Pressure-regulating vial adaptors

Abstract

To provide a vial adaptor configured to couple with a sealed vial.SOLUTION: In certain embodiments, a vial adaptor comprises a housing configured to couple the adaptor with a vial, an access channel, a regulator channel, and a regulator assembly. The access channel is configured to facilitate withdrawal of fluid from the vial when the adaptor is coupled to the vial. The regulator channel is configured to facilitate a flow of a regulating fluid from the regulator assembly to compensate for changes in volume of a medical fluid in the vial. In some embodiments, the regulator assembly includes a flexible member configured to expand and contract in accordance with changes in the volume of the medical 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 partly or completely located in a rigid enclosure.SELECTED DRAWING: Figure 1

Description

[Technical field]

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

[0002] Several embodiments disclosed herein relate to adapters for mating with drug vials, and components thereof, as well as methods for containing vapors and / or helping to regulate pressure within the drug vial. [Background technology]

[0003] It is common practice to store medications or other medical fluids in vials or other containers. In some cases, the medications or fluids so stored have a therapeutic effect when injected into the bloodstream, but are harmful if inhaled or come into contact with exposed skin. Some known systems for extracting potentially harmful medications from vials suffer from various drawbacks. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Pat. No. 5,685,866 [Patent Document 2] U.S. Patent No. 7,547,300 [Patent Document 3] US Patent Application Publication No. 2010 / 0049157 [Patent Document 4] US Patent Application Publication No. 2009 / 0216212 Summary of the Invention [Means for solving the problem]

[0005] In some embodiments, the adapter is configured to mate with the sealed vial and includes a containment device. In some cases, the containment device includes a distal extractor aperture 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 containment device. The adapter can also include an enclosure, such as a regulator enclosure, in fluid communication with the regulator flow path. In some configurations, 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 unfolded, and a second orientation in which at least a portion of the regulator enclosure is at least partially unexpanded or collapsed when fluid is drawn from the sealed vial through the extractor flow path. Additionally, the adapter can include a volume component, such as a filler material, disposed within the regulator enclosure. The filler material need not fill the entire enclosure. In some embodiments, the volume occupied or encompassed by the filler material can be less than a majority of the interior volume of the enclosure, or at least a majority of the interior volume of the enclosure, or substantially all of the interior volume of the enclosure. In some cases, the filler material is configured to secure an initial volume of regulator fluid within the regulator enclosure, such that the adapter can deliver regulator fluid from the regulator enclosure to the sealed vial when fluid is withdrawn from the sealed vial through the extractor opening.

[0006] In some configurations, the adapter is configured such that the regulator enclosure is outside of the sealed vial when the adapter is mated with the sealed vial, hi 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 containment device includes a medical connector interface in fluid communication with the extractor flow path and is configured to mate with a syringe configured to hold a defined volume of fluid in the barrel. In some such cases, the filler material is configured to ensure that an initial volume of the regulator fluid is equal to or greater than the defined volume of fluid. In some of such cases, the initial volume of the regulator fluid in the regulator enclosure is about 60 mL or greater. In some embodiments, the regulator enclosure is configured to hold a maximum volume of the regulator fluid when the regulator enclosure is fully expanded or deployed, the maximum volume being about 180 mL or greater.

[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 metallic component. For example, in some cases, the metallized coating includes aluminum.

[0009] In some embodiments, the pressure regulated vial adapter comprises a piercing member connected to the 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 contracting or collapsing the regulator enclosure as drug fluid is withdrawn from the sealed vial to substantially equilibrate the pressure on the opposite side of the regulator enclosure. In some cases, the regulator enclosure comprises a layer that is substantially impermeable to the drug fluid disposed within the vial, thereby preventing passage of the drug fluid between an exterior surface and an interior surface 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 mated with 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 foam material. For example, in some arrangements, the filler material is made from polyurethane ether foam.

[0011] In some embodiments, a method of withdrawing fluid from a sealed vial includes connecting a pressure regulated vial adapter to a sealed vial and withdrawing fluid from the sealed vial through the pressure regulated vial adapter. In some aspects, the pressure regulated vial adapter comprises a containment device with a distal extractor opening. In some cases, the distal extractor opening is configured to allow for withdrawal 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 extend through the containment device.

[0012] In some configurations, the pressure regulated vial adapter also includes 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 unfolded and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or collapsed when fluid is drawn from the sealed vial via the extractor flow path.

[0013] In some embodiments, the pressure regulated vial adapter further comprises a filler material disposed within the regulator enclosure, the filler material configured to provide an initial volume of regulator fluid within the regulator enclosure such that the adapter can deliver regulator fluid from the regulator enclosure to the sealed vial when fluid is drawn from the sealed vial through the extractor opening.

[0014] In various embodiments, a method of manufacturing an adapter for mating with a sealed vial includes providing a containment device with a distal extractor opening. In some cases, the distal extractor opening is configured to allow the adapter to draw fluid from the sealed vial when mated 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 containment device.

[0015] The method may also include disposing a filler material within the regulator enclosure, the filler material configured to secure an initial volume of regulator fluid within the regulator enclosure such that the adapter can deliver regulator fluid from the regulator enclosure to the sealed vial when fluid is drawn 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 unfolded, and a second orientation in which at least a portion of the regulator enclosure is less expanded or substantially or entirely contracted or folded when fluid is withdrawn from the sealed vial via the extractor flow path.

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

[0018] In various embodiments, the adapter configured to mate with a sealed vial comprises a containment device with a distal extractor opening configured to allow fluid to be drawn from the sealed vial when the adapter is mated 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 containment 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 unfolded, 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 a 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 unfold 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 when regulator fluid passes through the regulator flow path. In some cases, the first side comprises an inner surface that forms a portion of the inside of the regulator enclosure and an outer surface that forms 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 collapse as drug fluid is withdrawn from the sealed vial, substantially equilibrating the pressure on the other side of the regulator enclosure. In some embodiments, the regulator enclosure comprises a layer that is substantially impermeable to the drug fluid disposed within the vial, thereby preventing passage of the drug fluid between the exterior and interior surfaces of the enclosure.

[0021] The adapter may further include a hydrophobic filter disposed between the regulator enclosure and the distal regulator opening. The hydrophobic filter may be configured to allow regulator fluid to flow between the regulator enclosure and the vial when the adapter is mated with the vial.

[0022] The adapter can also include a filler material disposed within the regulator enclosure, the filler material configured to secure an initial volume of regulator fluid within the regulator enclosure such that the adapter can deliver 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, the vial adapter configured to mate with a sealed vial comprises a containment device comprising a distal extractor opening configured to allow the adapter to draw fluid from the sealed vial when mated 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 containment device. 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 unfolded 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 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 include 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 toward the storage device. In some cases, each of the first side and the second side is configured to expand, contract, fold, or unfold when a regulator fluid, such as air, gas, or steam, passes through the regulator flow path. In some configurations, the second side is configured to move away from or toward the storage device when the regulator fluid passes through the regulator flow path. In many cases, the regulator enclosure does not fit completely within the rigid housing.

[0025] In some embodiments, a vial adapter configured to mate with a sealed vial comprises a containment device comprising a distal extractor opening configured to allow fluid to be drawn from the sealed vial when the adapter is mated 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 containment device. In some embodiments, the vial adapter comprises a regulator enclosure in fluid communication with the regulator flow path and configured 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 unfolded 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 via the extractor flow path.

[0026] In some embodiments, the regulator enclosure has a first layer connected to a second layer opposite the first layer. The first layer and the second layer can be configured to receive a volume of the regulator fluid therebetween. In some configurations, each of the first side and the second side is configured to expand, contract, fold, or unfold when the regulator fluid passes through the regulator flow path. In some cases, the second side is configured to move away from or toward the containment device when the regulator fluid passes through the regulator flow path. In some cases, the regulator enclosure does not fit completely within the 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 at the periphery of the first layer and the second layer. In some cases, the first layer and the second layer each include a center portion and the first layer and the second layer are not connected at the center portion.

[0028] In some embodiments, a modular vial adapter configured to mate with a sealed vial comprises a pressure regulated vial adapter module and a regulator fluid module. In some cases, the pressure regulated vial adapter module comprises a containment device comprising a distal extractor opening configured to allow for drawing fluid from the sealed vial when the adapter is mated 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 containment device.

[0029] The pressure regulated vial adapter module can include a proximal regulator opening in fluid communication with the regulator flow path. In some configurations, the proximal regulator opening is configured such that the vial adapter module is coupled with a sealed vial to allow regulator fluid to flow therethrough or out as fluid is withdrawn from the vial.

[0030] In some cases, the regulator fluid module includes a regulator enclosure configured to mate with the proximal regulator opening and 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 regulator fluid passes through an enclosure opening in the regulator enclosure.

[0031] The regulator fluid module can include a fastener configured to couple the regulator enclosure to the proximal regulator opening. In some cases, the regulator enclosure does not fit completely within the rigid housing. In some cases, the fastener includes an anchoring member having a first surface and a second surface coated with an adhesive. In some such cases, the anchoring 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 mate with a sealed vial includes providing a pressure regulated vial adapter module and providing a regulator fluid module. The pressure regulated vial adapter module can include a containment device. The containment device can include a distal extractor opening configured to allow for drawing fluid from the sealed vial when the adapter is mated 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 containment device.

[0033] The pressure regulated vial adapter module can include a proximal regulator opening in fluid communication with the regulator flow path. The proximal regulator opening can be configured to allow regulator fluid to flow therethrough when the vial adapter module is mated with a sealed vial and fluid is withdrawn from the vial.

[0034] In some embodiments, the regulator fluid module comprises a regulator enclosure. The regulator enclosure may 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 contracted or folded when regulator fluid passes through an enclosure opening in the regulator enclosure. The regulator fluid module may comprise a fastener configured to couple the regulator enclosure with the proximal regulator opening. In some cases, the regulator enclosure does not fit completely within the rigid housing.

[0035] The method may further include aligning an enclosure opening of the regulator enclosure with a proximal regulator opening of the pressure regulated vial adapter module, hi some embodiments, the method also includes fastening the regulator fluid module to the pressure regulated vial adapter module.

[0036] In some cases, the fastener comprises an adhesively coated first surface and a second surface. In some such cases, the adhesive member is made from a material system that includes an elastic material. In some cases, the adhesive 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 clip onto the pressure regulated vial adapter module to form a vial adapter for mating with a sealed vial. The pressure regulated vial adapter module can include a containment device including a distal extractor opening configured to allow fluid to be drawn from the sealed vial when the adapter is mated 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 containment device. In some cases, the containment device also includes a proximal regulator opening 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 mated to the sealed vial and fluid is drawn 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 contracted or folded, when regulator fluid passes through an enclosure opening in the regulator enclosure.

[0039] The regulator fluid module can include a filler material in the regulator enclosure configured to provide an initial volume of regulator fluid in the regulator enclosure such that the adapter can provide regulator fluid from the regulator enclosure to the sealed vial when fluid is drawn from the sealed vial through the extractor opening.

[0040] In various embodiments, the regulator fluid module includes a fastener configured to couple the regulator enclosure to the proximal regulator opening such that the regulator fluid module is permitted to move small distances relative to the pressure regulated vial adapter module during routine operation without the fastener tearing, breaking, or otherwise being damaged. In some cases, the regulator enclosure does not fit completely within the rigid housing. In some configurations, the fastener substantially couples and hermetically seals the regulator enclosure and the proximal regulator opening.

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

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

[0043] In some embodiments, the method includes providing a regulator enclosure configured to be positioned in fluid communication with the opening, such that 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 regulator fluid passes through the opening in the regulator enclosure.

[0044] In many cases, the method further includes selecting a regulator enclosure from regulator enclosures of various sizes. In some embodiments, the selection may be based on a volume of drug fluid to be withdrawn from the sealed vial. In some cases, a flow of the regulator fluid passes between the opening and the sealed vial as drug fluid is withdrawn from the sealed vial via the access channel. In some cases, the opening is in fluid communication with ambient air prior to the regulator enclosure being positioned in fluid communication with the opening.

[0045] In some embodiments, the vial adapter comprises a housing configured to mate with 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 mated to the vial. The regulator flow path is configured to facilitate flow of the conditioning fluid from the regulator assembly to compensate for changes in the volume of the drug fluid in 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 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 the rigid enclosure. In some embodiments, at least a majority of the flexible member is disposed within the rigid enclosure. In some embodiments, the regulator assembly comprises a filter in the regulator flow path. In some embodiments, the regulator fluid assembly comprises a check valve capable of preventing fluid communication between the filter in the regulator flow path and the vial. In some embodiments, the check valve is capable of preventing fluid communication between the vial and a flexible member on an end of the regulator flow path.

[0046] In some embodiments, the vial adapter has a centerline on an axis and is configured for use within a predetermined area having a floor. The vial adapter may be configured to mate with a sealed vial. The vial adapter may have a piercing member and an extractor flow path, the extractor flow path extending between a proximal extractor opening and a distal extractor opening, and configured to allow for drawing fluid from the sealed vial when the vial adapter is mated 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 may include a regulator flow path extending 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 may be housed within the regulator flow path and may be configured to transition between closed and open configurations in response to rotation of the vial adapter about an 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. Additionally, the occluder valve may inhibit fluid from passing through the occluder valve toward the proximal regulator opening when the occluder valve is in the closed configuration. The axis of rotation may be perpendicular to an axial centerline of the vial adapter, and the manner in which the occluder valve transitions between the closed and open configurations may be substantially independent of the axis of rotation that rotates the vial.

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

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

[0050] In some embodiments, the vial adapter comprises a filter. The filter may be positioned in 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 specific embodiments, the vial adapter has a centerline on the axis and is configured to mate with a sealed vial. The vial adapter can include 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 includes a regulator flow path that can extend between a proximal regulator opening and a distal regulator opening, where at least a portion of the regulator flow path passes through at least a portion of the piercing member.

[0052] The vial adapter may include an occluder valve configured to be mounted in at least a portion of the regulator flow path via a mounting path. The occluder valve may be further configured to transition between a closed configuration and an open configuration. In some embodiments, the occluder valve includes a valve chamber in fluid communication with the regulator flow path. The valve chamber may have an occluding member, a travel path for the occluding member, and a valve seat. In some embodiments, the occluder valve includes a valve flow path in fluid communication with the valve chamber and the regulator flow path, the valve flow path having a flow path. The occluder valve may be configured to transition to the closed configuration when the occluding member engages the valve seat. In some embodiments, the occluder valve is configured to transition to the open configuration when the occluding member disengages from the valve seat. An angle between the travel path of the occluding member and the mounting path of the occluder valve may be greater than 0° and less than 180°. In some embodiments, the travel path for the occluding member is not substantially parallel to the mounting path of the occluder valve.

[0053] In some embodiments, the occlusion member may be a spherical ball, or may have a cylindrical shape with one tapered end, or may have an ellipsoid shape, or may have any other suitable shape or combination of shapes. In some embodiments, the angle between the movement path of the occlusion member and the installation path of the occlusion valve is greater than about 45° and less than about 135°. In some embodiments, the angle between the movement path and the installation path is about 90°. The angle between the movement path and the installation path may be substantially the same as the angle between the axial centerline of the vial adapter and the installation path. In some embodiments, the vial adapter includes a filter in the regulator flow path between the occlusion valve and the proximal regulator opening. The filter may be a hydrophobic filter.

[0054] A method of manufacturing a modular vial adapter configured to mate with a sealed vial can include selecting a connector interface having a centerline on an axis. The connector interface can have a piercing member and an extractor flow path, the extractor flow path passing 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, at least a portion of the regulator flow path passing through at least a portion of the piercing member.

[0055] In some embodiments, the method of manufacturing can include coupling a regulator assembly to a proximal regulator opening of the connector interface. The regulator assembly can include a regulator pathway configured to be in fluid communication with the regulator flow path when the regulator assembly is coupled to the connector interface. In some embodiments, the regulator includes an occluder valve at least partially mounted in one or more of the regulator flow path and the regulator pathway via a mounting pathway. The occluder valve can be configured to transition between a closed configuration and an open configuration. In some embodiments, the occluder valve includes a valve chamber in fluid communication with one or more of the regulator flow path and the regulator pathway. The valve chamber can have an occlusion member, a travel path for the occlusion member, and a valve seat. In some embodiments, the occluder valve can have a valve flow path in fluid communication with the valve chamber and the regulator flow path and one or more of the regulator pathway and the regulator pathway. Additionally, the valve flow path can have a flow path.

[0056] The occluder valve may be configured to transition to a closed configuration when the occluder member engages the valve seat. In some embodiments, the occluder valve is configured to transition to an open configuration when the occluder member disengages from the valve seat. An angle between the path of travel of the occluder member and the path of installation of the occluder valve may be greater than 0° and less than 180°.

[0057] The method of manufacturing a modular vial adapter may also include installing the occluder valve at least partially in one or more of the regulator flow path and the regulator pathway via an installation path. In some embodiments, the method includes selecting an occluder valve in which an angle between a travel path in the occluder valve and an installation path of the occluder valve is substantially the same as an angle between an installation path of the coupling interface and an axial centerline. The method may include aligning a protrusion of the regulator assembly with a proximal regulator opening of the connector interface, the protrusion and the proximal regulator opening being keyed. In some embodiments, the method includes aligning an alignment feature on the occluder valve with an alignment feature of the regulator flow path. Aligning an alignment feature of the occluder valve with an alignment feature of the regulator flow path may orient the occluder valve such that the travel path is substantially parallel to the axial centerline of the connector interface when the regulator assembly is coupled to the connector interface and the occluder valve is at least partially installed in one or more of the regulator flow path and the regulator pathway.

[0058] Various embodiments are illustrated in the accompanying drawings for purposes of illustration, and should in no way be construed as limiting the scope of the embodiments. In addition, various features of different disclosed embodiments can be combined to form additional embodiments that become part of this disclosure. [Brief description of the drawings]

[0059] [Figure 1] FIG. 1 shows a schematic of a system for withdrawing fluid from and / or injecting fluid into a vial. [Diagram 2] FIG. 1 shows a schematic of another system for withdrawing fluid from and / or injecting fluid into a vial. [Figure 2A] FIG. 1 shows a schematic of another system for withdrawing fluid from and / or injecting fluid into a vial. [Diagram 3]FIG. 1 illustrates another system for withdrawing fluid from and / or injecting fluid into a vial. [Figure 4] FIG. 2 is a perspective view of a vial adapter and a vial. [Diagram 5] FIG. 5 is a partial cross-sectional view of the vial adapter of FIG. 4 coupled with a vial in a high capacity stage. [Figure 6] FIG. 5 is a partial cross-sectional view of the vial adapter of FIG. 4 in an expanded stage and coupled with a vial. [Figure 7] FIG. 2 is an exploded perspective view of the vial adapter. [Figure 7A] 7A is a perspective view of the vial adapter of FIG. 7 in an assembled state, including a partial cross-sectional view taken along line 7A-7A of FIG. 7. [Figure 8] FIG. 8 is an exploded perspective view of a portion of the vial adapter of FIG. [Figure 9] FIG. 9 is an assembled perspective view of a portion of the vial adapter of FIG. 8. [Figure 10] FIG. 8 is an exploded perspective view of the base and cover of the coupling portion of the vial adapter of FIG. 7. [Figure 11] FIG. 11 is a top view of the coupling portion of FIG. [Figure 12] 12 is a cross-sectional view of the joint of FIG. 11 taken along line 12-12 of FIG. 11. [Figure 13] FIG. 2 is a partial cross-sectional view of a vial adapter coupled to a vial in an initial stage. [Figure 14] FIG. 14 is a partial cross-sectional view of the vial adapter of FIG. 13 coupled with an enlarged or high capacity stage vial. [Figure 15] FIG. 14 is a partial cross-sectional view of the vial adapter of FIG. 13 coupled with a vial in a deflated or low volume stage. [Figure 16] FIG. 13 is a partial cross-sectional view of a vial adapter coupled to a vial. [Figure 17] FIG. 13 is a partial cross-sectional view of a vial adapter with internal structure coupled to a vial. [Figure 18]FIG. 13 is a partial cross-sectional view of a vial adapter comprising multiple regulator assemblies coupled to a vial. [Figure 19] FIG. 13 is a partial cross-sectional view of a vial adapter with a counterweight coupled to a vial. [Figure 20A] 20 is a cross-sectional view of the keyed coupling of the vial adapter of FIG. 19 taken along line 20-20 of FIG. 19. [Figure 20B] 20 is a cross-sectional view of the keyed coupling of the vial adapter of FIG. 19 taken along line 20-20 of FIG. 19. [Figure 20C] 20 is a cross-sectional view of the keyed coupling of the vial adapter of FIG. 19 taken along line 20-20 of FIG. 19. [Figure 20D] 20 is a cross-sectional view of the keyed coupling of the vial adapter of FIG. 19 taken along line 20-20 of FIG. 19. [Figure 20E] 20 is a cross-sectional view of the keyed coupling of the vial adapter of FIG. 19 taken along line 20-20 of FIG. 19. [Figure 20F] 20 is a cross-sectional view of the keyed coupling of the vial adapter of FIG. 19 taken along line 20-20 of FIG. 19. [Figure 21] FIG. 13 is a partial cross-sectional view of a vial adapter with a check valve coupled to a vial. [Figure 22] FIG. 13 is a partial cross-sectional view of a vial adapter with multiple check valves coupled to a vial. [Figure 23] FIG. 13 is a partial cross-sectional view of a substantially axially centered vial adapter. [Figure 24] FIG. 13 is a partial cross-sectional view of a vial adapter with an annular bag coupled to a vial. [Figure 25A] FIG. 1 is a partial cross-sectional view of a reservoir including a bag and a rigid enclosure. [Figure 25B] FIG. 13 is a partial cross-sectional view of another reservoir comprising a partially rigid enclosure with a flexible annular ring. [Figure 25C] FIG. 13 is a partial cross-sectional view of another reservoir comprising a partially rigid enclosure with a rigid annular ring. [Figure 25D] FIG. 13 is a partial cross-sectional view of another reservoir comprising a series of rigid and flexible rings. [Figure 25E] FIG. 25E is a side view of the reservoir shown in FIG. 25D. [Figure 26A] FIG. 2 is a cross-sectional view of a vial adapter. [Figure 26B] FIG. 13 is a partial cross-sectional view of a vial adapter with a valve coupled to a vial. [Figure 26C] FIG. 8 is a perspective view of the vial adapter of FIG. 7 in an assembled state including a valve. [Figure 27A] FIG. 13 is a partial cross-sectional view of a portion of an inverted vial adapter including a ball check valve. [Figure 27B] FIG. 27B is an enlarged cross-sectional view of the ball check valve of FIG. 27A. [Figure 27C] FIG. 27B is a perspective cross-sectional view of the ball check valve of FIG. 27A. [Figure 28] 13 is a partial cross-sectional view of a portion of another vial adapter including a ball check valve. [Figure 29] FIG. 2 is an enlarged cross-sectional view of a dome-shaped valve. [Figure 30A] FIG. 2 is an enlarged cross-sectional view of a showerhead dome valve. [Figure 30B] FIG. 30B is an elevational view of the showerhead dome valve taken along line BB in FIG. [Figure 31A] FIG. 2 is an enlarged cross-sectional view of a flap check valve. [Figure 31B] FIG. 31B is a perspective cross-sectional view of the flap check valve of FIG. 31A. [Diagram 32] FIG. 13 is an enlarged cross-sectional view of a ball check valve in the piercing member of the adapter; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0060] Although specific embodiments and examples are disclosed herein, the subject matter of the present invention extends beyond the examples in the specifically disclosed embodiments to other alternative embodiments and / or applications, as well as modifications and equivalents thereof. Thus, 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 acts or operations of the methods or processes may be performed in any suitable order and are not necessarily limited to the specific disclosed order. Various operations may then be described as multiple discrete operations in a manner that may aid in the understanding of some embodiments, but the order of description should not be construed to imply that these operations are order-dependent. In addition, the structures, systems, and / or devices described herein may be embodied as integrated components or as separate components. For purposes of comparing various embodiments, certain aspects and advantages of these embodiments are described. It is not necessarily the case that all such aspects or advantages are achieved by a particular embodiment. Thus, for example, various embodiments may be implemented in a manner that achieves or optimizes one or more advantages as taught herein without necessarily achieving other aspects or advantages that may also be taught or suggested herein.

