whereby the regulator enclosure is configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when regulator fluid passes through an aperture in the regulator enclosure.

[0044] Often, the method further includes selecting a regulator enclosure from a variety of sizes of regulator enclosures. In some embodiments, this selection may be based on the volume of medicament fluid withdrawn from a sealed vial. In some cases, the regulator fluid flow passes between the aperture and the sealed vial when medicament fluid is withdrawn from the sealed vial through an access flow path. In some cases, the aperture is in fluid communication with ambient air prior to the regulator enclosure being positioned in fluid communication with the aperture.

[0045] In some embodiments, the vial adapter comprises a housing configured to couple to a vial, an access flow path, a regulator flow path, and a regulator assembly. The access flow path is configured to facilitate drawing fluid from the vial when the adapter is coupled to the vial. The regulator flow path is configured to facilitate the flow of regulated fluid from the regulator assembly and to compensate for changes in the volume of the pharmaceutical fluid within the vial. In some embodiments, the regulator assembly comprises a flexible member configured to expand and contract in response to changes in the volume of the pharmaceutical fluid within the vial. In some embodiments, the flexible member can expand and contract substantially freely. In some embodiments, the flexible member is not disposed, either partially or fully, within a rigid enclosure. In some embodiments, at least a majority of the flexible member is disposed within a rigid enclosure. In some embodiments, the regulator assembly comprises a filter within the regulator flow path. In some embodiments, the regulator fluid assembly comprises a check valve configured to prevent liquid communication between the filter within the regulator flow path and the vial. In some embodiments, the check valve is configured to prevent liquid communication between the vial and the flexible member at the end of the regulator flow path.

[0046] In some embodiments, the vial adapter has a centerline along an axis and is configured to be used within a predetermined area having a floor. The vial adapter can be configured to couple to a sealed vial. The vial adapter can have a piercing member and an extractor flow path that extends between a proximal extractor opening and a distal extractor opening and is configured to enable drawing fluid from the sealed vial when the vial adapter is coupled to the sealed vial. In some variations, at least a portion of the extractor flow path passes through at least a portion of the piercing member. The vial adapter can comprise a regulator flow path that extends between a proximal regulator opening and a distal regulator opening. In some embodiments, at least a portion of the regulator flow path passes through at least a portion of the piercing member.

[0047] The occluder valve can be housed within the regulator flow path and can be configured to transition between a closed configuration and an open configuration in response to rotation of the vial adapter about the axis of rotation between an upright position and an inverted position. In some configurations, the proximal extractor opening is farther from the floor than the distal opening when the vial adapter is in the upright position, and the proximal extractor opening is closer to the floor than the distal extractor opening when the vial adapter is in the inverted position. Further, the occluder valve can inhibit fluid from passing through the occluder valve and proceeding toward the proximal regulator opening when the occluder valve is in the closed configuration. The axis of rotation may be perpendicular to the centerline on the axis of the vial adapter, and the method of transitioning between the closed configuration and the open configuration of the occluder valve may be substantially independent of the axis of rotation for rotating the vial.

[0048] In some cases, the occluder valve transitions to a closed configuration when the vial adapter is rotated to the inverted position. Further, in some specific cases, the occluder valve transitions to an open configuration when the vial adapter is rotated to the upright position. The occluder valve can generally have a cylindrical shape and can have a centerline on its axis. In some embodiments, the occluder valve is rotatable about the centerline on the axis of the occluder valve relative to the regulator flow path.

[0049] The vial adapter can include a valve chamber that is in fluid communication with the regulator flow path, a closure member within the valve chamber, and a valve seat. In some embodiments, the occluder valve is configured to transition to a closed configuration after the closure member and the valve seat engage, and is configured to transition to an open configuration after the closure member disengages from the valve seat. In some cases, the closure member moves within the valve chamber under the influence of gravity. The closure member can be a spherical ball, or can have a cylindrical body portion with a tapered end, or can have an ellipsoidal shape, or can have a generally cylindrical shape with a centerline on its axis, or can have any other suitable shape or combination of shapes.

[0050] In some embodiments, the vial adapter comprises a filter. The filter can be positioned within the regulator flow path between the occluder valve and the proximal regulator opening. In some embodiments, the filter is a hydrophobic filter.

[0051] In some particular embodiments, the vial adapter has a centerline on an axis and is configured to couple with a sealed vial. The vial adapter can comprise a piercing member and an extractor flow path. At least a portion of the extractor flow path can pass through at least a portion of the piercing member. In some embodiments, the vial adapter comprises a regulator flow path that can extend between a proximal regulator opening and a distal regulator opening, and at least a portion of the regulator flow path passes through at least a portion of the piercing member.

[0052] The vial adapter can comprise an occluder valve configured to be installed into at least a portion of the regulator flow path via an installation path. The occluder valve can be further configured to transition between a closed configuration and an open configuration. In some embodiments, the occluder valve comprises a valve chamber that fluidly communicates with the regulator flow path. The valve chamber can have a closure member, a movement path for the closure member, and a valve seat. In some embodiments, the occluder valve comprises a valve flow path that fluidly communicates with the valve chamber and the regulator flow path, and the valve flow path has a flow path. The occluder valve can be configured to transition to a closed configuration when the closure member engages the valve seat. In some embodiments, the occluder valve is configured to transition to an open configuration when the closure member disengages from the valve seat. The angle formed by the movement path of the closure member and the installation path of the occluder valve can be greater than 0° and less than 180°. In some embodiments, the movement path with respect to the closure member is not substantially parallel to the installation path of the occluder valve.

[0053] In some embodiments, the occlusion member can be a spherical ball, or have a cylindrical shape with a tapered end on one side, or have an ellipsoidal shape, or have other suitable shapes or combinations of shapes. In some embodiments, the angle formed by the movement path of the occlusion member and the installation path of the occluder valve is greater than about 45° and less than about 135°. In some embodiments, the angle formed by the movement path and the installation path is about 90°. The angle formed by the movement path and the installation path may be substantially the same as the angle formed by the center line on the axis of the vial adapter and the installation path. In some embodiments, the vial adapter includes a filter in the regulator flow path between the occluder valve and the proximal regulator opening. The filter can be a hydrophobic filter.

[0054] A method of manufacturing a modular vial adapter configured to couple with a sealed vial can include the step of selecting a connector interface having a center line on an axis. The connector interface can have a piercing member and an extractor flow path that passes through at least a portion of the piercing member. In some embodiments, the connector interface has a regulator flow path extending between a proximal regulator opening and a distal regulator opening, and at least a portion of the regulator flow path passes through at least a portion of the piercing member.

[0055] In some embodiments, the manufacturing method can include the step of coupling a regulator assembly to a proximal regulator opening of a connector interface. The regulator assembly can comprise a regulator passage configured to be in fluid communication with a regulator flow path when the regulator assembly is coupled to the connector interface. In some embodiments, the regulator comprises an occlusion valve at least partially disposed within one or more of the regulator flow path and the regulator passage via an installation path. The occlusion valve can be configured to transition between a closed configuration and an open configuration. In some embodiments, the occlusion valve comprises a valve chamber in fluid communication with one or more of the regulator flow path and the regulator passage. The valve chamber can have an occlusion member, a movement path for the occlusion member, and a valve seat. In some embodiments, the occlusion valve can have a valve flow path in fluid communication with the valve chamber and one or more of the regulator flow path and the regulator passage. Further, the valve flow path can have a flow path.

[0056] The occlusion valve can be configured to transition to a closed configuration when the occlusion member engages the valve seat. In some embodiments, the occlusion valve is configured to transition to an open configuration when the occlusion member disengages from the valve seat. The angle formed by the movement path of the occlusion member and the installation path of the occlusion valve can be greater than 0° and less than 180°.

[0057] A method of manufacturing a modular vial adapter can also include installing an occlusion valve at least partially within one or more of a regulator flow path and a regulator path via an installation path. In some embodiments, the method includes selecting an occlusion valve in which the angle formed by the movement path within the occlusion valve and the installation path of the occlusion valve is substantially the same as the angle formed by the installation path of the coupling interface and the axial centerline. The method can include aligning a protrusion of a regulator assembly with a proximal regulator opening of a connector interface, the protrusion and the proximal regulator opening being keyed. In some embodiments, the method includes aligning alignment features on the occlusion valve with alignment features of the regulator flow path. By aligning the alignment mechanism of the occlusion valve with the alignment mechanism of the regulator flow path, the regulator assembly can be coupled to the connector interface and the occlusion valve can be oriented such that the movement path is substantially parallel to the axial centerline of the connector interface when the occlusion valve is at least partially installed in one or more of the regulator flow path and the regulator path.

[0058] Although various embodiments are shown in the accompanying drawings for illustrative purposes, they should in no way be construed as limiting the scope of the embodiments. In addition, by combining various features of the different disclosed embodiments, additional embodiments can be formed that are part of this disclosure.

Brief Description of the Drawings

[0059]

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DETAILED DESCRIPTION OF THE INVENTION

[0060] Although specific embodiments and examples are disclosed in this specification, the subject matter of the present invention extends beyond the examples in the specifically disclosed embodiments to other alternative embodiments and / or uses, and modifications and equivalents thereof. Accordingly, the scope of the appended claims is not limited to any of the specific embodiments described below. For example, in the methods or processes disclosed herein, the operations or acts of the method or process may be performed in a suitable order and are not necessarily limited to the specific disclosed order. The various operations may then be described as a plurality of discrete operations in a form that may be helpful in understanding some embodiments, but the order of the description should not be construed to mean that these operations are order-dependent. In addition, the structures, systems, and / or devices described herein may be embodied as an integrated component or as separate components. For purposes of comparing the various embodiments, some aspects and advantages of these embodiments are described. Not necessarily all such aspects or advantages are achieved by a particular embodiment. Thus, for example, the various embodiments may be implemented in a form that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other aspects or advantages as may be taught or suggested herein.

[0061] The drawings showing some embodiments are semi-diagrammatic and are not drawn to an exact scale. In particular, some of the dimensions are for clarity and are shown greatly exaggerated in the drawings.

[0062] For purposes of explanation, as used herein, the term "horizontal" is defined as a plane parallel to the plane or surface of the floor of the area in which the device being described is used or the method being described is performed, regardless of its orientation. The term "floor" may be exchanged with the term "ground". The term "vertical" refers to a direction that is perpendicular to the horizontal as just defined above. Expressions such as "above", "below", "bottom", "top", "side", "higher", "lower side", "upper side", "directly above", and "directly below" are defined with respect to the horizontal plane.

[0063] A number of drugs and other therapeutic fluids are stored and dispensed in drug vials or other containers of various shapes and sizes. These vials are hermetically sealed to prevent contamination or leakage of the stored fluid. The pressure difference between the inside of the sealed vial and a particular atmospheric pressure from which the fluid is later removed often causes various problems and also leads to the release of potentially harmful vapors.

[0064] For example, introducing a piercing member of a vial adapter through the septum of a vial can cause the pressure inside the vial to increase. This pressure increase can cause the fluid to leak at the junction of the septum and the piercing member or at the attachment junction of the adapter and a medical device such as a syringe. Also, it may be difficult to draw an accurate amount of fluid from a sealed vial using an empty syringe or a medical instrument because the fluid may be naturally biased to return into the vial when the syringe plunger is removed. Furthermore, when the syringe is disconnected from the vial, a certain amount of fluid often blows out of the syringe or the vial due to the pressure difference.

[0065] Furthermore, in some cases, introducing fluid into the vial can increase the pressure within the vial. For example, in some cases, it may be desirable to introduce a solvent (such as sterile saline) into the vial to, for example, reconstitute a lyophilized pharmaceutical within the vial. Introducing fluid into the vial in this way can cause the pressure within the vial to become higher than the pressure of the ambient environment, and as a result, there is a possibility that the fluid will leak at the joint surface between the diaphragm and the piercing member or at the attachment joint surface of the adapter and a medical device such as a syringe from the vial. Additionally, when the pressure within the vial increases, it can become difficult to introduce an accurate amount of fluid into the vial using a syringe or other medical instrument. Also, when the syringe is removed from the vial when the pressure inside the vial is greater than the ambient pressure (e.g., atmospheric pressure), a portion of the fluid may be blown out of the vial due to the pressure gradient.

[0066] In addition, in many cases, air bubbles are drawn into the syringe when fluid is withdrawn from the vial. Such air bubbles are generally undesirable because if they are injected into a patient, they can consequently cause embolisms. To remove air bubbles from the syringe after removing it from the vial, healthcare professionals often gently shake the syringe to collect all the air bubbles near the opening of the syringe and then expel the air bubbles. In doing so, a small amount of liquid is usually also expelled from the syringe. Healthcare providers generally do not perform a special procedure of reattaching the syringe to the vial before expelling the air bubbles and fluid. In some cases, this may even be prohibited by laws and regulations. Such laws and regulations may, in some cases, obligate the expulsion of fluid that has been drawn in too far outside a predetermined position on the outside of the vial. Furthermore, when attempting to reinsert excess air or fluid into the vial, the pressure difference can sometimes result in an inaccurate measurement of the fluid that has been drawn in.

[0067] To address these problems caused by pressure differentials, medical professionals often pre-fill an empty syringe with an accurate volume of outside air corresponding to the volume of fluid they intend to draw from a vial. The medical professional then punctures the vial and forces this outside air into the vial, temporarily increasing the pressure inside the vial. When the desired volume of fluid is later withdrawn, the pressure differential between the inside of the syringe and the inside of the vial is generally close to equilibrium. By then slightly adjusting the fluid volume within the syringe, air bubbles can be removed without resulting in a demonstrable pressure differential between the vial and the syringe. However, this approach has the significant disadvantage that, especially in a hospital environment, the outside air can contain viruses, bacteria, dust, spores, mold, and other unsanitary and harmful contaminants that float in the various airs. The pre-filled outside air within the syringe may contain one or more of these harmful substances and could then mix with the drug or other therapeutic fluid inside the vial. If this contaminated fluid is directly injected into a patient's bloodstream, it can be particularly dangerous as airborne pathogens can bypass many of the body's natural defense mechanisms against these airborne pathogens. Additionally, patients who require drugs and other therapeutic fluids are likely to be suffering from a reduced ability to fight infection.

[0068] In combination with oncology drugs and some other medications, all of the above problems can be particularly severe. Such drugs, while beneficial when injected into a patient's bloodstream, can be extremely harmful if inhaled or touched. Thus, such drugs can be dangerous if allowed to unexpectedly blow out of a vial due to a pressure differential. Additionally, these drugs are often volatile and can instantaneously aerosolize when exposed to outside air. Therefore, even if controlled, expelling a small amount of such a drug to remove air bubbles or excess fluid from a syringe is generally not a viable option, especially for medical personnel who may repeat such an operation several times a day.

[0069] In some devices, a rigid enclosure surrounds all or part of a volume change component or region to assist in the operation of regulating the pressure within the container. Such an enclosure can impart rigidity, but generally makes the device bulky and unbalanced. When such a device is coupled to a vial, it generally results in an unstable system with a heavy top that is prone to tipping over and, in some cases, spilling the contents of the device and / or the vial.

[0070] In fact, some of such coupling devices include relatively large and / or heavy, rigid components that are cantilevered or otherwise disposed at a certain distance from the center on the axis of the device, thus exacerbating the tendency of the device to tip over.

[0071] In addition, such rigid enclosures can increase the size of the device, thereby requiring more material to form the device and potentially increasing the costs associated with the manufacture, transportation, and / or storage of the device in some other way. Further, such rigid enclosures can sometimes prevent the device's ability to expand or contract to deliver a regulated fluid to the vial. None of the functions, structures, or steps disclosed herein are essential or indispensable.

[0072] FIG. 1 is a schematic view of a container 10, such as a drug vial, that can be coupled to an access mechanism 20 and a regulator 30. In some arrangements, the regulator 30 allows some or all of the contents of the container 10 to be removed via the access mechanism 20 without causing a significant change in the pressure within the container 10.

[0073] Generally, the container 10 is hermetically sealed to preserve the contents of the container 10 in a sterile environment. The container 10 can be evacuated or pressurized after sealing. In some cases, the container 10 is partially or completely filled with a liquid, such as a drug or other medical fluid. In such cases, one or more types of gas can also be sealed within the container 10. In some cases, a solid or powdery substance, such as a lyophilized pharmaceutical, is disposed within the container 10.

[0074] The access mechanism 20 generally provides means for accessing the contents of the container 10 such that the contents can be removed or added. In some configurations, the access mechanism 20 includes an opening between the inside and outside of the container 10. The access mechanism 20 can further include a passage between the inside and outside of the container 10. In some configurations, the passage of the access mechanism 20 can be selectively opened and closed. In some configurations, the access mechanism 20 includes a conduit that penetrates the surface of the container 10. The access mechanism 20 can be integrally formed with the container 10 before sealing or introduced into the container 10 after the container 10 is sealed.

[0075] In some configurations, the access mechanism 20 is in fluid communication with the container 10 as indicated by arrow 21. In some of these configurations, when the pressure inside the container 10 changes from the pressure of the ambient environment, transmission occurs through the access mechanism 20 when the access mechanism 20 is introduced into the container 10. For example, in some configurations, the pressure of the environment surrounding the container 10 exceeds the pressure within the container 10, such that after the access mechanism 20 is inserted into the container, outside air can flow into the access mechanism 20 from the environment. In other configurations, the pressure inside the container 10 exceeds the pressure of the ambient environment, such that the contents of the container 10 flow out through the access mechanism 20.

[0076] In some configurations, the access mechanism 20 is coupled to the exchange device 40. In some cases, the access mechanism 20 and the exchange device 40 are separable. In some cases, the access mechanism 20 and the exchange device 40 are integrally formed. The exchange device 40 is configured to receive fluid and / or gas from the container 10 via the access mechanism 20, introduce fluid and / or gas into the container 10 via the access mechanism 20, or perform some combination of these two operations. In some arrangements, the exchange device 40 is in fluid communication with the access mechanism 20 as indicated by arrow 24. In some configurations, the exchange device 40 comprises a medical device such as a syringe.

[0077] In some cases, the exchange device 40 is configured to remove some or all of the contents of the container 10 via the access mechanism 20. In some arrangements, the exchange device 40 can remove the contents regardless of whether there is a pressure difference between the inside of the container 10 and the surrounding environment. For example, if the pressure outside the container 10 exceeds the pressure inside the container 10, the exchange device 40 comprising a syringe can remove the contents of the container 10 when sufficient force is applied to withdraw the plunger from the syringe. The exchange device 40 can similarly introduce fluid and / or gas into the container 10 regardless of the pressure difference between the inside of the container 10 and the surrounding environment.

[0078] In some configurations, regulator 30 is coupled to container 10. Regulator 30 generally regulates the pressure within container 10. As used herein, the term "regulate" or its derivatives is a broad term used in its ordinary sense and includes any active, affirmative, or positive action, or any passive, reactive, responsive, adaptive, or compensating action that tends to bring about a change, unless otherwise specified. In some cases, regulator 30 substantially maintains a pressure differential or equilibrium between the interior of container 10 and the surrounding environment. As used herein, the term "maintain" or its derivatives is a broad term used in its ordinary sense and includes a tendency to hold the original state for a period of time while allowing for small, somewhat changes as appropriate in the situation. In some cases, regulator 30 maintains a substantially constant pressure within container 10. In some cases, the change in pressure within container 10 is about 1 psi or less, about 2 psi or less, about 3 psi or less, about 4 psi or less, or about 5 psi or less. In further examples, regulator 30 equalizes the pressure exerted on the contents of container 10. As used herein, the term "equalize" or its derivatives is a broad term used in its ordinary sense and includes a tendency to make or bring amounts closer to the same amount while allowing for small, somewhat changes as appropriate in the situation. In some configurations, regulator 30 is coupled to container 10 such that it enables or facilitates equalizing the pressure differential between the interior of container 10 and some other environment, such as the environment surrounding container 10 or within an exchange device 40. In some arrangements, a single device comprises regulator 30 and access mechanism 20. In other arrangements, regulator 30 and access mechanism 20 are separate units.

[0079] The regulator 30 is in fluid communication with the container 10, as generally indicated by arrow 31, and further with the storage tank 50, as indicated by another arrow 35. In some configurations, the storage tank 50 includes at least a portion of the environment surrounding the container 10. In some configurations, the storage tank 50 comprises a container, a canister, a bag, or other holder dedicated to the regulator 30. As used herein, the term "bag" or its derivatives is a broad term used in its ordinary meaning and includes, for example, a sack, balloon, bladder, receptacle, enclosure, diaphragm, or expandable and / or contractible membrane having a structure that includes a flexible, pliable, bendable, elastic, stretchable, and / or expandable material. In some embodiments, the storage tank 50 is filled with gas and / or liquid. As used herein, the term "flexible" or its derivatives is a broad term used in its ordinary meaning and describes, for example, the ability of a component to bend, expand, contract, fold, unfold, or otherwise substantially deform or change shape when fluid flows into or out of the container 10 (e.g., via the access mechanism 20). Also, as used herein, the term "rigid" or its derivatives is a broad term used in its ordinary meaning and describes, for example, the ability of a component to generally avoid substantial deformation in normal use when fluid flows into or out of the container 10 (e.g., via the access mechanism 20).

[0080] In some embodiments, regulator 30 provides fluid communication between container 10 and storage tank 50. In some of such embodiments, the fluid in storage tank 50 mainly comprises gas so as not to dilute the liquid contents of container 10 to a perceptible extent. In some arrangements, regulator 30 comprises a filter for purifying the gas or liquid entering container 10 or removing contaminants, thereby reducing the risk of contaminating the contents of container 10. In some arrangements, the filter is made hydrophobic such that air can enter container 10 but fluid cannot leak therefrom. In some configurations, regulator 30 operates or comprises a check valve sensitive in a direction to selectively inhibit fluid communication between container 10 and the filter. In some configurations, regulator 30 comprises a check valve that selectively inhibits fluid communication between the valve and / or container 10 and the filter when regulator 30 is oriented such that it is held above regulator 30 (e.g., farther from the floor than regulator 30).

[0081] In some embodiments, regulator 30 impedes fluid communication between container 10 and storage tank 50. In some of such embodiments, regulator 30 acts as an interface between container 10 and storage tank 50. In some arrangements, regulator 30 comprises a substantially impermeable bag capable of accommodating the inflow of gas and / or liquid into container 10 or the outflow of gas and / or liquid from container 10.

[0082] As schematically illustrated in FIG. 2, in some embodiments, the access mechanism 20, or a predetermined portion thereof, is disposed within the container 10. As described in detail above, the access mechanism 20 may be integrally formed with the container 10 or may be separated from the container 10. In some embodiments, the regulator 30, or a predetermined portion thereof, is disposed outside the container 10. In some configurations, the regulator 30 is integrally formed with the container 10. It is possible to have any combination of the access mechanism 20, or a part thereof, that is wholly or partially received within the container 10 or placed outside the container 10, and / or the regulator 30, or a part thereof, that is wholly or partially received within the container 10 or placed outside the container 10.

[0083] In some embodiments, the access mechanism 20 is in fluid communication with the container 10. In further embodiments, the access mechanism 20 is in fluid communication with the exchange device 40, as indicated by arrow 24.

[0084] The regulator 30 can be in fluid or non-fluid communication with the container 10. In some embodiments, the regulator 30 is disposed entirely outside the container 10. In some of such embodiments, the regulator 30 comprises a closed bag configured to expand or contract outside the container 10 to maintain a substantially constant pressure within the container 10. In some embodiments, the regulator 30 is in communication with the storage tank 50, either fluidly or non-fluidly, as indicated by arrow 35.

[0085] As schematically illustrated in FIG. 2A, in some embodiments, the access mechanism 20, or a predetermined portion thereof, may be disposed within the container 10. In some embodiments, the access mechanism 20, or a predetermined portion thereof, may be disposed outside the container 10. In some embodiments, the valve 25, or a predetermined portion thereof, may be disposed outside the container 10. In some embodiments, the valve 25, or a predetermined portion thereof, may be disposed within the container 10. In some embodiments, the regulator 30 is entirely disposed outside the container 10. In some embodiments, the regulator 30, or a predetermined portion thereof, may be disposed within the container 10. It is possible to have any combination of the access mechanism 20, or a part thereof, that is entirely or partially enclosed within the container 10 or placed outside the container 10, and / or the valve 25, or a part thereof, that is entirely or partially enclosed within the container 10 or placed outside the container 10. It is also possible to have any combination of the access mechanism 20, or a part thereof, that is entirely or partially enclosed within the container 10 or placed outside the container 10, and / or the regulator 30, or a part thereof, that is entirely or partially enclosed within the container 10 or placed outside the container 10.

[0086] The access mechanism 20 may be in fluid communication with the container 10, as indicated by arrow 21. In some embodiments, the access mechanism 20 may be in fluid communication with the exchange device 40, as indicated by arrow 24.

[0087] In some embodiments, the regulator 30 may be in fluid or non - fluid communication with the valve 25, as indicated by arrow 32. In some embodiments, the valve 25 may be integrally formed with the container 10 or may be separated from the container 10. In some embodiments, the valve 25 may be integrally formed with the regulator 30 or may be separated from the regulator 30. In some embodiments, the valve 25 may be in fluid or non - fluid communication with the container 10, as indicated by arrow 33.

[0088] In some embodiments, the regulator 30 may be in fluid or non-fluid communication with the surrounding environment, as indicated by arrow 35A. In some embodiments, the regulator 30 may be in fluid or non-fluid communication with the storage tank 50, as indicated by arrow 35B. In some embodiments, the storage tank 50 may comprise a bag or other flexible enclosure. In some embodiments, the storage tank 50 may comprise a rigid container surrounding the flexible enclosure. In some embodiments, the storage tank 50 may comprise an enclosure that is partially rigid.

[0089] According to some configurations, the regulator 30 may comprise a filter. In some embodiments, the filter can selectively inhibit the passage of liquid and / or contaminants between the valve 25 and the storage tank 50 or the surrounding environment. In some embodiments, the filter can selectively inhibit the passage of liquid and / or contaminants between the storage tank 50 or the surrounding environment and the valve 25.

[0090] In some embodiments, valve 25 may be a one-way check valve. In some embodiments, valve 25 may be a two-way check valve. According to some configurations, valve 25 can selectively inhibit liquid communication between filter and / or reservoir 50 and container 10. In some embodiments, valve 25 can selectively inhibit liquid communication between container 10 and filter and / or reservoir 50 when container 10 is oriented above exchange device 40. FIG. 3 illustrates one embodiment of a system 100 comprising vial 110, access mechanism 120, and regulator 130. Vial 110 includes a body portion 112 and a cap 114. In the illustrated embodiment, vial 110 contains a medical fluid 116 and a relatively small amount of sterilized air 118. In some arrangements, fluid 116 is removed from vial 110 when vial 110 is oriented with cap 114 facing down (e.g., cap 114 is between the fluid and the floor). Access mechanism 120 includes a conduit 122 fluidly connected to one end of an exchange device 140, such as a standard syringe 142 having a plunger 144. Conduit 122 passes through cap 114 and enters into fluid 116. Regulator 130 includes a bag 132 and a conduit 134. Bag 132 and conduit 134 are fluidly in communication with a reservoir 150 containing a fixed amount of purified and / or sterilized air. The outer surface of bag 132 is generally in contact with the outside air surrounding both system 100 and exchange device 140. Bag 132 includes a substantially impermeable material so that fluid 116, air 118 inside vial 110, and reservoir 150 are not in contact with the outside air.