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

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

[0063] Many medications and other therapeutic fluids are stored and dispensed in medication 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 the particular atmospheric pressure from which the fluid is later removed can often cause a variety of problems and can also lead to the release of potentially harmful vapors.

[0064] For example, the introduction of the piercing member of a vial adapter through the septum of the vial can cause a pressure increase within the vial. This pressure increase can cause fluid to leak from the vial at the interface between the septum and the piercing member or at the attachment interface between the adapter and a medical device such as a syringe. It can also be difficult to withdraw a precise amount of fluid from a sealed vial using an empty syringe or medical instrument because the fluid can naturally be biased back into the vial when the syringe plunger is removed. Additionally, when the syringe is uncoupled from the vial, a pressure differential often causes a volume of fluid to squirt out of the syringe or vial.

[0065] Furthermore, in some cases, the introduction of a fluid into the vial may increase the pressure in 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 product in the vial. This introduction of a fluid into the vial may cause the pressure in the vial to be higher than the pressure of the surrounding environment, which may result in the fluid leaking out of the vial at the interface between the septum and the piercing member or the attachment interface between the adapter and a medical device such as a syringe. Furthermore, the increased pressure in the vial may make it difficult to introduce a precise amount of fluid into the vial using a syringe, or other medical instrument. Also, if the syringe is removed from the vial when the pressure inside the vial is greater than the surrounding pressure (e.g., atmospheric pressure), a pressure gradient may cause some of the fluid to spray out of the vial.

[0066] In addition, in many cases, air bubbles are drawn into the syringe as the fluid is drawn from the vial. Such air bubbles are generally undesirable as they may result in embolisms when injected into a patient. To remove air bubbles from the syringe after removal from the vial, medical professionals often gently shake the syringe to gather all the air bubbles near the opening of the syringe and then push the air bubbles out. In doing so, a small amount of liquid is usually also expelled from the syringe. Medical personnel generally do not take special steps to recombine the syringe with 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 require that the overdrawn fluid be expelled at a predetermined location outside the vial. Furthermore, when attempting to reinsert the excess air or fluid into the vial, pressure differentials can sometimes result in inaccurate measurements of the drawn fluid.

[0067] To eliminate these problems caused by pressure differentials, medical professionals frequently pre-fill an empty syringe with a precise volume of outside air that corresponds to the volume of fluid they intend to draw from the vial. They then pierce the vial, forcing this outside air into the vial and momentarily increasing the pressure within the vial. When the desired volume of fluid is later drawn, the pressure difference between the inside of the syringe and the inside of the vial is generally close to equilibrium. The volume of fluid in the syringe can then be adjusted slightly to remove the air bubbles without resulting in a demonstrable pressure difference between the vial and the syringe. However, this approach has a significant disadvantage, especially in hospital environments, in that the outside air may harbor a variety of airborne viruses, bacteria, dust, spores, mold, and other unsanitary and harmful contaminants. The pre-filled outside air in the syringe may contain one or more of these harmful substances and may then mix with the medication or other therapeutic fluid in the vial. This contaminated fluid can be particularly dangerous if injected directly into a patient's bloodstream, as airborne pathogens evade many of the body's natural defenses against these airborne pathogens. Furthermore, patients requiring medications and other therapeutic fluids are likely to suffer from a reduced ability to fight infection.

[0068] All of the above problems can be particularly significant in the context of oncology drugs and some other drugs. Although such drugs are beneficial when injected into a patient's bloodstream, they can be extremely harmful if inhaled or touched. Thus, such drugs can be dangerous if allowed to inadvertently squirt out of the vial due to pressure differences. Furthermore, these drugs are often volatile and can instantly aerosolize when exposed to the atmosphere. Thus, expelling small amounts of such drugs, even in a controlled manner, to remove air bubbles or excess fluid from a syringe is generally not a feasible option, especially for medical personnel who may repeat such actions many times a day.

[0069] Some devices use a rigid enclosure to enclose all or part of a volume changing component or region to aid in regulating the pressure within the container. Although such enclosures may provide rigidity, they typically make the device bulky and unbalanced. Combining such devices with a vial typically results in a top-heavy, unstable system prone to tipping over and possibly spilling the contents of the device and / or the vial.

[0070] Indeed, some such coupling devices include relatively large and / or heavy, rigid components that are cantilevered or otherwise disposed at a fixed distance from the axial center of the device, thereby exacerbating the tendency of the device to tip over.

[0071] Additionally, such rigid enclosures may increase the size of the device, thereby requiring more material to form the device, and may otherwise increase the costs associated with manufacturing, shipping, and / or storing the device. Furthermore, such rigid enclosures may also impede the ability of the device to expand or contract to deliver the conditioning fluid to the vial. No feature, structure, or step disclosed herein is essential or required.

[0072] 1 is a schematic diagram of a container 10, such as a pharmaceutical vial, that may be coupled with an accessor 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 through the accessor 20 without causing a significant change in pressure within the container 10.

[0073] Generally, container 10 is hermetically sealed to preserve the contents of container 10 in a sterile environment. Container 10 may be evacuated or pressurized after sealing. In some cases, 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 may also be sealed within container 10. In some cases, a solid or powdered substance, such as a lyophilized pharmaceutical, is disposed within container 10.

[0074] The access mechanism 20 generally provides access to the contents of the container 10 so that contents may be removed or added. In some arrangements, the access mechanism 20 comprises an opening between the inside and outside of the container 10. The access mechanism 20 may further comprise a passageway between the inside and outside of the container 10. In some arrangements, the passageway of the access mechanism 20 may be selectively opened and closed. In some arrangements, the access mechanism 20 comprises a conduit that penetrates a surface of the container 10. The access mechanism 20 may be integrally formed with the container 10 prior to sealing or may be introduced into the container 10 after the container 10 is sealed.

[0075] In some configurations, the accessor 20 is in fluid communication with the container 10, as indicated by arrow 21. In some of these configurations, if the pressure inside the container 10 changes from the pressure of the surrounding environment, then communication occurs through the accessor 20 upon introduction of the accessor 20 into the container 10. For example, in some arrangements, the pressure of the environment surrounding the container 10 exceeds the pressure within the container 10, which may cause outside air to flow in from the environment through the accessor 20 after inserting the accessor 20 into the container. In other arrangements, the pressure inside the container 10 exceeds the pressure of the surrounding environment, which causes the contents of the container 10 to flow out through the accessor 20.

[0076] In some configurations, the accessor 20 is coupled with the exchange device 40. In some cases, the accessor 20 and the exchange device 40 are separable. In some cases, the accessor 20 and the exchange device 40 are integrally formed. The exchange device 40 is configured to receive fluids and / or gases from the container 10 via the accessor 20, introduce fluids and / or gases into the container 10 via the accessor 20, or perform some combination of these two operations. In some arrangements, the exchange device 40 is in fluid communication with the accessor 20, as indicated by arrow 24. In some configurations, the exchange device 40 comprises a medical instrument, 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 there being a pressure difference between the inside of the container 10 and the surrounding environment or the absence of a pressure difference. For example, if the pressure outside the container 10 exceeds the pressure within the container 10, an exchange device 40 comprising a syringe can remove the contents of the container 10 if sufficient force is applied to withdraw the plunger from the syringe. The exchange device 40 can similarly introduce fluids and / or gases into the container 10 regardless of the pressure difference between the inside of the container 10 and the surrounding environment.

[0078] In some configurations, the regulator 30 is coupled to the vessel 10. The regulator 30 generally regulates the pressure within the vessel 10. As used herein, the term "regulate" or any derivative thereof is intended to be broad and used in its ordinary sense and includes any active, affirmative, or positive action, or any passive, reactive, responsive, adaptive, or compensatory action that has a tendency to bring about a change, unless otherwise noted. In some cases, the regulator 30 substantially maintains a pressure differential, or equilibrium state, between the inside of the vessel 10 and the surrounding environment. As used herein, the term "maintain" or any derivative thereof is intended to be broad and used in its ordinary sense and includes a tendency to maintain an original state for a period of time, tolerating some degree of change, as small as appropriate in the circumstances. In some cases, the regulator 30 maintains a substantially constant pressure within the vessel 10. In some cases, the change in pressure within the vessel 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 a further example, the regulator 30 equalizes the pressure on the contents of the 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 the amounts the same or approach the same, allowing for some variation as small as appropriate in the context. In some configurations, the regulator 30 is coupled to the container 10 to allow or encourage equalization of a pressure difference between the inside of the container 10 and some other environment, such as the environment surrounding the container 10 or the environment within the exchange device 40. In some arrangements, a single device includes the regulator 30 and the access mechanism 20. In other arrangements, the regulator 30 and the access mechanism 20 are separate units.

[0079] The regulator 30 is generally in fluid communication with the container 10, as indicated by arrow 31, and with a reservoir 50, as indicated by further arrow 35. In some configurations, the reservoir 50 comprises at least a portion of the environment surrounding the container 10. In some configurations, the reservoir 50 comprises a container, canister, bag, or other holder dedicated to the regulator 30. As used herein, the term "bag" or any of its derivatives is intended to be broad in its ordinary sense and includes, for example, a sac, balloon, bladder, receptacle, enclosure, diaphragm, or expandable and / or contractible membrane comprising a structure that includes a flexible, pliable, yielding, elastic, stretchable, and / or distensible material. In some embodiments, the reservoir 50 contains a gas and / or liquid. As used herein, the term "flexible," or any of its derivatives, is a broad term used in its ordinary sense to describe, 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 any of its derivatives, is a broad term used in its ordinary sense to describe, 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, the regulator 30 provides fluid communication between the container 10 and the reservoir 50. In some of such embodiments, the fluid in the reservoir 50 comprises primarily gas so as not to appreciably dilute the liquid contents of the container 10. In some arrangements, the regulator 30 includes a filter to purify or remove contaminants from the gas or liquid entering the container 10, thereby reducing the risk of contaminating the contents of the container 10. In some arrangements, the filter is hydrophobic so that air can enter the container 10 but fluid cannot escape therefrom. In some arrangements, the regulator 30 includes a check valve that operates in an orientation or is sensitive to the orientation to selectively inhibit fluid communication between the container 10 and the filter. In some arrangements, the regulator 30 includes a check valve that selectively inhibits fluid communication between the container 10 and the filter when the regulator 30 is oriented such that it is held above the regulator 30 (e.g., further from the floor than from the regulator 30).

[0081] In some embodiments, the regulator 30 prevents fluid communication between the container 10 and the reservoir 50. In some of such embodiments, the regulator 30 acts as an interface between the container 10 and the reservoir 50. In some arrangements, the regulator 30 comprises a substantially impermeable bladder that can accommodate the flow of gas and / or liquid into the container 10 or the flow of gas and / or liquid out of the container 10.

[0082] As illustrated generally in FIG. 2, in some embodiments, the access mechanism 20, or portions thereof, are disposed within the container 10. As explained in detail above, the access mechanism 20 may be integrally formed with the container 10 or may be separate from the container 10. In some embodiments, the regulator 30, or portions thereof, are disposed outside the container 10. In some arrangements, the regulator 30 is integrally formed with the container 10. It is possible to have any combination of the access mechanism 20, or portions thereof, wholly or partially contained within the container 10 or located outside the container 10, and / or the regulator 30, or portions thereof, wholly or partially contained within the container 10 or located outside the container 10.

[0083] In some embodiments, the accessor 20 is in fluid communication with the container 10. In further embodiments, the accessor 20 is in fluid communication with an 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 either fluid or non-fluid communication with the reservoir 50, as indicated by arrow 35.

[0085] As illustrated generally in FIG. 2A, in some embodiments, the access mechanism 20, or portions thereof, may be located within the container 10. In some embodiments, the access mechanism 20, or portions thereof, may be located outside the container 10. In some embodiments, the valve 25, or portions thereof, may be located outside the container 10. In some embodiments, the valve 25, or portions thereof, may be located within the container 10. In some embodiments, the regulator 30 is located entirely outside the container 10. In some embodiments, the regulator 30, or portions thereof, may be located within the container 10. It is possible to have any combination of the access mechanism 20, or portions thereof, located entirely or partially within the container 10 or outside the container 10, and / or the valve 25, or portions thereof, located entirely or partially within the container 10 or outside the container 10. It is also possible to have any combination of an access mechanism 20, or a portion thereof, located wholly or partially within the container 10 or outside the container 10, and / or a regulator 30, or a portion thereof, located wholly or partially within the container 10 or outside the container 10.

[0086] The accessor 20 may be in fluid communication with the container 10, as indicated by arrow 21. In some embodiments, the accessor 20 may be in fluid communication with an 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 integral with the container 10 or may be separate from the container 10. In some embodiments, the valve 25 may be integral with the regulator 30 or may be separate 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 reservoir 50, as indicated by arrow 35B. In some embodiments, the reservoir 50 may comprise a bag or other flexible enclosure. In some embodiments, the reservoir 50 comprises a rigid container that encloses a flexible enclosure. In some embodiments, the reservoir 50 comprises an enclosure that is partially rigid.

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

[0090] In some embodiments, the valve 25 may be a one-way check valve. In some embodiments, the valve 25 may be a two-way check valve. According to some configurations, the valve 25 may selectively inhibit fluid communication between the filter and / or reservoir 50 and the container 10. In some embodiments, the valve 25 may selectively inhibit fluid communication between the container 10 and the filter and / or reservoir 50 when the container 10 is oriented above the exchange device 40. FIG. 3 illustrates an embodiment of a system 100 including a vial 110, an access mechanism 120, and a regulator 130. The vial 110 includes a body portion 112 and a cap 114. In the illustrated embodiment, the vial 110 contains a medical fluid 116 and a relatively small amount of sterile air 118. In some arrangements, the fluid 116 is removed from the vial 110 when the vial 110 is oriented with the cap 114 facing down (e.g., the cap 114 is between the fluid and the floor). The access mechanism 120 comprises a conduit 122 fluidly connected to one end of an exchange device 140, such as a standard syringe 142 having a plunger 144. The conduit 122 penetrates the cap 114 into the fluid 116. The regulator 130 comprises a bag 132 and a conduit 134. The bag 132 and the conduit 134 are in fluid communication with a reservoir 150 that contains a volume of purified and / or sterilized air. The outer surface of the bag 132 is generally in contact with the outside air surrounding both the system 100 and the exchange device 140. The bag 132 comprises a substantially impermeable material to prevent the fluid 116, the air 118 inside the vial 110, and the reservoir 150 from contacting the outside air.

[0091] In the illustrated embodiment, the area outside the vial 110 is under atmospheric pressure. Thus, the pressure on the syringe plunger 144 is equal to the pressure on the inside of the bladder 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 the fluid 116. Retracting the flange 144 increases the effective volume of the vial 110, which reduces the pressure within the vial 110. This reduction in pressure within the vial 110 increases the pressure differential between the vial 110 and the syringe 142, which causes the fluid 116 to flow into the syringe 142 and the fluid within the reservoir 150 to flow into the vial 110. Additionally, the reduction in pressure within the vial 110 increases the pressure differential between the outside and inside of the bladder 132, which causes the bladder 132 to reduce or contract its internal volume, which then forces a volume of conditioning fluid through the conduit 134 and into the vial 110. In effect, the bladder 132 contracts outside the vial 110 to reach a new volume that compensates for the volume of fluid 116 being withdrawn from the vial 110. Thus, when the plunger 144 stops withdrawing from the vial 110, the system is again in equilibrium. With the system 100 operating closer to equilibrium, withdrawal of the fluid 116 is facilitated. Furthermore, because the system 100 is in equilibrium, the plunger 144 remains in the position where it was withdrawn, thereby allowing a precise amount of fluid 116 to be removed from the vial 110.

[0092] In some arrangements, the reduced volume of bladder 132 is approximately equal to the volume of liquid removed from vial 110. In some arrangements, the rate at which the volume of bladder 132 decreases as more fluid is withdrawn from vial 110 slows, such that the volume of fluid withdrawn from vial 110 is greater than the reduced volume of bladder 132.

[0093] In some arrangements, the bag 132 may be substantially and / or completely deflated, such that there is substantially no volume inside the bag 132. In some cases, this deflation of the bag 132 actually creates a pressure differential between the inside of the bag 132 and the inside of the vial 110. For example, a vacuum (relative to the outside air) may be created inside the vial 110 when the bag 132 is deflated. In some cases, this deflation of the bag 312 does not substantially create a restoring force that would tend to create a pressure differential between the inside of the bag 132 and the inside of the vial 110, such as when the bag 132 is not generally resilient.

[0094] In some embodiments, the syringe 142 comprises fluid contents 143. A portion of the fluid contents 143 can be introduced into the vial 110 by depressing the plunger 144 (e.g., toward the vial), which may be desirable in some cases. For example, in some cases it may be desirable to introduce a solvent and / or compounding fluid into the vial 110. In some cases, more fluid 116 than desired may be inadvertently drawn out initially. In some cases, some of the air 118 present in the vial 110 may be drawn out initially, causing undesirable air bubbles in the syringe 142. Thus, it may be desirable to return some of the drawn fluid 116 and / or air 118 back into the vial 110.

[0095] When the plunger 144 is pressed, the fluid contents 143 of the syringe flow into the vial 110, which reduces the effective volume of the vial 110, which increases the pressure in the vial 110. When the pressure in the vial 110 increases, the pressure difference between the outside and the inside of the bladder 132 increases, which causes the air 118 to flow into the bladder 132, which then expands. In effect, the bladder 132 expands or grows 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 is again in equilibrium. When the system 100 operates close to equilibrium, the introduction of the contents 143 is easier to perform. Moreover, because the system 100 is in equilibrium, the plunger 144 generally remains in the position in which it was pressed, which allows the exact amount of the contents 143 of the syringe 142 to be introduced into the vial 110.

[0096] In some arrangements, the increased volume of the bag 132 is approximately equal to the volume of air 118 removed from the vial 110. In some arrangements, the rate at which the volume of the bag 132 increases as more contents 143 are introduced into the vial 110 slows, such that the volume of the contents 143 introduced into the vial 110 is greater than the increased volume of the bag 132.

[0097] In some arrangements, the bladder 132 may be stretched, expanding beyond its rest volume. In some cases, this stretching creates a restoring force that actually creates a pressure differential between the inside of the bladder 132 and the inside of the vial 110. For example, a slight overpressure (relative to the outside air) may be created inside the vial 110 when the bladder 132 is stretched.

[0098] FIG. 4 illustrates one embodiment of a vial adapter 200 for coupling with a vial 210. The vial 210 may comprise a container suitable for storing a medical fluid. In some cases, the vial 210 may comprise any of many standard medical vials known in the art, such as those produced by Abbott Laboratories, Abbott Park, Illinois. In some embodiments, the vial 210 may 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 hard, 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 may comprise an elastomeric material that may deform to form a substantially airtight seal around an article when pierced by the article. For example, in some cases, the septum 216 comprises silicone rubber or butyl rubber. The casing 218 may comprise a material suitable for sealing the vial 210. In some cases, the casing 218 comprises metal that is crimped around the septum 216 and a portion of 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 comprises 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 its derivatives refers to a 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 its derivatives refers to the opposite direction. In some configurations, the piercing member 220 comprises a sheath 222. The sheath 222 may be substantially cylindrical, as shown, or may have other geometric configurations. In some cases, the sheath 222 tapers 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. The sheath 222 may comprise a rigid material, such as a metal or plastic, suitable for insertion through the septum 216. In some embodiments, the sheath 222 comprises polycarbonate plastic.

[0100] In some configurations, the piercing member 220 includes a tip 224. The tip 224 may have a variety of shapes and configurations. In some cases, the tip 224 is configured to facilitate insertion of the sheath 222 through the septum 216 via an insertion axis. In some embodiments, the insertion axis corresponds to a direction in which a force required to couple the adapter 200 to the vial 210 is applied when coupling the adapter 200 to the vial 210. The insertion axis may be substantially perpendicular to a plane on which the cap 214 rests. In some embodiments, as illustrated in FIG. 4, the insertion axis is substantially parallel to the axial centerline A of the adapter 200. Additionally, in some embodiments, the insertion axis is substantially parallel to the piercing member 220. As illustrated, the tip 224, or a portion thereof, may be substantially conical, reaching at or near a central point on the axis of the piercing member 220. In some configurations, the tip 224 is angled from one side of the piercing member 220 to the other. In some cases, the tip 224 is separable from the sheath 222. In other cases, the tip 224 and the sheath 222 may be permanently connected and integrally formed. In various embodiments, the tip 224 comprises 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 substantially conform 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 a polycarbonate plastic. In some arrangements, the cap connector 230 includes a sleeve 235 configured to snap over the ridge 219 and tightly engage the cap 214. As described more fully below, in some cases, the cap connector 230 includes a material around an inner surface of the sleeve 235 to form a substantially airtight seal with the cap 214. The cap 230 may be or include an adhesive tape as known to those skilled in the art. In some embodiments, the cap connector 230 includes a resilient material that stretches 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 Figures 6 and 7, which is described in the specification of U.S. Patent No. 5,393,326, which is incorporated by reference and made a part of this specification.

[0102] In some embodiments, the adapter 200 comprises a connector interface 240 for coupling the adapter 200 to a medical connector 241, another medical device (not shown), or another instrument used in extracting or injecting fluid from or into the vial 210. In some embodiments, the connector interface 240 comprises a sidewall 248 that forms a proximal portion of an access channel 245 through which fluid may flow. In some cases, the access channel 245 penetrates the cap connector 230 and also penetrates a portion of the piercing member 220 such that the connector interface 240 is in fluid communication with the piercing member 220. The sidewall 248 can be of any suitable configuration for coupling with the medical connector 241, a medical device, or another instrument. In the illustrated embodiment, the sidewall 248 is substantially cylindrical and extends generally proximally from the cap connector 230.

[0103] In some configurations, the connector interface 240 includes a flange 247 to aid in coupling the adapter 200 with a medical connector 241, a medical device, or another instrument. The flange 247 can be configured to receive a suitable medical connector 241, including a connector that can seal after the medical device is removed from the flange 247. In some cases, the flange 247 is sized and configured to receive a Clave® connector, available from ICU Medical, Inc., San Clemente, Calif. Some features of Clave® are disclosed in U.S. Patent No. 5,399,993, the entire contents of which are incorporated herein by reference. Many other variations of connectors can also be used, including other needleless connectors. The connector 241 can be permanently or releasably attached to the connector interface 240. In other arrangements, the flange 247 is threaded or configured to receive a luer connector, or has some other shape that is directly attached to a medical device, such as a syringe, or other instrument.

[0104] In some embodiments, connector interface 240 is generally centered axially with adapter 200. Such a configuration provides vertical stability to a system including adapter 200 coupled with vial 210 such that the coupled system is less likely to tip over. Thus, adapter 200 is less likely to leak or spill supplies or come apart due to adapter 200 or vial 210 being inadvertently bumped or knocked 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 may be joined in a suitable manner, such as by adhesive, epoxy, ultrasonic welding, or the like. The connection between the joined pieces may form a substantially airtight bond between the pieces. In some arrangements, either the piercing member 220, the cap connector 230, or the connector interface 240 may 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 U.S. Patent Nos. 5,993,949 and 5,993,962, each of which is incorporated herein by reference in its entirety.

[0106] In some embodiments, the adapter 200 includes a regulator flow path 225 that passes through the connector interface 240 and / or the cap connector 230, as well as 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 in a regulator opening 228.

[0107] In some embodiments, the adapter 200 comprises a regulator assembly 250. In some embodiments, the regulator assembly 250 comprises 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 substantial airtight engagement, thereby placing the coupling portion 252 in fluid communication 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 can comprise complementary threads, such that the coupling portion 252 can be threadedly engaged with the lumen 226. In some embodiments, the coupling portion 252 comprises a passageway 253 extending therethrough.

[0108] In the illustrated embodiment, the regulator assembly includes a bladder 254 having an internal chamber 255. The bladder 254 is generally configured to stretch, flex, unfold, or otherwise expand, contract, or cause a change in internal volume. 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 channel 225, thereby allowing fluid to pass from the regulator flow channel 225 to the internal chamber 255 and / or from the internal chamber 255 to the regulator flow channel 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 filler material 256 that may be disposed within the interior chamber 255 of the bladder 254. As used herein, the term "filler material" or any of its derivatives is intended to be broadly defined as used in its ordinary sense and includes, for example, supports, fillers, spacers, batting, padding, lining, enclosures, reservoirs, or other structures configured to inhibit or prevent the bladder 254 from completely collapsing at ambient pressure, or combinations of such structures. In some configurations, the filler material 256 occupies substantially the entire volume of the entire interior chamber 255. In other arrangements, the filler material 256 occupies only a portion of the volume of the interior chamber 255. In some configurations, the filler material 256 includes a mesh of woven or non-woven fibers. In some embodiments, the filler material 256 is porous, which allows the conditioning fluid (e.g., air) within the interior chamber 255 to enter a mesh of hollow bodies or hollow bodies within the filler material 256. For example, in some cases, the filler material 256 is a sponge-like material. In some configurations, the filler material 256 is configured to be compressed by the bladder 254 without causing damage to the bladder 254. In some embodiments, the filler material 256 has a lower durometer than the bladder 254.

[0110] As shown, the filler material 256 may be positioned within the sack 254. In some embodiments, the filler material 256 is positioned at a radial center within the sack 254. In other cases, the position of the filler material 256 is offset relative to the center of the sack 254. In some embodiments, the position of the filler material 256 changes relative to the sack 254. For example, in some embodiments, the filler material 256 moves (e.g., due to gravity) relative to the sack 254 when the sack 254 changes volume, such as when the sack 254 expands. Such a configuration can, for example, enhance the ability of the sack 254 to expand and reduce the likelihood that the sack 254 will get caught or tightly bound by the filler material 256.

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

[0112] 5 and 6 are cross-sectional views of the vial adapter 200 mated with a vial 210. FIG. 5 shows a not fully expanded state, and FIG. 6 shows a fully expanded state. In the illustrated embodiment, the cap connector 230 secures the adapter 200 to the cap 214, and the piercing member 220 penetrates the septum 216 into the interior of the vial 210. Additionally, the regulator assembly 250 engages the connector interface 240 such that the interior chamber 255 of the bladder 254 is in fluid communication with the regulator flow channel 255 through the coupling 252. In some embodiments, the piercing member 220 is oriented substantially perpendicular to the cap 214 when the adapter 200 and vial 210 are mated. Other configurations are contemplated.

[0113] In some embodiments, the cap connector 230 includes one or more protrusions 237 that aid in securing the adapter 200 to the vial 210. The one or more protrusions 237 extend toward the center 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 an upper surface of the one or more protrusions 237 abuts a lower surface of the ridge 219 to help secure the adapter 200 in place.

[0114] The protrusion(s) 237 may be rounded, chamfered, or some other shape to facilitate mating of the adapter 200 and the vial 210. For example, when an adapter 200 having a rounded protrusion 237 is introduced into the vial 210, the lower surface of the rounded protrusion 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 advances further into the vial 210, the elastic force of the deformed cap connector 230 secures the protrusion(s) 237 under the ridge 219, securing the adapter 200 in place.

[0115] In some embodiments, the cap connector 230 is sized and configured such that an 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 septum 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 comprises a sheath 222 and a tip 224. The sheath 222 is generally sized and dimensioned to allow insertion through the septum 216 without rupturing the septum 216 and, in some cases, with relative ease. 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, the cross-sectional area is less than about 0.075 square inches, less than about 0.060 square inches, or about 0.055 square inches or less. In still other embodiments, the cross-sectional area is about 0.025 square inches or more, about 0.035 square inches or more, or about 0.045 square inches or more. In some embodiments, the cross-sectional area is about 0.050 square inches.

[0117] The sheath 222 can have any of a number of cross-sectional geometries, such as, for example, oval, elliptical, square, rectangular, hexagonal, or diamond shaped. The cross-sectional geometries 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 geometry provides the sheath 222 with substantially equal strength in all radial directions, which prevents bending or breaking that might otherwise occur after the sheath 222 is inserted. The symmetrical opening formed in the septum 216 by the circular sheath 222 prevents pinching that might occur with angular geometries, which makes it easier to insert the sheath 222 through the septum 216. Advantageously, the matching circular symmetry of the piercing member 220 and the opening in the septum 216 provides a secure fit between the piercing member 220 and the septum 216, even if the adapter 200 is inadvertently twisted. Thus, the risk of dangerous liquids or gases leaking out of the vial 210, or of contaminated air entering the vial 210 and contaminating its contents, may be reduced in some cases 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 substantially conform to one another such that the sheath 222 has a substantially uniform thickness. In various embodiments, the thickness is about 0.015 inches to about 0.040 inches, about 0.020 inches to about 0.030 inches, or about 0.024 inches to about 0.026 inches. In other embodiments, the thickness 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 is about 0.040 inches or less, about 0.035 inches or less, or about 0.030 inches or less. In some embodiments, the thickness is about 0.025 inches.

[0119] In some embodiments, the inner surface of the sheath 222 has a different configuration than the outer surface of the sheath 222. Thus, in some arrangements, 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 about 0.015 inches to about 0.050 inches, about 0.020 inches to about 0.040 inches, or about 0.025 inches to about 0.035 inches, and the thickness at the other end, such as the distal end 223, is about 0.015 inches to about 0.040 inches, about 0.020 inches to about 0.030 inches, or about 0.023 inches to about 0.027 inches. In some embodiments, the thickness of the sheath 222 at one end 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 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 of the sheath 222 at one end 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 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 of the sheath 222 at the proximal end is about 0.030 inches, and the thickness at the distal end 223 is about 0.025 inches. In some arrangements, the cross-section of the inner surface of the sheath 222 has a different shape than 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 about 0.08 inches to about 1.4 inches, about 0.9 inches to about 1.3 inches, or 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 an outer boundary of a distal portion of the regulator flow path 225 and an outer boundary of a distal portion of the access flow path 245. An inner wall 227 extending from an inner surface of the sheath 222 to a distal portion of the medical connector interface 240 defines an inner boundary between the regulator flow path 225 and the access flow path 245.

[0122] In the illustrated embodiment, the access channel 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 mated with the connector interface 240, the medical device is in fluid communication with the inside of the vial 210. In such an arrangement, the contents of the vial 210 and 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 the regulator opening 228. In some arrangements, such as the illustrated arrangement, the regulator opening 228 is in fluid communication with the passageway 253 of the coupling 252, which in turn is in fluid communication with the interior chamber 255 of the bladder 254. Thus, in such an arrangement, the interior chamber 255 is in fluid communication with the regulator flow path 225. Additionally, in the illustrated embodiment, the filler material 256 is disposed within the interior chamber 255, such that the filler material 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 in the regulator flow path 225 in the lumen 226. In other embodiments, the filter 260 is disposed in the regulator flow path 225 in the sheath 222. In yet other embodiments, the filter 260 is disposed in the passageway 253 in the coupling 252. Further embodiments have the filter 260 positioned in the interior chamber 255 of the bag 254. Typically, the filter 260 is held in place chemically or mechanically, for example, by an adhesive or a retaining ring. Some embodiments include multiple filters 260. For example, some embodiments have a first filter disposed in the lumen 226 and a second filter disposed in the coupling 252.

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

[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 nearly all, or about 99.9%, of airborne particles with 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, e.g., activated charcoal. In some configurations, the filter 260 includes a mat of fibers, e.g., fiberglass, arranged in an ordered or irregular configuration. In some configurations, the filter 260 includes a Gortex® material or a Teflon® material.

[0127] In the illustrated embodiment, the lumen 226 is a hollow cylindrical member extending radially outward from the connector interface 240. In other embodiments, the lumen 226 comprises other shapes, such as a cone. The lumen 226 can have a variety of cross-sectional shapes, such as a circle, a square, a rectangle, an oval, a diamond, a star, a polygon, or an irregular shape. 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 may space the regulator assembly 250 from the remainder of the adapter 200 and from the vial 210 to facilitate connection with the regulator assembly 250.

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

[0129] The coupling 252 can be configured to engage with the lumen 226. For example, in the illustrated embodiment, the coupling 252 is configured to be received by the lumen 226. In other cases, the coupling 252 is configured to receive the lumen 226. In some cases, the coupling 252 and the lumen 226 connect via a slip fit or an interference fit. In some configurations, the coupling 252 and the lumen 226 connect via a hose barb connection. In some arrangements, the coupling 252 and the lumen 226 connect via a threaded connection. For example, in some cases, the coupling 252 and the lumen 226 have a corresponding standard luer lock connection. In some embodiments, the connection between the coupling 252 and the lumen 226 is substantially airtight, thereby inhibiting or preventing outside air from entering the regulator flow path 225. Such a configuration can reduce the possibility of microorganisms or impurities entering the vial 210, and therefore can increase 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 audio signal, such as a click, snap, or similar sound, to indicate that the coupling 252 has connected with 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 coupling 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 with a permanent snap-fit ​​mechanism (e.g., a substantially 90° hook and a corresponding substantially 90° valley), such that the coupling 252 and the lumen 226 are substantially constrained from separating after the snap-fit ​​mechanism is engaged. The permanent connection between the coupling 252 and the lumen 226 may facilitate a single use of the adapter 200, including a single use of the regulator assembly 250. Additionally, the permanent connection of the regulator assembly 250 and to the remainder of the adapter 200 reduces the total number of unique parts that are inventoried, maintained, and prepared prior to use. In some embodiments, coupling portion 252 is substantially monolithically formed with (eg, molded in the same operation as) the remainder of adapter 200 .

[0132] In some cases, the coupling portion 252 and the lumen 226 are connected during the process of manufacturing the adapter 200, for example, at a factory. In some configurations, the regulator assembly 250 is separate from the remainder of the adapter 200 and is configured to be connected to the remainder of the adapter 200 by a user. For example, the piercing member 220, the cap connector 230, and the connector interface 240 can be provided in a first package, and the regulator assembly 250 can be provided in a second package. In some user connection configurations, the connection is substantially permanent. For example, in some cases, one of the coupling portion 252 and the lumen 226 includes an adhesive (e.g., double-sided tape) that substantially permanently bonds the coupling portion 252 to the lumen 226 when a user connects the coupling portion 252 to the lumen 226. Meanwhile, in some user connection embodiments, the coupling portion 252 is configured to be detachable from the lumen 226 even after the coupling portion 252 is connected to the lumen 226. For example, in some embodiments, the coupling 252 and lumen 226 are releasably coupled to a thread or release mechanism, such as a detent or set screw. Such a configuration can facilitate operations (e.g., bulk drug compounding operations) in which it is desired to transfer a volume of regulator fluid from the regulator assembly 250 into the vial 210 that is larger than the volume of regulator fluid contained 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, such as with a one-way valve.

[0133] In the illustrated embodiment, the coupling member 252 is coupled to the bladder 254. In some cases, the bladder 254 and the coupling 252 are welded or adhesively coupled. As shown, the connection between the bladder 254 and the coupling 252 generally fluidly connects the passageway 253 with the interior chamber 255 of the bladder 254. To facilitate fluid communication, the bladder 254 can include a bladder opening 257, such as a slit or hole. In some cases, the bladder opening 257 is created with a high temperature tool, such as a soldering iron.

[0134] The bladder 254 is generally configured to unfold from a fold, unfold from a roll, expand, contract, inflate, deflate, compress, and / or decompress. The bladder 254 may comprise any of a variety of flexible and / or expandable materials. For example, in some embodiments, the bladder 254 comprises polyester, polyethylene, polypropylene, saran, latex rubber, polyisoprene, silicone rubber, vinyl, polyurethane, or other materials. In some embodiments, the bladder 254 comprises a material having a metal component to further inhibit leakage of fluids (including gas or air) through the bladder material, such as metalized biaxially oriented polyethylene terephthalate (also known as PET and commercially available under the trademark Mylar®). In some embodiments, the bladder 254 comprises a laminate. For example, the bladder 254 may 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 comprises a material capable of forming a substantially airtight seal with the bond 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 comprises a material that is generally impermeable to liquids and air. In some embodiments, the bag 254 comprises a material that is inert to the intended contents of the vial 210. For example, in some cases, the bag 254 comprises a material that does not react with some drugs used in chemotherapy. In some embodiments, the bag 254 comprises a latex-free silicone having a durometer of about 10 to about 40.

[0135] In some configurations, the bladder 254 includes a coating. For example, in some embodiments, the bladder 254 includes a coating that reduces the porosity of the bladder 254. In some cases, the coating is evaporated aluminum or evaporated gold. In some cases, the coating includes 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 bladder 254. In other cases, the coating is applied to the inside of the bladder 254. In some cases, the coating is applied to the inside and outside of the bladder 254. In some embodiments, the coating is a polyolefin.

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

[0137] In some embodiments, the bladder 254 is configured to be free to expand without being constrained, for example, by a rigid enclosure. Such unconstrained expansion of the bladder 254 can reduce the force required to expand the bladder 254. For example, because the bladder 254 does not contact a rigid enclosure, there are no frictional forces between the bladder 254 and such enclosure that could increase the force, if any, that would be required to expand the bladder 254. In some embodiments, the unconstrained expansion of the bladder 254 reduces the likelihood that the bladder 254 will be damaged when expanding. For example, because the bladder 254 does not contact a rigid enclosure, there is less risk that the bladder 254 will be damaged (e.g., punctured, torn, or caught on burrs or other imperfections in such enclosures) when expanding or collapsing. Additionally, the unconstrained movement of the bladder 254 reduces the likelihood that a coating on the bladder 254 will smear or flake off. In some embodiments, as the bladder 254 expands, it does not bump, scrape, slide against, or otherwise statically or dynamically contact any hard surfaces of the adapter 200. In some configurations, the bladder 254 is in contact only with the interface 252, the conditioning fluid, and the outside air.

[0138] In some embodiments, the bladder 254 comprises 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 coupling portion 252, but the second side 259 is not. In some configurations, the first side 258 connects to the second side 259. In some such cases, the first side 258 connects to the second side 259 at a peripheral edge of each of the sides 258, 259. In some cases, the second side 259 does not contact a hard surface upon expansion of the bladder 254. In some configurations, substantially all or a majority of the surface area of ​​the bladder 254 exposed to the surrounding environment is flexible. In some embodiments, generally the entire bladder 254 is flexible.

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

[0140] In some cases, the inner surface of each of the sides 258, 259 is oriented toward the interior of the bag 254. As used herein, the phrase "oriented toward" or variations thereof is a broad term used in its ordinary sense, e.g., to describe something generally aligned or positioned 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. If 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 258 is oriented toward the connector interface 240.

[0141] In some cases, the outer surface of each of the sides 258, 259 is oriented outwardly from the bag 254. In some cases, the second side 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 259 does not intersect the connector interface 240.

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

[0143] In some embodiments, the bladder 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 to describe, for example, a thickness of material, a ply of material, or a stratum of material. In some embodiments, a layer may include multiple components, plies, or stratums of material. In some cases, the first layer is the first side 258 and the second layer is the second side 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 may be integrally or monolithically formed with the perimeter of the second layer. Such a configuration may aid in forming the bladder 254, for example, by making the bladder 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 and second layers are affixed (e.g., heat-sealed) together at the periphery. In some embodiments, the first and second layers each have a central portion. For example, in configurations in which the periphery shape of each of the first and second layers is substantially circular, the central portion may be about the radial center of each of the first and second layers. 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 and second portions 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 sublayers. For example, the first and / or second layer can include a plastic sublayer and a metal sublayer, respectively. In some embodiments, the first sublayer and the second sublayer have mating surfaces that are bonded together. In some cases, substantially the entire surface of the mating surfaces is bonded. In general, the sublayers are not configured to receive a substantial or significant volume (e.g., of conditioning fluid) therebetween. On the other hand, in some embodiments, the first layer and the second layer are configured to receive a conditioning fluid therebetween. For example, in a configuration where the first layer is the first side 258 and the second layer is the second side 259, a conditioning 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 fully or partially contains the bag 254. For example, the volume of the bag inside the rigid enclosure may encompass less than half the volume of the bag 254 (if at all) or only a small portion of the bag's volume (e.g., less than or equal to the volume inside the piercing 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 less than or equal to half the volume inside the vial or vials to which the adapter is configured to connect (if at all). A rigid enclosure adds weight and total material to the adapter 200, which increases material and manufacturing costs. Furthermore, because the rigid enclosure is positioned at a distance away from the axial center of the adapter, the omission of the rigid enclosure eliminates the moment of force caused by the weight of such an enclosure. Thus, the adapter 200 may be more stable and less likely to tip over. Adapter and vial stability may be particularly important when handling cytotoxic drugs, as tipping may increase the likelihood of spillage or other forms of unintended exposure and / or release.

[0146] Some embodiments of adapter 200 have a center of gravity that is not substantially displaced from the axial center of adapter 200 when regulator assembly 250 is connected with the remainder of adapter 200 and adapter 200 is mated with vial 210. For example, some embodiments of adapter 200 have a center of gravity that is about 0.50 inches or less, about 0.25 inches or less, about 0.125 inches or less, or about 0.063 inches or less from the axial center of adapter 200.

[0147] In some cases, the bag 254 is expandable to substantially fill a range of volumes so that a single adapter 200 can be configured to work 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 in 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 in the vial 210 prior to coupling the adapter 200 and the vial 210. In various embodiments, the fluid in the bag 254 is a gas, such as air, sterilized air, purified air, nitrogen, oxygen, an inert gas (e.g., argon), or other gas. In some embodiments, sterilized air can be provided by introducing ambient air into the bag and then sterilizing the bag and air together.

[0148] The bladder 254 has a fully expanded configuration (FIG. 6) and at least one not fully expanded configuration (FIG. 5). In some cases, in the fully expanded configuration, the volume of the interior chamber 255 of the bladder 254 is at its maximum recommended volume. In some cases, in the fully expanded configuration, the bladder 254 contains 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 bladder 254 holds at least about 250 mL of fluid. In some embodiments, in the fully expanded configuration, the bladder 254 contains at least about 180 mL of fluid.