[0091] In the illustrated embodiment, the region outside the vial 110 is under atmospheric pressure. Thus, the pressure on the syringe plunger 144 is equal to the pressure applied inside the bag 132, and the system 100 is in a general equilibrium state. The plunger 144 can be withdrawn to fill a portion of the syringe 142 with fluid 116. Pulling out the flange 144 increases the effective volume of the vial 110, thereby reducing the pressure within the vial 110. When the pressure thus decreases within the vial 110, the pressure differential between the vial 110 and the syringe 142 increases, causing the fluid 116 to flow into the syringe 142 and the fluid within the reservoir 150 to flow into the vial 110. In addition, when the pressure within the vial 110 decreases, the pressure differential between the outside and inside of the bag 132 increases, causing the bag 132 to reduce its internal volume or contract, and then a certain amount of conditioning fluid is passed through the conduit 134 and into the vial 110. In fact, the bag 132 contracts outside the vial 110 to reach a new volume that compensates for the volume of the fluid 116 withdrawn from the vial 110. Thus, when the plunger 144 stops being withdrawn from the vial 110, the system returns to an equilibrium state. When the system 100 operates near equilibrium, it becomes easier to withdraw the fluid 116. Further, because the system 100 is in an equilibrium state, the plunger 144 remains in the position where it was withdrawn, thereby enabling an accurate amount of fluid 116 to be removed from the vial 110.

[0092] In some arrangements, the reduced volume of the bag 132 is approximately equal to the volume of liquid withdrawn from the vial 110. In some arrangements, as a greater amount of fluid is withdrawn from the vial 110, the rate at which the volume of the bag 132 decreases slows, and the volume of fluid withdrawn from the vial 110 becomes greater than the volume by which the bag 132 decreases.

[0093] In some configurations, the bag 132 can be substantially and / or completely collapsed, and thus the volume inside the bag 132 is substantially eliminated. In some cases, when the bag 132 collapses in this way, in fact, a pressure difference occurs between the inside of the bag 132 and the inside of the vial 110. For example, a vacuum (relative to the outside air) can occur inside the vial 110 when the bag 132 is collapsed. In some cases, when the bag 312 collapses in this way, when the bag 132 is generally not elastic, etc., a restoring force that tends to generate a pressure difference between the inside of the bag 132 and the inside of the vial 110 is substantially not generated.

[0094] In some embodiments, the syringe 142 comprises a fluid content 143. A portion of the fluid content 143 can be introduced into the vial 110 by pressing the plunger 144 (e.g., towards the vial), which may be desirable in some cases. For example, in some cases, it is desirable to introduce a solvent and / or a formulated fluid into the vial 110. In some cases, more fluid 116 than desired may be inadvertently withdrawn first. In some cases, a portion of the air 118 inside the vial 110 may be withdrawn first, creating unwanted air bubbles in the syringe 142. Thus, it may be desirable to return some of the fluid 116 and / or air 118 that is withdrawn back into the vial 110.

[0095] When the plunger 144 is pressed, the fluid contents 143 of the syringe flow into the vial 110, thereby reducing the effective volume of the vial 110 and increasing the pressure within the vial 110. As the pressure within the vial 110 increases, the pressure differential between the outside and inside of the bag 132 increases, causing air 118 to flow into the bag 132 and then the bag 132 to expand. In fact, the bag 132 expands or increases to a new volume that compensates for the volume of the contents 143 of the syringe 142 introduced into the vial 110. Thus, when the pressing of the plunger 144 stops, the system returns to equilibrium again. When the system 100 operates near equilibrium, the introduction of the contents 143 is facilitated. Further, because the system 100 is in an equilibrium state, the plunger 144 generally remains in the position where it was pressed, enabling the introduction of an accurate amount of the contents 143 of the syringe 142 into the vial 110.

[0096] In some configurations, the increased volume of the bag 132 is approximately equal to the volume of the air 118 removed from the vial 110. In some configurations, as a greater amount of the contents 143 is introduced into the vial 110, the rate at which the volume of the bag 132 increases slows, and the volume of the contents 143 introduced into the vial 110 becomes greater than the increasing volume of the bag 132.

[0097] In some configurations, the bag 132 can be stretched and expanded beyond its resting volume. In some cases, this stretching generates a restoring force and actually creates a pressure differential between the inside of the bag 132 and the inside of the vial 110. For example, a slight overpressure (relative to the outside air) can occur inside the vial 110 when the bag 132 is stretched.

[0098] FIG. 4 illustrates an embodiment of a vial adapter 200 for coupling to a vial 210. The vial 210 can comprise a container suitable for storing a medical fluid. In some cases, the vial 210 comprises any of a number of standard medical vials known in the art, such as those produced by Abbott Laboratories of Abbott Park, Ill. In some embodiments, the vial 210 can be hermetically sealed. In some configurations, the vial 210 comprises a body portion 212 and a cap 214. The body portion 212 preferably comprises a rigid, substantially impermeable material such as plastic or glass. In some embodiments, the cap 214 comprises a septum 216 and a casing 218. The septum 216 can comprise an elastomeric material that can deform to form a substantially airtight seal around an article when the article punctures the septum. For example, in some cases, the septum 216 comprises silicone rubber or butyl rubber. The casing 218 can comprise a material suitable for sealing the vial 210. In some cases, the casing 218 comprises a metal that is crimped around a portion of the septum 216 and the body portion 212 to form a substantially airtight seal between the septum 216 and the vial 210. In some embodiments, the cap 214 forms a ridge 219 that extends outwardly from the top of the body portion 212.

[0099] In some embodiments, the adapter 200 includes a piercing member 220 having an axial centerline A and a proximal end 221 (see FIG. 5) and a distal end 223. As used herein, the term "proximal," or derivatives thereof, refers to the direction along the axial length of the piercing member 220 toward the cap 214 when the piercing member 220 is inserted into the vial 210, and the term "distal," or derivatives thereof, indicates the opposite direction. In some configurations, the piercing member 220 includes a sheath 222. The sheath 222 can be substantially cylindrical or take on other geometric configurations, as illustrated. In some cases, the sheath 222 is tapered toward the distal end 223. In some arrangements, the distal end 223 forms a point that is centered relative to the axial centerline A or an offset therefrom. In some embodiments, the distal end 223 is angled from one side of the sheath 222 to the other side. The sheath 222 can include a rigid material such as metal or plastic suitable for insertion through the septum 216. In some embodiments, the sheath 222 includes polycarbonate plastic.

[0100] In some configurations, the piercing member 220 includes a tip portion 224. The tip portion 224 may have various shapes and configurations. In some cases, the tip portion 224 is configured to facilitate the insertion of the sheath 222 through the septum 216 via the insertion shaft. In some embodiments, the insertion shaft corresponds to the direction in which the force required to couple the adapter 200 to the vial 210 is applied when the adapter 200 is coupled to the vial 210. The insertion shaft may be substantially perpendicular to the plane on which the cap 214 is placed. In some embodiments, as illustrated in FIG. 4, the insertion shaft is substantially parallel to the centerline A on the axis of the adapter 200. Further, in some embodiments, the insertion shaft is substantially parallel to the piercing member 220. As illustrated, the tip portion 224, or a portion thereof, may be substantially conical and reach a central point on the axis of the piercing member 220, or in the vicinity thereof. In some configurations, the tip portion 224 is angled from one side of the piercing member 220 to the other side. In some cases, the tip portion 224 is separable from the sheath 222. In other cases, the tip portion 224 and the sheath 222 may be permanently connected and integrally formed. In various embodiments, the tip portion 224 includes acrylic plastic, ABS plastic, or polycarbonate plastic.

[0101] In some embodiments, the adapter 200 includes a cap connector 230. As shown, the cap connector 230 may be substantially conforming to the shape of the cap 214. In some configurations, the cap connector 230 includes a rigid material such as plastic or metal that substantially maintains its shape after slight deformation. In some embodiments, the cap connector 230 includes polycarbonate plastic. In some arrangements, the cap connector 230 includes a sleeve 235 configured to snap over the ridge 219 and engage tightly with the cap 214. In some cases, as will be more fully described below, the cap connector 230 includes a material for forming a substantially airtight seal with the cap 214 around the inner surface of the sleeve 235. The cap 230 may be an adhesive tape as known to those skilled in the art or may include an adhesive tape. In some embodiments, the cap connector 230 includes an elastic material that extends over the ridge 219 to form a seal around the cap 214. In some embodiments, the cap connector 230 is similar to or identical to the structure shown in FIGS. 6 and 7, which is described in the specification of Patent Document 1, which is incorporated herein by reference and made a part of this specification.

[0102] In some embodiments, the adapter 200 includes a connector interface 240 for coupling the adapter 200 with a medical connector 241, another medical device (not shown), or some other instrument used to withdraw fluid from or inject fluid into the vial 210. In some embodiments, the connector interface 240 includes sidewalls 248 that form a proximal portion of an access flow path 245 through which fluid can flow. In some cases, the access flow path 245 passes through the cap connector 230 and through a portion of the piercing member 220 such that the connector interface 240 is in fluid communication with the piercing member 220. The sidewalls 248 can be configured to couple with the medical connector 241, a medical device, or some other instrument. In the illustrated embodiment, the sidewalls 248 are substantially cylindrical and generally extend proximally from the cap connector 230.

[0103] In some configurations, the connector interface 240 includes a flange 247 for assisting in coupling the adapter 200 with the medical connector 241, a medical device, or some other instrument. The flange 247 can be configured to receive a suitable medical connector 241 that includes a connector that can be sealed after removal of the medical device from the flange 247. In some cases, the flange 247 has a size and configuration to receive a Clave® connector, available from ICU Medical, Inc., of San Clemente, California. Some features of Clave® are disclosed in Patent Document 1, the entire contents of which are incorporated herein by reference. Many other variations of connectors, including other needleless connectors, can also be used. The connector 241 can be permanently or removably attached to the connector interface 240. In other arrangements, the flange 247 has some other shape that is threaded or configured to receive a luer connector or is directly attachable to a medical device, such as a syringe, or some other instrument.

[0104] In some embodiments, the connector interface 240 generally aligns its center with the center on the axis of the adapter 200. Such a configuration provides vertical stability to a system comprising the adapter 200 coupled to the vial 210, such that the coupled system is less likely to tip over. Thus, the adapter 200 is less likely to cause leakage, spillage, or disassembly of the supply caused by the adapter 200 or the vial 210 accidentally bumping or falling over.

[0105] In some embodiments, the piercing member 220, the cap connector 230, and the connector interface 240 are integrally formed from a single piece of material such as polycarbonate plastic. In other embodiments, one or more of the piercing member 220, the cap connector 230, and the connector interface 240 comprise separate pieces. The separate pieces can be joined by suitable methods such as adhesives, epoxies, ultrasonic welding, etc. The connection between the joined pieces can form a bonding portion that is substantially airtight between the pieces. In some arrangements, any of the piercing member 220, the cap connector 230, or the connector interface 240 can comprise multiple pieces. Details and examples of some embodiments of the piercing member 220, the cap connector 230, and the connector interface 240 are presented in Patent Document 2 and Patent Document 3, which are each incorporated herein by reference in their entirety.

[0106] In some embodiments, the adapter 200 comprises a regulator flow path 225 that passes through the connector interface 240 and / or the cap connector 230, and also through the piercing member 220 (see, e.g., FIG. 5). In the illustrated embodiment, the regulator flow path 225 passes through a lumen 226 that extends radially outward from the connector interface 240. In some embodiments, the flow path 225 is formed as part of the cap connector 230. In some embodiments, the regulator flow path 225 terminates within a regulator opening 228.

[0107] In some embodiments, the adapter 200 includes a regulator assembly 250. In some embodiments, the regulator assembly 250 includes a coupling portion 252. The coupling portion 252 can be configured to connect the regulator assembly 250 to the remainder of the adapter 200. For example, the coupling portion 252 can be connected to the lumen 226 by a substantially airtight engagement, thereby fluidly communicating the coupling portion 252 with the regulator flow path 225. In some cases, the coupling portion 252 and the lumen 226 engage by a slip fit or an interference fit. In some embodiments, the coupling portion 252 and the lumen 226 include complementary threads, whereby the coupling portion 252 can be screwed onto the lumen 226. In some embodiments, the coupling portion 252 includes a passage 253 that extends through the coupling portion 252.

[0108] In the illustrated embodiment, the regulator assembly includes a bladder 254 having an internal chamber 255. The bladder 254 is generally configured to expand, contract, or otherwise change its internal volume by stretching, bending, unfolding, or otherwise expanding or contracting. In some cases, the bladder 254 includes one or more folds, pleats, or the like. In some arrangements, the internal chamber 255 of the bladder 254 is in fluid communication with the regulator flow path 225, thereby allowing fluid to pass from the regulator flow path 225 into the internal chamber 255 and / or from the internal chamber 255 into the regulator flow path 225. In some arrangements, the internal chamber 255 is in fluid communication with the passage 253 of the coupling portion 252.

[0109] In some embodiments, the regulator assembly 250 includes a filling material 256, which can be disposed within the interior chamber 255 of the bag 254. As used herein, the term "filling material" or its derivatives are broad terms used in the ordinary sense and include, for example, a support material, a stuffing, a spacer, a wadding, a padding, a lining, an enclosure, a storage tank, or other structures configured to inhibit or prevent the bag 254 from completely collapsing under ambient pressure, or combinations of these structures. In some configurations, the filling material 256 substantially occupies the entire volume of the interior chamber 255. In other arrangements, the filling material 256 occupies only a portion of the volume of the interior chamber 255. In some configurations, the filling material 256 includes a web of woven or non-woven fibers. In some embodiments, the filling material 256 is porous, such that a regulating fluid (e.g., air) within the interior chamber 255 can enter into a network of hollow bodies or a plurality of hollow bodies within the filling material 256. For example, in some cases, the filling material 256 is a spongy material. In some configurations, the filling material 256 is configured to be compressed by the bag 254 without causing damage to the bag 254. In some embodiments, the filling material 256 has a lower durometer than the bag 254.

[0110] As shown, the filling material 256 can be positioned within the bag 254. In some embodiments, the filling material 256 is positioned at the radiation center within the bag 254. In other cases, the position of the filling material 256 is offset relative to the center of the bag 254. In some embodiments, the position of the filling material 256 varies with respect to the bag 254. For example, in some embodiments, the filling material 256 moves relative to the bag 254 (e.g., by gravity) when the bag 254 changes volume, such as when the bag 254 expands. Such a configuration can, for example, enhance the ability of the bag 254 to expand and reduce the likelihood that the bag 254 will snag or bind tightly to the filling material 256.

[0111] In other embodiments, the position of the filler 256 is substantially fixed relative to the bag 254 and / or the joint 252. In some such embodiments, the filler 256 moves substantially together with the bag 254. For example, the filler 256 can be configured to expand and contract at substantially the same rate as the bag 254. In some embodiments, the filler 256 is fixed to the bag 254. In some such cases, the filler 256 is adhesively attached to at least a portion of the bag 254 or is at least partially adhesively attached. In some cases, at least a portion of the filler 256 is formed as part of the bag 254. In some embodiments, at least a portion of the filler 256 is held in place by one or more flexible legs that abut the inner surface of the bag 254. In some configurations, at least a portion of the filler 256 is held in place by one or more beams that connect to the joint 252. In some arrangements, at least a portion of the filler 256 is connected to the joint 252.

[0112] FIGS. 5 and 6 are cross-sectional views of the vial adapter 200 coupled to the vial 210. FIG. 5 shows a state where it is not fully expanded, and FIG. 6 shows a fully expanded state. In the illustrated embodiment, the cap connector 230 firmly fixes the adapter 200 to the cap 214, and the piercing member 220 passes through the septum 216 and enters the inside of the vial 210. In addition, the regulator assembly 250 engages the connector interface 240 such that the internal chamber 255 of the bag 254 is in fluid communication with the regulator flow path 255 through the joint 252. In some embodiments, the piercing member 220 is oriented substantially perpendicular to the cap 214 when the adapter 200 and the vial 210 are coupled. Other configurations are also contemplated.

[0113] In some embodiments, the cap connector 230 includes one or more protrusions 237 that assist in fixing the adapter 200 to the vial 210. The one or more protrusions 237 extend in a central direction on the axis of the cap connector 230. In some configurations, the one or more protrusions 237 include a single circular flange that extends around the inner periphery of the cap connector 230. The cap connector 230 can be sized and configured such that the upper surface of the one or more protrusions 237 abuts the lower surface of the raised portion 219, facilitating fixing the adapter 200 in place.

[0114] The one or more protrusions 237 can have a rounded shape, a chamfered shape, or some other shape to facilitate coupling the adapter 200 and the vial 210. For example, when an adapter 200 having rounded protrusions 237 is introduced into the vial 210, the lower surface of the rounded protrusions 237 abuts the top surface of the cap 214. As the adapter 200 advances onto the vial 210, the rounded surface causes the cap connector 230 to expand radially outward. As the adapter 200 further advances and enters the vial 210, the elastic force of the deformed cap connector 230 fixes the one or more protrusions 237 under the raised portion 219, fixing the adapter 200 in place.

[0115] In some embodiments, the cap connector 230 is sized and configured such that the inner surface 238 of the cap connector 230 contacts the cap 214. In some embodiments, a portion of the cap connector 230 contacts the cap 214 in a substantially airtight engagement. In some embodiments, a portion of the inner surface 238 that surrounds either the diaphragm 216 or the casing 218 is lined with a material such as rubber or plastic, thereby ensuring the formation of a substantially airtight seal between the adapter 200 and the vial 210.

[0116] In the illustrated embodiment, the piercing member 220 includes a sheath 222 and a tip portion 224. The sheath 222 generally has a size and dimensions that can penetrate through the diaphragm 216 and be inserted relatively easily without breaking the diaphragm 216. Thus, in various embodiments, the sheath 222 has a cross-sectional area of about 0.025 to about 0.075 square inches, about 0.040 to about 0.060 square inches, or about 0.045 to about 0.055 square inches. In other embodiments, this cross-sectional area is less than about 0.075 square inches, less than about 0.060 square inches, or less than or equal to about 0.055 square inches. In still other embodiments, this cross-sectional area is greater than or equal to about 0.025 square inches, greater than or equal to about 0.035 square inches, or greater than or equal to about 0.045 square inches. In some embodiments, the cross-sectional area is about 0.050 square inches.

[0117] The sheath 222 can take any of a number of geometric cross-sectional shapes, such as, for example, oval, elliptical, square, rectangular, hexagonal, or diamond-shaped. The geometric cross-sectional shape of the sheath 222 may vary in size and / or shape along its length. In some embodiments, the sheath 222 has a substantially circular cross-section along a substantial portion of its length. The circular geometric shape provides the sheath 222 with substantially equal strength in all radial directions, thereby preventing any possible bending or breakage that may occur in some other form after the sheath 222 is inserted. Since the opening formed in the diaphragm 216 by the circular sheath 222 is symmetric, pinching that may occur with angled geometric shapes is prevented, thereby making it easier to insert the sheath 222 through the diaphragm 216. Advantageously, the aligned circular symmetry between the piercing member 220 and the opening in the diaphragm 216 ensures a secure fit between the piercing member 220 and the diaphragm 216 even if the adapter 200 is inadvertently twisted. Thus, in some cases, the risk of dangerous liquids or gases leaking from the vial 210 or of dirty air entering the vial 210 and contaminating its contents can be reduced by the circularly symmetric configuration.

[0118] In some embodiments, the sheath 222 is hollow. In the illustrated embodiment, the inner and outer surfaces of the sheath 222 are substantially conformable to each other such that the sheath 222 has a substantially uniform thickness. In various embodiments, the thickness is from about 0.015 inches to about 0.040 inches, from about 0.020 inches to about 0.030 inches, or from about 0.024 inches to about 0.026 inches. In other embodiments, the thickness is at least about 0.015 inches, at least about 0.020 inches, or at least about 0.025 inches. In still other embodiments, the thickness is at most about 0.040 inches, at most about 0.035 inches, or at most about 0.030 inches. In some embodiments, the thickness is about 0.025 inches.

[0119] In some embodiments, the inner surface of the sheath 222 is configured differently from the outer surface of the sheath 222. Thus, in some configurations, the thickness varies along the length of the sheath 222. In various embodiments, the thickness at one end, such as the proximal end of the sheath, is from about 0.015 inches to about 0.050 inches, from about 0.020 inches to about 0.040 inches, or from about 0.025 inches to about 0.035 inches, and the thickness at the other end, such as the distal end 223, is from about 0.015 inches to 0.040 inches, from about 0.020 inches to 0.030 inches, or from about 0.023 inches to about 0.027 inches. In some embodiments, the thickness at one end of the sheath 222 is about 0.015 inches or more, about 0.020 inches or more, or about 0.025 inches or more, and the thickness at the other end thereof is about 0.015 inches or more, about 0.020 inches or more, or about 0.025 inches or more. In still other embodiments, the thickness at one end of the sheath 222 is about 0.050 inches or less, about 0.040 inches or less, or about 0.035 inches or less, and the thickness at the other end thereof is about 0.045 inches or less, about 0.035 inches or less, or about 0.030 inches or less. In some embodiments, the thickness at the proximal end of the sheath 222 is about 0.030 inches, and the thickness at the distal end 223 is about 0.025 inches. In some configurations, the cross-section of the inner surface of the sheath 222 has a shape different from the shape of the outer surface. The shape and thickness of the sheath 222 can be varied, for example, to optimize the strength of the sheath 222.

[0120] In some cases, the length of the sheath 222 measured from the distal surface of the cap connector 230 to the distal end 223 is from about 0.08 inches to about 1.4 inches, from about 0.9 inches to about 1.3 inches, or from about 1.0 inches to 1.2 inches. In other cases, the length is about 0.8 inches or more, about 0.9 inches or more, or about 1.0 inches or more. In still other cases, the length is about 1.4 inches or less, about 1.3 inches or less, or about 1.2 inches or less. In some embodiments, the length is about 1.1 inches.

[0121] In some embodiments, the sheath 222 at least partially surrounds one or more flow paths. For example, in the embodiment of FIG. 5, the sheath 222 partially surrounds the regulator flow path 225 and the access flow path 245. In some arrangements, the sheath 222 defines the outer boundary of the distal portion of the regulator flow path 225 and the outer boundary of the distal portion of the access flow path 245. An inner wall 227 extending from the inner surface of the sheath 222 to the distal portion of the medical connector interface 240 defines the inner boundary between the regulator flow path 225 and the access flow path 245.

[0122] In the illustrated embodiment, the access flow path 245 extends from an access opening 246 formed in the sheath 222, through the cap connector 230, and through the connector interface 240. Thus, when a medical device such as a syringe is connected to the medical connector 241 and then coupled to the connector interface 240, the medical device is in fluid communication with the interior of the vial 210. In such an arrangement, the contents of the vial 210 and the contents of the medical device can be exchanged between the vial 210 and the medical device.

[0123] In the illustrated embodiment, the regulator flow path 225 extends from the distal end 223 of the sheath 222, through the cap connector 230, through a portion of the connector interface 240, through the lumen 226, and terminates at a regulator opening 228. In some arrangements, such as the illustrated arrangement, the regulator opening 228 is in fluid communication with a passage 253 of the junction 252, and the junction 252 is in fluid communication with an internal chamber 255 of the bag 254. Thus, in such an arrangement, the internal chamber 255 is in fluid communication with the regulator flow path 225. In addition, in the illustrated embodiment, since the filler 256 is disposed within the internal chamber 255, the filler 256 is also in fluid communication with the regulator flow path 225.

[0124] In some configurations, the adapter 200 includes a filter 260. In the illustrated embodiment, the filter 260 is disposed within the regulator flow path 225 in the lumen 226. In other embodiments, the filter 260 is disposed within the regulator flow path 225 in the sheath 222. In yet other embodiments, the filter 260 is disposed within the passage 253 in the junction 252. In further embodiments, there is a filter 260 positioned within the interior chamber 255 of the bag 254. Generally, the filter 260 is held in place chemically or mechanically, for example, by an adhesive or a retaining ring. Some embodiments include a plurality of filters 260. For example, some embodiments have a first filter disposed within the lumen 226 and a second filter disposed within the junction 252.

[0125] In some arrangements, the filter 260 is a hydrophobic membrane and is generally configured to allow the passage of gas but to inhibit or prevent the passage of liquid. In some configurations, gas (e.g., sterilized air) can pass through the filter 260 and move between the vial 210 and the bag 254, but liquid from the vial 210 is blocked by the filter 260. Embodiments of the adapter 200 in which the filter 260 is disposed within the regulator flow path 225 thus reduce the likelihood of liquid spilling from the vial 210 even when the regulator assembly 250 is detached.

[0126] In some configurations, the filter 260 can remove particles and / or contaminants from the gas passing through the filter. For example, in some embodiments, the filter 260 is configured to remove substantially all, or about 99.9%, of the airborne particulate matter having a diameter of 0.3 micrometers. In some cases, the filter 260 is configured to remove microorganisms. In some embodiments, the filter 260 includes nylon, polypropylene, polyvinylidene fluoride, polytetrafluoroethylene, or other plastics. In some embodiments, the filter 260 includes activated carbon, such as activated charcoal. In some configurations, the filter 260 includes a mat of fibers arranged regularly or irregularly, such as glass fibers. In some arrangements, the filter 260 includes a Gore-Tex (registered trademark) material or a Teflon (registered trademark) material.

[0127] In the illustrated embodiment, the lumen 226 is a hollow cylindrical member that extends radially outward from the connector interface 240. In other embodiments, the lumen 226 has other shapes, such as conical. The lumen 226 can have various cross-sectional shapes, such as circular, square, rectangular, elliptical, diamond-shaped, star-shaped, polygonal, or irregular. As shown, in some embodiments, the lumen 226 extends radially outward less than the sleeve 235 of the cap connector 230. However, in some configurations, the lumen 226 extends radially outward beyond the sleeve 235 of the cap connector 230. For example, such a configuration can space the regulator assembly 250 from the remainder of the adapter 200 and from the vial 210 and facilitate connection to the regulator assembly 250.

[0128] In some embodiments, the coupling portion 252 has a shape that corresponds to, or is complementary to, the shape of the lumen 226. For example, in some cases, the lumen 226 has a triangular shape, and the coupling portion 252 likewise has a triangular shape. The coupling portion 252 can have almost any cross-sectional shape, such as circular, square, rectangular, oval, diamond, star, polygonal, or irregular. In some configurations, the coupling portion 252 and the lumen 226 have corresponding shapes that encourage the orientation of the coupling portion 252 (and thus the regulator assembly 250) with respect to the lumen 226 (and thus the rest of the adapter 200), as described below.