[0149] In some cases, in the not fully expanded configuration, the bladder 254 contains 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 bladder 254 is a fully deflated configuration, in which case the volume of the interior chamber 255 of the bladder 254 is approximately zero. In some such cases, in the fully deflated configuration, the bladder 254 contains substantially no fluid.

[0150] The bag 254 further has an initial configuration (e.g., a configuration before conditioning fluid is transferred between the vial 210 and the bag 254). Generally, the bag 254 contains a volume of fluid in the initial configuration to facilitate quick and accurate withdrawal of fluid from the vial 210 after 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 volume of fluid that generally corresponds to the volume of one or more standard medical devices to which the adapter is configured to be attached. For example, in some cases, in the initial configuration, the bag 254 holds at least about 30 mL of fluid, which corresponds to the volume of a 30 mL syringe. In such a case, upon connecting the adapter 200 with the vial 210, approximately 30 mL of fluid is immediately available to be transferred between the bladder 254 and the vial 210, thereby allowing 30 mL of fluid to be immediately transferred between the vial 210 and the syringe. In some embodiments, the bladder 254 has an initial volume at least approximately equal to the sum of the interior volume of the cap and the interior volume of the piercing member, or a volume at least approximately twice as large as the sum of the interior volume of the cap and the interior volume of the piercing member.

[0151] In various configurations, the bag 254 has an outer dimension (e.g., diameter or cross-sectional width or height) D of about 1.0 inches to about 6.0 inches, about 2.0 inches to about 5.0 inches, or about 3.0 inches to about 4.0 inches. In some configurations, 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 configurations, 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 outer dimension of the bag is less than or equal to the height or cross-sectional width of the vial or vials to which the adapter is configured to attach. In various configurations, the bag 254 has a maximum overall thickness T of about 0.50 inches to about 2.00 inches, about 0.60 inches to about 0.90 inches, and about 0.70 inches to about 0.80 inches. In other arrangements, the maximum overall thickness is less than about 1.00 inches, less than about 0.90 inches, or less than about 0.80 inches. In some arrangements, the maximum overall thickness is about 0.75 inches. 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 the bag 254 is spaced apart from and aligned with the vial 210 even in a fully deployed state.

[0152] In some configurations, the bladder 254 has a wall thickness W of about 0.001 inches to about 0.025 inches, about 0.001 inches to about 0.010 inches, or about 0.010 inches to about 0.025 inches. In other configurations, the wall thickness is greater than about 0.001 inches, greater than about 0.005 inches, greater than about 0.010 inches, greater than about 0.015 inches, or greater than about 0.020 inches. In still other configurations, the wall thickness is less than about 0.025 inches, less than about 0.020 inches, less than about 0.015 inches, less than about 0.010 inches, or less than about 0.005 inches. In some configurations, the wall thickness is about 0.015 inches. 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 in the region of the bladder 254 around the bond 252.

[0153] In some configurations, in a not fully expanded configuration, the sacs 254 have a substantially irregular shape, as shown in FIG. 5. In other configurations, the sacs 254 have 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 sacs 254 have a generally oblate spheroid shape. In some cases, the sacs 254 are substantially bulbous. In some arrangements, the sacs 254 have a convex shape. In some configurations, the sacs 254 have a concave shape. In some configurations, the shape of the sacs 254 generally conforms to the shape of the filler material 256. In some arrangements, the sacs 254 generally conform to the shape of the filler material 256 in a not fully expanded configuration and deviates from the shape of the filler material 256 in a fully expanded configuration.

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

[0155] In general, the filler material 256 is configured to provide a ready supply of conditioning fluid, e.g., sterile air, to the vial 210. As described above, when the adapter 200 engages the vial 210 and a medical device (such as a syringe) and a portion of the fluid in the vial 210 is transferred from the vial 210 through the adapter 200 and into the medical device, the volume of the fluid in the vial 210 decreases, causing a decrease in pressure within the vial 210, which creates a pressure gradient between the inside and 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 interface between the septum 216 and the piercing member 220 or the attachment interface between the adapter 200 and the medical device. Furthermore, such a pressure gradient can create a restoring force that impedes the ability to withdraw a precise amount of fluid from the vial 210. However, filler material 256 immediately supplies conditioning fluid to adapter 200, generally replacing some or all of the volume of fluid transferred to maintain equilibrium conditions within vial 210, thereby reducing or preventing the aforementioned problems.

[0156] In some arrangements, as fluid is removed from the vial 210 through the extraction channel 245, a corresponding amount of conditioning fluid from the filler material 256 is introduced into the vial 210 through the bag opening 257, the passageway 253 in the coupling portion 252, and the regulator channel 225 substantially simultaneously, thereby maintaining an equilibrium condition. In some arrangements, the filler material 256 is adapted to provide a ready supply of conditioning fluid before the regulator assembly 250 is connected with the remainder of the adapter 200. In some embodiments, the filler material 256 provides a reservoir of conditioning fluid to the adapter 200. In some arrangements, the filler material 256 is configured such that substantial portions of the first side 258 and the second side 259 of the bag 254 are not in contact with each other.

[0157] In some configurations, the filler 256 has a shape similar to the sack 254. For example, in some cases, in a fully expanded configuration, the sack 254 and the filler 256 each have a shape as a generally flattened spheroid. In other configurations, the filler 256 has a shape different from the sack 254. For example, in some cases, in a fully expanded configuration, the sack 254 has a substantially spheroidal shape and the filler 256 has a substantially cylindrical shape. In some such cases, the longitudinal axis of the cylindrically shaped filler 256 is generally parallel to the axial centerline of the adapter 200. In other such cases, the longitudinal axis of the cylindrically shaped filler 256 is perpendicular to the axial centerline of the adapter 200.

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

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

[0160] In some arrangements, the filler 256 is configured to contain a 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 cotton wadding. In some arrangements, 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 from a low density foam. For example, in some embodiments, the filler 256 is made from a polyurethane ether foam, having a weight of, for example, about 1.05 pounds per cubic foot and an indentation load (ILD) of, for example, about 38. In some embodiments, the filler 256 is made from a polyether, polyester, polyethylene, or ether-like ester (ELE). In some cases, the filler 256 is made from nylon, polypropylene, polyvinylidene fluoride, polytetrafluoroethylene, or other plastics. In some embodiments, the filler material 256 is a metal, such as aluminum or stainless steel. In some embodiments, the filler material 256 is treated with an antimicrobial or other compound to enhance sterility. In some cases, the filler material 256 comprises a sealed chamber, such as a chamber containing sterile air, configured to open when fluid is withdrawn from the vial 210. In some embodiments, the filler material 256 is configured to bond with, absorb, generally neutralize, or in some other way chemically and / or mechanically interact with fluid (such as steam) entering the bag.

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

[0162] 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 in place. Thus, mating of the adapter 200 and the vial 210 can be performed in one simple step. In some cases, a medical connector 241 is mated with the medical connector interface 240. A medical device or other instrument (not shown), such as a syringe, can be mated with the interface 240 or, if present, with the medical connector 241 (see FIG. 4). For convenience, hereafter, reference will be made only to a syringe as an example of a medical device suitable for attachment to the medical connector interface 240, although there are many medical devices or other instruments that can be used in connection with the adapter 200 or the medical connector 241. In some cases, a syringe is placed in fluid communication with the vial 210. In some cases, the vial 210, adapter 200, syringe, and medical connector 241, if present, are inverted so that the cap 214 points downward (e.g., toward the floor). Any of the above steps, or combinations of these steps, can be performed in any order possible.

[0163] In some cases, a volume of fluid is drawn from the vial 210 and placed into the syringe. As explained above, the pressure in the vial 210 decreases as fluid is drawn. Thus, in some cases, the conditioning fluid in the filler material 256 in the bladder 254 flows through the regulator flow path 225 and into the vial 210. In some cases, the conditioning fluid passes through the filter 260. In some cases, the bladder 254 collapses as conditioning fluid is transferred from the filler material 256. In some arrangements, an equilibrium condition in the vial 210 is generally maintained as conditioning fluid is transferred from the filler material 256 and / or other locations in the bladder 254 into the vial 210. In some cases, the volume of conditioning fluid transferred from the filler material 256 into the vial 210 is approximately equal to the volume of fluid drawn from the vial 210 into the syringe.

[0164] In some cases, a volume of fluid is introduced into the vial 210 from a syringe. For example, in some cases, a volume of fluid is introduced into the vial 210 to reconstitute a lyophilized drug or for drug compounding purposes. As another example, in some cases, more fluid than desired may be inadvertently drawn from the vial 210 by the syringe. As explained above, as fluid is introduced into the vial 210, the pressure within the vial 210 increases. Thus, in some cases, the conditioning fluid within the vial 210 flows through the regulator flow path 225 and into the bladder 254, as shown by the arrows in FIG. 6. In some cases, the conditioning fluid passes through the filter 260. In some cases, the bladder 254 expands as the conditioning fluid is transferred from the vial 210. In some such cases, as the bladder 254 expands, it stretches, unfolds, or expands outward. In some embodiments, the bladder 254 is sufficiently flexible to substantially avoid the generation of restoring forces (e.g., forces that oppose the expansion or contraction of the bladder 254). In some embodiments, the bladder 254 exerts restoring forces. In some arrangements, as the conditioning fluid is transferred from the vial 210 into the bladder 254, an equilibrium condition within the vial 210 is maintained. In some cases, the volume of conditioning fluid transferred from the vial 210 into the bladder 254 is approximately equal to the volume of fluid introduced into the vial 210 from the syringe.

[0165] Thus, in some embodiments, adapter 200 can accommodate withdrawing fluid from or adding fluid to vial 210 to maintain pressure within vial 210. In many cases, the change in pressure within vial 210 is no more than about 1 psi, no more than about 2 psi, no more than about 3 psi, no more than about 4 psi, or no more than about 5 psi.

[0166] In some embodiments, the process for containing gas and / or vapor includes providing a piercing member 220, a cap connector 230, and a connector interface 240. Typically, the process also includes piercing a septum of the vial 210 with the piercing member 220. The piercing member 220 may also allow access to the medical fluid in the vial 210. In some embodiments, the process includes coupling a regulator assembly 250 with 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 storing gas and / or vapor displaced by the fluid introduced into the vial 210. In some configurations, all or a portion of the gas and / or vapor is stored in 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 surrounding environment. In some embodiments, the process includes de-mounting the regulator assembly 250.

[0167] As is evident from the embodiments and processes described above, the adapter 200 allows a user to introduce liquid into the vial 210 (including returning unwanted liquid and / or air) and withdraw liquid from the vial 210 without significantly changing the pressure within the vial 210. As previously described, the ability to inject liquid into the vial may be particularly desirable for reconstituting lyophilized drugs. Also, as previously described, the ability to inject air bubbles and excess fluid into the vial 210 may also be particularly desirable in the context of oncology drugs.

[0168] Additionally, the above discussion illustrates that some embodiments of adapter 200 may be configured to regulate the pressure within vial 210 without introducing outside or ambient air into vial 210. For example, in some embodiments, bag 254 includes a substantially impermeable material that is used as a barrier, rather than a passageway, between the inside of vial 210 and the surrounding environment. Some embodiments of adapter 200 substantially reduce the risk of introducing airborne contaminants into a patient's bloodstream.

[0169] As noted above, in some cases, the vial 210 is oriented so that the cap 214 points downward when liquid is removed from the vial 210. In some embodiments, the access opening 246 is located adjacent to a bottom surface of the cap 214, which allows most or substantially all of the liquid in the vial 210 to be removed. In other embodiments, the access opening 246 is located near the distal end 223 of the piercing member 220. In some arrangements, the adapter 200 includes multiple access openings 246 to aid in the removal of substantially all of the liquid in the vial 210.

[0170] 7-12 illustrate another embodiment of an adapter 300. The adapter 300 is similar or identical in many respects to the adapter 200 described above. Accordingly, the numbers used to identify features of the adapter 200 have been incremented by 100 to identify similar features of the adapter 300. This numbering convention generally applies to the other figures. Any components or steps disclosed in an embodiment herein may be used in the other embodiments.

[0171] In some embodiments, the adapter 300 comprises 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 provided in U.S. Patent Application Publication No. 2010 / 0139994, each of which is incorporated herein by reference in its entirety. For clarity, the vial 210 is not shown. The adapter 300 may mate with the vial 210 in a manner similar to that of the adapter 200. For example, when the adapter 300 mates with the vial 210, the piercing member 320 penetrates the septum 216 into the inside of the vial 210.

[0172] In some embodiments, such as in the illustrated embodiment, the cap connector 330 comprises a body portion 380 which in turn comprises 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 may be supported at a proximal end of the tab 382 by the central portion 381 of the body portion 380. As shown, a distal end of each of the tabs 382 may be unconstrained to allow the tab to deflect outwardly.

[0173] Body portion 380, including center portion 381 and tabs 382, ​​can aid in releasably securing vial adapter 300 to an exterior surface of vial 210 and can aid in facilitating removal of vial adapter 300 from vial 210. In some embodiments, body portion 380 defines only one tab 382, ​​as opposed to a pair of opposing tabs 382, ​​where the single tab is configured to releasably secure vial adapter 300 to an exterior surface of vial 210 and facilitate removal of vial adapter 300 from vial 210. The single tab 382 can have any 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 a body portion 380. As shown, the piercing member 320 may project distally from a central portion 381 of the body portion 380. The piercing member 320 may include an access channel 345 and a regulator channel 325. In some embodiments, the regulator channel 325 begins at a distal regulator opening 328a, passes generally through the piercing member 320, passes through a lumen 326 that extends radially outward from the connector interface 340, and terminates at a proximal regulator opening 328 (FIG. 8). In some cases, the lumen 326 extends radially outward from the connector interface 340 in only one direction. In some cases, the lumen 326 extends radially outward from the connector interface 340 in multiple directions, e.g., two opposing directions.

[0175] In some embodiments, the lumen 326 includes a barrier 383, such as a wall, cap, plug, dam, cork, partition, or others. 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 conditioning fluid from exiting the adapter 300.

[0176] The regulator assembly 350 can include a coupling portion 352, a fastening member 384, and a bladder 354. In some cases, the bladder includes a filler (not shown), such as the filler 254 described above. The bladder 354 can include a bladder opening 357, which is illustrated as a linear slit but can take the form of almost any opening in the bladder. In some configurations, the bladder 354 is made from multiple sheets of material that are joined (e.g., heat sealed) around the periphery. In some such configurations, as shown in FIG. 8, a sealing operation forms a peripheral ridge 354a on the bladder 354. In some cases, the bladder 354 is made from a balloon having a narrowed neck (such as the "4 Inch Balloon" produced by Pioneer Balloon Company, Wichita, Kansas). 7, the neck is removed and the bag 354 is heat sealed circumferentially to surround the volume therein (except for the bag opening 357). In some cases, removing the neck results in a flattened, truncated, or otherwise asymmetrical portion of the bag 359, as shown in FIG.

[0177] In some embodiments, the adhesive member 384 connects the coupling portion 352 with the bladder 354. For example, in some cases, the adhesive member 384 comprises a double-sided adhesive, e.g., one adhesive side facing the coupling portion 352 and one adhesive side facing the bladder 354. In the illustrated embodiment, the adhesive member 384 comprises an adhesive first surface 384a and an adhesive second surface 384b. As shown, the adhesive member 384 can comprise an opening 384c. In some embodiments, the adhesive member 384 is about 0.015 inches thick. In some embodiments, the thickness of the adhesive member 384 is at least 0.01 inches and / or no more than about 0.03 inches.

[0178] In some embodiments, the fastening member 384 is made from a flexible material that can provide resiliency to the connections between the fastening member 384 and the coupling portion 352 and between the fastening member 384 and the bladder 354, for example. Such resiliency can allow the coupling portion 352 to move slightly relative to the bladder 350. Similarly, such resiliency can reduce the likelihood that the bladder 354 will tear, rip, or otherwise be damaged during manipulation of the regulator assembly 350, such as the process of connecting the regulator assembly 350 with the remainder of the adapter 300. In some configurations, the fastening member 384 is a foam (e.g., urethane, polyethylene, or other material), non-rigid plastic, rubber, paper, or fabric (e.g., cotton) material. In some embodiments, the fastening member 384 is made of double-sided foam tape.

[0179] In some cases, the coupling portion 352 comprises a base 385 and a cover 386, which may further comprise an outer surface 386a (FIG. 8). In some embodiments, the fastening member 384 is configured to adhere or otherwise couple to the outer surface 386a. In some embodiments, the fastening member 384 is configured to adhere or otherwise couple to the bladder 354. The connection between the fastening member 384 and the outer surface 386a, as well as the connection between the fastening member 384 and the bladder 354, is substantially fluid-tight (e.g., air-tight) such that fluid passing between the coupling portion 352 and the bladder 354 is prevented from leaking. In some embodiments, the connections between the fastening member 384 and the coupling portion 352 and between the fastening member 384 and the bladder 354 are substantially permanent, and once these components are coupled, they are not intended to be separated. In some embodiments, the connections between the fastening member 384 and the coupling portion 352, and between the fastening member 384 and the bladder 354 are configured to be temporary or removable.

[0180] 8, the filter 360 may be housed between a base 385 and a cover 386. The cover 386 may be substantially sealably received by the base 385 such that substantially all of the fluid permitted to flow through the filter 360 flows through an opening 387 formed in the cover 386. The base 385 and the cover 386 may 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 may be press-fitted or otherwise attached to the base 385 using adhesive, ultrasonic welding, or another similar or suitable means. For example, as illustrated in FIG. 12, the cover 386 may be attached to the base 385 by one or more ultrasonic welds 388. The cover 385 and base 386 may be coupled together such that an annular projection 389 of the cover 385 is adjacent to an annular projection 390 on the base 385. The projection 390 may have a stepped or extended lip 390a that may overlap the projection 389 formed on the cover 386 in an assembled configuration. The base 385 and cover 386 may be made from a variety of materials, such as metal or plastic. In some cases, the base 385 and 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 conditioning fluid flows through the filter 360, thereby providing sufficient conditioning fluid to compensate for the introduction or withdrawal of fluid into or from the vial 210. As explained above, providing sufficient conditioning fluid can reduce or avoid pressure gradients (e.g., vacuums) between the inside and outside of the vial, and can reduce or eliminate restoring forces on the syringe plunger. 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 about 2 to about 9 times larger than the cross-sectional area of ​​the proximal regulator opening 328, or ranges from any value to any value within these ranges. Similarly, in some embodiments, the cross-sectional area of ​​the filter 360 can be about 400 times larger than the cross-sectional area of ​​the distal regulator opening 328a. In some embodiments, the cross-sectional area of ​​filter 360 is about 100 to about 250 times larger than the cross-sectional area of ​​distal adjuster opening 328a, about 250 to about 400 times larger, about 400 to about 550 times larger, or any value within these ranges.

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

[0184] As illustrated in FIG. 9, in some configurations, the coupling portion 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 substantially sealably received within or around the periphery of the proximal regulator opening 328. The protrusion 385a can generally define the regulator passageway. 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, a weld, or other material or feature can be used to provide the connection between the protrusion 385a and the proximal regulator opening 328. In some cases, the protrusion 385a and the proximal regulator opening 328 are solvent bonded. The protrusion 385a may be sized and configured with sufficient wall thickness and diameter to ensure that the protrusion 385a is not inadvertently broken during use by inadvertently contacting the coupling 352. In some embodiments, the regulator pathway may be in fluid communication with the regulator flow channel 425 when the protrusion 385a is connected to the proximal regulator opening 328.

[0185] Opening 387a can be formed through prong 385a such that fluid flowing between base 385 and cover 386 is filtered by filter 360 before flowing through opening 387 or 387a. The size of opening 387a formed through prong 385a, and also opening 387 formed in cover 386, can be designed to ensure a sufficient amount of fluid flow through filter 360. The diameter of proximal regulator opening 328 can be adjusted to accommodate any desired or suitable outer diameter of prong 385a.

[0186] 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 openings 391a, 392a form a volume of space 393 between the inner surface of the cover 386 and the surface of the filter 360, into which the 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 projections 390, 394, 395 and the openings 394a, 395a form a volume of space 396 between the inner surface of the base 386 and the surface of the filter 360 into which the conditioning fluid can flow and circulate before or after passing through the filter 360. In some configurations, the conditioning fluid has access to substantially the entire surface area of ​​the filter 360.

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

[0188] In some cases, the annular projections 390, 394, 395 are configured to maintain the shape and position of the filter 360 relative to the base 385 and cover 386. For example, the annular projection 390 can be configured to maintain the filter 360 approximately radially centered on the base 385 and cover 386, which can reduce the probability of fluid passing around (rather than through) the filter 360. In some configurations, the annular projections 394, 395 are configured to substantially inhibit the filter 360 from becoming concave as conditioning fluid passes through the filter 360, which can reduce the likelihood that the filter 360 will tear or otherwise be damaged.

[0189] In some embodiments, the adapter 300 is modular in construction. Such construction can, for example, increase productivity and improve user convenience by standardizing one or more parts of the adapter 300. For example, in some cases, the configuration of the piercing member 320, cap connector 330, connector interface 340, and coupling 352 remain substantially unchanged regardless of the volume of fluid transferred between the medical device and the vial 210. Such standardization can, for example, reduce the number of unique components to purchase, store, and inventory while maintaining the functionality of the adapter 300.

[0190] In some modular embodiments, the adapter 300 comprises 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 separate and spaced apart from the second portion in the first arrangement and is connected to the second portion in the second arrangement. In some embodiments, various configurations (e.g., sizes) of the bag 354 can be matched with a common configuration of the remainder of the adapter 300. For example, in some embodiments, 20 mL, 40 mL, and 60 mL configurations of the bag 354 are each connectable with a common configuration of the remainder of the adapter 300. In some embodiments, the configuration of the bag 354 can be selected without changing the remainder of the adapter 300. In some cases, the configuration of the bag 354 is selected based on the volume of fluid to be transferred between the medical device (e.g., a syringe) and the vial 210. For example, if approximately 25 mL of fluid is to be transferred from the medical device into the vial 210, a bag 354 configuration capable of containing more than approximately 25 mL of fluid can be selected and connected to the remainder of the adapter 300, however, if it is determined that a different volume of fluid is to be transferred from the medical device into the vial 210, the selection of bag 354 can be changed without modifying the remainder of the adapter 300.

[0191] Some modular embodiments can immediately provide filtered or otherwise purified conditioning fluid without connecting to the bag 354. For example, in some embodiments, the opening 387 in the cover 386 of the coupling 352 is in fluid communication with the outside air, thereby providing filtered air through the coupling 352, through the regulator channel 325, and into the vial 210 when the piercing member 320 is disposed within the vial 210 and fluid is drawn through the access channel 345. In some cases, the adapter 300 does not include the bag 354 and / or the fastening member 384. In some embodiments, the lumen 326 is configured to connect to a source of filtered or otherwise purified conditioning fluid. For example, the lumen 326 can be configured to connect to a tube in fluid communication with a tank of sterile air.

[0192] In some embodiments, the process of manufacturing the vial adapter 300 includes forming the piercing member 320, the cap connector 330, and the connector interface 340 in a first assembly. For example, in some embodiments, the piercing 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 may also include forming the coupling portion 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 mating the coupling portion 352 with the lumen 326, as shown in FIG. 9. Additionally, the process may include coupling the fastening member 384 with the outer surface 386a of the cover 386. In some cases, the fastening member 384 is coupled with 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 to allow conditioning fluid to flow between the vial 210 and the bag 354.

[0193] In some cases, the process for manufacturing vial adapter 300 can allow for producing adapter 300 in separate subassemblies, for example, thereby increasing productivity. For example, a first subassembly can include piercing member 320, cap connector 330, and connector interface 340, a second subassembly can include coupling portion 352 (base 385, cover 386, and filter 360), and a third subassembly can include bag 354 and fastening member 384. Of course, other subassemblies are contemplated, for example, second subassembly can include coupling portion 352 and fastening member 384. In some cases, one or more of the subassemblies are supplied separately to a user (e.g., a medical professional).

[0194] 13, 14, and 15 illustrate another embodiment of an adapter 400. The adapter 400 may 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 adapter 400 comprises 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 comprises 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 ), which may provide increased strength and aid in extracting fluid from the neck region of the vial 210 when the vial 210 is inverted, as described above. Also as shown, the piercing member 420 includes an access channel 445 and a regulator channel 425, each of which terminates near the distal end 423 of the piercing member 420.

[0196] As shown, the cap connector 430 can include a lumen 426 such that the regulator flow path 425 follows a path through the cap connector 430. The lumen 426 extends radially outward through a connecting member 429. The illustrated connecting member 429 is a slip-fit ​​flange, but many other configurations are contemplated, such as threads, press-fit, barbed connections, or other means. A filter 460, which can be hydrophobic, is disposed within the lumen 426. The regulator assembly 450 includes an annular washer 451, a coupling 452, a bladder 454, and a filler material 456. The coupling 452 includes a passageway 453 extending through the coupling 452 and a flange 461 extending outward. The coupling 452 is positioned with the flange 461 inside the bladder 454 through a bladder opening 457. The washer 451 is positioned on the exterior of the bladder 454, generally opposite the flange 461. In some cases, the bladder 454 is compressed or otherwise held between the washer 451 and the flange 461. For example, in some embodiments, the coupling portion 452 is externally threaded and the center of the annular washer is correspondingly threaded, such that the washer can be threaded onto the coupling portion 452 and the bladder 454 can be compressed between the washer 451 and the flange 461. As shown, the coupling portion 452 is received within the connecting member 429, such that the bladder 454 is in fluid communication with the vial 210 through the regulator flow path 425.

[0197] 13, the bladder 454 is shown in an initial state, which may be the state of the bladder 454 when, for example, the regulator assembly 450 is initially connected with the cap connector 430. The filler material 456 may contain a volume of a conditioning fluid, such as sterile air. As shown, in this embodiment, the filler material 456 substantially fills the volume of the bladder 454 in this state. In some aspects, the bladder 454 substantially conforms to the shape of the filler material 456.

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

[0199] In FIG. 15, the bladder 454 is shown in an at least partially deflated state, which may be the state of the bladder 456 after, for example, a volume of fluid has been drawn from the vial 210 through the access channel 445. This drawing of fluid causes the volume of conditioning fluid within the bladder 454 to flow through the bladder opening 457, the passageway 453, the connecting member 429, the filter 460, the lumen 426, the regulator channel 425, and into the vial 210, as generally indicated by the arrows in FIG. 15. As shown, this transfer of conditioning fluid can at least partially deflate the bladder 454. In some embodiments, such as the illustrated embodiment, the filler material 456 is configured to compress as the bladder 454 deflates. As shown, in some arrangements, the filler material 456 is configured to provide a structural framework for the bladder 454 (even in the deflated state), which can inhibit the bladder 454 from sagging. In some embodiments, the bladder 354 includes a material that is sufficiently rigid to inhibit the bladder 454 from sagging.

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

[0201] FIG. 16 illustrates an embodiment of an adapter 500 that may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. The adapter 500 includes a filter 560 disposed within a coupling portion 552. Additionally, the adapter 500 includes a filler material 556 that is substantially round in cross section. In some embodiments, the filler material 556 is spheroidal. In other embodiments, the filler material 556 is substantially cylindrical. The adapter 500 also includes a bag 554 and a coupling portion 552 having a flange 561. As shown, the bag 554 may be coupled to the flange 561, for example, by welding, gluing, or otherwise. In some embodiments, the filler material 556 is also coupled to the flange 561, which facilitates stationary positioning of the bag 554 relative to the coupling portion 552. In some arrangements, the filler material 556 acts as a secondary filter for gas passing between the vial 210 and the bag 554. For example, in some cases, some impurities that pass through filter 560 are captured by filler material 556 before such impurities pass into bag 554. In some arrangements, filler material 556 acts as a pre-filter for filter 560, thereby reducing the amount of impurities that pass through filter 560 into vial 210.

[0202] FIG. 17 illustrates an embodiment of an adapter 600 that may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. The adapter 600 includes a bladder 654 that includes an internal structure rather than or in addition to a filler. Such an internal structure may inhibit or prevent the bladder 654 from fully collapsing, for example, to provide an initial supply of conditioning fluid. In the illustrated embodiment, the internal structure includes a plurality of inwardly extending elongated members 662. In some configurations, the elongated members are generally flexible. In other configurations, the elongated members are substantially rigid. As shown, the elongated members 662 may contact and interfere with one another as the bladder 654 collapses, thereby preventing the bladder 654 from fully collapsing. In some embodiments, the conditioning fluid is stored within a network of voids 663, which provide an initial, readily available source of conditioning fluid for supplying the vial 210. In some such arrangements, the voids 663 are disposed between the elongated members 662.

[0203] Other embodiments include various other types of internal structures. For example, in some embodiments, the internal structure includes a plurality of inwardly protruding bumps, ridges, rings, hemispheres, or the like. In some embodiments, the initial structure divides the bladder 654 into several segments. For example, in some configurations, the internal structure is a membrane that divides the bladder 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 bladder 654 changes volume, the amount of conditioning fluid in the first portion changes (e.g., decreases) faster than in the second portion. In some configurations, the first portion and the second portion are fluidly connected by a valve. In some such configurations, the valve allows conditioning fluid to flow from the second portion into the first portion after a desired pressure differential between the portions is achieved. In some cases, the first portion fully inflates or deflates before the second portion begins to inflate or deflate.

[0204] Another embodiment of an adapter 700 is illustrated in FIG. 18. The adapter 700 may have components or portions that are the same or similar to components or portions 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 adjuster assemblies 750, 750'. In some embodiments, the expansion assemblies 750, 750' include bladders 754, 754' and filler materials 756, 756', respectively. In some embodiments, such as in the illustrated embodiment, the piercing member 720, the cap connector 730, and the connector interface 740 are substantially monolithic. In some embodiments, each bladders 754, 754' connects with the cap connector 730 with adhesive, a pipe clamp, a retaining ring, or the like.

[0205] In some configurations, multiple regulator assemblies 750, 750' provide a greater total volume of conditioning fluid than a single regulator assembly. In some embodiments, the volume of conditioning fluid is divided between multiple regulator assemblies 750, 750', thereby reducing the size of each of the regulator assemblies 750, 750' (and thus the overall adapter 600) when compared to, for example, a single regulator assembly embodiment. Additionally, the regulator assemblies 750, 750' may be symmetrically spaced relative to the rest of the adapter 600, thereby increasing stability and reducing the likelihood of tipping over.

[0206] Various embodiments have a different number 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 evenly spaced radially around the circumference of the adapter 700 or positioned in some other manner that enhances the stability of the adapter 700.

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

[0208] In some embodiments, regulator assemblies 750, 750' operate in tandem, e.g., exhibiting substantially simultaneous and approximately equal amounts of volume change. For example, in some cases, when about 5.0 mL of fluid is withdrawn from vial 210, about 2.5 mL of conditioning fluid flows from regulator assembly 750 into vial 210, and at the same time, about 2.5 mL of conditioning fluid flows from regulator assembly 750' into 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 its expanding or collapsing action. In some cases, the first regulator assembly changes volume first, and then the second regulator assembly changes volume after a condition is met. In some cases, the condition is a certain pressure difference between the interior of the second regulator assembly and the vial 210 (e.g., at least about 1 psi, at least about 2 psi, or at least about 5 psi). In some configurations, a valve (e.g., a duckbill valve) is configured to open when the condition is met.

[0210] 19 illustrates an embodiment of an adapter 800 that may have components or portions that are the same 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 coupling 852. As used herein, the term "keyed coupling" is used in its broad, ordinary sense to include a coupling having a shape configured to mate with another coupling in one or more orientations. Additionally, the illustrated embodiment of the adapter 800 does not include a filler material. In some such embodiments, the adapter 800 includes a bladder 854 that has sufficient rigidity to substantially inhibit the bladder 854 from completely collapsing (e.g., enclosing about zero volume).

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

[0212] In the illustrated embodiment, the seal 864 comprises a membrane with a slit 865. In some cases, for example, when the regulator assembly 850 is connected to the adapter 800 and fluid is introduced or withdrawn through the access channel 845, a pressure differential between the vial 210 and the bag 854 causes the slit 865 to open, thereby allowing the regulator fluid to flow between the regulator assembly 850 and the vial 210. Various other types and configurations of seal 864 are contemplated. For example, in some embodiments, the seal 864 is a duckbill valve. As another example, in some embodiments, the seal 864 comprises a substantially continuous (e.g., unslit) 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, the seal 864 is disposed within the coupling portion 852. In some other embodiments, the seal 864 is disposed in an alternative arrangement. For example, the seal 864 may be disposed within the passageway 826. In some arrangements, the seal 864 is configured to be removed or detached from the adapter 800 when fluid is introduced or withdrawn through the access channel 845. For example, in some cases, the seal 864 can be removed from the regulator channel 825 when fluid is withdrawn from the vial 210 through the access channel 845, thereby allowing the regulator fluid to flow into the vial 210. In some such cases, the seal 864 is a tab or sticker. In some such cases, the seal 864 separates from the adapter 800 and drops into the 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, increase the stability of the mated vial 210 and adapter 800 and reduce the likelihood of the combination tipping over. In some arrangements, the counterweight 831 is configured to place the center of gravity of the adapter 800 substantially on the axial centerline 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 outwardly extending connecting member 829 and the mass of the regulator assembly 850 in the initial configuration. In some cases, the counterweight 831 includes a mass of material generally located on the opposite side of the axial centerline from the regulator assembly 850. In some cases, the counterweight 831 includes an area of ​​less mass (e.g., a groove, notch, or thinner wall) on the same side of the axial centerline as the adjuster assembly 850.

[0215] As shown in FIGS. 20A-20F, which show cross-sectional views of various examples of coupling portion 852, coupling portion 852 may be keyed or have some other special shape. Connection member 829 may typically be correspondingly keyed or have some other special shape. Such a configuration may be beneficial to signal, control, or limit the regulator assemblies 850 that may be connected with a given adapter 800. For example, a relatively large regulator assembly 850 (e.g., initially containing at least about 100 mL of regulator fluid) may be keyed so as not to mate with a relatively small adapter 800 (e.g., sized and configured to mate with a vial 210 containing less than about 3 mL of fluid). In some cases, the combination of a large regulator assembly with a small vial may be unstable, more prone to tipping over, and therefore undesirable. However, such problems may be mitigated or avoided by sizing the keyway of regulator assembly 850 to mate only with an appropriately sized adapter 800. In various embodiments, coupling portion 852 can be male or female, and connecting member 829 can be correspondingly female or male.

[0216] Various types of keyed coupling portion 852 are contemplated. In some embodiments, the shape of coupling portion 852 inhibits or prevents rotation of the adjuster assembly relative to the remainder of adapter 800. For example, as shown in FIG. 20A, coupling portion 852 may be substantially rectangular. Connecting member 829 may be correspondingly rectangular to matingly engage coupling portion 852. Similarly, as shown in FIG. 20B, coupling portion 852 may be substantially diamond shaped. Connecting member 829 may be correspondingly diamond shaped to matingly engage coupling portion 852. Similarly, as shown in FIG. 20C, coupling portion 852 may include notches, grooves, bumps, or the like. Connecting member 829 may be correspondingly shaped to matingly engage coupling portion 852's notches, grooves, bumps, or the like.

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

[0218] Some embodiments provide feedback to alert the user that mating engagement of coupling portion 852 and connecting member 829 has been achieved. For example, in some cases, the connection between coupling portion 852 and connecting member 829 includes a detent mechanism, such as a ball detent, that provides a tactile indication that engagement has occurred. Some embodiments include an audio 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 in a manner that inhibits or prevents 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 in a mating engagement. In some other arrangements, the mating engagement of the coupling portion 852 and the connecting member 829 engages a one-way snap-fit ​​feature.

[0220] 21 illustrates another embodiment of an adapter 900. The adapter 900 may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. In the illustrated embodiment, the adapter 900 includes a piercing member 920, a cap connector 930, a connector interface 940, and a regulator assembly 950. As shown, apart from the regulator flow channel 925, the piercing member 920 is substantially solid, which can add strength and rigidity for piercing vials having stiff or unyielding septa. Such a configuration for the piercing member 920 can also increase manufacturability.

[0221] In the illustrated embodiment, the regulator assembly 950 includes a coupling 952, a bladder 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, the check valve 966 allows fluid to flow into the coupling 952 from the surrounding environment. Such a configuration can provide conditioning fluid to the vial 210 even when there is substantially no conditioning fluid in the bladder 954. Such a scenario can be encountered, for example, when the bladder 954 contains a volume V1 of conditioning fluid and a volume V2 of fluid is drawn from the vial 210 via the access channel 945, where V1 is less than V2. Thus, in such a scenario, the bladder 954 will have insufficient conditioning fluid to compensate for the fluid drawn from the vial 210. To supply the deficit of conditioning fluid (eg, the difference between V2 and V1), check valve 966 can allow outside air to enter vial 210 through adapter 800.

[0222] Typically, the check valve 966 is opened by a certain pressure gradient (e.g., at least about 1 psi, at least about 2 psi, at least about 5 psi), also referred to as the cracking pressure, from one side of the valve to the other. As explained above, as fluid is withdrawn from the vial 210, the pressure in the vial 210 decreases. Generally, the conditioning fluid in the bladder 954 maintains an equilibrium state in the vial 210, but as the volume of conditioning fluid in the bladder 954 is depleted, the pressure in the vial 210 may begin to decrease. However, when the pressure difference between the inside and outside of the vial 210 exceeds the cracking pressure of the check valve 966, the check valve 966 opens, thereby allowing outside air (through the adapter 900) to enter the vial 210, thereby substantially maintaining the equilibrium state therein. Thus, the check valve 966 may facilitate the withdrawal of fluid from the vial 210 even when the bladder 954 is fully deflated.

[0223] 22 illustrates an embodiment of an adapter 1000 that may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. The adapter 1000 includes a first check valve 1066 and a second check valve 1067. Similar to the check valve 966 described above in connection with the adapter 900, the first check valve 1066 can compensate for a lack of conditioning fluid in the outside air. Thus, the first check valve 1066 can facilitate maintaining an equilibrium condition in the vial 210 when the regulator assembly 1050 is fully deflated. In some cases, the first check valve 1066 is positioned in the lumen 1026. In other cases, the first check valve 1066 is disposed in the coupling 1052.

[0224] As shown, in some arrangements, the second check valve 1067 is positioned to permit conditioning fluid to enter the regulator assembly 1050 and block such fluid from exiting the regulator assembly 1050. Such a configuration may 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 channel 1045, the conditioning fluid flows from the vial 210, through the regulator channel 1025 and the filter 1060, through the second check valve 1067, and into the regulator assembly 1050. The second check valve 1067 inhibits or prevents such conditioning fluid from exiting the regulator assembly 1050, so that to the extent the regulator fluid contains harmful components, such components are substantially captured within the regulator assembly 1050 and may be disposed of. In the illustrated embodiment, when fluid is drawn from the vial 210 through the access channel 1045, the second check valve 1067 substantially blocks the conditioning fluid from flowing out of the bag 1054, while the first check valve 1066 opens to supply conditioning fluid (e.g., outside air) to the vial 210 to maintain equilibrium 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 included. In some other cases, only the second check valve 1067 is included.

[0226] As shown, in some configurations, the bladder 1054 of the regulator assembly 1050 contacts the vial 210. This can allow for a wide array of bladder 1054 geometries, for example. In some cases, in a fully expanded state, the bladder 1054 contacts the vial 210. In other configurations, the bladder 1054 remains spaced apart from the vial 210. This can, for example, reduce stress on the bladder 1054 and reduce the likelihood that the structural integrity of the bladder 1054 will be compromised, for example, by a flash or label on the vial 210 puncturing the bladder 1054.

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

[0228] In the illustrated embodiment, the regulator assembly 1150 includes a bladder 1154 and a filler material 1156. However, in some implementations, the regulator assembly 1150 does not include a filler material 1156. The filler material 1156 is illustrated as being annular and having a triangular cross-section, but may have a variety of other configurations. In some embodiments, the bladder 1154 is annular. In some embodiments, the bladder 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 connects in a substantially airtight engagement with the cap connector 1130, and the proximal end 1168 connects in a substantially airtight engagement with the connector interface 1140. As illustrated, the regulator flow path 1125 and the extraction flow path 1145 may extend through a portion or the entire axial length of the bladder 1154. As also shown, the interior of the bladder 1154 can be in fluid communication with the regulator flow path 1125 via a second regulator opening 1169. The bladder 1154 can contain a conditioning fluid, such as a sterilized gas.

[0229] In some arrangements, the regulator flow path 1125 comprises a substantially serpentine (e.g., winding, bending, undulating, or the like) portion. Such a configuration can inhibit or prevent liquid in the vial 210 from flowing into the bag 1154, for example, without the use of a liquid-repelling filter. In some embodiments, such as in the illustrated embodiment, the regulator flow path 1125 comprises a hairpin turn 1172, which reverses the direction of fluid flowing through the regulator flow path 1125 (e.g., from a proximal direction to a distal direction). In some arrangements, 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 comprising a catch basin 1173 for directing liquid into the serpentine portion of the regulator flow path 1125.

[0230] In the illustrated embodiment, the bladder 1154 is substantially centrally positioned relative to the axial center of the adapter 1100. Such a configuration can, for example, improve the stability of the adapter 1100 and reduce the likelihood of the adapter 1100 tipping over when mated with 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 deflated state, the bladder 1154 has an axial height greater than its diagonal width. In some embodiments, in a fully expanded state, the bladder 1154 has an axial height greater than its diagonal width. In some embodiments, in a fully expanded state, the bladder 1154 does not extend radially outward beyond the radially widest point of the cap connector 1130, thereby providing a more compact adapter 1100. In other embodiments, in some states (such as a fully expanded state), the bladder 1154 comprises the radially widest portion of the adapter 1100. In such embodiments, the bladder 1154 is generally the first portion of the adapter 1100 that contacts another surface (e.g., a tabletop) if the adapter 1100 is tipped over. In some such embodiments, the bladder 1154 acts as a pillow, cushion, damper, shock absorber, or the like 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, provide structure for, and / or protect the regulator assembly 1150. For example, the rigid housing can inhibit or prevent the regulator assembly 1150 from being punctured or otherwise damaged. Some variations of the rigid housing have an interior space in which a portion of the regulator assembly 1150 is disposed. In some implementations, the regulator assembly 1150 is disposed entirely within the interior space. In some embodiments, a portion of the interior space is in fluid communication with the surrounding environment, such as through 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 may contain conditioning fluid. Some embodiments of the bladder 1154 contain conditioning fluid prior to coupling of the adapter 1100 and the vial 210. In some examples, the regulator assembly 1150 has a sufficient volume of conditioning fluid after (e.g., immediately after) coupling of the adapter 1100 and the vial 210. Some embodiments of the regulator assembly 1150 have a sufficient volume of conditioning fluid to compensate for a certain amount of drug fluid withdrawn from the vial 210. For example, the bladder 1154 may contain approximately 5 mL of conditioning 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 with the vial 210, the regulator assembly 1150 comprises a volume of conditioning fluid that is equal to or greater than the volume of drug fluid in the vial 210. In some examples, the bladder 1154 contracts within the rigid enclosure as the conditioning fluid leaves the bladder 1154.

[0233] In some embodiments, the bladder 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 bladder 1154 can expand within the rigid housing to receive a corresponding amount of conditioning fluid from the vial 210. In some examples, the bladder 1154 expands completely within the rigid housing. In some variations, a portion of the bladder 1154 extends out of the rigid housing as it expands, such that a portion of the bladder does not fit within the interior space of the rigid housing.

[0234] Some implementations of the bladder 1154 expand and contract between a maximum size and a minimum size based on the volume of conditioning fluid contained within the bladder 1154. For example, in some variations of the regulator assembly 1150, the maximum size of the bladder 1154 is large enough to contain a volume that is equal to or greater than the volume of the vial 210. In some embodiments, at the maximum size, the bladder 1154 has a volume that is at least about 25%, 50%, 75%, 99%, 200%, 300%, a value therebetween, 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 bladder 1154 when the bladder 1154 is at its maximum size. Some variations of the rigid housing are configured to completely contain the bladder 1154 when the bladder 1154 is at its maximum size. In some embodiments, the bladder 1154 contains substantially no conditioning fluid at its minimum size. In some embodiments, at its smallest size, the bag 1154 has a volume that is at least about 0.1%, 1%, 5%, 10%, 25%, a value therebetween, or some other value, of the volume of the vial 210.