[0129] The coupling portion 252 can be configured to engage with the lumen 226. For example, in the illustrated embodiment, the coupling portion 252 is configured to be received by the lumen 226. In other cases, the coupling portion 252 is configured to receive the lumen 226. In some cases, the coupling portion 252 and the lumen 226 are connected by a slip fit or an interference fit. In some configurations, the coupling portion 252 and the lumen 226 are connected by a hose barb connection. In some arrangements, the coupling portion 252 and the lumen 226 are connected by a threaded connection. For example, in some cases, the coupling portion 252 and the lumen 226 have corresponding standard luer lock type connectors. In some embodiments, the connection between the coupling portion 252 and the lumen 226 is substantially airtight, thereby suppressing or preventing outside air from entering the regulator flow path 225. Such a configuration can reduce the possibility that microorganisms or impurities enter the vial 210, and thus can enhance patient safety by reducing the possibility of contaminating the medical fluid.

[0130] In some arrangements, the connection between the coupling 252 and the lumen 226 includes a feedback device to alert the user that the connection has been made. For example, in some arrangements, the connection between the coupling 252 and the lumen 226 includes a detent mechanism, such as a ball detent, that can tactilely inform the user that the connection has been made. Some embodiments include an acoustic signal, such as a click, snap, or similar sound, indicating that the coupling 252 has been connected to the lumen 226.

[0131] In some embodiments, the connection between the coupling 252 and the lumen 226 is substantially permanent. For example, in some configurations, the junction 252 and the lumen 226 are ultrasonically welded. In some cases, the coupling 252 and the lumen 226 are permanently attached with an adhesive such as glue, epoxy, double-sided tape, solvent bonding, or other means. In some embodiments, the coupling 252 and the lumen 226 are connected by a permanent snap mechanism (e.g., a hook of approximately 90° and a corresponding valley of approximately 90°), and the coupling 252 and the lumen 226 are substantially constrained from separating after the snap mechanism is engaged. The permanent connection between the coupling 252 and the lumen 226 can encourage single use of the adapter 200, including single use of the regulator assembly 250. Further, the permanent connection of the regulator assembly 250 to the remainder of the adapter 200 will reduce the total number of unique parts for which inventory, maintenance, and pre-use preparation are made. In some embodiments, the coupling 252 is formed substantially monolithically with the remainder of the adapter 200 (e.g., molded in the same operation as the remainder).

[0132] In some cases, the junction 252 and the lumen 226 are connected, for example, at a factory, during the process of manufacturing the adapter 200. In some configurations, the regulator assembly 250 is separate from the rest of the adapter 200 and is configured to be connected by a user to the rest of the adapter 200. For example, the piercing member 220, the cap connector 230, and the connector interface 240 can be provided within a first package, and the regulator assembly 250 can be provided within a second package. In some user connection configurations, the connection is substantially permanent. For example, in some cases, one of the junction 252 and the lumen 226 includes an adhesive (e.g., double-sided tape) that substantially permanently affixes the junction 252 and the lumen 226 when the user connects the junction 252 and the lumen 226. On the other hand, in some embodiments of user connection, the junction 252 is configured to be detachable from the lumen 226 even after the junction 252 is connected to the lumen 226. For example, in some embodiments, the junction 252 and the lumen 226 are releasably coupled to a threaded or release mechanism, such as a detent or a set screw. Such a configuration can facilitate operations (e.g., large-scale pharmaceutical compounding operations) where a desired transfer of a fixed volume of regulator fluid from the regulator assembly 250 into the vial 210, which is larger than the volume of the regulator fluid accommodated within the regulator assembly 250, as described below. In some embodiments, when the regulator assembly 250 is detached, its contents are sealed from the environment using, for example, a one-way valve.

[0133] In the illustrated embodiment, the junction member 252 is connected to the bag 254. In some cases, the bag 254 and the junction 252 are welded or connected with an adhesive. As shown, the connection between the bag 254 and the junction 252 generally fluidly connects the passage 253 to the interior chamber 255 of the bag 254. To facilitate fluid communication, the bag 254 can include a bag opening 257, such as a slit or a hole. In some cases, the bag opening 257 is created with a hot tool, such as a soldering iron.

[0134] The bag 254 is generally configured to be unfolded from a folded state, unfolded from a rolled state, expanded, contracted, inflated, deflated, compressed, and / or depressurized. The bag 254 can include any of a variety of flexible and / or expandable materials. For example, in some embodiments, the bag 254 includes polyester, polyethylene, polypropylene, saran, latex rubber, polyisoprene, silicone rubber, vinyl, polyurethane, or other materials. In some embodiments, the bag 254 includes a material having a metal component to further suppress leakage of fluid (including gas or air) through the bag material. For example, in some embodiments, the bag 254 includes metallized biaxially oriented polyethylene terephthalate (also known as PET and commercially available under the trade name Mylar®). In some embodiments, the bag 254 includes a laminate. For example, the bag 254 can be made from a layer of 0.36 Mil (7.8#) metallized (e.g., aluminum) PET film and a layer of 0.65 Mil (9.4#) linear low density polyethylene. In some embodiments, the bag 254 includes a material that can form a substantially airtight seal with the joint 252. In some embodiments, the bag 254 is transparent or substantially transparent. In other embodiments, the bag 254 is opaque. In many cases, the bag 254 includes a material that is generally impermeable to liquids and air. In some embodiments, the bag 254 includes a material that is inert to the intended contents of the vial 210. For example, in some cases, the bag 254 includes a material that does not react with some of the drugs used in chemotherapy. In some embodiments, the bag 254 includes latex-free silicone having a durometer of about 10 to about 40.

[0135] In some configurations, the bag 254 comprises a coating. For example, in some embodiments, the bag 254 comprises a coating that reduces the porosity of the bag 254. In some cases, the coating is vapor-deposited aluminum or vapor-deposited gold. In some cases, the coating comprises a water-soluble plastic configured to form a barrier that inhibits the passage of gas. In some cases, the coating is applied to the outside of the bag 254. In other cases, the coating is applied to the inside of the bag 254. In some cases, the coating is applied to both the inside and the outside of the bag 254. In some embodiments, the coating is a polyolefin.

[0136] In some embodiments, the bag 254 is disposed entirely outside of the vial 210. In some arrangements, the bag 254 is positioned entirely outside of the remainder of the adapter (e.g., the piercing member 220, the cap connector 230, and the connector interface 240). In some embodiments, the bag 254 is substantially free and generally expandable in any direction. For example, in the illustrated embodiment, there is no rigid enclosure that surrounds or partially surrounds a portion of the bag 254. In some cases, the rigid housing does not include the substantial volume of the bag 254. In some embodiments, in a fully collapsed state, the bag 254 is not within a rigid enclosure. In some configurations, the bag 254 is substantially free and generally expandable in any direction, e.g., directions such as proximal, distal, radially away from the vial 210, radially toward the vial 210, etc.

[0137] In some embodiments, the bag 254 is configured to be able to expand freely without being restricted, for example, by a rigid enclosure. Such unrestricted expansion of the bag 254 can reduce the force required to expand the bag 254. For example, since the bag 254 does not contact a rigid enclosure, there is no frictional force between the bag 254 and such an enclosure that could otherwise increase the force required to expand the bag 254. In some aspects, the unrestricted expansion of the bag 254 reduces the likelihood that the bag 254 will be damaged during expansion. For example, since the bag 254 does not contact a rigid enclosure, there is a low risk that the bag 254 will be damaged (e.g., develop a hole, tear, or catch on a burr or other defective portion of such an enclosure) when expanding or collapsing. Further, the unrestricted movement of the bag 254 reduces the likelihood that the coating of the bag 254 will become soiled or peeled off. In some embodiments, the bag 254 does not bump, rub, hit, slide, or otherwise contact the rigid surface of the adapter 200 statically or dynamically when expanding. In some configurations, the bag 254 contacts only the joint 252, the regulating fluid, and the outside air.

[0138] In some embodiments, the bag 254 includes a first side 258 and a second side 259. In some cases, the first side 258 is closer to the connector interface 240 than the second side 259. In some cases, the first side 258 is secured to the joint 252, but the second side 259 is not. In some configurations, the first side 258 is connected to the second side 259. In some such cases, the first side 258 is connected to the second side 259 at the respective peripheral ends of the sides 258, 259. In some cases, the second side 259 does not contact a rigid surface when the bag 254 expands. In some configurations, substantially all or most of the surface area of the bag 254 exposed to the surrounding environment is flexible. In some embodiments, generally the entire bag 254 is flexible.

[0139] In some embodiments, each of the side portions 258, 259 comprises an inner surface and an outer surface. As illustrated in FIG. 6, the inner surface of each of the side portions 258, 259 may be in contact with the internal chamber 255, and the outer surface of each of the side portions 258, 259 may be in contact with the surrounding environment.

[0140] In some cases, the inner surface of each of the side portions 258, 259 is oriented toward the inside of the bag 254. As used herein, the phrase "oriented toward" or derivatives thereof is a broad term used in its ordinary meaning and, for example, represents generally aligning or positioning something in the direction of a member being indicated. For example, if a first member is oriented toward a second member, the first member is generally aligned or positioned in the direction of the second member. When a side or surface is oriented toward a member, the side or surface is aligned or positioned such that a normal from the side or surface intersects the member. In some configurations, the first side portion 258 is oriented toward the connector interface 240.

[0141] In some cases, the outer surface of each of the side portions 258, 259 is oriented outwardly from the bag 254. In some cases, the second side portion 259 is oriented in a direction away from the connector interface 240. In some such cases, a normal extending from the outer surface of the second side portion 259 does not intersect the connector interface 240.

[0142] In some embodiments, the second side portion 259 is oriented in a direction opposite to that of the first side portion 258. As used herein, the term "opposite" or its derivatives are broad terms used in the ordinary sense and, for example, designate the expression of something that is at the other end, side, or region from a member. For example, each side within a rectangle is opposite to the other side and not opposite to the two other sides. In some cases, the second side portion 259 is oriented in a direction away from the connector interface 240. In such a case, the normal extending from the outer surface of the second side portion 259 does not intersect the connector interface 240.

[0143] In some embodiments, the bag 254 comprises a first layer and a second layer. As used herein, the term "layer" or its derivatives is a broad term used in its ordinary sense and describes, for example, the thickness of a material, the ply of a material, or a stratum of a material. In some embodiments, a layer may include a plurality of components, plies, or strata of a material. In some cases, the first layer is the first side portion 258 and the second layer is the second side portion 259. In some configurations, the first layer and the second layer are connected. For example, the perimeter of the first layer may be connected to the perimeter of the second layer or formed integrally or monolithically with the perimeter of the second layer. Such a configuration can assist, for example, in forming the bag 254 by making the bag 254 substantially airtight around the perimeter. In some cases, the first layer is a first sheet of metallized PET and the second layer is a second sheet of metallized PET, and the first layer and the second layer are adhered together (e.g., heat-sealed) around the perimeter. In some embodiments, the first layer and the second layer each have a central portion. For example, in a configuration where the perimeter shape of each of the first layer and the second layer is substantially circular, the central portion may be around the radial center of each of the first layer and the second layer. In some cases, the central portion of the first layer is not attached or connected to the central portion of the second layer. Thus, in some such cases, the first portion and the second portion can move relative to each other.

[0144] In some embodiments, one or both of the first layer and the second layer can include one or more sub-layers. For example, the first and / or second layer can each include a plastic sub-layer and a metal sub-layer. In some embodiments, the first sub-layer and the second sub-layer have a bonding surface that is bonded together into one. In some cases, substantially the entire bonding surface is bonded. Generally, the sub-layers are not configured to receive a substantial or significant volume (e.g., of a regulating fluid) therebetween. On the other hand, in some embodiments, the first layer and the second layer are configured to receive a regulating fluid therebetween. For example, in a configuration where the first layer is the first side portion 258 and the second layer is the second side portion 259, a regulating fluid can be received between the first layer and the second layer (see FIG. 6).

[0145] In various embodiments, the adapter 200 does not include a rigid enclosure that wholly or partially houses the bag 254. For example, the volume of the bag inside the rigid enclosure can be less than half the volume of the bag 254 (if any) or a very small portion of the volume of the bag (e.g., less than or equal to the volume inside the perforating member on the adapter or less than or equal to the volume inside the cap of the connector). In some embodiments, the volume of the bag inside the rigid enclosure is (if any) less than half the volume inside one or more vials that the adapter is configured to be connected to. The rigid enclosure increases the weight and total material of the adapter 200, thereby increasing the cost of materials and manufacturing. Further, since the rigid enclosure is positioned at a distance away from the center on the axis of the adapter, omitting the rigid enclosure can eliminate the moment of force caused by the weight of such an enclosure. Thus, the adapter 200 can enhance stability and reduce the likelihood of tipping over. The stability of the adapter and the vial is considered particularly important when handling cytotoxic drugs because there is an increased risk of spillage or some other form of unintended exposure and / or release occurring if it is tipped over.

[0146] In some embodiments of the adapter 200, the regulator assembly 250 is connected to the remainder of the adapter 200 and has a center of gravity that is not substantially excluded from the center on the axis of the adapter 200 when the adapter 200 mates with the vial 210. For example, some embodiments of the adapter 200 have a center of gravity at or less than about 0.50 inches, at or less than about 0.25 inches, at or less than about 0.125 inches, or at or less than about 0.063 inches from the center on the axis of the adapter 200.

[0147] In some cases, the bag 254 is expandable to a size that substantially fills a range of volumes so that a single adapter 200 can be configured to operate with vials 210 of various sizes. In some embodiments, the bag 254 is configured to hold a volume equal to at least about 30 percent, at least about 70 percent, or at least about 90 percent of the volume of fluid contained within the vial 210 prior to coupling the adapter 200 and the vial 210. In some embodiments, the bag 254 is configured to hold a volume equal to about 70 percent of the volume of fluid contained within the vial 210 prior to coupling the adapter 200 and the vial 210. In various embodiments, the fluid within the bag 254 is a gas. For example, air, sterilized air, purified air, nitrogen, oxygen, an inert gas (e.g., argon), or other gas. In some embodiments, the sterilized air can be supplied by introducing outside air into the bag and then sterilizing the bag and the air together.

[0148] The bag 254 assumes a fully expanded configuration (Figure 6) and at least one not fully expanded configuration (Figure 5). In some cases, in the fully expanded configuration, the volume of the inner chamber 255 of the bag 254 is at its maximum recommended volume. In some cases, in the fully expanded configuration, the bag 254 accommodates at least about 100 mL, at least about 200 mL, or at least about 300 mL of fluid. In some cases, in the fully expanded configuration, the bag 254 holds at least about 250 mL of fluid. In some embodiments, in the fully expanded configuration, the bag 254 accommodates at least about 180 mL of fluid.

[0149] In some cases, in the not fully expanded configuration, the bag 254 accommodates about 5 mL or less, about 40 mL or less, about 100 mL or less, or about 250 mL or less of fluid. In some cases, the not fully expanded configuration of the bag 254 is a completely collapsed configuration, in which case the volume of the inner chamber 255 of the bag 254 is approximately zero. In some such cases, in the completely collapsed configuration, the bag 254 contains substantially no fluid.

[0150] The bag 254 further has an initial configuration (e.g., the configuration before the regulatory fluid is transferred between the vial 210 and the bag 254). Generally, the bag 254 contains a fixed volume of fluid in the initial configuration to facilitate the smooth step of quickly and accurately withdrawing fluid from the vial 210 after the connection of the vial 210 and the adapter 200. In some embodiments, in the initial configuration, the bag 254 contains at least about 10 mL, at least about 50 mL, or at least about 90 mL of fluid. In some embodiments, in the initial configuration, the bag 254 contains at least about 60 mL of fluid. In some embodiments, in the initial configuration, the bag 254 contains a fixed volume of fluid that generally corresponds to the volume of one or more standard medical devices at the attachment site configured to receive the adapter. For example, in some cases, in the initial configuration, the bag 254 holds at least about 30 mL of fluid corresponding to the volume of a 30 mL syringe. In such a case, when the adapter 200 is connected to the vial 210, about 30 mL of fluid is immediately available for transfer between the bag 254 and the vial 210, thereby enabling the immediate transfer of 30 mL of fluid between the vial 210 and the syringe. In some embodiments, the bag 254 has an initial volume that is at least approximately equal to the sum of the volume inside the cap and the volume inside the piercing member, or at least about twice the size of the sum of the volume inside the cap and the volume inside the piercing member.

[0151] In various arrangements, the outer dimension (e.g., diameter or cross-sectional width or height) D of the bag 254 is from about 1.0 inch to about 6.0 inches, from about 2.0 inches to about 5.0 inches, or from about 3.0 inches to about 4.0 inches. In some arrangements, the outer dimension is about 3.0 inches or more, about 4.0 inches or more, or about 6.0 inches or more. In other arrangements, the outer diameter is about 8.0 inches or less, about 7.5 inches or less, or about 7.0 inches or less. In some embodiments, the approximate dimension of the outer periphery of the bag is less than or equal to the height or cross-sectional width of one or more vials to which the adapter is configured to be attached. In various arrangements, the maximum overall thickness T of the bag 254 is from about 0.50 inch to about 2.00 inches, from about 0.60 inch to about 0.90 inches, and from about 0.70 inch to about 0.80 inches. In other arrangements, the maximum overall thickness is less than about 1.00 inch, less than about 0.90 inch, or less than about 0.80 inch. In some arrangements, the maximum overall thickness is about 0.75 inch. In some cases, the diameter of the bag 254 is greater than the maximum overall thickness of the bag 254. In some cases, the diameter of the bag 254 is greater than twice the maximum overall thickness of the bag 254. In some cases, it is desirable to prevent the bag 254 from pressing against the vial 210. Thus, in some cases, the bag 254 is configured (e.g., dimensioned) such that, even when fully deployed, the bag 254 is spaced apart from and aligned with the vial 210.

[0152] In some configurations, the wall thickness W of the bag 254 is from about 0.001 inch to about 0.025 inches, from about 0.001 inch to about 0.010 inches, or from about 0.010 inches to about 0.025 inches. In other configurations, the wall thickness is greater than about 0.001 inch, greater than about 0.005 inch, greater than about 0.010 inch, greater than about 0.015 inch, or greater than about 0.020 inch. In still other configurations, the wall thickness is less than about 0.025 inch, less than about 0.020 inch, less than about 0.015 inch, less than about 0.010 inch, or less than about 0.005 inch. In some configurations, the wall thickness is about 0.015 inch. In some embodiments, the wall thickness is substantially constant. In some embodiments, the wall thickness may vary. For example, in some configurations, the wall thickness increases within the region of the bag 254 around the joint 252.

[0153] In some configurations, in a configuration that is not fully expanded, the bag 254 has a substantially irregular shape, as shown in FIG. 5. In other configurations, the bag 254 has a shape that is generally spherical, generally conical, generally cylindrical, generally toroidal, or other shape. For example, in some embodiments, in a fully expanded configuration, the bag 254 has a shape that is generally a flattened ellipsoid of revolution. In some cases, the bag 254 is substantially bulbous. In some arrangements, the bag 254 has a convex shape. In some configurations, the bag 254 has a concave shape. In some configurations, the shape of the bag 254 generally conforms to the shape of the filler 256. In some arrangements, the bag 254 typically conforms to the shape of the filler 256 in a configuration that is not fully expanded and deviates from the shape of the filler 256 in a fully expanded configuration.

[0154] The filling material 256 can be configured to occupy various volumes within the bag 254. For example, in some arrangements, the volume occupied by the filling material 256 is at least about 30 percent, at least about 75 percent, or at least about 90 percent of the volume of the bag 254. In some arrangements, the filling material 256 is configured to maintain a space between the first side 258 and the second side 259 of the bag 254. In some arrangements, the filling material 256 is configured to ensure that the volume of the inner chamber 255 is non-zero.

[0155] Generally, the filling material 256 is configured to be able to supply a regulating fluid, such as sterilized air, to the vial 210 promptly. As described above, when the adapter 200 engages with the vial 210 and a medical device (such as a syringe) and a portion of the fluid within the vial 210 is transferred from the vial 210 through the adapter 200 into the medical device, the volume of the fluid within the vial 210 decreases, thereby causing the pressure within the vial 210 to drop, which results in a pressure gradient between the inside and the outside of the vial 210. This pressure gradient can cause ambient air, which may contain microorganisms, impurities, and other contaminants, to leak into the vial 210 at the joint surface between the septum 216 and the piercing member 220 or at the attachment joint surface between the adapter 200 and the medical device. Further, such a pressure gradient can generate a restoring force that hinders the ability to withdraw an accurate amount of fluid from the vial 210. However, the filling material 256 can supply the regulating fluid to the adapter 200 promptly and generally replaces a portion or all of the volume of the fluid transferred to maintain an equilibrium state within the vial 210, thereby reducing or preventing the aforementioned problems.

[0156] In some configurations, when fluid is removed from vial 210 through extraction flow path 245, a corresponding amount of conditioning fluid from packing 256 is introduced into vial 210 substantially simultaneously through bag opening 257, passage 253 in joint 252, and regulator flow path 225, thereby maintaining an equilibrium state. In some configurations, packing 256 is adapted to supply conditioning fluid immediately before regulator assembly 250 is connected to the remainder of adapter 200. In some aspects, packing 256 comprises a reservoir of conditioning fluid for adapter 200. In some configurations, packing 256 is configured such that substantial portions of the first side 258 and the second side 259 of bag 254 do not contact each other.

[0157] In some configurations, packing 256 has a shape similar to that of bag 254. For example, in some cases, in a fully expanded configuration, bag 254 and packing 256 each have a shape generally as a flattened ellipsoid. In other configurations, packing 256 has a shape different from that of bag 254. For example, in some cases, in a fully expanded configuration, bag 254 has a substantially ellipsoidal shape and packing 256 has a substantially cylindrical shape. In some such cases, the longitudinal axis of the cylindrical packing 256 is generally parallel to the centerline on the axis of adapter 200. In other such cases, the longitudinal axis of the cylindrical packing 256 is orthogonal to the centerline on the axis of adapter 200.

[0158] In some embodiments, packing 256 is configured to be deformed by bag 254 when bag 254 collapses. For example, in some cases, when bag 254 collapses, the volume of packing 256 decreases by at least about 30 percent, at least about 50 percent, or at least about 90 percent. In some cases, when bag 254 is in a fully expanded configuration, packing 256 has a first shape (e.g., ellipsoidal), and when bag 254 is in a fully collapsed configuration, packing 256 has a second shape (e.g., disk-shaped).

[0159] In some such embodiments, the filler 256 is crushable or compressible and is then configured to substantially return to its original shape. For example, when the bag 254 collapses from a fully deflated configuration, the bag 254 substantially crushes the filler 256, but then when the bag 254 expands, the filler 256 returns to substantially its original shape. In other embodiments, the filler 256 is configured to permanently deform when crushed. For example, in some cases, the filler 256 comprises a thin-walled hollow member (e.g., an aluminum foil ball), which is configured to be permanently or irreversibly deformed, crushed, or otherwise have its volume reduced when the bag 254 collapses. This can be an indicator that the adapter 200 has already been used. In some embodiments, the filler 256 substantially maintains its shape when the bag 254 collapses.

[0160] In some arrangements, the filler 256 is configured to contain a fixed volume of gas, such as sterilized air. In some cases, the filler 256 is porous. In some cases, the filler 256 is a sponge or sponge-like material. In some arrangements, the filler 256 comprises a cotton stuffing. In some configurations, the filler 256 comprises a mat of regularly or irregularly arranged fibers configured to form a network of cells or spaces therein. In some embodiments, the filler 256 is made of a low density foam. For example, in some embodiments, the filler 256 is made of a polyurethane ether foam and has a weight of, for example, about 1.05 pounds per cubic foot and an indentation load deflection (ILD) of, for example, about 38. In some embodiments, the filler 256 is made of a polyether, polyester, polyethylene, or ether-like ester (ELE). In some cases, the filler 256 is made of nylon, polypropylene, polyvinylidene fluoride, polytetrafluoroethylene, or other plastics. In some embodiments, the filler 256 is a metal, such as aluminum or stainless steel. In some embodiments, the filler 256 is treated with an antibacterial compound or other compound to enhance sterility. In some cases, the filler 256 comprises a sealed chamber configured to open when fluid is withdrawn from the vial 210, such as a chamber containing sterilized air. In some embodiments, the filler 256 is configured to chemically and / or mechanically interact with the fluid (such as vapor) entering the bag, such as by binding to, absorbing, generally neutralizing, or otherwise interacting with it.

[0161] In various arrangements, the outer dimension (e.g., diameter or cross-sectional width or height) of the filler 256 under atmospheric pressure is from about 1.0 inch to about 6.0 inches, from about 2.0 inches to about 5.0 inches, or from about 3.0 inches to about 4.0 inches. In some arrangements, the outer diameter of the filler 256 under atmospheric pressure is about 3.0 inches or more, about 4.0 inches or more, or about 6.0 inches or more. In some embodiments, the diameter of the filler 256 under atmospheric pressure is about 4.00 inches. In other arrangements, the outer diameter under atmospheric pressure is about 8.0 inches or less, about 7.5 inches or less, or about 7.0 inches or less. In various arrangements, the maximum overall thickness of the filler 256 under atmospheric pressure is from about 0.05 inch to about 0.99 inch, from about 0.20 inch to about 0.60 inch, and from about 0.25 inch to about 0.35 inch. In some embodiments, the thickness of the filler 256 under atmospheric pressure is about 0.30 inch. In some arrangements, the maximum overall thickness of the filler 256 under atmospheric pressure is about 1.00 inch. In some embodiments, the diameter and thickness of the filler 256 under atmospheric pressure are substantially the same as the diameter D and thickness T of the bag 254.

[0162] Continuing to refer to FIGS. 5 and 6, some processes for using the adapter 200 include inserting the piercing member 220 through the septum 216 until the cap connector 230 is securely seated in place. Thus, the coupling of the adapter 200 to the vial 210 can be performed in a single simple step. In some cases, the medical connector 241 is coupled to the medical connector interface 240. A medical device or other instrument (not shown), such as a syringe, can be coupled to the interface 240 or, if the medical connector 241 (see FIG. 4) is present, to it. For convenience, only a syringe will be referred to hereinafter as an example of a medical device suitable for attachment to the medical connector interface 240, but there are many medical devices or other instruments that can be used when connecting to the adapter 200 or the medical connector 241. In some cases, the syringe is placed in a position in fluid communication with the vial 210. In some cases, when the vial 210, adapter 200, syringe, and medical connector 241 are present, the medical connector 241 is inverted so that the cap 214 points downward (e.g., toward the floor). Any of the above procedures, or any combination of these procedures, can be performed in any possible order.