[0235] 24 illustrates a further embodiment of an adapter 1200. The adapter 1200 may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. In the illustrated embodiment, the adapter 1200 comprises 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 comprises an access channel 1245. In some embodiments, the second piercing member 1220' comprises a regulator channel 1225. In some arrangements, the regulator channel 1225 passes through the cap connector 1230 at an angle (e.g., at least about 45°) with respect to the axial centerline 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 with the vial 210. In some embodiments, a 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 bladder 1254 in fluid communication with the filler material 1256 and the regulator flow path 1225. As shown, the bladder 1254 can be annular, which can provide the adapter 1200 with a center of gravity approximately centerline on the axis of the adapter 1200, thus increasing stability.

[0237] FIG. 25A illustrates one embodiment of a reservoir 1350 that can be attached to the lumen 1326 of a vial adapter. As shown, the bag 1354 comprises an internal chamber 1355. The bag 1354 is generally configured to stretch, bend, unfold, or otherwise expand, contract, or cause a change in internal volume within the internal chamber 1355. In some cases, the bag 1354 comprises one or more folds, pleats, or the like. In some embodiments, the bag 1354 connects with the lumen 1326 of the vial adapter, such as with adhesive, a pipe clamp, a 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. Additionally, in some embodiments, the bag 1354 comprises an internal filler material. The filler material can be fabricated to inhibit the bladder 1354 from completely collapsing under ambient pressure. In some embodiments, the filler material can occupy a portion of the interior volume of the interior chamber 1355 or substantially the entire interior volume.

[0238] According to some embodiments, at least a majority of, or entirely or nearly entirely, the bag 1354 is contained within a rigid enclosure 1374. As shown, the bag 1354 is virtually 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 vent holes 1375. As shown, the vent 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 fixedly or removably attached to the lumen 1326.

[0239] In some embodiments, the reservoir 1350 comprises an intermediate chamber 1376 defined by the space between an exterior surface of the bag 1354 and an interior 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 reservoir 1350. In some embodiments, the connection between the bag opening 1357 and the lumen 1326 forms an airtight seal capable of preventing fluid communication between the regulator flow path 1325 and the intermediate chamber 1376.

[0240] In some embodiments, the bladder 1354 may be configured to expand as the regulator fluid moves from the regulator flow path 1325 to the internal volume 1355 of the bladder 1354 in response to fluid being injected into the container 10 via the exchange device 40. In some configurations, the expansion of the bladder 1354 is limited by the size of the rigid enclosure 1374. In some embodiments, the bladder 1354 is configured to contract as the regulator fluid moves from the internal volume 1355 of the bladder 1354 to 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 bladder 1354 can help maintain a substantially constant pressure in the container 10. In some embodiments, one or more vents 1375 in the rigid enclosure 1374 can help limit the increase and decrease in pressure in the intermediate enclosure 1376 as the bladder 1354 expands and contracts.

[0241] In some embodiments, the sack 1354 has a generally constant wall thickness T2. In some embodiments, the wall thickness T2 of the sack 1354 varies from the first side 1358 to the second side 1359 of the sack. In some embodiments, the variable thickness of the sack 1354 allows the sack 1354 to expand in one or more controlled directions. For example, the first side 1358 may expand faster than the second side 1359 due to a thinner wall at the first side 1358 compared to the second side 1359. Such a rate of variable expansion facilitates translation of the second side 1359 of the sack 1354 away from the sack opening 1357 as the sack 1354 expands.

[0242] 25B illustrates one embodiment of a reservoir 1450 that can be attached to the lumen 1426 of the vial adapter. As shown, the reservoir 1450 can comprise an enclosure 1454. In some embodiments, the enclosure comprises a first side 1458 and a second side 1450 that are connected to one another via an annular ring 1454A. The annular ring 1454A can be made from a flexible material that can be, for example, crumpled, folded, and / or stretched. The first side 1458 and the second side 1459 of the enclosure 1454 can be made from a rigid or semi-rigid material. The enclosure 1454 can comprise an interior 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 may be permitted to pass between the regulator flow path 1425 and the internal chamber 1455 via an opening 1457 in the enclosure 1454. Additionally, in some embodiments, the enclosure 1454 comprises an internal filler material. The filler material may be fabricated to inhibit the enclosure 1454 from completely collapsing under ambient pressure. In some embodiments, the filler material occupies a portion of the internal volume 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 stretch, unfold, uncrumple, 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 crumple, 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 help maintain a substantially constant pressure within the container 10 and the internal chamber 1455.

[0245] In some embodiments, as shown, the first side 1458 of the enclosure 1454 is an integral part of the lumen 1426. In some embodiments, the first side 1458 of the enclosure 1454 can be fixedly or removably attached to the lumen 1426. The first side 1458 of the enclosure 1454 can be attached to the lumen 1426 in an airtight sealed manner, which can inhibit leakage of fluid from the connection point between the first side 1458 and the lumen 1426. According to some embodiments, the annular ring 1454A of the enclosure 1454 is attached to the first side 1458 and the second side 1459 of the enclosure 1454 at the connection point 1452 via an adhesive or some other means capable of forming an airtight seal between the interior chamber 1455 and the surrounding environment. In some configurations, the width W2 of the annular ring 1454A and the height H of the enclosure 1454 may vary depending on the desired volumetric displacement within the internal chamber 1455 as the enclosure 1454 expands and / or contracts.

[0246] FIG. 25C illustrates one embodiment of a reservoir 1550 that can be attached to the lumen 1526 of the vial adapter. As shown, the reservoir 1550 comprises an enclosure 1554. In some embodiments, the enclosure 1554 comprises 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 are made from a flexible material that can be, 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 one another via an annular ring 1554A. In some embodiments, the annular ring 1554A is made from a rigid or semi-rigid material. Additionally, the enclosure 1554 can comprise an internal chamber 1555.

[0247] In some embodiments, the first side 1558 of the enclosure 1554 connects with the lumen 1526 of the vial adapter, such as with 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, allowing fluid to pass between the regulator flow path 1525 and the internal chamber 1555. In some embodiments, the enclosure 1554 comprises an internal filler material. The filler material can be fabricated to inhibit the enclosure 1554 from completely collapsing under ambient pressure. In some embodiments, the filler material 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 1558 and second 1559 sides of the enclosure 1554 at the connection point 1552 via an adhesive or some other means capable of forming an airtight seal between the internal chamber 1555 and the surrounding environment. In some arrangements, the first 1558 and second 1559 sides of the internal chamber 1555 are configured to stretch, unfold, uncrumple, and / or otherwise deform to increase the volume within the internal chamber 1555 in response to fluid being injected into the container 10 via the exchange device 40. In some embodiments, the first 1558 and second 1559 sides of the internal chamber 1555 are configured to crumple, fold, compress, and / or otherwise deform to decrease the volume within the internal chamber 1555 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 1554 can assist in maintaining a substantially constant pressure within the container 10.

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

[0250] In some embodiments, the area between the openings (e.g., the concentric rings 1654A) is made from a rigid or semi-rigid material. Additionally, in some embodiments, the ring 1654B is made from a flexible material. According to some embodiments, the ring 1654A is attached to the adjacent ring 1654B via an adhesive or some other means capable of forming an airtight seal between the internal chamber 1655 and the surrounding environment. In some configurations, the enclosure 1554 comprises an internal filler material. The filler material can be made to inhibit the enclosure 1654 from completely collapsing under ambient pressure. In some embodiments, the filler material occupies a portion or substantially the entire internal volume of the internal chamber 1655.

[0251] According to some configurations, the ring 1654B is configured to stretch, unfold, uncrumple, and / or otherwise deform to increase the volume within the internal 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 internal chamber 1655 is configured to crumple, fold, compress, and / or otherwise deform to decrease the volume within the internal 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 may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein, 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 may be substantially sealably attached to (e.g., received within or at an outer periphery of) the lumen 1726 of the regulator assembly 1750. The protrusion 2085a may facilitate fluid communication between two or more features of the regulator assembly (e.g., a filter, an enclosure, a bag, and / or a valve). In some embodiments, the protrusion 2085a may generally define a regulator pathway. The regulator pathway may 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 may be at least partially, substantially, or entirely perpendicular to the axial centerline of the adapter 1700. In some embodiments, the longitudinal axis of the protrusion 1785a and / or the lumen 1726 is at least partially, substantially, or entirely parallel to the axial centerline of the adapter 1700. In some embodiments, the angle between the longitudinal axis of the protrusion 1785 and the axial centerline of the adapter 1700 is about 5° or more and / or about 85° or less. In some embodiments, the angle is about 60°. In some embodiments, the angle between the longitudinal axis of the protrusion 1785 and the axial centerline of the adapter 1700 can be any angle between 0° and 90° or a variable angle selected by the user. Many variations are possible.

[0253] In some embodiments, the regulator assembly includes a filter 1760. The filter 1760 may include a hydrophobic filter. In some embodiments, the valve 1770, or a portion thereof, is disposed within the lumen 1726 of the adapter 1700. In some embodiments, the valve 1770, or a portion 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 allow 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 from the container 10 to the filter 1760.

[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 unrestricted fluid flow between the container 10 and the filter 1760 when the adapter 1700 is positioned above (e.g., further from the floor) 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 include components that move in response to gravity to open and / or close flow paths within the valve 1770. In some embodiments, the flow paths within the valve 1770 can be created such that the effect of gravity on fluid within the adapter 1700 can prevent or allow fluid to pass through the flow paths within the valve 1770.

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

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

[0259] According to some configurations, the valve 1770 can be a check valve capable of transitioning between two or more configurations (e.g., open and closed configurations). In some embodiments, the valve 1770 can change 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 a user can manipulate. The user interface can communicate (e.g., mechanically, electronically, and / or electromechanically) with the valve 1770 to 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, while simultaneously allowing fluid to pass in a second direction 1770B with a different pressure differential. For example, the pressure differential required to pass fluid through the filter 1770 in the first direction 1770A can be substantially higher than the pressure differential required to pass fluid through the filter 1770 in the second direction 1770B.

[0261] 26B illustrates one embodiment of an adapter 1800 that may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. The adapter 1800 includes a regulator assembly 1850, which in some embodiments may include a valve 1870. The valve 1870 may 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 fluids from the enclosure 1854 to the container 10. In some embodiments, the valve 1870 is configured to inhibit or prevent passage of fluids 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 unrestricted fluid flow 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. Additionally, 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] 26C illustrates an embodiment of an adapter 1900 that may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. The adapter 1900 may include a valve 1970 that is located in the regulator flow path 1925 in the protrusion 1985a of the regulator assembly 1950 between the container 10 and the filter 1960. In some embodiments, the valve 1970, or a portion thereof, is disposed in the regulator flow path 1925 outside of the protrusion 1985a. The regulator assembly 1950 may include an enclosure 1954. In some embodiments, the valve 1970 restricts the flow of fluid through the regulator flow path 1925 in substantially the same manner as other valves (e.g., 1770, 1870) described herein.

[0264] 27A-27C illustrate one embodiment of a vial adapter 2000 that may 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 vial adapter 2000 comprises a connector interface 2040 and a piercing member 2020 in partial communication with the connector interface 2040. In some embodiments, the vial adapter 2000 comprises a regulator assembly 2050.

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

[0266] In some configurations, the ball check valve 2070 is disposed within a lumen of the regulator assembly and / or within a lumen of the connector interface 2040. For example, the ball check valve 2070 can be disposed within the regulator flow path 2025 in 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 comprises a retaining member that prevents or impedes the ball 2073 from popping out of the ball check valve 2070 when removed from the regulator flow path 2025. The ball check valve 2070 can be rotatable about an axial centerline within the regulator flow path 2025. In some embodiments, the ball check valve 2070 can be located within another lumen of the vial adapter 2000. In some configurations, the regulator assembly 2050 includes a lumen or appendage or protrusion 2085a that can be substantially sealably attached to (e.g., received within or around) the lumen 2026 of the regulator assembly 2050. The protrusion 2085a can facilitate fluid communication between two or more features of the regulator assembly (e.g., a filter, an enclosure, a bag, and / or a valve). According to some configurations, the ball check valve 2070, or a portion thereof, can 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 a unitary piece. In some embodiments, the ball check valve 2070 and the lumen 2026 form a unitary piece.

[0267] In some embodiments, the ball check valve 2070 comprises a first chamber 2074 in fluid communication with the vial 10 via the regulator flow path 2025. The ball check valve 2070 can comprise a second chamber 2072 in selective 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 DV1 and a height H2. In some embodiments, the longitudinal axis of the first chamber 2074 is parallel to the axial center of the vial adapter 2000. In some embodiments, the longitudinal axis of the first chamber 2074 is positioned at an angle away from the axial center of the vial adapter 2000. The angle between the longitudinal axis of the first chamber 2074 and the axial centerline of the vial adapter 2000 can be about 15° or more and / or about 60° or less. In some embodiments, the angle between the longitudinal axis of the first chamber 2074 and the axial center 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 DV2. Many other variations of the configuration 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 above the vial adapter. In some embodiments, the angle θ 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 an open configuration. In some embodiments, the inner wall of the first chamber 2074 may gradually taper 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, the ball 2073 may rest on a circular seat when in the closed position. In some embodiments, the circular seat is formed by a 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 may define a general path of movement for the ball 2073 or other occlusion member (e.g., the ball 2073 may 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 for the occlusion member is not substantially parallel to the installation path of the ball check valve 2070. For example, the path of movement for the occlusion member may be substantially perpendicular to the installation path of the ball check valve 2070. In some variations, the longitudinal axis of the circular seat is at an angle with respect to the longitudinal axis of the first chamber 2074. The angle between the axial longitudinal 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, the 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 axial center of the adapter 2000. Such a configuration can reduce the likelihood that the ball 2073 will "stick" to the circular seat or to the inner wall of the first chamber 2074 when the 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 axial center of the ball check valve 2070. In some embodiments, the longitudinal axis of the first chamber 2074 may define a path of travel for the ball 2073. As illustrated in FIG. 27C, the longitudinal axis of the first chamber 2074 may be perpendicular to the axial center of the ball check valve 2070. In some embodiments, the angle between the longitudinal axis of the first chamber 2074 and the axial centerline of the ball check valve 2070 is greater than or equal to about 5° and / or less than or equal to about 90°. In some embodiments, the angle is about 60°. Many variations are possible. In some embodiments, the angle between the longitudinal axis of first chamber 2074 and the axial centerline of ball check valve 2070 is the same as the angle between the axial centerline of ball check valve 2070 and the axial centerline of vial adapter 2000. In some such embodiments, the longitudinal axis of first chamber 2074 can be aligned with the axial centerline of vial adapter 2000.

[0271] The ball check valve 2070 may 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 portion of the regulator flow path 2025 opposite the second chamber 2072 from the first chamber 2074. As illustrated in FIGS. 27A-27C, the ball check valve 2070 may include one or more seals 2079. The one or more seals 2079 may resist movement of the ball check valve 2070 within the regulator flow path 2025. In some embodiments, the one or more seals 2079 inhibit fluid from flowing around and bypassing the ball check valve 2070. In some embodiments, the one or more seals 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., an 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 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., an 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., an interface) between the first valve flow path 2071 and the regulator flow path 2025.

[0273] The ball check valve 2070 may be configured such that fluid entering or exiting the ball check valve 2070 through the distal opening 2075a and the proximal opening 2075b flows through the interface defined by the respective openings 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 defined by the proximal opening 2075b (vertical with respect to FIG. 27B). Similarly, the flow of liquid entering and exiting the ball check valve 2070 through the distal opening 2075a is 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 path of travel of the ball 2073 or other occlusion member. The angle between any interface and the path of travel of ball 2073 may be substantially the same as the angle between that same interface and the insertion axis of the adapter.

[0274] According to some embodiments, the occluder valve 2070 comprises a movable occluder, such as a ball 2073. All references to a ball herein may also apply to other shapes of occluders, such as generally 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 may be made of a material that has a higher density than the liquid L or other fluid in the vial 10. The ball 2073 may have a diameter DB. In some configurations, the diameter DB of the ball 2073 is smaller than the diameter DV1 and the 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 diameter DV2 of second chamber 2072 to diameter DB of ball 2073 is about 9:10 or less, and / or about 7:10 or more. In some embodiments, ball 2073 can move between at least two positions within first chamber 2074. For example, the movement of ball 2073 can be determined by gravity, an external force on the vial adapter, fluid in the regulator flow path, other forces, or a combination of forces.

[0275] 27A-27C, the ball 2073 in the ball check valve 2070 can be configured to rest on a shoulder 2078 at the opening of the second chamber 2072 when the adapter 2000 and vial 10 are oriented such that gravity affects the fluid contained in the vial being biased toward the vial adapter (e.g., when at least a portion of the vial 10 is above 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 axial centerline 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 connector interface 2040. For example, in such embodiments, the manner in which the ball 2073 moves toward the shoulder 2078 or 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 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 axial centerline of the vial adapter 2000, or about another other axis of rotation therebetween. Further, in such embodiments, the parallel alignment between the longitudinal axis of the first chamber 2074 and the axial centerline of the adapter 2000 may be a means to assist a user of the adapter 2000 in visualizing the alignment of the ball check valve 2070. In some configurations, contact between the ball 2073 and the shoulder 2078 may form a seal 2076. The seal 2076 can place the ball check valve 2070 in a closed configuration 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, the ball 2073 can be configured to move away from the shoulder 2078 when the adapter 2000 and vial 10 are biased away from the vial adapter under gravity (e.g., when at least a portion of the connector interface 2040 is positioned above the vial 10). In some embodiments (e.g., such as those in which the longitudinal axis of the first chamber 2074 and the circular seat are parallel to the axial centerline of the vial adapter 2000), the ball 2073 can be configured to move away from the shoulder 2078 in a substantially consistent manner regardless of the rotational orientation of the vial 10 and connector interface 2040. For example, in such an embodiment, the manner in which the ball 2073 moves away from the shoulder 2078 when the vial 10 is rotated from above the connector interface 2040 to below the connector interface 2040 is substantially consistent, regardless of whether the vial 10 and 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 axial centerline of the vial adapter 2000, or about some other axis of rotation therebetween. The movement of the ball 2073 away from the shoulder 2078 opens or breaks the seal 2076, causing the ball check valve 2070 to assume an open configuration and placing the first chamber 2074 and the second chamber 2072 in fluid communication. In some embodiments, the ball check valve 2070 comprises a resilient biasing member that can bias the ball 2073 towards the shoulder 2078, thus biasing the ball check valve 2070 in the 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 resilient biasing member can be less than the weight of the ball 2073.

[0277] In some embodiments, the ball 2073 can move about the first chamber 2074 under the influence of gravity. In some configurations, gravity can cause the ball 2073 to move toward the second chamber 2072 and rest on a shoulder 2078 at the opening of the second chamber 2072. As described above, the ball 2073 can rest on the shoulder 2078 to form a seal 2076, which causes the ball check valve 2070 to assume a closed configuration and inhibit liquid L and / or other fluids from exiting the vial 10 through the ball check valve 2070. In some configurations, gravity can cause the ball 2073 to move away from the shoulder 2078 under the influence of gravity. The movement of the ball 2073 away from the shoulder 2078 opens or breaks the seal 2076, causing the ball check valve 2070 to assume an open configuration and allowing the first chamber 2074 and the second chamber 2072 to be in fluid communication. The diameter or cross-section DV 1 of the first chamber is greater than the diameter or cross-section DB of the ball 2073 so that fluid can flow through the first chamber and around the outer surface of the ball 2073 .

[0278] Several aspects of the operation of the ball check valve 2070 while it is in a closed configuration will now be described. For example, in some embodiments, when no fluid is being introduced into or withdrawn from the vial 10 via the access channel 2045, the pressure in the vial 10 is substantially the same as the pressure in the valve channel 2071. In such a situation, the pressure in the first chamber 2074 may be substantially the same as the pressure in the second chamber 2072. In some embodiments, positioning the vial 10 over the connector interface 2040 allows liquid L or other fluid to move from the vial 10 to the first chamber 2074. In some embodiments, when pressure is in equilibrium between the first chamber 2074 and the second chamber 2072, the ball 2073 remains stationary on the shoulder 1078, forming a seal 2076. The seal 2076 may inhibit liquid L and / or other fluid from passing from the vial 10 through the ball check valve 2070.

[0279] In some embodiments, when fluid is drawn from the vial 10 through the access channel 2045, a pressure lower than the pressure in the second chamber 2072 may be created in the vial 10 and the first chamber 2074. This pressure difference may move the ball 2073 away from the step 2078 into the first chamber 2074. As the ball 2073 moves away from the step 2078, the seal 2076 breaks and the regulator fluid FR may pass through the second chamber 2072 and around the ball 2073. The regulator fluid FR may then pass through the first chamber 2074, through the regulator channel 2025, and into the vial 10. In some embodiments, the regulator fluid FR is a fluid that has passed through a filter in the regulator assembly 2050. In some embodiments, the regulator fluid FR is a fluid contained within the interior volume of the enclosure of the regulator assembly 2050. When the regulator fluid FR enters the vial 10, the pressure differential between the first chamber 2074 and the second chamber 2072 can be counterbalanced, reduced, substantially eliminated, or eliminated, and the ball 2073 can return to a resting position on the shoulder 2078. In some embodiments, when the regulator fluid FR enters the vial 10, it helps maintain an equilibrium between the inside of the vial 10 and the inside of the regulator assembly 2050. The return of the ball 2073 to a resting position on the shoulder 2078 can reform or create the seal 2076, preventing the liquid L or other fluid from exiting the vial 10 and passing through the ball check valve 2070.