[0163] In some cases, a fixed volume of fluid is withdrawn from vial 210 and placed into a syringe. As described above, the pressure within vial 210 decreases as the fluid is withdrawn. Thus, in some cases, the conditioning fluid within packing 256 within bag 254 flows into vial 210 through regulator flow path 225. In some cases, the conditioning fluid passes through filter 260. In some cases, bag 254 collapses as the conditioning fluid is transferred from packing 256. In some configurations, the equilibrium state within vial 210 is generally maintained when the conditioning fluid is transferred from packing 256 within bag 254 and / or other locations into vial 210. In some cases, the volume of conditioning fluid transferred from packing 256 into vial 210 is approximately equal to the volume of fluid drawn from vial 210 into the syringe.

[0164] In some cases, a fixed volume of fluid is introduced from the syringe into vial 210. For example, in some cases, a fixed volume of fluid is introduced into vial 210 to reconstitute a lyophilized drug or for the purpose of compounding a drug. As another example, in some cases, an amount of fluid in excess of the desired amount may be inadvertently withdrawn from vial 210 by the syringe. As described above, when fluid is introduced into vial 210, the pressure within vial 210 increases. Thus, in some cases, the regulatory fluid within vial 210 flows through regulator flow path 225 and into bag 254, as indicated by the arrow in FIG. 6. In some cases, the regulatory fluid passes through filter 260. In some cases, when the regulatory fluid is transferred from vial 210, bag 254 expands. In some of such cases, when bag 254 expands, it stretches, unfolds, or spreads outwardly. In some embodiments, bag 254 has sufficient flexibility to substantially avoid the generation of a restoring force (e.g., a force opposing the expansion or contraction of bag 254). In some embodiments, bag 254 exerts a restoring force. In some configurations, when the regulatory fluid is transferred from vial 210 into bag 254, the equilibrium state within vial 210 is maintained. In some cases, the volume of regulatory fluid transferred from vial 210 into bag 254 is approximately equal to the volume of fluid introduced from the syringe into vial 210.

[0165] Accordingly, in some embodiments, adapter 200 can respond to the step of withdrawing fluid from vial 210 or adding fluid to vial 210 to maintain the pressure within vial 210. In many cases, the change in pressure within vial 210 is about 1 psi or less, about 2 psi or less, about 3 psi or less, about 4 psi or less, or about 5 psi or less.

[0166] In some embodiments, the process for containing gas and / or vapor includes the steps of comprising a piercing member 220, a cap connector 230, and a connector interface 240. Generally, the process also includes the step of piercing the septum of the vial 210 with the piercing member 220. The piercing member 220 may also enable access to the medical fluid within the vial 210. In some embodiments, the process includes the step of connecting the regulator assembly 250 to the cap connector 230 or the connector interface 240, thereby fluidly connecting the regulator assembly 250 and the vial 210. In some embodiments, the process also includes the step of storing the gas and / or vapor displaced by the fluid introduced into the vial 210. In some configurations, all or part of the gas and / or vapor is stored within the regulator assembly 250. Thus, the gas and / or vapor - which may be substantially harmful to health - is isolated and generally maintained away from the ambient environment. In some embodiments, the process may include the step of detaching the regulator assembly 250.

[0167] As is apparent from the embodiments and processes described above, with the adapter 200, the user can introduce liquid into the vial 210 (including returning unwanted liquid and / or air) without significantly changing the pressure within the vial 210 and can draw liquid out of the vial 210. As already explained, the function of injecting liquid into the vial may be particularly desirable in returning lyophilized drugs. Also, as explained earlier, the function of injecting air bubbles and excess fluid into the vial 210 may be particularly desirable in the context of oncology drugs.

[0168] Furthermore, in the above description, it has been shown that some embodiments of the adapter 200 can be configured to adjust the pressure within the vial 210 without introducing outside air or ambient air into the vial 210. For example, in some embodiments, the bag 254 includes a substantially impermeable material that is used as a barrier rather than a passage between the inside of the vial 210 and the surrounding environment. Some embodiments of the adapter 200 substantially reduce the risk of introducing airborne contaminants into the patient's bloodstream.

[0169] As pointed out above, in some cases, the vial 210 is oriented such that the cap 214 points downward when the liquid is removed from the vial 210. In some embodiments, the access opening 246 is disposed adjacent to the bottom surface of the cap 214, whereby most or substantially all of the liquid within the vial 210 can be removed. In other embodiments, the access opening 246 is disposed near the distal end 223 of the piercing member 220. In some configurations, the adapter 200 includes a plurality of access openings 246 to assist in removing substantially all of the liquid within the vial 210.

[0170] Figures 7-12 illustrate another embodiment of the adapter 300. The adapter 300 is similar or identical to the adapter 200 described above in many respects. Accordingly, the numbers used to identify the features of the adapter 200 are incremented by only 100 to identify similar features of the adapter 300. This numbering convention generally applies to other figures as well. Any component or step disclosed in the embodiments of this specification can also be used in other embodiments.

[0171] In some embodiments, the adapter 300 includes a piercing member 320, a cap connector 330, a connector interface 340, and a regulator assembly 350. Further details and examples regarding some embodiments of the piercing member 320, the cap connector 330, and the connector interface 340 are presented in Patent Document 4, which is hereby incorporated by reference in its entirety and forms a part of the specification. For clarity, the vial 210 is not shown. The adapter 300 can be fitted to the vial 210 in a manner similar to the adapter 200. For example, when the adapter 300 is fitted to the vial 210, the piercing member 320 passes through the septum 216 and enters the inside of the vial 210.

[0172] In some embodiments, for example, in the illustrated embodiment, the cap connector 330 includes a body portion 380 having a central portion 381 (which may be curved) and one or more tabs 382 (which may be opposed) attached to the central portion 381. Each of the tabs 382 can be supported at its proximal end by the central portion 381 of the body portion 380. As shown, the distal ends of the tabs 382 can be unrestricted so as to be able to deflect the tabs outwardly.

[0173] The body portion 380 including the central portion 381 and the tabs 382 can help removably secure the vial adapter 300 to the outer surface of the vial 210 and can help facilitate removal of the vial adapter 300 from the vial 210. In some embodiments, the body portion 380 defines only one tab 382, opposite the pair of opposed tabs 382, and the single tab is configured to removably secure the vial adapter 300 to the outer surface of the vial 210 and to facilitate removal of the vial adapter 300 from the vial 210. The single tab 382 can take a suitable configuration, including those described herein.

[0174] In some configurations, such as the configuration illustrated in FIG. 7A, the piercing member 320 is supported by the body portion 380. As shown, the piercing member 320 may project distally from the central portion 381 of the body portion 380. The piercing member 320 can include an access flow path 345 and a regulator flow path 325. In some embodiments, the regulator flow path 325 begins at the distal regulator opening 328a, generally passes through the piercing member 320, passes through a lumen 326 that extends radially outwardly from the connector interface 340, and terminates at the proximal regulator opening 328 (FIG. 8). In some cases, the lumen 326 extends radially outwardly from the connector interface 340 in only one direction. In some cases, the lumen 326 extends radially outwardly from the connector interface 340 in a plurality of directions, for example, two opposing directions.

[0175] In some embodiments, the lumen 326 includes a barrier 383, such as a wall, cap, plug, dam, cork, partition, or other. In other configurations, the barrier 383 is configured to allow fluid to flow across the barrier 383. For example, in some cases, the barrier 383 is a filter, such as a hydrophobic or activated carbon filter. In some configurations, the barrier is configured to inhibit or prevent fluid from flowing across the barrier. For example, in some cases, the barrier is a continuous wall. In some such configurations, the barrier 383 blocks the regulated fluid from exiting the adapter 300.

[0176] The regulator assembly 350 can include a coupling portion 352, an attachment member 384, and a bag 354. In some cases, the bag includes a filling material (not shown), such as the filling material 254 described above. The bag 354 can include a bag opening 357, which is shown as a linear slit, but can take almost any form of opening within the bag. In some configurations, the bag 354 is made from a plurality of sheets of material that are connected (e.g., heat-sealed) around the perimeter. In some such configurations, as shown in FIG. 8, a peripheral ridge 354a is formed on the bag 354 by a sealing operation. In some cases, the bag 354 is made from a balloon having a narrowed neck (such as a "4 Inch Round" balloon produced by Pioneer Balloon Company of Wichita, Kansas), the neck is removed, and the bag 354 is heat-sealed around the perimeter to surround the volume portion therein (except for the bag opening 357). In some cases, when the neck is removed, a flat, cut-off, or otherwise asymmetric portion of the bag 359 is formed, as shown in FIG. 7.

[0177] In some embodiments, the attachment member 384 connects the coupling portion 352 to the bag 354. For example, in some cases, the attachment member 384 includes a double-sided adhesive, e.g., a member having one adhesive surface facing the coupling portion 352 and one adhesive surface facing the bag 354. In the illustrated embodiment, the attachment member 384 includes an adhesive first surface 384a and an adhesive second surface 384b. As shown, the attachment member 384 can include an opening 384c. In some embodiments, the attachment member 384 is about 0.015 inches thick. In some embodiments, the thickness of the attachment member 384 is at least 0.01 inches and / or about 0.03 inches or less.

[0178] In some embodiments, the securing member 384 is made of a flexible material that can provide elasticity, for example, to the connection between the securing member 384, the coupling portion 352, the securing member 384, and the bag 354. Such elasticity allows the coupling portion 352 to be moved slightly relative to the bag 350. Similarly, such elasticity can reduce the possibility that the bag 354 will tear, break, or otherwise be damaged during operation of the regulator assembly 350, such as during the process of connecting the regulator assembly 350 to the rest of the adapter 300. In some configurations, the securing member 384 is a foam (e.g., urethane, polyethylene, or other material), a non-rigid plastic, rubber, paper, or cloth (e.g., cotton) material. In some aspects, the securing member 384 consists of a double-sided foam tape.

[0179] In some cases, the coupling portion 352 includes a base 385 and a cover 386, which can further include an outer surface 386a (FIG. 8). In some embodiments, the securing member 384 is configured to adhere to or otherwise connect to the outer surface 386a. In some embodiments, the securing member 384 is configured to adhere to or otherwise connect to the bag 354. The connection between the securing member 384 and the outer surface 386a, and further the connection between the securing member 384 and the bag 354, is substantially fluid-tight (e.g., airtight) to prevent fluid leakage through the coupling portion 352 and the bag 354. In some embodiments, the connections between the securing member 384 and the coupling portion 352, and between the securing member 384 and the bag 354, are substantially permanent and are not intended to be separated once these components are connected. In some embodiments, the connections between the securing member 384 and the coupling portion 352, and between the securing member 384 and the bag 354, are configured to be temporary or detachable.

[0180] As shown in FIG. 8, the filter 360 can be housed between the base 385 and the cover 386. The cover 386 can be substantially sealingly received by the base 385 such that substantially all of the fluid permitted to flow through the filter 360 flows through the opening 387 formed within the cover 386. The base 385 and the cover 386 can be formed from any suitable material, such as plastic or metal. In some embodiments, the perimeter of the coupling portion 352 defines a non-circular shape, such as a square, triangle, polygon, or other suitable or desired shape.

[0181] The cover 386 can be press-fitted onto the base 385 using an adhesive, ultrasonic welding, or some other similar or suitable means, or attached in some other way. For example, as illustrated in FIG. 12, the cover 386 can be attached to the base 385 by one or more ultrasonic welds 388. The cover 385 and the base 386 can be joined together such that the annular protrusion 389 of the cover 385 is adjacent to the annular protrusion 390 on the base 385. The protrusion 390 can have a stepped or extended lip portion 390a that can overlap with the protrusion 389 formed on the cover 386 in the assembled configuration. The base 385 and the cover 386 can be made from various materials, such as metal or plastic. In some cases, the base 385 and the cover 386 are made from polycarbonate plastic.

[0182] In some embodiments, the cross-sectional area of the filter 360 is substantially larger than the cross-sectional area of the proximal regulator opening 328. Such a configuration increases the rate at which the regulating fluid flows through the filter 360, thereby providing sufficient regulating fluid to compensate for the introduction or withdrawal of fluid to or from the vial 210. As described above, providing sufficient regulating fluid can suppress or avoid the pressure gradient (e.g., vacuum) between the inside and outside of the vial, and can also reduce or eliminate the restoring force applied to the plunger of the syringe. In some embodiments, the cross-sectional area of the filter 360 is at least about 5 times larger than the cross-sectional area of the proximal regulator opening 328. In some embodiments, the cross-sectional area of the filter 360 is from about 2 times to about 9 times larger than the cross-sectional area of the proximal regulator opening 328, or within any range of values from any value within these ranges. Similarly, in some embodiments, the cross-sectional area of the filter 360 may be about 400 times larger than the cross-sectional area of the distal regulator opening 328a. In some embodiments, the cross-sectional area of the filter 360 is from about 100 times to about 250 times larger, from about 250 times to about 400 times larger, from about 400 times to about 550 times larger than the cross-sectional area of the distal regulator opening 328a, or within any range of values from any value within these ranges.

[0183] The filter 360 can be configured to remove or reduce particulate matter such as dirt or other debris, pathogens, viruses, bacteria, and / or other forms of contamination from the fluid flowing into the vial adapter 300. The filter 360 can be formed from any suitable filter material. In some embodiments, the filter 360 may be hydrophobic and may have an average pore size of about 0.1 micron, or from about 0.1 micron to about 0.5 micron.

[0184] As illustrated in FIG. 9, in some configurations, the coupling 352 can be received within the proximal regulator opening 328. In some embodiments, a protrusion 385a (e.g., a boss) extending from the base 385 is configured to be received substantially sealingly within or on the outer periphery of the proximal regulator opening 328. The protrusion 385a can generally define a regulator pathway. In some embodiments, the protrusion 385a is press-fit into the proximal regulator opening 328 to form a generally sealed connection between the protrusion 385a and the proximal regulator opening 328. In some embodiments, an adhesive, welding, or other material or feature can be used to provide a connection between the protrusion 385a and the proximal regulator opening 328. In some cases, the protrusion 385a and the proximal regulator opening 328 are affixed with a solvent. The protrusion 385a can be sized and configured to have a sufficient wall thickness and diameter to ensure that the protrusion 385a does not accidentally break during use by inadvertently contacting the coupling 352. In some embodiments, the regulator pathway can be in fluid communication with the regulator flow path 425 when the protrusion 385a is connected to the proximal regulator opening 328.

[0185] The opening 387a can be formed to pass through the protrusion 385a such that fluid flowing between the base 385 and the cover 386 is filtered by the filter 360 before flowing through the opening 387 or 387a. The size of the opening 387a formed to pass through the protrusion 385a, and further the opening 387 formed within the cover 386, can be designed to ensure that a sufficient amount of fluid flow passes through the filter 360. The diameter of the proximal regulator opening 328 can be adjusted to correspond to any desired or suitable outer diameter of the protrusion 385a.

[0186] Referring to FIGS. 10, 11, and 12, it can be seen that the cover 386 can have a first inner annular protrusion 391 having one or more openings 391a therethrough, a second inner annular protrusion 392 having one or more openings 392a therethrough, and an outer annular protrusion 389. In some embodiments, when the cover 386 is assembled with the base 385 and the filter 360, the annular protrusions 389, 391, 392, and the openings 391a, 392a form a fixed volume of space 393 between the inner surface of the cover 386 and the surface of the filter 360, into which conditioning fluid can flow and circulate before or after passing through the filter 360. Similarly, the base 385 can have a first inner annular protrusion 394 having one or more openings 394a therethrough, a second inner annular protrusion 395 having one or more openings 395a therethrough, and an outer annular protrusion 390. In some embodiments, when the base 385 is assembled with the cover 386 and the filter 360, the annular protrusions 390, 394, 395, and the openings 394a, 395a form a fixed volume of space 396 between the inner surface of the base 386 and the surface of the filter 360, into which conditioning fluid can flow and circulate before or after passing through the filter 360. In some configurations, the conditioning fluid can access substantially the entire surface area of the filter 360.

[0187] In some embodiments, the regulating fluid may flow into the space 393 defined between the cover 386 and the filter 360 through the opening 387 formed in the cover 386, pass through the filter 360, flow into the space 395 defined between the filter 360 and the base 385, pass through the opening 385a formed in the base 385, pass through the proximal regulator opening 382, and flow into the regulator flow path 325 formed in the vial adapter 300. Similarly, in some embodiments, the regulating fluid may pass through the regulator flow path 325 formed in the vial adapter 300, pass through the proximal regulator opening 382, pass through the opening 385a formed in the base 385, flow into the space 395 defined between the filter 360 and the base 385, pass through the filter 360, flow into the space 393 defined between the cover 386 and the filter 360, and flow through the opening 387 formed in the cover 386. In some cases, the opening 387 is in fluid communication with the outside air.

[0188] In some cases, the annular protrusions 390, 394, 395 are configured to hold the shape and position of the filter 360 relative to the base 385 and the cover 386. For example, the annular protrusion 390 can be configured to maintain the filter 360 at approximately the radial center of the base 385 and the cover 386, thereby reducing the probability that the fluid passes around (rather than through) the filter 360. In some configurations, the annular protrusions 394, 395 are configured to substantially suppress the filter 360 from becoming concave when the regulating fluid passes through the filter 360, thereby reducing the possibility that the filter 360 is torn or otherwise damaged.

[0189] In some embodiments, the adapter 300 has a modular configuration. Such a configuration can, for example, increase productivity and improve user convenience by standardizing one or more components of the adapter 300. For example, in some cases, the configurations of the piercing member 320, the cap connector 330, the connector interface 340, and the coupling portion 352 are substantially unchanged regardless of the volume of fluid transferred between the medical device and the vial 210. By performing such standardization, for example, the number of unique components to be purchased, stored, and inventoried can be reduced while maintaining the functionality of the adapter 300.

[0190] In some modular embodiments, the adapter 300 includes a first portion (e.g., the piercing member 320, the cap connector 330, the connector interface 340, and the coupling portion 352, i.e., as shown in FIG. 9) and a second portion (e.g., the bag 354). In some embodiments, the first portion is separated from the second portion and spaced apart in a first arrangement configuration and is connected to the second portion in a second arrangement configuration. In some embodiments, the various configurations (e.g., sizes) of the bag 354 can be matched with the common configuration of the remaining portion of the adapter 300. For example, in some embodiments, the 20 mL, 40 mL, and 60 mL configurations of the bag 354 are each connectable to the common configuration of the remaining portion of the adapter 300. In some embodiments, the configuration of the bag 354 is selectable without changing the remaining portion of the adapter 300. In some cases, the configuration of the bag 354 is selected based on the volume of fluid transferred between the medical device (e.g., a syringe) and the vial 210. For example, if approximately 25 mL of fluid is transferred from the medical device into the vial 210, a configuration of the bag 354 that can accommodate at least approximately 25 mL of fluid can be selected and connected to the remaining portion of the adapter 300, but if it is determined that a different volume of fluid is transferred from the medical device into the vial 210, the selection of the bag 354 can be changed without changing the remaining portion of the adapter 300.

[0191] Some modular embodiments can supply filtered or otherwise purified regulated fluid without connecting to the bag 354. For example, in some embodiments, the opening 387 of the cover 386 of the joint 352 is in fluid communication with the outside air, so that when the perforated member 320 is disposed in the vial 210 and the fluid is drawn through the access flow path 345, the filtered air is supplied through the joint 352, through the regulator flow path 325, and into the vial 210. In some cases, the adapter 300 does not include the bag 354 and / or the fixing member 384. In some embodiments, the lumen 326 is configured to connect to a source of regulated fluid that has been filtered or otherwise purified. For example, the lumen 326 can be configured to connect to a tube in fluid communication with a tank of sterilized air.

[0192] In some embodiments, the process of manufacturing the vial adapter 300 includes the step of forming the perforated member 320, the cap connector 330, and the connector interface 340 in a first assembly. For example, in some embodiments, the perforated member 320, the cap connector 330, and the connector interface 340 are produced in the same operation (e.g., molding, machining, or other process). The process can also include the step of forming the joint 352. For example, in some configurations, the base 385 and the cover 386 are assembled with the filter 360 therebetween as described above. In some embodiments, the process also includes the step of fitting the joint 352 with the lumen 326 as shown in FIG. 9. Further, the process can include the step of connecting the fixing member 384 to the outer surface 386a of the cover 386. In some cases, the fixing member 384 is connected to the bag 354. As shown in FIG. 7, the lumen 326, the opening 387a in the base, the opening 387 in the cover 386, and the bag opening 357 can be aligned so that the regulated fluid can flow between the vial 210 and the bag 354.

[0193] In some cases, the process of manufacturing the vial adapter 300 can, for example, enable the production of the adapter 300 in individual sub-assemblies, thereby improving productivity. For example, the first sub-assembly includes a piercing member 320, a cap connector 330, and a connector interface 340, the second sub-assembly includes a coupling portion 352 (base 385, cover 386, and filter 360), and the third sub-assembly can include a bag 354 and a securing member 384. Of course, other sub-assemblies are contemplated, for example, the second sub-assembly can include a coupling portion 352 and a securing member 384. In some cases, one or more of the sub-assemblies are supplied separately to a user (e.g., a healthcare provider).

[0194] Figures 13, 14, and 15 illustrate another embodiment of an adapter 400. The adapter 400 may have components or parts that are the same as or similar to the components or parts of other vial adapters disclosed herein. In some embodiments, the adapter 400 includes a piercing member 420, a cap connector 430, a connector interface 440, and a regulator assembly 450. In the illustrated embodiment, the cap connector 430 includes a platform 439.

[0195] The piercing member 420 includes a sheath 422 having a distal end 423. As shown, the piercing member 420 is relatively short (compared to the piercing member 220 of FIGS. 5 and 6), and thus, as described above, it can be made stronger and be more likely to extract fluid from the neck region of the vial 210 when the vial 210 is inverted. Also, as shown, the piercing member 420 has an access flow path 445 and a regulator flow path 425, and each of the access flow path 445 and the regulator flow path 425 terminates near the distal end 423 of the piercing member 420.

[0196] As shown, the cap connector 430 can include a lumen 426, whereby the regulator flow path 425 follows a path through the cap connector 430. The lumen 426 radially outwardly penetrates the connecting member 429. The illustrated connecting member 429 is a slip fit flange, although many other configurations are contemplated, such as threads, press fits, barb connections, or other means. A filter 460 that can be hydrophobic is disposed within the lumen 426. The regulator assembly 450 includes an annular washer 451, a joint 452, a bag 454, and a filler 456. The joint 452 includes a passage 453 that penetrates the joint 452 and a flange 461 that extends outwardly. The joint 452 is positioned via the bag opening 457 together with the flange 461 inside the bag 454. The washer 451 is positioned outside the bag 454 and generally faces the flange 461. In some cases, the bag 454 is compressed between the washer 451 and the flange 461 or held in some other manner. For example, in some embodiments, threads are cut on the outside of the joint 452, and correspondingly threaded in the central portion of the annular washer, whereby the washer can be screwed onto the joint 452 and the bag 454 can be pushed between the washer 451 and the flange 461. As shown, the joint 452 is received within the connecting member 429, whereby the bag 454 is in fluid communication with the vial 210 through the regulator flow path 425.

[0197] In FIG. 13, the bag 454 is shown in an initial state, which may be, for example, the state of the bag 454 when the regulator assembly 450 is first connected to the cap connector 430. The filler 456 can contain a fixed volume of regulating fluid, such as sterilized air. As shown, in this embodiment, the filler 456 substantially fills the volume of the bag 454 in this state. In some aspects, the bag 454 substantially follows the shape of the filler 456.

[0198] In FIG. 14, the bag 454 is shown in at least a partially inflated state, which may be the state of the bag 456, for example, after a fixed volume of fluid has been introduced into the vial 210 through the access channel 445. Such introduction of the fluid causes a fixed volume of regulating fluid within the vial 210 to enter the bag 454 through the regulator channel 425, lumen 426, filter 460, connecting member 429, passage 453, and bag opening 457, generally as indicated by the arrows in FIG. 14. In many embodiments, the filter 460 substantially blocks the liquid within the vial 210 from entering the bag 454. As shown, such transfer of the regulating fluid can expand the bag 454. In some embodiments, for example, in the illustrated embodiment, the filler 456 is configured to expand along with the expansion of the bag 454.

[0199] In FIG. 15, the bag 454 is shown in at least a partially deflated state, which may be the state of the bag 456, for example, after a fixed volume of fluid has been withdrawn from the vial 210 through the access channel 445. Such withdrawal of the fluid causes a fixed volume of regulating fluid within the bag 454 to enter the vial 210 through the bag opening 457, passage 453, connecting member 429, filter 460, lumen 426, and regulator channel 425, generally as indicated by the arrows in FIG. 15. As shown, such transfer of the regulating fluid can at least partially deflate the bag 454. In some embodiments, for example, in the illustrated embodiment, the filler 456 is configured to be compressed as the bag 454 deflates. As shown, in some arrangements, the filler 456 is configured to provide a structural framework for the bag 454 (even in the deflated state), which can prevent the bag 454 from sagging. In some embodiments, the bag 354 comprises a material having sufficient rigidity to prevent the bag 454 from sagging.

[0200] In various embodiments, the adapter 400 is configured to transition between the various states illustrated in FIGS. 13, 14, and 15. In some cases, the adapter 400 begins in the state illustrated in FIG. 13 and transitions to the state illustrated in FIG. 14 (e.g., fluid is introduced from the syringe into the vial 210). In some cases, the adapter 400 begins in the state illustrated in FIG. 13 and transitions to the state illustrated in FIG. 15 (e.g., fluid is withdrawn from the vial 210 into the syringe). In some cases, the adapter 400 begins in the state illustrated in FIG. 13, transitions to the state illustrated in FIG. 14, and then transitions to the state illustrated in FIG. 15 (e.g., fluid is introduced from the syringe into the vial 210 and then a volume of fluid larger than that introduced is withdrawn from the vial 210 into the syringe). In some cases, the adapter 300 begins in the state illustrated in FIG. 13, transitions to the state illustrated in FIG. 15, and then transitions to the state illustrated in FIG. 14 (e.g., fluid is withdrawn from the vial 210 into the syringe and then a volume of fluid larger than that withdrawn is introduced into the vial 210).

[0201] FIG. 16 illustrates an embodiment of an adapter 500 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. Adapter 500 includes a filter 560 disposed within a coupling 552. In addition thereto, adapter 500 includes a packing 556 having a substantially round cross-section. In some embodiments, packing 556 is an ellipsoid of revolution. In other embodiments, packing 556 is substantially cylindrical. Also, adapter 500 includes a coupling 552 having a bag 554 and a flange 561. As shown, bag 554 can be connected to flange 561, for example, by welding, adhesion, or other means. In some embodiments, packing 556 is also connected to flange 561, thereby facilitating placement of bag 554 in a stationary state relative to coupling 552. In some arrangements, packing 556 serves as a secondary filter for gas passing between vial 210 and bag 554. For example, in some cases, some impurities that pass through filter 560 are captured by packing 556 before such impurities enter bag 554. In some arrangements, packing 556 serves as a pre-filter to filter 560, thereby reducing the amount of impurities passing through filter 560 and entering vial 210.

[0202] FIG. 17 illustrates one embodiment of an adapter 600 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. Adapter 600 includes a bag 654 having an internal structure, either instead of or in addition to a filling material. Such an internal structure can, for example, inhibit or prevent the bag 654 from completely collapsing in order to provide an initial supply of conditioning fluid. In the illustrated embodiment, the internal structure includes a plurality of inwardly extending elongate members 662. In some configurations, the elongate members are generally flexible. In other configurations, the elongate members are substantially rigid. As shown, the elongate members 662 contact and interfere with each other as the bag 654 collapses, thereby preventing the bag 654 from completely collapsing. In some embodiments, the conditioning fluid is stored within a network of voids 663, which serves as an initially readily available source for supplying the conditioning fluid to the vial 210. In some such arrangements, the voids 663 are disposed between the elongate members 662.

[0203] Other embodiments include other various types of internal structures. For example, in some embodiments, the internal structure includes a plurality of inwardly projecting bumps, ridges, rings, hemispheres, or the like. In some embodiments, the initial structure divides the bag 654 into a number of segments. For example, in some configurations, the internal structure is a membrane that divides the bag 654 into a first portion and a second portion, each of which can contain a certain amount of conditioning fluid. In some arrangements, when the volume of the bag 654 changes, the amount of conditioning fluid in the first portion changes (e.g., decreases) faster than that in the second portion. In some configurations, the first portion and the second portion are fluidly connected by a valve. In some such configurations, it is permitted by the valve for the conditioning fluid to flow from the second portion into the first portion after a desired pressure differential between these portions is achieved. In some cases, the first portion fully expands or collapses before the second portion begins to expand or collapse.

[0204] Another embodiment of the adapter 700 is illustrated in FIG. 18. The adapter 700 may have components or parts that are the same as or similar to those of other vial adapters disclosed herein. In the illustrated embodiment, the adapter 700 includes a piercing member 720, a cap connector 730, a connector interface 740, and a plurality of regulator assemblies 750, 750'. In some embodiments, the expansion assemblies 750, 750' each include a bag 754, 754' and a filling material 756, 756'. In some embodiments, such as the illustrated embodiment, the piercing member 720, the cap connector 730, and the connector interface 740 are substantially monolithic. In some embodiments, each bag 754, 754' is connected to the cap connector 730 by an adhesive, a pipe clamp, a retaining ring, or the like.

[0205] In some configurations, the plurality of regulator assemblies 750, 750' supply a greater total volume of regulated fluid than a single regulator assembly. In some embodiments, the volume of the regulated fluid is divided among the plurality of regulator assemblies 750, 750', so that the respective sizes of the regulator assemblies 750, 750' (and thus the adapter 600 as a whole) are reduced compared to, for example, an embodiment of a single regulator assembly. Further, the regulator assemblies 750, 750' can be arranged at symmetric intervals relative to the remainder of the adapter 600, thereby increasing stability and reducing the likelihood of tipping over.

[0206] Various embodiments have various numbers of regulator assemblies. For example, some embodiments have three or more regulator assemblies. Some embodiments have at least four regulator assemblies. Generally, the regulator assemblies are arranged radially and equidistantly around the adapter 700 or positioned in some other manner that improves the stability of the adapter 700.

[0207] In some configurations, when the piercing member 720 is disposed within the vial 210, the interiors of the regulator assemblies 750, 750' are in fluid communication with the vial 210 via outwardly extending passages 728, 728' and regulator flow paths 725. Thus, when fluid is withdrawn from the vial 210 through the access flow path 745, regulated fluid flows from each of the regulator assemblies 750, 750' into the vial 210, thereby maintaining an equilibrium state within the vial 210. Similarly, when fluid is introduced into the vial 210 through the access flow path 745, regulated fluid flows from the vial 210 into each of the regulator assemblies 750, 750', thereby maintaining an equilibrium state within the vial 210.

[0208] In some embodiments, the regulator assemblies 750, 750' operate in tandem, e.g., substantially simultaneously and exhibiting substantially equal volume changes. For example, in some cases, when about 5.0 mL of fluid is withdrawn from the vial 210, about 2.5 mL of regulated fluid flows from the regulator assembly 750 into the vial 210, and simultaneously, about 2.5 mL of regulated fluid flows from the regulator assembly 750' into the vial 210.

[0209] In some embodiments, the regulator assemblies 750, 750' do not operate in tandem. For example, in some arrangements, the regulator assemblies 750, 750' operate in series. In some such cases, the first regulator assembly fully expands or fully collapses before the second regulator assembly begins to expand or collapse. In some cases, the first regulator assembly first changes volume and then, after conditions are met, the second regulator assembly changes volume. In some cases, the condition is a specific pressure difference (e.g., at least about 1 psi, at least about 2 psi, or at least about 5 psi) between the interior of the second regulator assembly and the vial 210. In some configurations, a valve (e.g., a duckbill valve) is configured to open when the condition is met.

[0210] FIG. 19 illustrates an embodiment of an adapter 800 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. The adapter includes a regulator assembly 850 having a seal 864, a counterweight 831, and a keyed joint 852. As used herein, "keyed joint" is used in its broad ordinary meaning and includes a joint having a shape configured to mate with another joint in one or more orientations. Further, the illustrated embodiment of the adapter 800 is filler-free. In some such embodiments, the adapter 800 includes a bag 854 having sufficient rigidity to substantially prevent the bag 854 from collapsing completely (e.g., enclosing a volume of approximately zero).

[0211] In some embodiments, the seal 864 is configured to inhibit or prevent regulated fluid from unintentionally exiting the regulator assembly 850 and / or outside air from unintentionally entering the regulator assembly 850. For example, in the illustrated embodiment, the seal 864 generally blocks the initial volume of regulated fluid (which may be under a pressure higher than ambient pressure) contained within the regulator assembly 850 from leaking into the ambient environment before the regulator assembly 850 is connected to the remainder of the adapter 800. In addition, the seal 864 can generally block outside air, which may contain microorganisms or impurities, from entering the regulator fluid 850.

[0212] In the illustrated embodiment, seal 864 comprises a membrane with slit 865. In some cases, for example, when regulator assembly 850 is connected to adapter 800 and fluid is introduced or withdrawn through access flow path 845, slit 865 opens due to the pressure differential between vial 210 and bag 854, thereby allowing regulated fluid to flow between regulator assembly 850 and vial 210. Various other types and configurations of seal 864 are contemplated. For example, in some embodiments, seal 864 is a duckbill valve. As another example, in some embodiments, seal 864 comprises a substantially continuous (e.g., slitless) membrane configured to rupture at a particular pressure differential (e.g., at least about 1 psi, at least about 2 psi, at least about 5 psi).

[0213] In the illustrated embodiment, seal 864 is disposed within joint 852. In some other embodiments, seal 864 is disposed in an alternative location. For example, seal 864 may be disposed within passage 826. In some arrangements, seal 864 is configured to be removed or detached from adapter 800 when fluid is introduced or withdrawn through access flow path 845. For example, in some cases, when fluid is withdrawn from vial 210 through access flow path 845, seal 864 is removed from regulator flow path 825, thereby allowing regulated fluid to flow into vial 210. In some such cases, seal 864 is a tab or sticker. In some such cases, seal 864 separates from adapter 800 and drops into vial 210.

[0214] As shown, some configurations of the adapter 800 include a cap connector 830, which in turn includes a counterweight 831. The counterweight 831 can, for example, enhance the stability of the fitted vial 210 and the adapter 800 and reduce the likelihood that this combination will tip over. In some arrangements, the counterweight 831 is configured to place the center of gravity of the adapter 800 substantially on the centerline along the axis of the adapter 800 when the regulator assembly 850 is connected to the adapter 800. In some arrangements, the counterweight 831 has a mass approximately equal to the sum of the mass of the outwardly extending connecting member 829 and the mass of the regulator assembly 850 in its initial configuration. In some cases, the counterweight 831 includes the mass of material generally disposed on the side of the axis centerline opposite the regulator assembly 850. In some cases, the counterweight 831 includes a region of less mass (e.g., a groove, notch, or thinner wall) on the same side of the axis centerline as the regulator assembly 850.

[0215] As shown in FIGS. 20A - 20F showing cross - sectional views of various examples of the coupling portion 852, the coupling portion 852 may be key - grooved or have some other special shape. The connecting member 829 may typically be correspondingly key - grooved or have some other special shape. Such a configuration may be beneficial for sending, controlling, or limiting signals to the regulator assembly 850 that can be connected to a given adapter 800. For example, a relatively large regulator assembly 850 (e.g., initially containing at least about 100 mL of regulating fluid) can be key - grooved so as not to fit with a relatively small adapter 800 (e.g., having a size and configuration that mates with a vial 210 containing less than about 3 mL of fluid). In some cases, the combination of a large regulator assembly and a small vial may be unstable, have a strong tendency to tip over, and thus be undesirable. However, the size of the key - groove of the regulator assembly 850 that only fits with an adapter 800 of appropriate size can reduce or avoid such problems. In various embodiments, the coupling portion 852 can be male or female, and the connecting member 829 can be correspondingly female or male.

[0216] Various types of key - grooved coupling portions 852 are contemplated. In some embodiments, the shape of the coupling portion 852 inhibits or prevents rotation of the regulator assembly relative to the remainder of the adapter 800. For example, as shown in FIG. 20A, the coupling portion 852 may be substantially rectangular. The connecting member 829 can correspondingly be rectangular and engageably fit with the coupling portion 852. Similarly, as shown in FIG. 20B, the coupling portion 852 may be substantially rhombic. The connecting member 829 can correspondingly be rhombic and engageably fit with the coupling portion 852. Similarly, as shown in FIG. 20C, the coupling portion 852 may include notches, grooves, bumps, or the like. The connecting member 829 can correspondingly be shaped to engageably fit with the notches, grooves, bumps, or the like of the coupling portion 852.

[0217] In some embodiments, the shape of the coupling portion 852 defines the orientation of the regulator assembly 850 relative to the remainder of the adapter 800. For example, in the embodiment illustrated in FIG. 20C, the coupling portion 852 (and thus the regulator assembly 850) is configured to mate with the connecting member 829 in only two possible orientations. In some embodiments, such as in the embodiments illustrated in FIGS. 20D, 20E, and 20F, the coupling portion 852 (and thus the regulator assembly 850) is configured to mate with the connecting member 829 in only a single possible orientation.

[0218] Some embodiments provide feedback that warns the user that engagement by mating of the coupling portion 852 and the connecting member 829 has been achieved. For example, in some cases, the connection between the coupling portion 852 and the connecting member 829 includes a detent mechanism, such as a ball detent, that can provide a tactile indication of engagement. Some embodiments include an acoustic signal, such as a click, snap, or similar sound, to indicate engagement.

[0219] In some embodiments, the coupling portion 852 and the connecting member 829 are linked to inhibit or prevent subsequent separation. For example, some arrangements include an adhesive in one or both of the coupling portion 852 and the connecting member 829 to bond the coupling portion 852 and the connecting member 829 together upon engagement by mating. In some other arrangements, a one-way snap feature is engaged upon engagement by mating of the coupling portion 852 and the connecting member 829.

[0220] FIG. 21 illustrates another embodiment of adapter 900. Adapter 900 may have components or parts that are the same as or similar to those of other vial adapters disclosed herein. In the illustrated embodiment, adapter 900 includes a piercing member 920, a cap connector 930, a connector interface 940, and a regulator assembly 950. As shown, separate from regulator flow path 925, piercing member 920 is not substantially hollow, thereby adding strength and rigidity for piercing a vial having a stiff or non-bending septum. Such a configuration for piercing member 920 can also enhance productivity.

[0221] In the illustrated embodiment, regulator assembly 950 includes a junction 952, a bag 954, a filter 960, and a check valve 966. Various types and kinds of check valves can be used, such as duckbill valves, flapper valves, diaphragm check valves, lift check valves, or other valves. In some configurations, check valve 966 permits fluid to flow into junction 952 from the surrounding environment. Such a configuration can supply regulated fluid to vial 210 even when there is substantially no regulated fluid in bag 954. Such a scenario can occur, for example, when bag 954 contains a volume V1 of regulated fluid and a volume V2 of fluid is withdrawn from vial 210 via access flow path 945 and V1 is less than V2. Thus, in such a scenario, bag 954 will have insufficient regulated fluid to compensate for the fluid withdrawn from vial 210. To supply the shortfall of regulated fluid (e.g., the difference between V2 and V1), check valve 966 can permit outside air to enter vial 210 via adapter 800.

[0222] Generally, check valve 966 is opened by a specific pressure gradient (e.g., at least about 1 psi, at least about 2 psi, at least about 5 psi) from one side of the valve to the other side, also referred to as the cracking pressure. As described above, when fluid is withdrawn from vial 210, the pressure within vial 210 decreases. Generally, the regulatory fluid within bag 954 maintains the equilibrium state within vial 210, but when the volume of the regulatory fluid within bag 954 is depleted, the pressure within vial 210 may begin to decrease. However, when the pressure difference between the inside and outside of vial 210 exceeds the cracking pressure of check valve 966, check valve 966 opens, allowing outside air to enter vial 210 (via adapter 900), and thus substantially maintaining the equilibrium state therein. Accordingly, check valve 966 enables easier withdrawal of fluid from vial 210 even when bag 954 is completely deflated.

[0223] FIG. 22 illustrates one embodiment of an adapter 1000 that can have components or portions that are the same as or similar to other vial adapter components or portions disclosed herein. Adapter 1000 includes a first check valve 1066 and a second check valve 1067. Similar to check valve 966 described above in connection with adapter 900, first check valve 1066 can compensate for a deficiency of regulatory fluid with outside air. Accordingly, when regulator assembly 1050 is completely deflated, first check valve 1066 can facilitate maintaining the equilibrium state within vial 210. In some cases, first check valve 1066 is positioned within lumen 1026. In other cases, first check valve 1066 is disposed within junction 1052.

[0224] As shown, in some arrangements, the second check valve 1067 is positioned to allow regulated fluid to enter the regulator assembly 1050 and block such fluid from exiting the regulator assembly 1050. Such a configuration can form a trap for aerosolized or gaseous components of the contents of the vial 210. In some cases, when fluid is introduced into the vial 210 through the access flow path 1045, the regulated fluid flows from the vial 210, through the regulator flow path 1025 and the filter 1060, through the second check valve 1067, and into the regulator assembly 1050. Since the second check valve 1067 inhibits or prevents such regulated fluid from exiting the regulator assembly 1050, as long as the regulator fluid contains harmful components, such components can be substantially trapped and disposed of within the regulator assembly 1050. In the illustrated embodiment, when fluid is withdrawn from the vial 210 through the access flow path 1045, the second check valve 1067 substantially blocks the regulated fluid from flowing out of the bag 1054, so the first check valve 1066 opens to supply regulated fluid (e.g., outside air) to the vial 210 and maintain the equilibrium state therein.

[0225] In some embodiments, such as the illustrated embodiment, the adapter 1000 includes a first check valve 1066 and a second check valve 1067. In some other cases, only the first check valve 1066 is provided. In some other cases, only the second check valve 1067 is provided.

[0226] As shown, in some configurations, the bag 1054 of the regulator assembly 1050 contacts the vial 210. This can allow, for example, the geometric shape of the extensive array of bags 1054. In some cases, in the fully expanded state, the bag 1054 contacts the vial 210. In other configurations, the bag 1054 remains spaced from the vial 210. This can, for example, reduce the stress on the bag 1054 and reduce the possibility that the structural integrity of the bag 1054 is compromised, for example, by a burr or label on the vial 210 puncturing the bag 1054.

[0227] FIG. 23 illustrates another embodiment of the adapter 1100. The adapter 1100 may have components or parts that are the same as or similar to those of the other vial adapters disclosed herein. In the illustrated embodiment, the adapter 1100 includes a piercing member 1120, a cap connector 1130, a connector interface 1140, and a regulator assembly 1150. In some configurations, the piercing member 1120 includes a first regulator opening 1168 that is in fluid communication with a regulator flow path 1125 and then in fluid communication with a second regulator opening 1169.

[0228] In the illustrated embodiment, the regulator assembly 1150 includes a bag 1154 and a filler 1156. However, in some implementations, the regulator assembly 1150 does not include the filler 1156. The filler 1156 is illustrated as being annular and having a triangular cross-section, but can take a variety of other configurations. In some embodiments, the bag 1154 is annular. In some embodiments, the bag 1154 has a proximal end 1168 with a proximal opening 1169 and a distal end 1170 with a distal opening 1171. In some arrangements, the distal end 1170 is connected in a substantially airtight engagement with the cap connector 1130, and the proximal end 1168 is connected in a substantially airtight engagement with the connector interface 1140. As shown, the regulator flow path 1125 and the extraction flow path 1145 can extend through part or all of the axial length of the bag 1154. Also as shown, the interior of the bag 1154 can be in fluid communication with the regulator flow path 1125 via a second regulator opening 1169. The bag 1154 can be provided with a regulated fluid, such as a sterilized gas.

[0229] In some arrangements, the regulator flow path 1125 includes portions that are substantially serpentine (e.g., winding, curved, undulating, or the like). Such a configuration can, for example, inhibit or prevent liquid in the vial 210 from flowing into the bag 1154 without using a filter to repel the liquid. In some embodiments, such as the illustrated embodiment, the regulator flow path 1125 includes a hairpin curve 1172, which reverses the direction of the fluid flowing within the regulator flow path 1125 (e.g., from the proximal direction to the distal direction). In some configurations, the regulator flow path 1125 is substantially sinusoidal in shape. In some embodiments, the regulator flow path 1125 extends distally beyond the second regulator opening 1169, thereby providing a drain pan 1173 for flowing liquid into the serpentine portion of the regulator flow path 1125.

[0230] In the illustrated embodiment, the bag 1154 is positioned substantially centered relative to the center on the axis of the adapter 1100. Such a configuration can, for example, improve the stability of the adapter 1100 and reduce the likelihood of tipping when the adapter 1100 is coupled to a vial (not shown). In some arrangements, such a configuration can reduce the radial size of the adapter 1100. In some embodiments, in a fully collapsed state, the bag 1154 has an axial height greater than the diagonal width. In some embodiments, the bag 1154 has an axial height greater than the diagonal width in a fully expanded state. In some embodiments, in a fully expanded state, the bag 1154 does not extend radially outward beyond the radially widest point of the cap connector 1130, thus providing a more compact adapter 1100. In other embodiments, in some states (such as a fully expanded state), the bag 1154 comprises the radially widest portion of the adapter 1100. In such embodiments, even if the adapter 1100 tips over, the bag 1154 is generally the first portion of the adapter 1100 that contacts another surface (e.g., a tabletop). In some such embodiments, the bag 1154 acts as a pillow, cushion, damper, or shock absorber to reduce the likelihood of damage to the adapter 1100 or the vial.

[0231] In various embodiments, the regulator assembly 1150 is positioned within a rigid housing (not shown), which can support the regulator assembly 1150, provide a structure for the regulator assembly 1150, and / or protect the regulator assembly 1150. For example, the rigid housing can inhibit or prevent the regulator assembly 1150 from bursting or otherwise being damaged. Some variations of the rigid housing have an internal space in which a portion of the regulator assembly 1150 is disposed. In some implementations, the regulator assembly 1150 is disposed entirely within the internal space. In some embodiments, a portion of the internal space is in fluid communication with the surrounding environment, such as via an opening in the rigid housing. Some embodiments of the rigid housing extend between the cap connector 1130 and the connector interface 1140.

[0232] As noted above, the bladder 1154 of the regulator assembly 1150 can contain a regulatory fluid. Some embodiments of the bladder 1154 contain the regulatory fluid prior to coupling the adapter 1100 and the vial 210. In some examples, the regulator assembly 1150 has a sufficient volume of regulatory fluid after coupling the adapter 1100 and the vial 210 (e.g., immediately thereafter). Some embodiments of the regulator assembly 1150 have a volume of regulatory fluid sufficient to compensate for a quantity of drug fluid withdrawn from the vial 210. For example, the bladder 1154 can contain approximately 5 mL of regulatory fluid to compensate for approximately 5 mL of drug fluid withdrawn from the vial 210. In some embodiments, at the time the adapter 1100 is coupled to the vial 210, the regulator assembly 1150 comprises a volume of regulatory fluid that is greater than the volume of the drug fluid within the vial 210. In some examples, the bladder 1154 contracts within the rigid enclosure as the regulatory fluid exits the bladder 1154.

[0233] In some embodiments, the bag 1154 can expand within the rigid housing. For example, when a certain amount of diluent fluid (e.g., saline) is introduced into the vial 210, the bag 1154 expands within the rigid housing and can receive a corresponding amount of conditioning fluid from the vial 210. In some examples, the bag 1154 expands completely within the rigid housing. In some variations, a portion of the bag 1154 extends out of the rigid housing when it expands, such that a portion of the bag does not fit within the internal space of the rigid housing.

[0234] Some examples of the bag 1154 expand and contract between a maximum size and a minimum size based on the volume of the conditioning fluid contained within the bag 1154. For example, in some variations of the regulator assembly 1150, the maximum size of the bag 1154 is large enough to include a volume that is equal to or greater than the volume of the vial 210. In some embodiments, at the maximum size, the bag 1154 has a volume that is at least about 25%, 50%, 75%, 99%, 200%, 300%, a value between these, or some other value of the volume of the vial 210. In some embodiments, the rigid housing is configured to at least partially contain the bag 1154 when the bag 1154 is at its maximum size. Some variations of the rigid housing are configured to completely contain the bag 1154 when the bag 1154 is at its maximum size. In some embodiments, the bag 1154 does not substantially contain any conditioning fluid at the minimum size. In some embodiments, at the minimum size, the bag 1154 has a volume that is at least about 0.1%, 1%, 5%, 10%, 25%, a value between these, or some other value of the volume of the vial 210.

[0235] FIG. 24 illustrates a further embodiment of the adapter 1200. The adapter 1200 may have components or parts that are the same as or similar to those of the other vial adapters disclosed herein. In the illustrated embodiment, the adapter 1200 includes a first piercing member 1220, a second piercing member 1220', a cap connector 1230, a connector interface 1240, and a regulator assembly 1250. In some embodiments, the first piercing member 1220 includes an access flow path 1245. In some embodiments, the second piercing member 1220' includes a regulator flow path 1225. In some arrangements, the regulator flow path 1225 passes through the cap connector 1230 at an angle (e.g., at least about 45°) with respect to a centerline on the axis of the adapter 1200. In various embodiments, the first piercing member 1220 and the second piercing member 1220' each pierce the septum of the vial 210 when the adapter 1200 is coupled to the vial 210. In some embodiments, the distal end of one or both of the first piercing member 1220 and the second piercing member 1220' is angled from one side to the opposite side.

[0236] As shown, the regulator assembly 1250 can include a bag 1254 that is in fluid communication with the fill material 1256 and the regulator flow path 1225. As shown, the bag 1254 can be annular, thereby enabling the adapter 1200 to have a center of gravity substantially on the centerline on the axis of the adapter 1200, and thus increasing stability.

[0237] FIG. 25A illustrates one embodiment of a storage tank 1350 that can be attached to the lumen 1326 of a vial adapter. As shown, the bag 1354 includes an internal chamber 1355. The bag 1354 is generally configured to extend, bend, unfold, or otherwise expand within the internal chamber 1355, and to contract or otherwise cause a change in internal volume. In some cases, the bag 1354 includes one or more folds, creases, or the like. In some embodiments, the bag 1354 is connected to the lumen 1326 of the vial adapter using an adhesive, pipe clamp, retaining ring, or other means. In some arrangements, the internal chamber 1355 of the bag 1354 is in fluid communication with the regulator flow path 1325, thereby allowing fluid to pass from the regulator flow path 1325 to the internal chamber 1355 and / or from the internal chamber 1355 to the regulator flow path 1325. Further, in some embodiments, the bag 1354 includes an internal filling material. The filling material can be made to prevent the bag 1354 from completely collapsing under ambient pressure. In some embodiments, the filling material can occupy a portion or substantially the entire internal volume of the internal chamber 1355.

[0238] According to some embodiments, at least a majority, or all or substantially all of the bag 1354 is housed within a rigid enclosure 1374. As shown, the bag 1354 is in fact almost entirely surrounded by the rigid enclosure 1374. In some configurations, the rigid enclosure 1374 has substantially the same shape as the bag 1354. In some embodiments, the rigid enclosure 1374 includes one or more ventilation holes 1375. As shown, the ventilation holes 1375 can be smaller than the outer diameter of the lumen 1326. In the illustrated embodiment, the rigid enclosure 1374 and the lumen 1326 are a single piece. In some embodiments, the rigid enclosure 1374 can be fixed to or removably attached to the lumen 1326.

[0239] In some embodiments, the storage tank 1350 includes an intermediate chamber 1376 defined by the space between the outer surface of the bag 1354 and the inner surface of the rigid enclosure 1374. According to some configurations, the intermediate chamber 1376 is in fluid or non-fluid communication with the surrounding environment of the storage tank 1350. In some embodiments, the connection between the bag opening 1357 and the lumen 1326 forms an airtight seal that can prevent fluid communication between the regulator flow path 1325 and the intermediate chamber 1376.

[0240] In some embodiments, the bag 1354 can be configured to expand when regulator fluid moves from the regulator flow path 1325 into the internal volume 1355 of the bag 1354 in response to fluid being injected into the container 10 via the exchange device 40. In some configurations, the expansion of the bag 1354 is limited by the size of the rigid enclosure 1374. In some embodiments, the bag 1354 is configured to contract when regulator fluid moves from the internal volume 1355 of the bag 1354 into the regulator flow path 1325 in response to fluid being withdrawn from the container 10 via the exchange device 40. In some embodiments, the expansion and contraction of the bag 1354 can assist in maintaining a substantially constant pressure within the container 10. In some embodiments, one or more vent holes 1375 within the rigid enclosure 1374 can assist in suppressing increases and decreases in pressure within the intermediate enclosure 1376 when the bag 1354 expands and contracts.

[0241] In some embodiments, the bag 1354 generally has a constant wall thickness T2. In some embodiments, the wall thickness T2 of the bag 1354 varies between the first side 1358 and the second side 1359 of the bag. In some embodiments, because the thickness of the bag 1354 is variable, the bag 1354 can be expanded in one or more controlled directions. For example, since the wall is thinner at the first side 1358 compared to the second side 1359, the first side 1358 can expand faster than the second side 1359. Such a variable expansion rate facilitates the translation of the second side 1359 of the bag 1354 away from the bag opening 1357 when the bag 1354 expands.

[0242] FIG. 25B illustrates one embodiment of a storage tank 1450 that can be attached to the lumen 1426 of the vial adapter. As shown, the storage tank 1450 can include an enclosure 1454. In some embodiments, the enclosure includes a first side 1458 and a second side 1450 that are connected to each other via an annular ring 1454A. The annular ring 1454A can be made of a flexible material that can be crumpled, folded, and / or stretched, for example. The first side 1458 and the second side 1459 of the enclosure 1454 can be made of a rigid or semi-rigid material. The enclosure 1454 can include an internal chamber 1455.