[0280] In some embodiments, when fluid is introduced into the vial 10 through the access channel 2045 (e.g., when a diluent, mixed fluid, or overdrawn fluid is injected into the vial 10 through the exchange device 40), a pressure higher than the pressure in the second chamber 2072 may be created in the vial 10 and the first chamber 2074. This pressure difference may force the ball 2073 onto the shoulder 2078, thus tightening the seal 2076. Tightening the seal 2076 may inhibit liquid L from passing from the vial 10 through the ball check valve 2070. In some embodiments, tightening the seal 2076 may allow the internal pressure in the vial 10 and the first chamber 2074 to continue to increase as more fluid is introduced into the vial 10 through the access channel 2045. In some embodiments, as the pressure within the vial 10 and first chamber 2074 continues to increase, the force required to introduce more fluid to a prohibitive level may increase dramatically, ultimately increasing the likelihood of fluid leakage from or between the vial 10 and adapter 2000. Therefore, it may be desirable for the ball check valve 2070 to be in the open position when fluid is injected into the vial 10.

[0281] Movement of ball 2073 away from shoulder 2078 may open or break seal 2076 and place ball check valve 2070 in an open configuration. Several aspects of the operation of ball check valve 2070 while it is in an open configuration will now be described. For example, in some embodiments, when no fluid is being introduced into or withdrawn from vial 10 via access channel 2045, the pressure within vial 10 remains substantially constant. In some embodiments, vial 10 is in fluid communication with and has the same substantially constant internal pressure as first chamber 2074, second chamber 2072, and valve channel 2071 of ball check valve 2070.

[0282] In some embodiments, when fluid is drawn from the vial 10 through the access channel 2045, the pressure in the vial 10 may decrease, and subsequently the pressure in the first chamber 2074 may also decrease. This decrease in pressure in the vial 10 and the first chamber 2074 may create a pressure differential between the first chamber 2074 and the second chamber 2072 of the ball check valve 2070. This pressure differential may allow the regulator fluid FR to pass through the first chamber 2074, through the regulator channel 2025, and into the vial 10. In some embodiments, the regulator fluid FR is a fluid that has passed through a filter in the regulator assembly 2050. In some embodiments, the regulator fluid FR is a fluid contained within the interior volume of the enclosure of the regulator assembly 2050. Once the regulator fluid FR is in the vial 10, the pressure differential between the first chamber 2074 and the second chamber 2072 may be counteracted, reduced, substantially eliminated, or eliminated. In some embodiments, once the regulator fluid FR is in the vial 10 , it helps maintain equilibrium between the inside of the vial 10 and the inside of the regulator assembly 2050 .

[0283] In some embodiments, when fluid is introduced into the vial 10 through the access channel 2045 (e.g., when a diluent, mixing fluid, or overdrawn fluid is injected into the vial 10 through the exchange device 40), a pressure higher than the pressure in the second chamber 2072 may be created in the vial 10 and the first chamber 2074. This pressure difference may allow fluid from the vial 10 to pass from the vial 10 through the ball check valve 2070 and into the regulator assembly 2050. In some embodiments, the fluid from the vial 10 may pass through the check valve 2070 and through a filter. In some embodiments, the fluid from the vial 10 may pass through the check valve 2070 and into a bag or other enclosure. As the fluid passes from the vial 10 through the ball check valve 2070, the pressure in the vial 10 may decrease and an equilibrium may be maintained between the inside of the vial 10 and the inside of the regulator assembly 2050. In some embodiments, the regulator fluid FR is ambient air or a sterilized gas, or filtered air or gas.

[0284] In some embodiments, particularly in those in which parts of the vial adapter are modular or replaceable, the interior and / or exterior cross-section of the lumen 2026 may include one or more alignment features. For example, the interior and / or exterior cross-section of the lumen may be keyed or have some other special shape. Some examples of potential shapes and their advantages are shown in FIGS. 20A-20F and described above. The protrusion 2085a and / or the ball check valve 2070 may include corresponding alignment features (e.g., corresponding keyed or other special shapes). Such a configuration may be beneficial to signal, control, or restrict the regulator assembly 2050, which may be connected to or formed integrally with the adapter 2000. For example, the keyway or shape of the ball check valve 2070 and / or the flow passage in which it sits may provide a means for a user of the adapter 2000 to ensure that the check valve 2070 is properly aligned (e.g., aligning the first chamber 2074 with the side in the vial 10) within the regulator assembly 2050. Such alignment of the ball check valve 2070 may enable the function of the regulator assembly 2050 to operate properly and / or predictably.

[0285] In some embodiments, the exterior of the regulator assembly 2050 can include one or more visual indicators to indicate the alignment of the ball check valve 2070. In some embodiments, the visual indicators include notches, words (e.g., top and / or bottom), arrows, or other indicators of alignment. In some embodiments, the protrusion 2085a, lumen 2026, and / or body portion of the valve 2070 are made from a substantially transparent material that allows a user of the adapter 2000 to visually verify the configuration of the valve (e.g., to view the position of the ball, which indicates 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 lights, chemiluminescent lights, etc.) that can be 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 provide power to at least one of the one or more indicators. In some embodiments, the ball 2073 is made from 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 the one or more indicators when a vial 10 is held on the adapter 2000.

[0287] 28 illustrates one embodiment of an adapter 2100 that may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. In some embodiments, the ball check valve 2170 comprises a first valve flow path 2171A 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 may comprise a second valve flow path 2171B in selective 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 in the regulator flow path 2125 within the protrusion 2185a. In some embodiments, the ball check valve 2170, or a portion thereof, is positioned in 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 a unitary piece. In some embodiments, the ball check valve 2170 and the lumen 2126 form a unitary piece.

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

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

[0290] In some embodiments, the dome-shaped portion 2273 comprises 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-shaped valve 2270 can inhibit and / or prevent fluid from passing through the regulator flow channel 2225 when the one or more slits 2274 are in a closed position. In some embodiments, the one or more slits 2274 are configured to open in response to one or more cracking pressures to allow fluid to flow through the one or more slits 2274. In some embodiments, the geometry and / or material of the dome-shaped valve 2270 can result in a cracking pressure required to allow fluid to flow through the one or more slits 2274 in a first direction F1 being substantially higher than a cracking pressure required to allow fluid to flow through the one or more slits 2274 in a second direction F2.

[0291] Several aspects of the operation of the dome-shaped valve 2270 will now be described. For example, in some embodiments, when no fluid is being introduced into or withdrawn from the vial 10 through the access channel 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 channel 2225 in the region of the convex side 2275A of the dome-shaped valve 2270 and has a substantially constant internal pressure therein equal to the pressure P1. In some embodiments, the pressure P2 in the region of the concave side 2275B of the dome-shaped valve 2270 is substantially the same as the pressure P1 when no fluid is being introduced into or withdrawn from the vial 10. In such a configuration, the one or more slits 2274 of the dome-shaped valve 2270 can be biased to a closed position by the dome-shaped portion 2273 of the dome-shaped valve 2270.

[0292] In some embodiments, as fluid is withdrawn from the vial 10 through the access channel 2045, the pressure in the vial 10 may decrease, followed by a decrease in pressure P1 in the region of the convex side 2275A. This decrease in pressure P1 may create a pressure differential between the convex side 2275A and the concave side 2275B of the dome-shaped valve 2270. In some embodiments, as fluid is withdrawn from the vial 10, the pressure differential across the dome-shaped valve 2270 may be high enough to overcome the cracking pressure of the dome-shaped valve 2270, causing one or more slits 2274 to open, allowing fluid to flow through the dome-shaped valve 2270 in the second direction F2. In some configurations, the regulator fluid FR flows through the dome-shaped valve 2270 in the second direction F2 when the one or more slits 2274 are opened and the pressure P2 on the concave side 2275B of the valve 2270 becomes higher than the pressure P1 on the convex side 2275A of the valve 2270. As the regulator fluid FR passes through the dome-shaped valve 2270 and / or into the vial 10, the pressure in the vial 10 may increase. As the pressure in the vial 10 increases, the pressure P1 in the area of ​​the convex surface 2275A of the dome-shaped valve 2270 may increase. As the pressure P1 in the area of ​​the convex surface 2275A increases, the pressure difference across the valve 2270 becomes lower than the cracking pressure and may close the one or more slits 2274. In some embodiments, the regulator fluid FR passes through the dome-shaped valve 2270 in the second direction F2 to facilitate maintaining an equilibrium between the inside of the vial 10 and the inside of the regulator assembly 2050 as the fluid is drawn from the vial 10 through the access channel 2245. In some embodiments, the regulator fluid FR is a fluid that has passed through a filter in the regulator assembly 2250. In some embodiments, the regulator fluid FR is a fluid contained within the interior volume of the enclosure of the regulator assembly 2250.

[0293] In some embodiments, when fluid is introduced into the vial 10 through the access channel 2245 (e.g., when a diluent, mixed fluid, or overdrawn fluid is injected into the vial 10 through the exchange device 40), the pressure in the vial 10 may increase. When the pressure in the vial 10 increases, the pressure P1 in the area of ​​the convex surface 2275A of the dome shaped valve 2273 may increase. When the pressure P1 in the area of ​​the convex surface 2275A increases, a pressure differential may be created on the dome shaped valve 2273. In some embodiments, when fluid is introduced into the vial 10, the pressure differential across the dome shaped valve 2270 may be high enough to overcome the cracking pressure of the dome shaped valve 2270, causing the one or more slits 2274 to open and allow the fluid to flow through the dome shaped valve 2270 in the 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 the dome-side valve 2270 in the second direction F2. In some embodiments, as fluid flows from the vial 10 through the dome-shaped valve 2270 in the first direction F1, the pressure in the vial 10 may decrease. As the pressure in the vial 10 decreases, the pressure P1 in the area of ​​the convex surface 2275A decreases, and the pressure difference across the valve 2270 becomes lower than the cracking pressure, allowing the one or more slits 2274 to close. In some embodiments, as fluid passes through the dome-shaped valve 2270 in the first direction F1, it becomes easier to maintain an equilibrium state between the inside of the vial 10 and the inside of the regulator assembly 2250.

[0294] 30A-30B illustrate an embodiment of a valve with multiple openings, such as an adapter 2300 and a showerhead dome shaped valve 2370. The adapter 2300 may have components or portions that are the same as or similar to components or portions of other vial adapters disclosed herein. The showerhead dome shaped 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, the showerhead dome shaped valve 2370 may comprise an annular flange 2378 attached to the dome shaped portion 2373. In some embodiments, the annular flange 2378 and the dome shaped portion 2373 comprise 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 shaped valve 2370.

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

[0296] In some embodiments, the dome-shaped portion 2373 comprises one or more openings or central slits 2374. In some embodiments, the one or more central slits 2374 are arranged in a generally cross-shaped configuration. In some embodiments, the one or more central slits 2374 are generally parallel to one another. 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, one or more of the central slits 2374 and / or the outer slits 2374A are biased to a closed position by the dome-shaped portion 2373 and / or the annular flange 2378. The showerhead dome valve 2370 can inhibit and / or prevent fluid from passing through the regulator flow channel 2325 when the slits 2374, 2374A are in a closed position. In some embodiments, the slits 2374, 2374A are configured to open in response to one or more cracking pressures to allow fluid to flow through the slits 2374, 2374A. In some embodiments, the geometry and / or materials of the showerhead dome valve 2370 can result in the cracking pressure required to allow fluid to flow through the slits 2374, 2374A in a first direction F1 being substantially higher than the cracking pressure required to allow fluid to flow through the slits 2374, 2374A in a second direction F2. In some embodiments, the cracking pressure required to allow fluid to flow in the first direction F1 and the second direction F2 through the showerhead dome side valve 2370 is less than the cracking pressure required to allow fluid to flow in the first direction F1 and the second direction F2 through the dome side valve 2270, respectively. 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 removed from the vial 10 via the access channel 2345.

[0298] 31A-31B illustrate an embodiment of an adapter 2400 that may have components or portions that are the same or similar to components or portions of other vial adapters disclosed herein. In some embodiments, the regulator assembly 1450 includes an occluder valve 2470, such as a flap check valve 2470, that opens and closes, with a portion of the occlusion component remaining attached to a structure within the vial adapter 2400 as the occluder valve 2470 transitions between an open state and a closed state. The flap check valve 2470 may include a sealing portion 2479. The sealing portion 2479 may include, for example, a hollow stopper shaped to fit snugly within the regulator flow path 2425 of the regulator assembly 2450, 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 in 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 a 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 vial 10 are oriented such that the vial 10 is above 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 inside 2472 and the outside 2474 of the flap check valve 2470. The seal 2476 can place the flap check valve 2470 in a closed configuration and inhibit liquid L and / or other fluids from passing from the vial 10 through the flap check valve 2470. In some embodiments, the flap 2473 can be configured to rotate away from the seat 2477 when the adapter 2400 and vial 10 are oriented such that the connector interface of the adapter 2400 is above the vial 10. Movement of the flap 2473 away from the seat member 2477 displaces the seal 2476 and places the flap check valve 2470 in an open configuration, with the inner side 2472 and the outer side 2474 of the flap check valve 2470 in fluid communication.

[0301] In some embodiments, the flap 2473 can move toward and away from the seat 2477 under the influence of gravity. As described above, contact between the flap 2473 and the seat 2477 can form a seal 2476 between the inner side 2472 and the outer side 2474 of the flap check valve 2470, which can place the flap check valve 2470 in a closed configuration and inhibit liquid L and / or other fluids from passing through the flap check valve 2470 from the vial 10. In some configurations, gravity can cause the flap 2473 to move away from the seat 2477 and break the seal 2475. Movement of the flap 2473 away from the seat member 2477 under the influence of gravity can displace the seal 2476 and place the flap check valve 2470 in an open configuration, placing the outer side 2474 and the inner side 2472 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 (e.g., tension, shape memory material, magnets, etc.) suitable for biasing the flap 2473 towards the seat 2477. In some embodiments, the biasing torque applied to the flap 2473 at the first end 2473A is less than the torque that occurs 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 over the flap 2473).

[0302] Some aspects of the operation of the flap check valve 2470 while the flap check valve 2470 is in a closed configuration will now be described. For example, in some embodiments, when no fluid is being introduced into or withdrawn from the vial 10 via the access channel 2445, 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, positioning the vial 10 over the flap check valve 2470 allows liquid L or other fluid to move from the vial 10 to the outside 2474 of the flap check valve 2470. In some embodiments, when 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 a seal 2476. The seal 2476 can inhibit liquid L and / or other fluids from passing from the vial 10 through the flap check valve 2470.

[0303] In some embodiments, when fluid is drawn from the vial 10 through the access channel 2445, a pressure lower than the pressure on the inside 2472 of the flap check valve 2470 may be generated in the vial 10 and on the outside 2474 of the flap check valve 2470. This pressure difference may cause the flap 2473 to move away from the seat 2477. As the flap 2473 moves away from the seat 2477, the seal 2476 may be broken, allowing the fluid FR to move from the inside 2472 of the flap check valve 2470 to the outside 2474 of the flap check valve 2470. The conditioning fluid FR may then pass through the regulator channel 2425 and into the vial 10. In some embodiments, the regulator fluid FR is a fluid that has passed through a filter in the regulator assembly 2450. In some embodiments, the regulator fluid FR is a fluid contained within the interior volume of the enclosure of the regulator assembly 2450. When the regulator fluid FR enters the vial 10, the pressure differential between the first outside 2474 and the inside 2472 of the flap check valve 2470 can be counterbalanced, reduced, substantially eliminated, or eliminated, and the flap 2473 can return to a resting position on the seat 2477. In some embodiments, when the regulator fluid FR enters the vial 10, it helps maintain an equilibrium between the inside of the vial 10 and the inside of the regulator assembly 2450. The return of the flap 2473 to a resting position on the seat 2477 can reform the seal 2476 and prevent the liquid L and / or other fluids from exiting the vial 10 and passing through the flap check valve 2470.

[0304] In some embodiments, when fluid is introduced into the vial 10 through the access channel 2445 (e.g., when a diluent, mixed fluid, or overdrawn fluid is injected into the vial 10 through the exchange device 40), a pressure higher than the pressure inside 2472 of the flap check valve 2470 may be generated in the vial 10 and outside 2474 of the flap check valve 2470. This pressure difference may force the flap 2473 onto the seat 2477, thus tightening the seal 2476. Tightening the seal 2476 may inhibit the liquid L from passing from the vial 10 through the flap check valve 2470. In some embodiments, tightening the seal 2476 may allow the pressure P1 inside the vial 10 and in the area outside 2474 of the flap check valve 2470 to continue to increase as more fluid is introduced into the vial 10 through the access channel 2445. In some embodiments, as the pressure within the vial 10 continues to increase, the force required to introduce more fluid to a prohibitive level may increase dramatically, ultimately increasing the likelihood of fluid leakage from or between the vial 10 and adapter 2400. Therefore, it may be desirable for the flap check valve 2470 to be in the open position when fluid is injected into the vial 10.

[0305] Movement of the flap 2473 away from the seat 2477 can displace the seal 2476 and place the flap check valve 2470 in an open configuration. In some embodiments, the open flap check valve 2470 functions much the same as the open ball check valve 2070 described above with respect to the passage of fluid through the flap check valve 2470 after introducing or withdrawing fluid from the vial 10 via the access channel 2445. In some embodiments, the regulator assembly 2450 can have many of the same keyways, shapes, and / or alignment features (e.g., transparent materials, visual alignment indicators, shaped flow channels, and / or shaped valves) as described above with respect to the ball check valve 2070.

[0306] FIG. 32 illustrates one embodiment of an 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 channel 2545 in communication with the exchange device 40. In some embodiments, the piercing member 2530 includes a regulator channel 2525 that includes a gravity or orientation occluder valve, such as the ball check valve 2520. The ball check valve 2570 can include a first channel 2574 having a substantially circular cross-section and a diameter D1 in fluid communication with the vial 10. In some embodiments, the ball check valve 2570 can include a second channel 2572 having a substantially circular cross-section and a diameter D2 in selective fluid communication with the first channel 2574. Many other variations of the configuration of the first and second chambers 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 passage 2574 and the second flow passage 2572. In some embodiments, the angle θ2 between the step 2578 and the wall of the first flow passage 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 passage 2572 is in fluid communication with the first flow passage 2574 when the ball check valve 2570 is in an open configuration. In some embodiments, the inner wall of the first flow passage 2574 can be gradually tapered into the inner wall of the second flow passage 2572 such that the first flow passage 2574 and the second flow passage 2572 form a single frusto-conical flow passage.

[0308] The occluder valve can include an occluder, such as a ball 2573. In some embodiments, the ball 2573 is made of a material having a higher density than the liquid L and / or other fluids in the vial 10. The ball 2573 can be a sphere or some other suitable shape. In some embodiments, the 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 the 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 the 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 restrain the ball 2570 from exiting the first channel 2574 .

[0309] In some configurations, the ball 2573 may behave in much the same way as the ball 2073 of the ball check valve 2070. For example, the ball 2573 may move within the first channel 2574 under the influence of forces in much the same way that the ball 2573 may move around in the first chamber 2074 of the ball check valve 2070. The ball 2573 may abut against a shoulder 2578 of the ball check valve 2570 to form a seal 2560 that may inhibit liquid L and / or other fluids in the vial from entering the regulator channel 2525. In many respects, the ball check valve 2570 behaves in the same or substantially the same way as the ball check valve 2070 under the influence of gravity, alignment of the adapter 2570, and / or other forces.

[0310] The following list summarizes exemplary embodiments that are within the scope of this disclosure. The exemplary embodiments listed should not be construed as limiting the scope of the embodiments in any way. Various features of the exemplary embodiments listed can be removed, added, or combined to form additional embodiments, which form part of this disclosure.

[0311] 1. An adapter configured to mate with a sealed vial, comprising: a containment device including a distal extractor opening configured to allow for drawing 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 containment device; a regulator enclosure in fluid communication with the regulator flow path, the 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 unfolded and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or collapsed when fluid is withdrawn from the sealed vial via the extractor flow path; a filler disposed within the regulator enclosure and configured to secure 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 as fluid is withdrawn from the sealed vial through the extractor opening.

[0312] 2. The adapter of 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 of embodiment 1, wherein at least a substantial portion of the regulator enclosure is not within a rigid housing.

[0314] 4. The adapter of embodiment 1, wherein the storage device is in fluid communication with the extractor flow path and has a medical connector interface configured to couple with a syringe configured to hold a defined volume of fluid in a barrel, and the filler is configured to ensure that the initial volume of regulator fluid is equal to or greater than the defined volume of fluid.

[0315] 5. The adapter of embodiment 4, wherein the initial volume of regulator fluid in the regulator enclosure is greater than or equal to about 60 mL.

[0316] 6. An adapter as described in 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, the maximum volume being greater than or equal to about 180 mL.

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

[0318] 8. The adapter of embodiment 7, wherein the polyethylene terephthalate film includes a metallized coating.

[0319] 9. The adapter of embodiment 8, wherein the metallized coating comprises aluminum.

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

[0321] 11. The adapter of embodiment 1, wherein the pressure within the sealed vial is regulated by contracting or collapsing the regulator enclosure to substantially equilibrate pressure on opposite sides of the regulator enclosure as drug fluid is withdrawn from the sealed vial.

[0322] 12. An adapter as described in embodiment 1, wherein the regulator enclosure includes a layer that is substantially impermeable to a drug fluid disposed within the vial, thereby preventing passage of the drug fluid between an outer surface and an inner surface of the regulator enclosure.

[0323] 13. The adapter of 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 of embodiment 13, wherein the hydrophobic filter is disposed within the regulator flow path.

[0325] 15. The adapter of embodiment 1, wherein the filler material comprises a foam material.

[0326] 16. The adapter of embodiment 15, wherein the filler material comprises a polyurethane-ether foam.

[0327] 17. A method of withdrawing fluid from a sealed vial, comprising: connecting a pressure regulated vial adapter to the sealed vial, the pressure regulated vial adapter comprising: a containment device including a distal extractor opening configured to allow for drawing 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 containment device; a regulator enclosure in fluid communication with the regulator flow path, the 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 unfolded and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or collapsed when fluid is withdrawn from the sealed vial via the extractor flow path; a filler material 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 as fluid is withdrawn from the sealed vial through the extractor opening; and drawing fluid from the sealed vial through the pressure regulated vial adapter.