[0243] In some embodiments, the internal chamber 1455 is in fluid or non-fluid communication with the regulator flow path 1425. In such embodiments, fluid is permitted to pass between the regulator flow path 1425 and the internal chamber 1455 through an opening 1457 in the enclosure 1454. Further, in some embodiments, the enclosure 1454 includes an internal filler. The filler can be made to prevent the enclosure 1454 from being completely crushed under ambient pressure. In some embodiments, the filler occupies a portion or substantially the entire internal volume of the internal chamber 1455.

[0244] According to some embodiments, the annular ring 1454A of the enclosure is configured to expand, deploy, uncrinkle, and / or otherwise deform to increase the volume within the internal chamber 1455 in response to fluid being injected into the container 10 via the exchange device 40. In some embodiments, the annular ring 1454A is configured to crinkle, fold, compress, and / or otherwise deform to decrease the volume within the internal chamber 1455 in response to fluid being withdrawn from the container 10 via the exchange device 40. According to some embodiments, the expansion and contraction of the enclosure 1454 can assist in maintaining a substantially constant pressure within the container 10 and the internal chamber 1455.

[0245] In some embodiments, as shown, the first side portion 1458 of the enclosure 1454 is an integral part of the lumen 1426. In some embodiments, the first side portion 1458 of the enclosure 1454 can be fixedly or removably attached to the lumen 1426. The first side portion 1458 of the enclosure 1454 can be attached to the lumen 1426 in a hermetic sealing manner, thereby suppressing fluid leakage from the connection point between the first side portion 1458 and the lumen 1426. According to some embodiments, the annular ring 1454A of the enclosure 1454 is attached to the first side portion 1458 and the second side portion 1459 of the enclosure 1454 at the connection point 1452 via an adhesive or some other means that can form a hermetic seal between the internal chamber 1455 and the surrounding. In some configurations, the width W2 of the annular ring 1454A and the height H of the enclosure 1454 can vary in response to a desired volume displacement within the internal chamber 1455 when the enclosure 1454 expands and / or contracts.

[0246] FIG. 25C illustrates one embodiment of a storage tank 1550 that can be attached to the lumen 1526 of a vial adapter. As shown, the storage tank 1550 includes an enclosure 1554. In some embodiments, the enclosure 1554 includes a first side 1558 and a second side 1559. According to some configurations, the first side 1558 and / or the second side 1559 of the enclosure 1554 is made of a flexible material that can be deformed, for example, crumpled, folded, stretched, and / or otherwise deformed. In some embodiments, the first side 1558 and the second side 1559 of the enclosure 1554 are attached to each other via an annular ring 1554A. In some embodiments, the annular ring 1554A is made of a rigid or semi-rigid material. Further, the enclosure 1554 can include an internal chamber 1555.

[0247] In some embodiments, the first side 1558 of the enclosure 1554 is connected to the lumen 1526 of the vial adapter using an adhesive, a pipe clamp, a retaining ring, or other means. In some arrangements, the internal chamber 1555 of the enclosure 1554 is in fluid or non-fluid communication with the regulator flow path 1525, whereby fluid can pass between the regulator flow path 1525 and the internal chamber 1555. In some embodiments, the enclosure 1554 includes an internal filler. The filler can be made to prevent the enclosure 1554 from being completely crushed under ambient pressure. In some embodiments, the filler occupies a portion or substantially the entire internal volume of the internal chamber 1555.

[0248] According to some embodiments, the annular ring 1554A of the enclosure 1554 is attached to the first side 1558 and the second side 1559 of the enclosure 1554 at the connection point 1552 via an adhesive or some other means that can form an airtight seal between the interior chamber 1555 and the surrounding that encloses it. In some arrangements, the first side 1558 and the second side 1559 of the interior chamber 1555 are configured to expand, deploy, unwind from being wrinkled, and / or otherwise deform to increase the volume within the interior chamber 1555 in response to fluid being injected into the container 10 via the exchange device 40. In some embodiments, the first side 1558 and the second side 1559 of the interior chamber 1555 are configured to wrinkle, fold, compress, and / or otherwise deform to decrease the volume within the interior chamber 1555 in response to fluid being drawn out of the container 10 via the exchange device 40. According to some embodiments, the expansion and contraction of the enclosure 1554 can assist in maintaining a substantially constant pressure within the container 10.

[0249] Figures 25D - 25E illustrate one embodiment of a storage tank 1650 that can be attached to the lumen 1626 of a vial adapter. In some embodiments, the storage tank 1650 includes an enclosure 1654. The enclosure 1654 can also include an interior chamber 1655. In some configurations, the enclosure 1654 includes a plurality of openings such as those formed by a series of generally concentric rings 1654A, 1654B as shown. In some embodiments, the enclosure 1654 includes an opening 1657 that can be connected to the lumen 1626 of the vial adapter using an adhesive, pipe clamp, retaining ring, or other means. In some arrangements, the interior chamber 1655 of the enclosure 1654 is in fluid or non - fluid communication with the regulator flow path 1625, whereby fluid can pass between the regulator flow path 1625 and the interior chamber 1655.

[0250] In some embodiments, the region between the openings (e.g., the concentric ring 1654A) is made of a rigid or semi-rigid material. Further, in some embodiments, the ring 1654B is made of a flexible material. According to some embodiments, the ring 1654A is attached to the adjacent ring 1654B via an adhesive or some other means that can form an airtight seal between the inner chamber 1655 and the surrounding that encloses it. In some configurations, the enclosure 1554 includes an internal filler. The filler can be made to prevent the enclosure 1654 from being completely crushed under ambient pressure. In some embodiments, the filler occupies a part or substantially the entire internal volume of the inner chamber 1655.

[0251] According to some configurations, the ring 1654B is configured to expand, deploy, unwind from being wrinkled, and / or otherwise deform to increase the volume within the inner chamber 1655 in response to fluid being injected into the container 10 via the exchange device 40. In some embodiments, the ring 1654B of the inner chamber 1655 is configured to wrinkle, fold, compress, and / or otherwise deform to decrease the volume within the inner chamber 1655 in response to fluid being withdrawn from the container 10 via the exchange device 40. According to some embodiments, the expansion and contraction of the enclosure 1654 can assist in maintaining a substantially constant pressure within the container 10.

[0252] FIG. 26A illustrates an embodiment of an adapter 1700 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein, and which also includes a valve 1770. The adapter 1700 is configured to engage with a vial 10. In some embodiments, the adapter 1700 includes a regulator assembly 1750. In some configurations, the regulator assembly 1750 includes a protrusion 1785a that can be substantially sealingly attached (e.g., received therein or on its outer periphery) to the lumen 1726 of the regulator assembly 1750. The protrusion 2085a can facilitate fluid communication between two or more features (e.g., filters, enclosures, bags, and / or valves) of the regulator assembly. In some embodiments, the protrusion 2085a can generally define a regulator path. The regulator path can be in fluid communication with the regulator flow path 1725 of the regulator assembly 1750. The longitudinal axis of the protrusion 1785a and / or the lumen 1726 can be at least partially, substantially, or entirely perpendicular to the centerline on the axis of the adapter 1700. In some embodiments, the longitudinal axis of the protrusion 1785a and / or the lumen 1726 can be at least partially, substantially, or entirely parallel to the centerline on the axis of the adapter 1700. In some embodiments, the angle formed between the longitudinal axis of the protrusion 1785 and the centerline on the axis of the adapter 1700 is at least about 5° or less and / or about 85°. In some embodiments, this angle is about 60°. In some embodiments, the angle formed between the longitudinal axis of the protrusion 1785 and the centerline on the axis of the adapter 1700 can be any angle between 0° and 90° or a variable angle selected by the user. Many modifications are possible.

[0253] In some embodiments, the regulator assembly comprises a filter 1760. The filter 1760 may be a hydrophobic filter. In some embodiments, the valve 1770 or a part thereof is disposed within the lumen 1726 of the adapter 1700. In some embodiments, the valve 1770 or a part thereof is disposed outside the lumen 1726 of the adapter 1700 within the protrusion 1785a of the regulator assembly 1750.

[0254] According to some embodiments, the valve 1770 is configured to permit air or other fluid that has passed through the filter 1760 to enter the container 10. In some embodiments, the valve 1770 is configured to selectively inhibit fluid from passing through the valve 1770 and toward the filter 1760 from the container 10.

[0255] In some configurations, the valve 1770 is selectively opened and / or closed depending on the orientation of the adapter 1700. For example, the valve 1770 can be configured to allow fluid to flow unrestrictedly between the container 10 and the filter 1760 when the adapter 1700 is positioned above (e.g., further from the floor than) the vial 10 to which the adapter is attached. In some embodiments, the valve 1770 can be configured to prevent fluid flow from the container 10 to the filter 1760 when the vial 10 is positioned above the adapter 1700.

[0256] In some embodiments, the valve 1770 can open and / or close in response to the effect of gravity on the valve 1770. For example, the valve 1770 can comprise a component that moves in response to gravity to open and / or close a flow path within the valve 1770. In some embodiments, the flow path within the valve 1770 can be fabricated such that the effect of gravity on the fluid within the adapter 1700 can prevent or allow the fluid to pass through the flow path within the valve 1770.

[0257] For example, valve 1770 can comprise a rollover valve that senses orientation or is orientation-dependent. In some embodiments, the rollover valve 1770 can comprise a weighted sealing member. In some embodiments, the weighted sealing member can be biased to seal and / or close valve 1770 when vial 10 is positioned on adapter 1700. In some embodiments, the sealing member can be biased by gravity to seal valve 1770. In some embodiments, the sealing member can be biased to seal valve 1770 by using a compression spring. The sealing member can be configured to transition to an operation of opening valve 1770 when adapter 1700 is positioned on vial 10. For example, the weight of the sealing member can be sized to overcome the force of the compression spring and move to the open position when adapter 1700 is positioned on vial 10.

[0258] In some embodiments, valve 1770 can be a swing check valve. In some embodiments, valve 1770 can comprise a weighted panel rotatably connected to the wall of regulator flow path 1925. The weighted panel can be oriented such that when adapter 1700 is positioned on vial 10, the weighted panel rotates to an open position where the weighted panel does not inhibit the flow of fluid through regulator flow path 1925. In some embodiments, the weighted panel can be configured to rotate to a closed position where the weighted panel inhibits the flow of fluid through regulator flow path 1925 when vial 10 is positioned on adapter 1700.

[0259] According to some configurations, the valve 1770 can be a check valve that can transition between two or more configurations (e.g., an open / closed configuration). In some embodiments, the valve 1770 can change its configuration based on user input. For example, the valve 1770 and / or the regulator assembly 1750 can include a user interface (e.g., a button, slider, knob, capacitive surface, switch, toggle, keypad, etc.) that can be operated by a user. The user interface can communicate with the valve 1770 (e.g., mechanically, electronically, and / or electromechanically) and move the valve 1770 between an open configuration and a closed configuration. In some embodiments, the adapter 1700 and / or the regulator assembly 1750 can include a visual indicator that indicates whether the valve 1770 is in an open configuration or a closed configuration.

[0260] According to some embodiments, the valve 1770 is configured to operate as a two-way valve. In such a configuration, the valve 1770 can allow fluid to pass through the valve 1770 in a first direction 1770A with one pressure differential, and at the same time, allow fluid to pass through in a second direction 1770B with a different pressure differential. For example, the pressure differential required for fluid to pass through the filter 1770 in the first direction 1770A can be substantially higher than the pressure differential required for fluid to pass through the filter 1770 in the second direction 1770B.

[0261] FIG. 26B illustrates one embodiment of an adapter 1800 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. The adapter 1800 can include a regulator assembly 1850 that can include a valve 1870 in some embodiments. The valve 1870 can be disposed within a regulator flow path 1825 within a lumen 1826 of the adapter 1800 between the container 10 and a bag or other enclosure 254. In some embodiments, the valve 1879 or a portion thereof is disposed outside of the lumen 1826 and within a coupling 1852 of the regulator assembly 1850. In some embodiments, the valve 1870 is configured to permit passage of regulator fluid and / or other fluid from the enclosure 1854 to the container 10. In some embodiments, the valve 1870 is configured to inhibit or prevent passage of fluid from the container 10 to the enclosure 1854.

[0262] In some configurations, the valve 1870 is selectively opened and / or closed depending on the orientation of the adapter 1800. For example, the valve 1870 can be configured to allow fluid to flow unrestricted between the container 10 and the enclosure 1854 when the adapter 1800 is oriented over the vial 10 to which the adapter is attached. In some embodiments, the valve 1870 is configured to prevent fluid flow from the container 10 to the enclosure 1854 when the vial 10 is positioned over the adapter 1800. Further, in some embodiments, the valve 1870 is configured to act as a two-way valve in substantially the same manner as described above with respect to the valve 1770.

[0263] FIG. 26C illustrates one embodiment of an adapter 1900 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. Adapter 1900 can include a valve 1970 disposed within a regulator flow path 1925 within a protrusion 1985a of a regulator assembly 1950 between a container 10 and a filter 1960. In some embodiments, valve 1970, or a portion thereof, is disposed within regulator flow path 1925 outside of protrusion 1985a. Regulator assembly 1950 can include an enclosure 1954. In some embodiments, valve 1970 restricts the flow of fluid through regulator flow path 1925 in substantially the same manner as other valves described herein (e.g., 1770, 1870).

[0264] FIGS. 27A-27C illustrate one embodiment of a vial adapter 2000 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. In some embodiments, vial adapter 2000 includes a connector interface 2040 and a piercing member 2020 that partially communicates with connector interface 2040. In some embodiments, vial adapter 2000 includes a regulator assembly 2050.

[0265] The regulator assembly 2050 can include a blocking valve that operates in a direction, depends on a direction, or senses a direction, such as a ball check valve 2070. In some embodiments, the blocking valve can be removably inserted into one or more lumens of the regulator assembly 2050 via an installation path. The installation path can be defined by a centerline or a portion thereof on the axis of the lumen into which the blocking valve is inserted. In some embodiments, the blocking valve is configured to transition between an open configuration and a closed configuration based on the orientation of the vial adapter 2000 (e.g., the orientation of the vial adapter 2000 with respect to the floor). In some such embodiments, the blocking valve is configured to transition from a first configuration corresponding to a first orientation of the vial adapter 2000 to a second configuration corresponding to a second orientation of the vial adapter 2000. The blocking valve can be configured to transition from the first orientation to the second orientation regardless of the path of rotation of the vial adapter 2000. In some embodiments, the blocking valve can include a blocking member configured to move rotationally within a valve chamber. For example, the blocking member can be configured to engage and disengage from a valve seat within the valve chamber depending on the configuration of the blocking valve and the orientation of the vial adapter 2000. The blocking member can have an ellipsoidal shape, a spherical shape, a generally cylindrical shape with tapered ends, or another suitable shape.

[0266] In some configurations, the ball check valve 2070 is disposed within the lumen of the regulator assembly and / or within the lumen of the connector interface 2040. For example, the ball check valve 2070 may be disposed within the regulator flow path 2025 within the lumen 2026 of the regulator assembly 2050. In some embodiments, the ball check valve 2070 is removable from the regulator flow path 2025. In some variations, the ball check valve 2070 includes a retaining member that prevents or inhibits the ball 2073 from popping out of the ball check valve 2070 when the ball check valve 2070 is removed from the regulator flow path 2025. The ball check valve 2070 may be rotatable about the central axis within the regulator flow path 2025. In some embodiments, the ball check valve 2070 can be installed within other lumens of the vial adapter 2000. In some configurations, the regulator assembly 2050 includes a lumen or appendage or protrusion 2085a that can be substantially sealingly attached (e.g., received therein or on its outer periphery) to the lumen 2026 of the regulator assembly 2050. The protrusion 2085a can facilitate fluid communication between two or more features (e.g., filters, enclosures, bags, and / or valves) of the regulator assembly. According to some configurations, the ball check valve 2070, or a portion thereof, may be disposed within the regulator flow path 2025 within the protrusion 2085a. In some embodiments, the ball check valve 2070 and the protrusion 2085a form an integral part. In some embodiments, the ball check valve 2070 and the lumen 2026 form an integral part.

[0267] In some embodiments, the ball check valve 2070 includes a first chamber 2074 that is in fluid communication with the vial 10 via the regulator flow path 2025. The ball check valve 2070 can include a second chamber 2072 that is selectively in fluid communication with the first chamber 2074. According to some configurations, the first chamber 2074 has a substantially circular cross-section with a diameter or cross-sectional distance of DV1 and a height of H2. In some embodiments, the longitudinal axis of the first chamber 2074 is parallel to the center on the axis of the vial adapter 2000. In some embodiments, the longitudinal axis of the first chamber 2074 is positioned at an angle away from the center on the axis of the vial adapter 2000. The angle formed between the longitudinal axis of the first chamber 2074 and the center line on the axis of the vial adapter 2000 can be about 15° or more and / or about 60° or less. In some embodiments, the angle formed between the longitudinal axis of the first chamber 2074 and the center on the axis of the vial adapter 2000 is about 45°. Many variations are possible. In some embodiments, the second chamber 2072 also has a substantially circular cross-section with a diameter or cross-sectional distance of DV2. Many other variations in the structure of the first and second chambers are possible. For example, other cross-sectional shapes may be suitable.

[0268] In some embodiments, the ball check valve 2070 can include a step 2078 between the first chamber 2074 and the second chamber 2072. The step 2078 can include an inclined or tapered surface configured to move the ball 2073 toward the closed position under the influence of gravity when the vial adapter is oriented such that the vial is on top of the vial adapter. In some embodiments, the angle θ formed between the step 2078 and the wall of the first chamber 2074 is about 90° or less. In some embodiments, the angle θ is about 75° or less and / or about 30° or more. In some embodiments, the second chamber 2072 is in fluid communication with the first chamber 2074 when the ball check valve 2070 is in the open configuration. In some embodiments, the inner wall of the first chamber 2074 may be gradually tapered into the inner wall of the second chamber 2072 such that the first chamber 2074 and the second chamber 2072 form a single generally frustoconical chamber.

[0269] In some embodiments, ball 2073 may rest on a circular seat when in the closed position. In some embodiments, the circular seat is formed by step 2078. In some embodiments, the longitudinal axis of the circular seat is parallel to the longitudinal axis of the first chamber 2074. In some embodiments, the longitudinal axis of the first chamber 2074 can define a general path of movement relative to ball 2073 or other closure member (e.g., ball 2073 can generally move to and / or from the closed position in a direction generally parallel to the longitudinal axis of the first chamber 2074). In some embodiments, the path of movement relative to the closure member is not substantially parallel to the installation path of ball check valve 2070. For example, the path of movement relative to the closure member may be substantially perpendicular to the installation path of ball check valve 2070. In some variations, the longitudinal axis of the circular seat forms an angle with respect to the longitudinal axis of the first chamber 2074. The angle formed between the longitudinal axis on the axis of the circular seat and the longitudinal axis of the first chamber 2074 may be about 5° or more and / or about 30° or less. In some embodiments, this angle is about 10°. Many variations are possible. In some embodiments, the longitudinal axes of the first chamber 2074 and the circular seat are parallel to the center on the axis of adapter 2000. Such a configuration can reduce the likelihood that ball 2073 "sticks" to the circular seat or the inner wall of the first chamber 2074 when ball check valve 2070 is transitioned between the open and closed configurations, as described below.

[0270] In some configurations, the longitudinal axis of the first chamber 2074 may be substantially parallel to the center on the axis of the ball check valve 2070. In some embodiments, the longitudinal axis of the first chamber 2074 can define the movement path of the ball 2073. As illustrated in FIG. 27C, the longitudinal axis of the first chamber 2074 may be perpendicular to the center on the axis of the ball check valve 2070. In some embodiments, the angle formed between the longitudinal axis of the first chamber 2074 and the center line on the axis of the ball check valve 2070 is about 5° or more and / or about 90° or less. In some embodiments, this angle is about 60°. Many variations are possible. In some embodiments, the angle formed between the longitudinal axis of the first chamber 2074 and the center line on the axis of the ball check valve 2070 is the same as the angle formed between the center line on the axis of the ball check valve 2070 and the center line on the axis of the vial adapter 2000. In some such embodiments, the longitudinal axis of the first chamber 2074 can be aligned with the center line on the axis of the vial adapter 2000.

[0271] The ball check valve 2070 can also include a valve flow path 2071. According to some embodiments, the valve flow path 2071 is in fluid communication with the second chamber 2072. In some embodiments, the valve flow path 2071 generally defines a flow path between the second chamber 2072 and a part of the regulator flow path 2025 facing the second chamber 2072 from the first chamber 2074. As illustrated in FIGS. 27A-27C, the ball check valve 2070 can include one or more sealing portions 2079. The one or more sealing portions 2079 can resist the movement of the ball check valve 2070 within the regulator flow path 2025. In some embodiments, the one or more sealing portions 2079 suppress the fluid from flowing around and bypassing the ball check valve 2070. In some embodiments, the one or more sealing portions 2079 include one or more annular protrusions extending from the valve flow path 2071. Many variations are possible.

[0272] As illustrated in FIG. 27A, the ball check valve 2070 has a distal opening 2075a. In some embodiments, the ball check valve 2070 has a plurality of distal openings. The distal opening 2075a defines a fluid boundary (e.g., interface) between the first chamber 2074 and the regulator flow path 2025. In some embodiments, the ball check valve 2070 comprises a first valve flow path that is in fluid communication with both the regulator flow path 205 and the first chamber 2074. In such embodiments, the distal opening 2075a defines a fluid boundary (e.g., interface) between the first valve flow path and the regulator flow path 2025. The ball check valve 2070 further comprises a proximal opening 2075b that defines a fluid boundary (e.g., interface) between the first valve flow path 2071 and the regulator flow path 2025.

[0273] The ball check valve 2070 can be configured such that fluid entering and exiting the ball check valve 2070 through the distal opening 2075a and the proximal opening 2075b flows through an interface defined by each opening in a direction generally perpendicular to the interface. For example, as illustrated in FIG. 27B, the regulator fluid FR entering and / or exiting the ball check valve 2070 through the proximal opening 2075b has a flow direction (horizontal with respect to FIG. 27B) that is generally perpendicular to the interface (perpendicular with respect to FIG. 27B) defined by the proximal opening 2075b. Similarly, the flow of liquid entering and exiting the ball check valve 2070 through the distal opening 2075a is a flow in a direction generally perpendicular to the interface defined by the proximal opening 2075a. In some embodiments, the direction of flow through one or more of the distal opening 2075a and the proximal opening 2075b is oblique or perpendicular to the movement path of the ball 2073 or other blocking member. The angle formed between any interface and the movement path of the ball 2073 may be substantially the same as the angle formed between the same interface and the insertion axis of the adapter.

[0274] According to some embodiments, the occluder valve 2070 includes a movable occluder such as a ball 2073. All references to balls herein can generally be applied to occluders of other shapes, such as cubic occluders, generally cylindrical occluders, generally conical occluders, combinations of these shapes, etc. In some embodiments, the ball 73 is generally spherical or has another suitable shape. The ball 2073 can be made of a material having a higher density than the liquid L or other fluid within the vial 10. The ball 2073 can have a diameter DB. In some configurations, the diameter DB of the ball 2073 is smaller than the diameter DV1 and height H2 of the first chamber 2074. For example, in some embodiments, the ratio of the diameter DB of the ball 2073 to the diameter DV1 of the first chamber 2074 is about 9:10 or less, and / or about 7:10 or more. In some configurations, the diameter DB of the ball 2073 is larger than the diameter DV2 of the second chamber 2072. For example, in some embodiments, the ratio of the diameter DV2 of the second chamber 2072 to the diameter DB of the ball 2073 is about 9:10 or less, and / or about 7:10 or more. In some embodiments, the ball 2073 can move between at least two positions within the first chamber 2074. For example, the movement of the ball 2073 can be determined by gravity, an external force applied to the vial adapter, fluid within the regulator flow path, other forces, or a combination of forces.

[0275] As illustrated in FIGS. 27A - 27C, the ball 2073 within the ball check valve 2070 can be configured to rest on the step 2078 at the opening of the second chamber 2072 when the adapter 2000 and the vial 10 are oriented such that the fluid contained within the vial, in which gravity biases towards the vial adapter (e.g., when at least a portion of the vial 10 is over the connector interface 2040). The ball check valve 2070 can be oriented such that the longitudinal axis of the first chamber 2074 and the longitudinal axis of the circular seat are substantially parallel to the centerline on the axis of the vial adapter 2000. In such an embodiment, the ball 2073 can be configured to transition to a closed position (e.g., on the circular seat) in a substantially consistent manner regardless of the rotational orientation of the vial 10 and the connector interface 2040. For example, in such an embodiment, the manner in which the ball 2073 moves towards the step 2078 or the circular seat when the vial 10 is rotated from below the connector interface 2040 to above the connector interface 2040 is substantially consistent and is independent of whether the vial 10 and the connector interface 2040 are rotated about the longitudinal axis of the lumen 2026, about an axis perpendicular to the longitudinal axis of the lumen 2026 and the centerline on the axis of the vial adapter 2000, or about some other axis of rotation between these. Further, in such an embodiment, the parallel alignment between the longitudinal axis of the first chamber 2074 and the centerline on the axis of the adapter 2000 can serve as a means to assist the user of the adapter 2000 in visualizing the alignment of the ball check valve 2070. In some configurations, a seal 2076 can be formed by the contact between the ball 2073 and the step 2078. The seal 2076 can close the ball check valve 2070 and inhibit liquid L and / or other fluids from exiting the vial 10 and passing through the ball check valve 2070 when the vial 10 is oriented above the connector interface 2040.

[0276] In some embodiments, ball 2073 can be configured to move away from step 2078 when adapter 2000 and vial 10 are biased in a direction such that the fluid within the vial moves away from the vial adapter under gravity (e.g., when at least a portion of connector interface 2040 is positioned above vial 10). In some embodiments (such as embodiments where the longitudinal axis of the first chamber 2074 and the circular seat is parallel to the centerline on the axis of vial adapter 2000), ball 2073 can be configured to move away from step 2078 in a substantially consistent manner regardless of the direction of rotation of vial 10 and connector interface 2040. For example, in such embodiments, the manner in which ball 2073 moves away from step 2078 when vial 10 is rotated from above connector interface 2040 to below connector interface 2040 is substantially consistent and is independent of whether vial 10 and connector interface 2040 are rotated around the longitudinal axis of lumen 2026, around an axis perpendicular to the longitudinal axis of lumen 2026 and the centerline on the axis of vial adapter 2000, or around some other axis of rotation between them. When ball 2073 moves away from step 2078, seal 2076 opens or breaks, ball check valve 2070 assumes an open configuration, and the first chamber 2074 and the second chamber 2072 are in fluid communication. In some embodiments, ball check valve 2070 includes a biasing member having elasticity that biases ball 2073 toward step 2078 and thus biases ball check valve 2070 into a closed configuration. In some configurations, the biasing member can be a spring. In some configurations, the biasing member can be a flexible member. In some embodiments, the biasing force provided by the elastic biasing member can be less than the weight of ball 2073.

[0277] In some embodiments, the ball 2073 can move around in the first chamber 2074 under the influence of gravity. In some configurations, due to gravity, the ball 2073 can move towards the second chamber 2072 and rest on the step portion 2078 at the opening of the second chamber 2072. As described above, when the ball 2073 rests on the step portion 2078, a seal 2076 can be formed, whereby the ball check valve 2070 assumes a closed configuration and liquid L and / or other fluids can be prevented from exiting the vial 10 and passing through the ball check valve 2070. In some configurations, due to gravity, the ball 2073 can move away from the step portion 2078. When the ball 2073 moves away from the step portion 2078 under the influence of gravity, the seal 2076 opens or breaks, the ball check valve 2070 assumes an open configuration, and the first chamber 2074 and the second chamber 2072 are in fluid communication. Since the diameter or cross-section DV1 of the first chamber is larger than the diameter or cross-section DB of the ball 2073, the fluid can pass through the first chamber and flow around the outer surface of the ball 2073.

[0278] Next, some aspects of the operation of the ball check valve 2070 while the ball check valve 2070 is in the closed configuration will be described. For example, in some embodiments, when there is no fluid being introduced into or withdrawn from the vial 10 via the access flow path 2045, the pressure within the vial 10 is substantially the same as the pressure within the valve flow path 2071. In such a situation, the pressure within the first chamber 2074 may be substantially the same as the pressure within the second chamber 2072. In some embodiments, by positioning the vial 10 over the connector interface 2040, liquid L or other fluids can move from the vial 10 into the first chamber 2074. In some embodiments, when the pressure is balanced between the first chamber 2074 and the second chamber 2072, the ball 2073 remains stationary on the step portion 1078 and forms the seal 2076. The seal 2076 can prevent liquid L and / or other fluids from passing through the ball check valve 2070 out of the vial 10.

[0279] In some embodiments, when fluid is drawn out of vial 10 through access flow path 2045, a pressure lower than the pressure in second chamber 2072 can occur within vial 10 and first chamber 2074. Due to this pressure difference, ball 2073 can move away from step 2078 and into first chamber 2074. As ball 2073 moves in a direction away from step 2078, seal 2076 breaks and regulator fluid FR can pass through second chamber 2072 and move around ball 2073. The regulator fluid FR can then pass through first chamber 2074 and through regulator flow path 2025 and into vial 10. In some embodiments, the regulator fluid FR is fluid that has passed through a filter within regulator assembly 2050. In some embodiments, the regulator fluid FR is fluid contained within the internal volume of the enclosure of regulator assembly 2050. When the regulator fluid FR enters vial 10, the pressure difference between first chamber 2074 and second chamber 2072 is canceled, reduced, substantially eliminated, or eliminated, and ball 2073 can return to its rest position on step 2078. In some embodiments, when the regulator fluid FR enters vial 10, it becomes easier to maintain an equilibrium state between the inside of vial 10 and the inside of regulator assembly 2050. As ball 2073 returns to its rest position on step 2078, seal 2076 is reformed or created, preventing liquid L or other fluid from exiting vial 10 and passing through ball check valve 2070.

[0280] In some embodiments, when fluid is introduced into vial 10 through access flow path 2045 (e.g., when a diluent, a mixed fluid, or an overly withdrawn fluid is injected into vial 10 via exchange device 40), a pressure higher than the pressure in second chamber 2072 can occur in vial 10 and first chamber 2074. Due to this pressure difference, ball 2073 can be pushed onto step 2078, and thus seal 2076 can be tightened. When seal 2076 is tightened, liquid L can be prevented from passing from vial 10 through ball check valve 2070. In some embodiments, when seal 2076 is tightened, the internal pressure in vial 10 and first chamber 2074 can continue to increase as more fluid is introduced into vial 10 via access flow path 2045. In some embodiments, as the pressure in vial 10 and first chamber 2074 continues to increase, the force required to introduce more fluid to a prohibitive level is dramatically increased, and ultimately, the likelihood of fluid leakage from vial 10 and adapter 2000 or between these components can increase. Thus, ball check valve 2070 is desirably in an open position when fluid is injected into vial 10.

[0281] When ball 2073 moves in a direction away from step 2078, seal 2076 can open or break, and ball check valve 2070 can assume an open configuration. Next, some aspects of the operation of ball check valve 2070 while it is in the open configuration will be described. For example, in some embodiments, when there is no fluid being introduced into vial 10 or withdrawn from vial 10 via access flow path 2045, the pressure in vial 10 remains substantially constant. In some embodiments, vial 10 is in fluid communication with first chamber 2074, second chamber 2072, and valve flow path 2071 of ball check valve 2070 and has the same substantially constant internal pressure as them.

[0282] In some embodiments, when fluid is drawn from vial 10 through access flow path 2045, the pressure in vial 10 can drop, and then the pressure in the first chamber 2074 can also drop. When the pressures in vial 10 and the first chamber 2074 drop in this way, a pressure difference can occur between the first chamber 2074 and the second chamber 2072 of ball check valve 2070. Due to this pressure difference, regulated fluid FR can pass through the first chamber 2074 and through regulator flow path 2025 into vial 10. In some embodiments, regulated fluid FR is fluid that has passed through a filter within regulator assembly 2050. In some embodiments, regulated fluid FR is fluid contained within the internal volume of the enclosure of regulator assembly 2050. When regulated fluid FR enters vial 10, the pressure difference between the first chamber 2074 and the second chamber 2072 can be canceled, reduced, substantially eliminated, or eliminated. In some embodiments, when regulated fluid FR enters vial 10, it becomes easier to maintain an equilibrium state between the inside of vial 10 and the inside of regulator assembly 2050.

[0283] In some embodiments, when fluid is introduced into vial 10 through access flow path 2045 (e.g., when a diluent, mixed fluid, or overly drawn fluid is injected into vial 10 via exchange device 40), a pressure higher than the pressure in the second chamber 2072 can occur in vial 10 and the first chamber 2074. Due to this pressure difference, fluid from vial 10 can enter vial 10, pass through ball check valve 2070, and enter regulator assembly 2050. In some embodiments, fluid from vial 10 can pass through check valve 2070 and through a filter. In some embodiments, fluid from vial 10 passes through check valve 2070 and enters a bag or other enclosure. When fluid passes from vial 10 through ball check valve 2070, the pressure in vial 10 drops, and an equilibrium state can be maintained between the inside of vial 10 and the inside of regulator assembly 2050. In some embodiments, regulated fluid FR is outside air or sterilized gas, or filtered air or gas.

[0284] In some embodiments, particularly in embodiments where the vial adapter portion is modular or replaceable, the internal and / or external cross-section of lumen 2026 can comprise one or more alignment features. For example, the internal and / or external cross-section of the lumen can be grooved or have some other special shape. Some examples of potential shapes and their advantages are shown in FIGS. 20A - 20F and described above. Protrusion 2085a and / or ball check valve 2070 can comprise corresponding alignment features (e.g., corresponding keyways or other special shapes). Such a configuration can be beneficial for sending, controlling, or limiting signals to regulator assembly 2050 that can be connected to or integrally formed with adapter 2000. For example, the keyway or shape of the ball check valve 2070 and / or the flow path in which it is placed can be a means for the user of adapter 2000 to confirm that the check valve 2070 is properly aligned within regulator assembly 2050 (e.g., aligning first chamber 2074 at the side in vial 10). Such alignment of the ball check valve 2070 can enable the function of regulator assembly 2050 to operate properly and / or predictably.

[0285] In some embodiments, the exterior of regulator assembly 2050 can comprise one or more visual indicators indicating the alignment of ball check valve 2070. In some embodiments, visual indicators include notches, words (e.g., top and / or bottom), arrows, or other indicators of alignment. In some embodiments, the protrusion 2085a of valve 2070, lumen 2026, and / or body portion are made of a substantially transparent material to enable the user of adapter 2000 to visually confirm the configuration of the valve (e.g., display the position of the ball indicating whether the valve is in an open or closed configuration).

[0286] In some embodiments, the regulator assembly 2050 can include one or more indicators (e.g., visual or audible) that indicate when the ball 2073 is in the closed position. For example, the regulator assembly 2050 can include one or more light sources (e.g., LED light, light by chemiluminescence, etc.) configured to emit light when the ball 2073 is in the closed position. In some embodiments, the adapter 2000 can include a power source (e.g., one or more batteries, AC input, DC input, solar cell, etc.) configured to supply power to at least one of the one or more indicators. In some embodiments, the ball 2073 is made of a conductive material. In such embodiments, the ball check valve 2070 can be configured such that the ball 2073 forms a circuit between the power source and the light source when the ball 2073 is in the closed position. In some embodiments, the adapter 2000 can include a gyroscope sensor configured to sense when the ball 2073 is in the closed position. In some such embodiments, a controller to which the sensor is connected can send power to activate one or more indicators when the vial 10 is held over the adapter 2000.

[0287] FIG. 28 illustrates one embodiment of an adapter 2100 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. In some embodiments, the ball check valve 2170 includes a first valve flow path 2171A that is in fluid communication with both the regulator flow path 2125 and a first chamber 2174 of the ball check valve 2170. The ball check valve 2100 can include a second valve flow path 2171B that is selectively in fluid communication with a second chamber 2172 of the ball check valve 2170. In some embodiments, the ball check valve 2170, or a portion thereof, is positioned within the regulator flow path 2125 within the protrusion 2185a. In some embodiments, the ball check valve 2170, or a portion thereof, is positioned within the regulator flow path 2125 within the lumen 2126 of the adapter 2100. In some embodiments, the ball check valve 2170, or a portion thereof, is positioned within the regulator flow path 2125 outside of the protrusion 2185a. In some embodiments, the ball check valve 2170, or a portion thereof, is positioned within the regulator flow path 2125 outside of the lumen 2126 of the adapter 2100. In some embodiments, the ball check valve 2170 and the protrusion 2185a form an integral part. In some embodiments, the ball check valve 2170 and the lumen 2126 form an integral part.

[0288] FIG. 29 illustrates one embodiment of an adapter 2200 that can have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. In some embodiments, the regulator assembly 2250 includes a flexible valve, such as a dome valve 2270. The dome valve 2270 can include a dome-shaped portion 2273. The dome-shaped portion 2273 can include a concave side 2275B and a convex side 2275A. In some embodiments, the dome valve 2270 can include an annular flange 2278 attached to the dome-shaped portion 2273. In some embodiments, the annular flange 2278 and the dome-shaped portion 2273 constitute an integral part. The dome-shaped portion 2273 can have a wall thickness T3. The wall thickness T3 may be substantially constant throughout the dome-shaped portion 2273. In some embodiments, the thickness T3 of the dome-shaped portion 2273 may vary throughout the dome valve 2270.

[0289] In some embodiments, the dome valve 2270, or a portion thereof, is positioned within the regulator flow path 2225 within the lumen 2226 of the adapter 2200. In some embodiments, the dome valve 2270, or a portion thereof, is positioned within the regulator flow path 2225 outside the protrusion 2285a. In some embodiments, the dome valve 2270, or a portion thereof, is positioned within the regulator flow path 2225 outside the lumen 2226 of the adapter 2200. In some embodiments, the dome valve 2270 is fixed within the regulator flow path 2225. The dome valve 2270 can be fixed within the regulator flow path 2225, for example, by an adhesive, welding, fitting of the flow path within the regulator flow path 2225, or other means.

[0290] In some embodiments, the dome-shaped portion 2273 includes one or more slits 2274 or some other opening. In some embodiments, the one or more slits 2274 are biased to a closed position by the dome-shaped portion 2273 and / or the annular flange 2278. The dome valve 2270 can inhibit and / or prevent fluid from passing through the regulator flow path 2225 when the one or more slits 2274 are in the closed position. In some embodiments, the one or more slits 2274 are configured to open in response to one or more cracking pressures and permit fluid to flow through the one or more slits 2274. In some embodiments, due to the geometry and / or material of the dome valve 2270, the cracking pressure required to permit fluid to flow through the one or more slits 2274 in a first direction F1 can be substantially higher than the cracking pressure required to permit fluid to flow through the one or more slits 2274 in a second direction F2.

[0291] Next, some aspects of the operation of the dome valve 2270 will be described. For example, in some embodiments, when there is no fluid introduced into the vial 10 or withdrawn from the vial 10 via the access flow path 2245 of the adapter 2200, the pressure within the vial 10 remains substantially constant. In some embodiments, the vial 10 is in fluid communication with the regulator flow path 2225 within the region of the convex side 2275A of the dome valve 2270 and has a substantially constant internal pressure that is the same as the pressure P1 therein. In some embodiments, the pressure P2 within the region of the concave side 2275B of the dome valve 2270 is substantially the same as the pressure P1 when there is no fluid introduced into the vial 10 or withdrawn from the vial 10. In such a configuration, the one or more slits 2274 of the dome valve 2270 can be biased to a closed position by the dome-shaped portion 2273 of the dome valve 2270.

[0292] In some embodiments, when fluid is withdrawn from vial 10 through access flow path 2045, the pressure within vial 10 decreases, and subsequently the pressure P1 within the region of convex side 2275A may also decrease. When the pressure P1 thus decreases, a pressure difference may occur between the convex side 2275A and the concave side 2275B of dome valve 2270. In some embodiments, when fluid is withdrawn from vial 10, the pressure difference applied to dome valve 2270 becomes high enough to overcome the cracking pressure of dome valve 2270, causing one or more slits 2274 to open and allowing fluid to flow through dome valve 2270 in a second direction F2. In some configurations, regulator fluid FR flows in a second direction F2 through dome valve 2270 when one or more slits 2274 are opened and the pressure P2 applied to the concave shape 2275B of valve 2270 is higher than the P1 pressure applied to the convex side 2275A of valve 2270. When regulator fluid FR passes through dome valve 2270 and / or enters vial 10, the pressure within vial 10 may increase. When the pressure within vial 10 increases, the pressure P1 within the region of the convex surface 2275A of dome valve 2270 may increase. When the pressure P1 within the region of convex surface 2275A increases, the pressure difference applied to valve 2270 becomes lower than the cracking pressure, allowing one or more slits 2274 to be closed. In some embodiments, when regulator fluid FR passes through dome valve 2270 in a second direction F2, it becomes easier to maintain the equilibrium state between the inside of vial 10 and the inside of regulator assembly 2050 when fluid is withdrawn from vial 10 through access flow path 2245. In some embodiments, regulator fluid FR is fluid that has passed through a filter within regulator assembly 2250. In some embodiments, regulator fluid FR is fluid contained within the internal volume of the enclosure of regulator assembly 2250.

[0293] In some embodiments, when fluid is introduced into vial 10 through access flow path 2245 (e.g., when a diluent, a mixed fluid, or an overly withdrawn fluid is injected into vial 10 via exchange device 40), the pressure within vial 10 can increase. When the pressure within vial 10 increases, the pressure P1 within the region of convex surface 2275A of dome - shaped valve 2273 can increase. When the pressure P1 within the region of convex surface 2275A increases, a pressure differential can occur across dome - shaped valve 2273. In some embodiments, when fluid is introduced into vial 10, the pressure differential applied to dome - shaped valve 2270 becomes high enough to overcome the cracking pressure of dome - shaped valve 2270, causing one or more slits 2274 to open and allowing fluid to flow through dome - shaped valve 2270 in a first direction F1. In some configurations, as described above, the cracking pressure required to allow fluid to flow in the first direction F1 is substantially higher than the cracking pressure required to allow fluid to flow through dome - side valve 2270 in a second direction F2. In some embodiments, when fluid flows from vial 10 through dome - shaped valve 2270 in the first direction F1, the pressure within vial 10 can decrease. When the pressure within vial 10 decreases, the pressure P1 within the region of convex surface 2275A decreases, the pressure differential applied to valve 2270 becomes lower than the cracking pressure, and one or more slits 2274 can close. In some embodiments, when fluid passes through dome - shaped valve 2270 in the first direction F1, it becomes easier to maintain an equilibrium state between the inside of vial 10 and the inside of regulator assembly 2250.

[0294] Figures 30A - 30B illustrate an embodiment of a valve having a plurality of openings such as adapter 2300 and showerhead dome valve 2370. Adapter 2300 may be the same as or similar to components or parts of other vial adapters disclosed herein. Showerhead dome valve 2370 may comprise a dome - shaped portion 2373. The dome - shaped portion 2373 may comprise a concave side 2375B and a convex side 2375A. In some embodiments, showerhead dome valve 2370 may comprise an annular flange 2378 attached to the dome - shaped portion 2373. In some embodiments, annular flange 2378 and dome - shaped portion 2373 constitute an integral part. The dome - shaped portion 2373 may have a wall thickness T4. The wall thickness T4 may be substantially constant throughout the dome - shaped portion 2373. In some embodiments, the thickness T4 of the dome - shaped portion 2373 may vary throughout the showerhead dome valve 2370.

[0295] In some embodiments, showerhead dome valve 2370, or a portion thereof, is positioned within regulator flow path 2325 within lumen 2326 of adapter 2300. In some embodiments, showerhead dome valve 2370, or a portion thereof, is positioned within regulator flow path 2325 outside of protrusion 2385a. In some embodiments, showerhead dome valve 2370, or a portion thereof, is positioned within regulator flow path 2325 outside of lumen 2326 of adapter 2300. In some embodiments, showerhead dome valve 2370 is fixed within regulator flow path 2325. Showerhead dome valve 2370 can be fixed within regulator flow path 2325, for example, by an adhesive, welding, fitting of the flow path within regulator flow path 2325, or other means.

[0296] In some embodiments, the dome-shaped portion 2373 comprises one or more openings or a central slit 2374. In some embodiments, the one or more central slits 2374 are generally arranged in a cross-shaped configuration. In some embodiments, the one or more central slits 2374 are generally parallel to each other. In some embodiments, the dome-shaped portion 2373 comprises one or more outer slits 2374A. In some embodiments, the number of outer slits 2374A is about 30 or less and / or about 4 or more.

[0297] In some embodiments, the one or more central slits 2374 and / or outer slits 2374A are biased to a closed position by the dome-shaped portion 2373 and / or the annular flange 2378. The showerhead dome-shaped valve 2370 can suppress and / or prevent fluid from passing through the regulator flow path 2325 when the slits 2374, 2374A are in the closed position. In some embodiments, the slits 2374, 2374A are configured to open in response to one or more cracking pressures and permit fluid to flow through the slits 2374, 2374A. In some embodiments, due to the geometry and / or material of the showerhead dome-shaped valve 2370, the cracking pressure required to permit fluid to flow through the slits 2374, 2374A in a first direction F1 can be substantially higher than the cracking pressure required to permit fluid to flow through the slits 2374, 2374A in a second direction F2. In some embodiments, the cracking pressures required to permit fluid to flow through the showerhead dome-side valve 2370 in the first direction F1 and the second direction F2 are each lower than the cracking pressures required to permit fluid to flow through the dome-side valve 2270 in the first direction F1 and the second direction F2. In some embodiments, the showerhead dome-shaped valve 2370 functions in substantially the same manner as the dome-shaped valve 2270 when fluid is introduced into or withdrawn from the vial 10 via the access flow path 2345.

[0298] Figures 31A - 31B illustrate one embodiment of an adapter 2400 that can have components or parts that are the same as or similar to components or parts of other vial adapters disclosed herein. In some embodiments, the regulator assembly 1450 includes a blocking valve 2470 that opens and closes, such as a flap check valve 2470, and a portion of the blocking component remains adhered to the structure within the vial adapter 2400 as the blocking valve 2470 transitions between an open state and a closed state. The flap check valve 2470 can include a sealing portion 2479. The sealing portion 2479 can be, for example, a hollow stopper having a shape that fits snugly within the regulator flow path 2425 of the regulator assembly 2450, or can include one or more annular protrusions or some other feature suitable for securing the flap check valve 2470 in place within the regulator flow path 2425. In some embodiments, the flap check valve 2470, or a portion thereof, is positioned within the regulator flow path 2425 within the lumen 2426 of the adapter 2400. In some embodiments, the flap check valve 2470, or a portion thereof, is positioned within the regulator flow path 2425 outside of the protrusion 2485a. In some embodiments, the flap check valve 2470, or a portion thereof, is positioned within the regulator flow path 2425 outside of the lumen 2426 of the adapter 2400. In some embodiments, the flap check valve 2470 is fixed within the regulator flow path 2425.

[0299] According to some configurations, the flap check valve 2470 can include a seat 2477 attached to the sealing portion 2479. In some embodiments, the seat 2477 and the sealing portion 2479 form an integral part. In some embodiments, the seat 2477 and the sealing portion 2479 are separate parts. The flap check valve 2470 can include a flap 2473. The flap 2473 can have a first end 2473A and a second end 2473B. The first end 2473A of the flap 2473 can be rotatably attached to the sealing portion 2479 and / or the seat 2477.

[0300] In some embodiments, the flap 2473 can be configured to rest on the seat 2477 when the adapter 2400 and the vial 10 are oriented such that the vial 10 is over the connector interface of the adapter 2400. In some configurations, contact between the flap 2437 and the seat 2477 can form a seal 2476 between the inner 2472 and outer 2474 of the flap check valve 2470. The seal 2476 can close the flap check valve 2470 and inhibit liquid L and / or other fluids from passing through the flap check valve 2470 from the vial 10. In some embodiments, the flap 2473 can be configured to rotate away from the seat 2477 when the adapter 2400 and the vial 10 are oriented such that the connector interface of the adapter 2400 is over the vial 10. Movement of the flap 2473 away from the seat member 2477 eliminates the seal 2476, the flap check valve 2470 assumes an open configuration, and the inner 2472 and outer 2474 of the flap check valve 2470 are in fluid communication.

[0301] In some embodiments, the flap 2473 can move towards and away from the seat 2477 under the influence of gravity. As described above, contact between the flap 2473 and the seat 2477 forms a seal 2476 between the inner 2472 and outer 2474 of the flap check valve 2470, thereby closing the flap check valve 2470 and suppressing the passage of liquid L and / or other fluids from the vial 10 through the flap check valve 2470. In some configurations, gravity can cause the flap 2473 to move away from the seat 2477 and break the seal 2475. When the flap 2473 moves away from the seat member 2477 under the influence of gravity, the seal 2476 is eliminated and the flap check valve 2470 assumes an open configuration, allowing the outer 2474 and inner 2472 to be in fluid communication. In some embodiments, the flap 2473 is biased to a closed position. The biasing force can be provided, for example, by one or more torsion springs, or another feature suitable for biasing the flap 2473 towards the seat 2477 (e.g., tension, shape memory material, magnet, etc.). In some embodiments, the biasing torque applied to the flap 2473 at the first end 2473A is less than the torque generated at the first end 2473A when the weight of the flap 2473 is pulled away from the seat 2477 by gravity (e.g., when the seat 2477 is positioned above the flap 2473).

[0302] Next, some aspects of the operation of the flap check valve 2470 while it is in the closed configuration will be described. For example, in some embodiments, when there is no fluid being introduced into the vial 10 via the access flow path 2445 or being withdrawn from the vial 10, the pressure within the vial 10 is substantially the same as the pressure on the inside 2472 of the flap check valve 2470. In such a situation, the pressure P2 on the inside 2472 of the flap check valve 2470 may be substantially the same as the pressure P1 on the outside 2474 of the flap check valve 2470. In some embodiments, by positioning the vial 10 over the flap check valve 2470, liquid L or other fluid can move from the vial 10 to the outside 2474 of the flap check valve 2470. In some embodiments, when the pressure is balanced between the outside 2474 and the inside 2472 of the flap check valve, the flap 2473 remains stationary on the seat 2477, forming the seal 2476. The seal 2476 can prevent liquid L and / or other fluid from passing from the vial 10 through the flap check valve 2470.

[0303] In some embodiments, when fluid is drawn from vial 10 through access flow path 2445, a pressure lower than the pressure inside 2472 of flap check valve 2470 can occur outside 2474 of vial 10 and flap check valve 2470. Due to this pressure difference, flap 2473 can move in a direction away from seat 2477. When flap 2473 moves in a direction away from seat 2477, seal 2476 can be broken, and fluid FR can be allowed to move from inside 2472 of flap check valve 2470 to outside 2474 of flap check valve 2470. Then, regulating fluid FR can enter vial 10 through regulator flow path 2425. In some embodiments, regulator fluid FR is fluid that has passed through a filter within regulator assembly 2450. In some embodiments, regulator fluid FR is fluid contained within the internal volume of the enclosure of regulator assembly 2450. When regulator fluid FR enters vial 10, the pressure difference between the first outside 2474 and inside 2472 of flap check valve 2470 is canceled, reduced, substantially eliminated, or eliminated, and flap 2473 can return to a stationary position on seat 2477. In some embodiments, when regulator fluid FR enters vial 10, it becomes easier to maintain an equilibrium state between the inside of vial 10 and the inside of regulator assembly 2450. When flap 2473 returns to the stationary position on seat 2477, seal 2476 is reformed, and liquid L and / or other fluids can be prevented from exiting vial 10 and passing through flap check valve 2470.

[0304] In some embodiments, when fluid is introduced into vial 10 through access flow path 2445 (e.g., when a diluent, mixed fluid, or overly withdrawn fluid is injected into vial 10 via exchange device 40), a pressure higher than the pressure inside 2472 of flap check valve 2470 can occur outside 2474 of vial 10 and flap check valve 2470. Due to this pressure difference, flap 2473 can be pushed onto seat 2477, and thus seal 2476 can be tightened. When seal 2476 is tightened, liquid L can be prevented from passing from vial 10 through flap check valve 2470. In some embodiments, when seal 2476 is tightened, the internal pressure of vial 10 and the pressure P1 in the region outside 2474 of flap check valve 2470 can be made to increase as more fluid is introduced into vial 10 via access flow path 2445 and continues to increase. In some embodiments, as the pressure in vial 10 continues to increase, the force required to introduce more fluid to a prohibitive level is dramatically increased, and ultimately, fluid leakage from vial 10 and adapter 2400 or between these components can be more likely to occur. Thus, flap check valve 2470 is desirably in an open position when fluid is injected into vial 10.

[0305] When flap 2473 moves away from seat 2477, seal 2476 can be removed and flap check valve 2470 can be placed in an open configuration. In some embodiments, open flap check valve 2470 performs substantially the same function as open ball check valve 2070, described above, with respect to introducing fluid into vial 10 via access flow path 2445 or passing fluid through flap check valve 2470 after withdrawing from vial 10. In some embodiments, regulator assembly 2450 can have many of the same key grooves, shapes, and / or alignment features (e.g., transparent material, visual alignment indicators, shaped flow paths, and / or shaped valves) as described above with respect to ball check valve 2070.

[0306] FIG. 32 illustrates an embodiment of the adapter 2500. The adapter 2500 can include a piercing member 2520. In some embodiments, the piercing member 2520 is disposed within the vial 10. The piercing member 2520 can include an access flow path 2545 that communicates with the exchange device 40. In some embodiments, the piercing member 2530 includes a regulator flow path 2525 that includes a gravity or orientation blocker valve, such as a ball check valve 2520. The ball check valve 2570 can include a first flow path 2574 having a substantially circular cross-section and diameter D1 that is in fluid communication with the vial 10. In some embodiments, the ball check valve 2570 can include a second flow path 2572 having a substantially circular cross-section and diameter D2 that is selectively in fluid communication with the first flow path 2574. Many other variations of the structure of the first chamber and the second chamber are possible. For example, other cross-sectional shapes may be suitable.

[0307] The ball check valve 2570 can include a step 2578 between the first flow path 2574 and the second flow path 2572. In some embodiments, the angle θ2 formed between the step 2578 and the wall of the first flow path 2574 can be about 90°. In some embodiments, the angle θ2 can be less than or greater than 90°. For example, in some embodiments, the angle θ2 is about 75° or less and / or about 30° or more. In some embodiments, the second flow path 2572 is in fluid communication with the first flow path 2574 when the ball check valve 2570 is in the open configuration. In some embodiments, the inner wall of the first flow path 2574 may be tapered gradually into the inner wall of the second flow path 2572 such that the first flow path 2574 and the second flow path 2572 form a single frustoconical flow path.

[0308] The closure valve can include a closure such as ball 2573. In some embodiments, ball 2573 is made of a material having a density higher than that of the liquid L and / or other fluids within vial 10. Ball 2573 may be spherical or of any other suitable shape. In some embodiments, ball 2573 has a diameter DB2. The diameter DB2 can be smaller than the diameter D1 of the first flow path 2574 and larger than the diameter D2 of the second flow path 2572. For example, in some embodiments, the ratio of the diameter DB2 of ball 2573 to the diameter D1 of the first flow path 2574 is about 9:10 or less and / or about 7:10 or more. In some embodiments, the ratio of the diameter D2 of the second flow path 2572 to the diameter DB2 of ball 2573 is about 9:10 or less and / or about 7:10 or more. In some embodiments, the ball check valve 2570 can include a capture member 2577. The capture member 2577 can prevent ball 2570 from exiting the first flow path 2574.

[0309] In some configurations, ball 2573 may exhibit behavior similar to that of ball 2073 of ball check valve 2070. For example, ball 2573 can move within the first flow path 2574 under the influence of forces in much the same way that ball 2073 can move about within the first chamber 2074 of ball check valve 2070. By abutting ball 2573 against the step 2578 of ball check valve 2570, seal 2560 can be formed, which can prevent the liquid L and / or other fluids within the vial from entering the regulator flow path 2525. In many respects, ball check valve 2570 exhibits the same or substantially the same behavior as ball check valve 2070 under the influence of gravity, alignment of adapter 2570, and / or other forces.

[0310] The following list summarizes exemplary embodiments within the scope of the present disclosure. The exemplary embodiments in the list should in no way be construed as limiting the scope of the embodiments. Additional embodiments can be formed by removing, adding, or combining various features of the exemplary embodiments in the list, and these form part of the present disclosure.

[0311] 1. An adapter configured to couple with a sealed vial, a storage device comprising a distal extractor opening configured to allow fluid to be drawn from the sealed vial when the adapter is coupled to the sealed vial, wherein at least a portion of the extractor flow path and at least a portion of the regulator flow path pass through the storage device, the storage device, and a regulator enclosure in fluid communication with the regulator flow path, the regulator enclosure being configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or folded when fluid is drawn from the sealed vial through the extractor flow path, the regulator enclosure, and a filler disposed within the regulator enclosure and configured to ensure an initial volume of regulator fluid within the regulator enclosure, thereby enabling the adapter to supply regulator fluid from the regulator enclosure to the sealed vial when fluid is drawn from the sealed vial through the extractor opening.

[0312] 2. The adapter according to embodiment 1, wherein the adapter is configured such that the regulator enclosure is outside the sealed vial when the adapter is coupled to the sealed vial.

[0313] 3. The adapter according to embodiment 1, wherein at least a substantial portion of the regulator enclosure is not within a rigid housing.

[0314] 4. The storage device comprises a medical connector interface configured to be coupled with a syringe configured to be in fluid communication with the extractor flow path and hold a defined volume of fluid within the cylinder, and the filler is the adapter according to Embodiment 1 configured to ensure that the initial volume of the regulator fluid is equal to or greater than the defined volume of the fluid.

[0315] 5. The adapter according to Embodiment 4, wherein the initial volume of the regulator fluid within the regulator enclosure is about 60 mL or more.

[0316] 6. The adapter according to Embodiment 1, wherein the regulator enclosure is configured to hold a maximum volume of regulator fluid when the regulator enclosure is fully expanded or deployed, and the maximum volume is about 180 mL or more.

[0317] 7. The adapter according to Embodiment 1, wherein the regulator enclosure is made of a material system including a polyethylene terephthalate film.

[0318] 8. The adapter according to Embodiment 7, wherein the polyethylene terephthalate film includes a metallized coating.

[0319] 9. The adapter according to Embodiment 8, wherein the metallized coating includes aluminum.

[0320] 10. The pressure regulating vial adapter comprises a piercing member connected to the storage device, and the enclosure is at least partially disposed within the piercing member. The adapter according to Embodiment 1.

[0321] 11. The pressure within the sealed vial is adjusted by causing the regulator enclosure to contract or fold when the pharmaceutical fluid is withdrawn from the sealed vial, substantially equalizing the pressure on the opposite side of the regulator enclosure. The adapter according to Embodiment 1.

[0322] 12. The adapter according to embodiment 1, wherein the regulator enclosure comprises a layer that is substantially impermeable to the pharmaceutical fluid disposed within the vial, thereby preventing passage of the pharmaceutical fluid between the outer and inner surfaces of the regulator enclosure.

[0323] 13. The adapter according to embodiment 1, further comprising a hydrophobic filter disposed between the regulator enclosure and a distal regulator opening configured to allow regulator fluid to flow between the regulator enclosure and the vial when the adapter is coupled to the vial.

[0324] 14. The adapter according to embodiment 13, wherein the hydrophobic filter is disposed within the regulator flow path.

[0325] 15. The adapter according to embodiment 1, wherein the packing material comprises a foamed material.

[0326] 16. The adapter according to embodiment 15, wherein the packing material comprises a polyurethane-ether foam.

[0327] 17. A method of withdrawing fluid from a sealed vial, comprising: connecting a pressure-regulating vial adapter to the sealed vial, the pressure-regulating vial adapter being a storage device comprising a distal extractor opening configured to allow fluid to be withdrawn from the sealed vial when the adapter is coupled to the sealed vial, at least a portion of an extractor flow path and at least a portion of a regulator flow path passing through the storage device; and a storage device; A regulator enclosure that is in fluid communication with the regulator flow path, wherein at least a portion of the regulator enclosure is configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when fluid is withdrawn from the sealed vial through the extractor flow path, and a regulator enclosure; Disposing a filling material within the regulator enclosure, the filling material being configured to ensure an initial volume of regulator fluid within the regulator enclosure, thereby enabling the adapter to supply regulator fluid from the regulator enclosure to the sealed vial when fluid is withdrawn from the sealed vial through the extractor opening; A method comprising withdrawing fluid from the sealed vial through the pressure regulating vial adapter.

[0328] 18. A method of manufacturing an adapter for coupling to a sealed vial, Providing a storage device having a distal extractor opening configured to enable fluid to be withdrawn from the sealed vial when the adapter is coupled to the sealed vial, wherein at least a portion of the extractor flow path and at least a portion of the regulator flow path pass through the storage device; Disposing a filling material within the regulator enclosure, the filling material being configured to ensure an initial volume of regulator fluid within the regulator enclosure, thereby enabling the adapter to supply regulator fluid from the regulator enclosure to the sealed vial when fluid is withdrawn from the sealed vial through the extractor opening; The step of disposing the regulator enclosure in fluid communication with the regulator flow path, wherein the regulator enclosure is configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or folded when fluid is withdrawn from the sealed vial through the extractor flow path.

[0329] 19. The step of disposing a packing material within the regulator enclosure comprises forming a filling opening within the regulator enclosure configured to allow passage of the packing material therethrough; filling the regulator enclosure with the packing material through the filling opening; and closing the filling opening, the method of embodiment 18.

[0330] 20. The step of disposing a regulator enclosure in fluid communication with the regulator flow path comprises aligning an enclosure opening within the regulator enclosure with a proximal regulator opening of a storage device; and securing the regulator enclosure to the storage device, the method of embodiment 18.

[0331] 21. A storage device comprising an adapter configured to couple to a sealed vial, the storage device having a distal extractor opening configured to enable withdrawal of fluid from the sealed vial when the adapter is coupled to the sealed vial, wherein at least a portion of an extractor flow path and at least a portion of a regulator flow path pass through the storage device A regulator enclosure that is in fluid communication with the regulator flow path, wherein at least a portion of the regulator enclosure is at least partially expanded or deployed in a first orientation, and when fluid is withdrawn from the sealed vial through the extractor flow path, at least a portion of the regulator enclosure is at least partially reduced or folded in a second orientation, and is configured to move between the first orientation and the second orientation, and includes a regulator enclosure. The rigid housing is an adapter that does not include the substantial volume of the regulator enclosure.

[0332] 22. The adapter according to embodiment 21, wherein the regulator enclosure includes a first side and a second side opposite the first side, and each of the first side and the second side is configured to expand, contract, fold, or deploy when regulator fluid flows between the regulator flow path and the regulator enclosure.

[0333] 23. The adapter according to embodiment 22, wherein the second side is configured to move away from the storage device or toward the storage device when regulator fluid passes through the regulator flow path.

[0334] 24. The adapter according to embodiment 22, wherein the first side includes an inner surface forming a part of the inside of the regulator enclosure and an outer surface forming a part of the outside of the regulator enclosure, and the outer surface of the first side is oriented toward the storage device.

[0335] 25. The adapter according to embodiment 21, wherein the pressure within the sealed vial is adjusted by contracting or folding the regulator enclosure to substantially equalize the pressure on the opposite side of the regulator enclosure when the pharmaceutical fluid is withdrawn from the sealed vial.

[0336] 26. The adapter according to embodiment 21, wherein the regulator enclosure comprises a layer that is substantially impermeable to the pharmaceutical fluid disposed within the vial, thereby preventing passage of the pharmaceutical fluid between the outer and inner surfaces of the enclosure.

[0337] 27. The adapter according to embodiment 21, further comprising a hydrophobic filter disposed between the regulator enclosure and a distal regulator opening configured to allow regulator fluid to flow between the regulator enclosure and the vial when the adapter is coupled to the vial.

[0338] 28. The adapter according to embodiment 21, further comprising a filler disposed within the regulator enclosure and configured to ensure an initial volume of regulator fluid within the regulator enclosure, thereby enabling the adapter to supply regulator fluid from the regulator enclosure to the sealed vial when fluid is withdrawn from the sealed vial through the extractor opening.

[0339] 29. A vial adapter configured to couple to a sealed vial, a storage device comprising a distal extractor opening configured to allow fluid to be withdrawn from the sealed vial when the adapter is coupled to the sealed vial, wherein at least a portion of the extractor flow path and at least a portion of the regulator flow path pass through the storage device, a regulator enclosure in fluid communication with the regulator flow path, the regulator enclosure being configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or folded when fluid is withdrawn from the sealed vial through the extractor flow path. The regulator enclosure has a first side and a second side opposite the first side, the first side comprising an inner surface forming part of the inside of the regulator enclosure and an outer surface forming part of the outside of the regulator enclosure, the outer surface of the first side being oriented towards the storage device, Each of the first side and the second side is configured to expand, contract, fold, or unfold as regulator fluid passes through the regulator flow path, The second side is configured to move away from or towards the storage device as regulator fluid passes through the regulator flow path, The regulator enclosure is a vial adapter that does not fit entirely within the rigid housing.

[0340] 30. A vial adapter configured to couple with a sealed vial, A storage device comprising a distal extractor opening configured to enable fluid to be withdrawn from the sealed vial when the adapter is coupled to the sealed vial, at least a portion of the extractor flow path and at least a portion of the regulator flow path passing through the storage device, A regulator enclosure in fluid communication with the regulator flow path and configured to receive a volume of regulator fluid, the regulator enclosure being configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when fluid is withdrawn from the sealed vial via the extractor flow path, The regulator enclosure has a first layer, the first layer being connected to a second layer opposite the first layer, the first layer and the second layer being configured to receive the volume of regulator fluid therebetween, Each of the first side portion and the second side portion is configured to expand, contract, fold, or deploy when regulator fluid passes through the regulator flow path. The second side portion is configured to move away from or toward the storage device when regulator fluid passes through the regulator flow path. The regulator enclosure is a vial adapter that does not fully fit within a rigid housing.

[0341] 31. The vial adapter according to embodiment 30, wherein the first layer is made from a first sheet of material and the second layer is made from a second sheet of material.

[0342] 32. The vial adapter according to embodiment 30, wherein the first layer and the second layer are connected at the outer periphery of the first layer and the second layer.

[0343] 33. The vial adapter according to embodiment 30, wherein the first layer and the second layer each comprise a central portion, and the first layer and the second layer are not connected at the central portion.

[0344] 34. A modular vial adapter configured to couple with a sealed vial, a pressure regulating vial adapter module, a storage device comprising a distal extractor opening configured to allow fluid to be withdrawn from the sealed vial when the adapter is coupled to the sealed vial, at least a portion of an extractor flow path and at least a portion of a regulator flow path passing through the storage device, and the storage device; a proximal regulator opening in fluid communication with the regulator flow path, the proximal regulator opening being configured to allow regulator fluid to flow in or out therethrough when the vial adapter module is coupled to the sealed vial and fluid is withdrawn from the vial, and the pressure regulating vial adapter module. A regulator fluid module configured to couple with the proximal regulator opening, A regulator enclosure configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when regulator fluid passes through an enclosure opening in the regulator enclosure, And a fixture configured to couple the regulator enclosure and the proximal regulator opening, The regulator enclosure comprises a modular vial adapter comprising a regulator fluid module that does not fit entirely within a rigid housing.

[0345] 35. The adapter according to embodiment 34, wherein the fixture comprises a fastening member having a first surface and a second surface coated with an adhesive.

[0346] 36. The adapter according to embodiment 35, wherein the fastening member is made of a material system including an elastic material.

[0347] 37. A method of manufacturing a vial adapter configured to couple with a sealed vial, the method comprising: Providing a pressure regulating vial adapter module, the pressure regulating vial adapter module comprising A storage device comprising a distal extractor opening configured to enable fluid to be withdrawn from the sealed vial when the adapter is coupled to the sealed vial, wherein at least a portion of an extractor flow path and at least a portion of a regulator flow path pass through the storage device, A proximal regulator opening that is in fluid communication with the regulator flow path, wherein the proximal regulator opening is configured such that when the vial adapter module is coupled to the sealed vial, regulator fluid can flow in or out therethrough when fluid is withdrawn from the vial, and a step comprising the proximal regulator opening; Providing a regulator fluid module configured to couple with the proximal regulator opening, wherein the regulator fluid module A regulator enclosure configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when regulator fluid passes through an enclosure opening in the regulator enclosure, and a regulator enclosure; A fastener configured to couple the regulator enclosure and the proximal regulator opening, and The step that the regulator enclosure does not completely fit within the rigid housing; Aligning the enclosure opening of the regulator enclosure with the proximal regulator opening of the pressure regulating vial adapter module; A method including attaching the regulator fluid module to the pressure regulating vial adapter module.

[0348] 38. The method according to embodiment 37, wherein the fastener comprises a fixing member having a first surface and a second surface coated with an adhesive.

[0349] 39. The method according to embodiment 38, wherein the fixing member is made from a material system including an elastic material.

[0350] 40. The method according to embodiment 39, wherein the fixing member has a thickness of about 0.01 inches or more and about 0.03 inches or less.

[0351] 41. A regulator fluid module configured to be fastened to a pressure regulating vial adapter module to form a vial adapter for coupling with a sealed vial, the pressure regulating vial adapter module comprising a housing, the housing having a distal extractor opening configured to allow fluid to be drawn from the sealed vial when the adapter is coupled to the sealed vial, at least a portion of the extractor flow path and at least a portion of the regulator flow path passing through the housing, a proximal regulator opening fluidly communicating with the regulator flow path, the proximal regulator opening being configured to allow regulator fluid to flow in or out therethrough when the vial adapter module is coupled to the sealed vial and fluid is drawn from the vial, the regulator fluid module comprising a regulator enclosure configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when regulator fluid passes through an enclosure opening in the regulator enclosure, a filler material within the regulator enclosure configured to ensure an initial volume of regulator fluid within the regulator enclosure, thereby allowing the adapter to supply regulator fluid from the regulator enclosure to the sealed vial when fluid is drawn from the sealed vial through the extractor opening, a fastener configured to couple the regulator enclosure to the proximal regulator opening such that the fastener allows the regulator fluid module to move a small distance with respect to the pressure regulating vial adapter module without tearing, breaking, or otherwise damaging the fastener during routine operation of the vial adapter, The regulator enclosure is a regulator fluid module that does not fit entirely within a rigid housing.

[0352] 42. A method of manufacturing a modular adapter for coupling to a sealed vial and regulating the pressure within the sealed vial, comprising: forming a housing device having a distal access opening configured to permit fluid transfer between a medical device and the sealed vial when the adapter is coupled to the sealed vial, wherein at least a portion of the access flow path and at least a portion of the regulator flow path pass through the housing device, and the regulator flow path is in fluid communication with the sealed vial when the adapter is coupled to the sealed vial; connecting a coupling assembly such that the coupling assembly is in fluid communication with the regulator flow path, the coupling assembly comprising a membrane and a cover, the cover having an opening, the coupling assembly being configured to permit flow of a regulating fluid between the opening and the regulator flow path, the flow of the regulating fluid passing through the membrane; providing a regulator enclosure configured to be positioned in fluid communication with the opening, the regulator enclosure being configured to move between a first orientation in which at least a portion of the regulator enclosure is at least partially expanded or deployed, and a second orientation in which at least a portion of the regulator enclosure is at least partially reduced or folded when regulator fluid passes through an opening within the regulator enclosure.

[0353] 43. The method of embodiment 42, further comprising selecting the regulator enclosure from a plurality of regulator enclosures of different sizes, the selection being based on the volume of medicament fluid withdrawn from the sealed vial.

[0354] 44. The method of embodiment 42, wherein the flow of the regulating fluid passes between the opening and the sealed vial when medicament fluid is withdrawn from the sealed vial through the access flow path.

[0355] 45. The method according to embodiment 42, wherein the opening is in fluid communication with the outside air before the regulator enclosure is placed in a position in fluid communication with the opening.

[0356] 46. A vial adapter having an insertion shaft, the vial adapter being used in a region with a floor and configured to couple with a sealed vial, the vial adapter A housing assembly comprising a piercing member configured to pierce the septum of the sealed vial when the piercing member is biased against the septum of the vial; An extractor flow path extending between a proximal extractor opening and a distal extractor opening and configured to draw fluid from the sealed vial when the vial adapter is coupled to the sealed vial, at least a portion of the extractor flow path passing through at least a portion of the housing assembly; an extractor flow path; A regulator flow path extending between a proximal regulator opening and a distal regulator opening, at least a portion of the regulator flow path passing through at least a portion of the housing assembly; a regulator flow path; An occluder valve housed within the regulator flow path and configured to transition between a closed configuration and an open configuration in response to rotation of the vial adapter about an axis of rotation between an upright position and an inverted position, the proximal extractor opening being farther from the floor than the distal extractor opening when the vial adapter is in the upright position and closer to the floor than the distal extractor opening when the vial adapter is in the inverted position, the vial adapter comprising an occluder valve; The occluder valve inhibits fluid from passing through the occluder valve and proceeding toward the proximal regulator opening when the occluder valve is in the closed configuration, the axis of rotation being perpendicular to the insertion shaft of the vial adapter, and the occluder valve continuously transitions between the closed configuration and the open configuration substantially independently of the axis of rotation for rotating the vial adapter.

[0357] 47. The stopper valve is the vial adapter according to embodiment 46, which transitions to a closed configuration when the vial adapter is rotated to the inverted position.

[0358] 48. The stopper valve is the vial adapter according to embodiment 46, which transitions to an open configuration when the vial adapter is rotated to the upright position.

[0359] 49. The stopper valve includes a valve chamber that is in fluid communication with the regulator flow path, a closing member within the valve chamber, and a valve seat. The stopper valve is configured to transition to a closed configuration after the closing member and the valve seat engage, and the stopper valve is configured to transition to an open configuration after the closing member disengages from the valve seat. The vial adapter according to embodiment 46.

[0360] 50. The closing member moves within the valve chamber under the influence of gravity. The vial adapter according to embodiment 49.

[0361] 51. The closing member is a spherical ball. The vial adapter according to embodiment 49.

[0362] 52. The closing member has a cylindrical main body portion with a tapered end. The vial adapter according to embodiment 49.

[0363] 53. The closing member has an ellipsoidal shape. The vial adapter according to embodiment 49.

[0364] 54. The stopper valve generally has a cylindrical shape and a central axis on the axis. The vial adapter according to embodiment 46.

[0365] 55. The stopper valve is rotatable about the central axis on the axis of the stopper valve with respect to the regulator flow path. The vial adapter according to embodiment 54.

[0366] 56. The vial adapter further includes a filter positioned within the regulator flow path between the stopper valve and the proximal regulator opening. The vial adapter according to embodiment 46.

[0367] 57. The filter is the vial adapter according to embodiment 56, which is a hydrophobic filter.

[0368] 58. A vial adapter configured to couple with a sealed vial, the vial adapter having an insertion shaft, A housing assembly comprising a piercing member that can pierce the septum of the sealed vial when the piercing member is biased against the septum of the vial, An extractor flow path, at least a portion of the extractor flow path passing through at least a portion of the housing assembly, the extractor flow path; A regulator flow path, the regulator flow path defining a regulator fluid flow path and extending between a proximal regulator opening and a distal regulator opening, at least a portion of the regulator flow path passing through at least a portion of the housing assembly, the regulator flow path; An occluder valve disposed in at least a portion of the regulator flow path and having a proximal opening closest to the proximal regulator opening and a distal opening closest to the distal regulator opening, the occluder valve further configured to transition between a closed configuration and an open configuration, the occluder valve Fluidly communicating with the regulator flow path and the regulator fluid flow path, and having a valve chamber having an occlusion member, a movement path for the occlusion member, and a valve seat; A valve flow path fluidly communicating with the valve chamber, the regulator flow path, and the regulator fluid flow path; A proximal interface defining a fluid boundary between the proximal opening and the regulator flow path; A distal interface defining a fluid boundary between the distal opening and the regulator flow path, Comprising an occluder valve, The occluder valve is configured to transition to a closed configuration when the occlusion member engages the valve seat, and the occluder valve is configured to transition to an open configuration when the occlusion member disengages from the valve seat, and the angle formed between the movement path for the occlusion member and the regulator fluid flow path at one or more of the proximal interface and the distal interface is oblique or perpendicular, the vial adapter.

[0369] 59. The movement path for the occlusion member is oblique or perpendicular to the installation path of the occluder valve, the vial adapter according to embodiment 58.

[0370] 60. The angle formed between the movement path and the installation path is greater than about 45° and less than about 135°, the vial adapter according to embodiment 59.

[0371] 61. The occlusion member is a spherical ball, the vial adapter according to embodiment 58.

[0372] 62. The occlusion member has a cylindrical body portion with a tapered end, the vial adapter according to embodiment 58.

[0373] 63. The occlusion member has an ellipsoidal shape, the vial adapter according to embodiment 58.

[0374] 64. The angle formed between the movement path and the installation path is about 90°, the vial adapter according to embodiment 60.

[0375] 65. The angle formed between the movement path and the installation path is substantially the same as the angle formed between the insertion axis of the vial adapter and the installation path, the vial adapter according to embodiment 58.

[0376] 66. The movement path is substantially parallel to the insertion axis of the vial adapter, the vial adapter according to embodiment 58.

[0377] 67. The vial adapter further comprises a filter in the regulator flow path between the occluder valve and the proximal regulator opening, the vial adapter according to embodiment 58.

[0378] 68. The filter is a hydrophobic filter, the vial adapter according to embodiment 67.

[0379] 69. A method of manufacturing a modular vial adapter configured to couple with a sealed vial, selecting a connector interface having an insertion shaft, the connector interface comprising a housing assembly having a piercing member configured to pierce a septum of a sealed vial when the piercing member is biased against the septum of the vial, an extractor flow path, at least a portion of the extractor flow path passing through at least a portion of the housing assembly, a regulator flow path extending between a proximal regulator opening and a distal regulator opening, at least a portion of the regulator ...

Claims

**Claim 1** A vial adapter configured to couple with a sealed vial, a housing assembly comprising a piercing member that can pierce the septum of the sealed vial when the piercing member is biased along an insertion axis against the septum of the vial, an extractor flow path that extends between a proximal extractor opening and a distal extractor opening and is configured to enable fluid to be withdrawn from the sealed vial when the vial adapter is coupled to the sealed vial, and at least a portion of the extractor flow path passes through at least a portion of the housing assembly, the extractor flow path; a regulator flow path that extends between a proximal regulator opening and a distal regulator opening, at least a portion of the regulator flow path passes through at least a portion of the housing assembly, and the distal regulator opening communicates with the interior space of the vial when the vial adapter is coupled to the sealed vial, the regulator flow path; a flexible reservoir configured to receive a regulating fluid from the regulator flow path; a valve in the regulator flow path configured to transition between a closed configuration and an open configuration in response to rotation of the vial adapter about a rotation axis between an upright position and an inverted position, the rotation axis being orthogonal to the insertion axis and the piercing member facing downward in the upright position, the valve; comprising the valve transitions between a closed configuration and an open configuration regardless of the direction of the rotation axis for rotating the vial adapter, the vial adapter, wherein when the valve is in the closed configuration, the valve inhibits fluid from passing through the valve and toward the proximal regulator opening. **Claim 2** The vial adapter according to claim 1, wherein the valve transitions to a closed configuration when the vial adapter is rotated to the inverted position. **Claim 3** The vial adapter according to claim 1, wherein the valve transitions to an open configuration when the vial adapter is rotated to the upright position. **Claim 4** The vial adapter according to claim 1, wherein the valve comprises a valve chamber in fluid communication with the regulator flow path, a closure member within the valve chamber, and a valve seat, and the valve is configured to transition to a closed configuration after the closure member and the valve seat engage, and the valve is configured to transition to an open configuration after the closure member disengages from the valve seat. **Claim 5** The vial adapter according to claim 1, having a generally cylindrical shape and a central axis on the axis. Claim 6 The vial adapter according to claim 1, further comprising a filter positioned within a regulator flow path between the valve and a proximal regulator opening. Claim 7 The vial adapter according to claim 1, configured to be used within an area having a floor, wherein the proximal extractor opening is farther from the floor than the distal extractor opening when the vial adapter is in an upright position, and the proximal extractor opening is closer to the floor than the distal extractor opening when the vial adapter is in an inverted position.

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