[0328] 18. A method of making an adapter for mating with a sealed vial, comprising: providing a containment device including a distal extractor opening configured to allow for 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 containment device; disposing a filler material within a regulator enclosure, the filler material configured to secure an initial volume of regulator fluid within the regulator enclosure, thereby enabling the adapter to deliver regulator fluid from the regulator enclosure to the sealed vial as fluid is withdrawn from the sealed vial through the extractor opening; and placing the regulator enclosure in fluid communication with the regulator flow path, the 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 unfolded, and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or collapsed when fluid is withdrawn from the sealed vial via the extractor flow path.

[0329] 19. The step of disposing a filler material within the regulator enclosure comprises: forming a fill opening in the regulator enclosure configured to allow the filler material to pass therethrough; filling the regulator enclosure with the filler material through the fill opening; 20. The method of claim 18, comprising closing the fill opening.

[0330] 20. The step of placing a regulator enclosure in fluid communication with the regulator flow path comprises: aligning an enclosure opening in the regulator enclosure with a proximal regulator opening of a storage device; 19. The method of claim 18, further comprising fastening the regulator enclosure to the storage device.

[0331] 21. An adapter configured to mate with a sealed vial, comprising: a containment device including a distal extractor opening configured to allow for drawing 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 containment device; a regulator enclosure in fluid communication with the regulator flow path, the 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 unfolded and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or collapsed when fluid is withdrawn from the sealed vial via the extractor flow path; The rigid housing does not include a substantial volume of the regulator enclosure.

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

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

[0334] 24. The adapter of embodiment 22, wherein the first side has 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 being oriented toward a storage device.

[0335] 25. The adapter of embodiment 21, wherein the pressure within the sealed vial is regulated by contracting or collapsing the regulator enclosure to substantially equilibrate the pressure on opposite sides of the regulator enclosure as drug fluid is withdrawn from the sealed vial.

[0336] 26. The adapter of embodiment 21, wherein the regulator enclosure includes a layer that is substantially impermeable to a drug fluid disposed within the vial, thereby preventing passage of the drug fluid between the exterior and interior surfaces of the enclosure.

[0337] 27. The adapter of 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 of 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 as fluid is withdrawn from the sealed vial through the extractor opening.

[0339] 29. A vial adapter configured to mate with a sealed vial, comprising: a containment device including a distal extractor opening configured to allow for drawing 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 containment device; a regulator enclosure in fluid communication with the regulator flow path, the 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 unfolded and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or collapsed when fluid is withdrawn from the sealed vial via the extractor flow path; the regulator enclosure has a first side and a second side opposite the first side, the first side including an inner surface forming a portion of an interior of the regulator enclosure and an outer surface forming a portion of an exterior of the regulator enclosure, the outer surface of the first side being oriented toward the storage device; each of the first side and the second side is configured to expand, contract, fold, or unfold when a regulator fluid passes through the regulator flow path; the second side is configured to move away from or toward the containment device as regulator fluid passes through the regulator flow path; The regulator enclosure is a vial adapter that does not fit completely within a rigid housing.

[0340] 30. A vial adapter configured to mate with a sealed vial, comprising: a containment device including a distal extractor opening configured to allow for drawing 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 containment device; a regulator enclosure in fluid communication with the regulator flow path and configured to receive a volume of a regulator fluid, the 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 unfolded, and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or collapsed when fluid is withdrawn from the sealed vial via the extractor flow path; the regulator enclosure has a first layer connected to a second layer opposite the first layer, the first layer and the second layer configured to receive the volume of regulator fluid therebetween; each of the first side and the second side is configured to expand, contract, fold, or unfold when a regulator fluid passes through the regulator flow path; the second side is configured to move away from or toward the containment device as regulator fluid passes through the regulator flow path; The regulator enclosure is a vial adapter that does not fit completely within a rigid housing.

[0341] 31. The vial adapter of 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 of embodiment 30, wherein the first layer and the second layer are connected at a periphery of the first layer and the second layer.

[0343] 33. The vial adapter of 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 portions.

[0344] 34. A modular vial adapter configured to mate with a sealed vial, comprising: 1. A pressure regulated vial adapter module comprising: a containment device including a distal extractor opening configured to allow for drawing 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 containment device; a pressure regulated vial adapter module comprising: a proximal regulator opening in fluid communication with the regulator flow path, the proximal regulator opening configured to allow regulator fluid to flow therethrough when the vial adapter module is coupled to the sealed vial and fluid is withdrawn from the vial; a regulator fluid module configured to mate 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 unfolded and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or folded when a regulator fluid passes through an enclosure opening in the regulator enclosure; a fastener configured to couple the regulator enclosure and the proximal regulator opening; the regulator enclosure does not fit completely within a rigid housing; and a regulator fluid module.

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

[0346] 36. An adapter as described in embodiment 35, wherein the fastening member is made from a material system including an elastic material.

[0347] 37. A method of manufacturing a vial adapter configured to mate with a sealed vial, comprising: providing a pressure regulated vial adapter module, said pressure regulated vial adapter module comprising: a containment device including a distal extractor opening configured to allow for drawing 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 containment device; a proximal regulator opening in fluid communication with the regulator flow path, the proximal regulator opening configured to allow regulator fluid to flow therethrough when the vial adapter module is coupled to the sealed vial and fluid is withdrawn from the vial; providing a regulator fluid module configured to mate with the proximal regulator opening, 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 unfolded and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or folded when a regulator fluid passes through an enclosure opening in the regulator enclosure; a fastener configured to couple the regulator enclosure and the proximal regulator opening; the regulator enclosure does not entirely fit within a rigid housing; and aligning the enclosure opening of the regulator enclosure with the proximal regulator opening of the pressure regulated vial adapter module; and clasping the regulator fluid module to the pressure regulated vial adapter module.

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

[0349] 39. The method of embodiment 38, wherein the fastening member is made from a material system that includes an elastic material.

[0350] 40. The method of claim 39, wherein the fastening 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 clip onto a pressure regulated vial adapter module to form a vial adapter for mating with a sealed vial, the pressure regulated vial adapter module comprising a containment device, the containment device comprising: a distal extractor opening configured to allow fluid to be drawn from the sealed vial when the adapter is mated 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 containment device; and a proximal regulator opening in fluid communication with the regulator flow path, the proximal regulator opening configured to allow regulator fluid to flow therethrough or therethrough when the vial adapter module is mated with 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 unfolded and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or folded when a regulator fluid passes through an enclosure opening in the regulator enclosure; a filler material in the regulator enclosure configured to secure an initial volume of regulator fluid in the regulator enclosure, thereby enabling the adapter to supply regulator fluid from the regulator enclosure to the sealed vial as fluid is withdrawn from the sealed vial through the extractor opening; and a fastener configured to couple the regulator enclosure with the proximal regulator opening such that the regulator fluid module is permitted to move a small distance relative to the pressure regulated vial adapter module during routine operation of the vial adapter without the fastener tearing, breaking, or otherwise being damaged; The regulator enclosure does not entirely fit within a rigid housing.

[0352] 42. A method of manufacturing a modular adapter for mating with and regulating pressure within a sealed vial, comprising: forming a containment apparatus with a distal access opening configured to allow transfer of fluid between a medical device and the sealed vial when the adapter is coupled to the sealed vial, wherein at least a portion of an access flow path and at least a portion of a regulator flow path pass through the containment apparatus, 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 comprising an opening, the coupling assembly configured to allow flow of a conditioning fluid between the opening and the regulator flow path, the flow of conditioning fluid passing through the membrane; and providing a regulator enclosure configured to be positioned in fluid communication with the opening, the 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 unfolded, and a second orientation in which at least a portion of the regulator enclosure is at least partially contracted or folded when regulator fluid passes through an opening in the regulator enclosure.

[0353] 43. The method of embodiment 42, further comprising the step of selecting the regulator enclosure from regulator enclosures of various sizes, the selection being based on a volume of drug fluid to be drawn from the sealed vial.

[0354] 44. The method of embodiment 42, wherein the flow of conditioning fluid passes between the opening and the sealed vial as drug fluid is withdrawn from the sealed vial via the access channel.

[0355] 45. The method of embodiment 42, wherein the opening is in fluid communication with the outside atmosphere before the regulator enclosure is placed in fluid communication with the opening.

[0356] 46. ​​A vial adapter having an insertion shaft, the vial adapter configured for use in an area with a bed and for mating with a sealed vial, the vial adapter a housing assembly including a piercing member capable of piercing a septum of a 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 allow for drawing fluid from a 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; 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; an occluder valve contained 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, wherein the proximal extractor opening is farther from the floor than the distal extractor 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; A vial adapter, wherein the obturator valve inhibits fluid from passing past the obturator valve toward the proximal regulator opening when the obturator valve is in a closed configuration, the axis of rotation is perpendicular to an insertion axis of the vial adapter, and the obturator valve continuously transitions between the closed and open configurations substantially independent of the axis of rotation about which the vial adapter is rotated.

[0357] 47. The vial adapter of embodiment 46, wherein the occluder valve transitions to a closed configuration when the vial adapter is rotated to an inverted position.

[0358] 48. The vial adapter of embodiment 46, wherein the occluder valve transitions to an open configuration when the vial adapter is rotated to an upright position.

[0359] 49. A vial adapter as described in embodiment 46, wherein the occluder valve comprises a valve chamber in fluid communication with the regulator flow path, an occluder member within the valve chamber, and a valve seat, the occluder valve being configured to transition to a closed configuration after the occluder member and the valve seat are engaged, and the occluder valve being configured to transition to an open configuration after the occluder member disengages from the valve seat.

[0360] 50. A vial adapter as described in embodiment 49, wherein the closure member moves within the valve chamber under the influence of gravity.

[0361] 51. A vial adapter as described in embodiment 49, wherein the closure member is a spherical ball.

[0362] 52. A vial adapter as described in embodiment 49, wherein the closure member has a cylindrical body portion with a tapered end.

[0363] 53. A vial adapter as described in embodiment 49, wherein the closure member has an ellipsoid shape.

[0364] 54. A vial adapter as described in embodiment 46, wherein the occluder valve has a generally cylindrical shape and an axial centerline.

[0365] 55. A vial adapter as described in embodiment 54, wherein the occluder valve is rotatable about an axial centerline of the occluder valve relative to the regulator flow path.

[0366] 56. The vial adapter of embodiment 46, further comprising a filter positioned in the regulator flow path between the occluder valve and the proximal regulator opening.

[0367] 57. A vial adapter as described in embodiment 56, wherein the filter is a hydrophobic filter.

[0368] 58. A vial adapter configured to mate with a sealed vial, the vial adapter having an insertion axis; a housing assembly including a piercing member capable of piercing 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, 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; an occluder valve disposed in at least a portion of the regulator flow path and having a proximal opening proximate the proximal regulator opening and a distal opening proximate the distal regulator opening, the occluder valve further configured to transition between a closed configuration and an open configuration, the occluder valve a valve chamber in fluid communication with the regulator flow passage and the regulator fluid flow path, the valve chamber having an obstruction member, a travel path for the obstruction member, and a valve seat; a valve passage in fluid communication with the valve chamber and the regulator passage 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. an occluder valve; A vial adapter, wherein the occluder valve is configured to transition to a closed configuration when the occluder member engages the valve seat, and the occluder valve is configured to transition to an open configuration when the occluder member disengages from the valve seat, and an angle between a path of travel for the occluder member and a regulator fluid flow path at one or more of the proximal and distal interfaces is oblique or perpendicular.

[0369] 59. A vial adapter as described in embodiment 58, wherein the path of movement for the occlusion member is oblique or perpendicular to the installation path of the occlusion valve.

[0370] 60. A vial adapter as described in embodiment 59, wherein the angle between the movement path and the installation path is greater than about 45° and less than about 135°.

[0371] 61. A vial adapter as described in embodiment 58, wherein the closure member is a spherical ball.

[0372] 62. The vial adapter of embodiment 58, wherein the closure member has a cylindrical body portion with a tapered end.

[0373] 63. A vial adapter as described in embodiment 58, wherein the closure member has an ellipsoid shape.

[0374] 64. A vial adapter as described in embodiment 60, wherein the angle between the travel path and the installation path is approximately 90°.

[0375] 65. A vial adapter as described in embodiment 58, wherein the angle between the movement path and the installation path is substantially the same as the angle between the insertion axis of the vial adapter and the installation path.

[0376] 66. A vial adapter as described in embodiment 58, wherein the path of movement is substantially parallel to the insertion axis of the vial adapter.

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

[0378] 68. A vial adapter as described in embodiment 67, wherein the filter is a hydrophobic filter.

[0379] 69. A method of manufacturing a modular vial adapter configured to mate with a sealed vial, comprising: selecting a connector interface having an insertion axis, the connector interface a housing assembly including a piercing member capable of piercing 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 flow path passing through at least a portion of the housing assembly; coupling a regulator assembly with a proximal regulator opening of the connector interface, the regulator assembly comprising a regulator pathway configured to be in fluid communication with the regulator flow path when the regulator assembly is coupled with the connector interface, the regulator flow path and the regulator pathway defining a regulator fluid flow path, the regulator assembly further comprising an occluder valve at least partially mounted in one or more of the regulator flow path and the regulator pathway via a mounting pathway and having a proximal opening closest to the proximal regulator opening and a distal opening closest to the distal regulator opening, the occluder valve configured to transition between a closed configuration and an open configuration, the occluder valve a valve chamber in fluid communication with the regulator fluid flow path and having an obstruction member, a travel path for the obstruction member, and a valve seat; a valve flowpath having a flow path in fluid communication with the valve chamber and the regulator fluid flowpath; 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. and A method in which 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 an angle between a movement path for the occlusion member and a regulator fluid flow path at one or more of the proximal and distal interfaces is oblique or perpendicular.

[0380] 70. The method of embodiment 69, further comprising installing an occluder valve at least partially in one or more of the regulator flow path and the regulator path via an installation path. ...

Claims

1. A housing having an interface, a cap connector, and a lumen, the interface configured to connect to a syringe, and the cap connector configured to connect to a vial having a septum; a piercing member configured to be inserted through the septum of the vial; an access channel configured to convey fluid between the syringe and the vial; a regulator enclosure having a flexible first side and a flexible second side, the regulator enclosure positioned outside the vial; a regulator flow path configured to carry a regulator fluid, the regulator flow path extending between the regulator enclosure and the vial; a coupling disposed intermediate the regulator enclosure and the lumen, the regulator flow path passing through the coupling; a first valve configured to open to allow ambient air to enter the regulator flow path; a second valve configured to control the flow of a regulator fluid in the regulator flow path; Equipped with the flexible first side and the flexible second side are configured to receive a conditioning fluid therebetween, and the flexible first side and the flexible second side are each configured to expand in response to liquid being introduced into the vial through the access channel. Pressure-regulating vial adapter.

2. A pressure-regulating vial adapter as described in claim 1, wherein the first valve is provided with a check valve.

3. A pressure-regulating vial adapter as described in claim 1, wherein the first valve is a diaphragm check valve.

4. A pressure-regulating vial adapter as described in claim 1, wherein the first valve is located on the joint.

5. A pressure regulated vial adapter as described in claim 1, wherein the second valve comprises an orientation-sensing valve.

6. A pressure-regulated vial adapter as described in claim 1, wherein the second valve comprises a dome valve.

7. A pressure-regulated vial adapter as described in claim 1, wherein the second valve comprises a two-way valve.

8. A pressure regulated vial adapter as described in claim 1, wherein the regulator enclosure comprises a bag.

9. A pressure-regulated vial adapter as described in claim 1, wherein the regulator enclosure is configured to extend laterally outward from the housing.

10. A pressure regulated vial adapter as described in claim 1, further comprising a rigid housing, wherein the regulator enclosure is configured to extend from the rigid housing.

11. A pressure-regulating vial adapter as described in claim 1, wherein the flexible second side is located laterally outward of the flexible first side.

12. A pressure-regulating vial adapter as described in claim 1, wherein the flexible first side portion comprises a first sheet, the flexible second side portion comprises a second sheet, and the first sheet and the second sheet are fixed together at the outer peripheries of the first sheet and the second sheet.

13. A pressure regulated vial adapter as described in claim 1, further comprising a filter configured to filter outside air entering the pressure regulated vial adapter.

14. A pressure regulated vial adapter as described in claim 1, wherein the interface is located at the top of the housing, the cap connector is located at the bottom of the housing, and the lumen is located at a lateral side of the housing.

15. A pressure-regulated vial adapter as described in claim 1, further comprising a center of gravity and a central axis, wherein the center of gravity is sufficiently close to the central axis so as to prevent the pressure-regulated vial adapter from tipping over when connected to the vial.

16. A pressure-regulating vial adapter as described in claim 1, wherein the first valve comprises a diaphragm check valve and the second valve comprises a dome valve.

17. A pressure-regulated vial adapter as described in claim 1, wherein the first valve is located at the joint and the second valve is located within the regulator flow path.

18. A pressure regulated vial adapter as described in claim 1, wherein the first valve comprises a diaphragm check valve on the joint and the second valve comprises a dome valve in the regulator flow path.

19. A housing having an interface, a cap connector, and a lumen, the interface configured to connect to a syringe and the cap connector configured to connect to a vial having a septum; a piercing member configured to be inserted through the septum of the vial; an access channel configured to convey fluid between the syringe and the vial; a regulator enclosure having a flexible first side and a flexible second side, the regulator enclosure positioned outside the vial; a regulator flow path configured to carry a regulator fluid between the regulator enclosure and the vial; Equipped with the flexible first side and the flexible second side are configured to unfold in response to liquid being introduced into the vial such that at least one of the flexible first side and the flexible second side moves in a direction away from the vial; the flexible first side and the flexible second side are further configured to crinkle and curl in response to liquid being drawn from the vial. Pressure-regulating vial adapter.

20. A pressure regulated vial adapter as described in claim 19, wherein the regulator enclosure is further configured to be deployed laterally outward relative to the longitudinal axis of the pressure regulated vial adapter.

21. A pressure-regulating vial adapter as described in claim 19, further comprising a coupling portion connected to the lumen, wherein the regulator flow path passes through at least the coupling portion and the lumen.

22. A pressure-regulated vial adapter as described in claim 21, wherein the lumen and the coupling portion extend laterally outward relative to the longitudinal axis of the pressure-regulated vial adapter.

23. A pressure regulated vial adapter as described in claim 21, wherein the coupling portion is partially received within the lumen.

24. A pressure-regulated vial adapter as described in claim 19, wherein when the pressure-regulated vial adapter is connected to the vial in an upright orientation, the interface faces upward, the cap connector faces downward, and the lumen faces sideways.

25. A pressure-regulating vial adapter as described in claim 19, wherein the flexible first side portion comprises a first sheet, the flexible second side portion comprises a second sheet, and the first sheet and the second sheet are connected at the outer periphery of the first sheet and the second sheet.

26. A housing configured to mate with a vial having a septum, comprising: a piercing member configured to be inserted through the septum of the vial; an access channel configured to carry a medical fluid; and a regulator flow path configured to carry a conditioning fluid; a housing comprising: a reservoir disposed outside the vial, a first rigid side connected to the housing; a second rigid side; and a flexible ring disposed between the first rigid side and the second rigid side; a reservoir comprising: A pressure regulating vial adapter comprising: The pressure regulating vial adapter, in response to the medical fluid being introduced into the vial through the access channel, a conditioning fluid flows from the regulator flow path into the reservoir; the flexible ring and the second rigid side move relative to the first rigid side; A pressure-regulating vial adapter configured to:

27. ​​A pressure regulated vial adapter as described in claim 26, wherein the pressure regulated vial adapter is further configured such that the flexible ring crumples and curls up in response to medical fluid being drawn from the vial.

28. A pressure regulated vial adapter as described in claim 26, further configured such that the second rigid side portion moves away from the first rigid side portion in response to medical fluid being introduced into the vial.

29. A pressure regulated vial adapter as described in claim 26, further configured to increase the volume within the reservoir in response to medical fluid being introduced into the vial.

30. The pressure regulated vial adapter of claim 26, further configured such that the flexible ring unfolds or extends in response to medical fluid being introduced into the vial.

31. A pressure regulated vial adapter as described in claim 26, wherein the flexible ring is located inside the first rigid side portion and the second rigid side portion.

32. A pressure regulated vial adapter as described in claim 26, wherein the flexible ring is attached to the first rigid side portion and the second rigid side portion.

33. A housing configured to mate with a vial having a septum, the housing including a piercing member configured to be inserted distally through the septum of the vial, the piercing member having a distal tip; a rigid enclosure having an interior space; a reservoir including a first flexible side and a second flexible side, the reservoir configured to expand in the distal direction from a deflated state to an expanded state in response to a conditioning fluid being received between the first flexible side and the second flexible side; Equipped with When the housing is coupled to the vial in the deflated state, the reservoir is located in the interior space of the rigid enclosure and outside the vial; during inflation from the deflated state to the inflated state, a portion of the reservoir extends from the rigid enclosure such that a portion of the reservoir is in the rigid enclosure and a portion of the reservoir is not in the rigid enclosure. Pressure-regulating vial adapter.

34. A pressure-regulating vial adapter as described in claim 33, wherein the reservoir is annular.

35. A pressure regulated vial adapter as described in claim 33, wherein the reservoir comprises a bag.

36. A pressure regulated vial adapter as described in claim 33, wherein the reservoir crumples and curls in response to regulating fluid being drawn from between the first flexible side and the second flexible side.

37. A pressure regulated vial adapter as described in claim 33, wherein the first flexible side is made from a first sheet of material and the second flexible side is made from a second sheet of material, the first sheet and the second sheet being connected at peripheral edges.

38. A housing configured to mate with a vial having a septum, the housing including a piercing member configured to be inserted through the septum of the vial; a rigid enclosure having an interior space; 1. A reservoir comprising a first sheet of flexible material and a second sheet of flexible material, the first sheet and the second sheet of flexible material are connected at peripheral edges, and the reservoir is configured to expand from a deflated state to an expanded state in response to a conditioning fluid being received between the first flexible sheet and the second flexible sheet; When the housing is in the collapsed state and coupled to the vial, the reservoir is located in the interior space of the rigid enclosure and outside the vial. Pressure-regulating vial adapter.

39. A pressure regulated vial adapter as described in claim 38, wherein the reservoir is folded when the housing is coupled to the vial in the deflated state.

40. The piercing member extends distally from the housing, the piercing member having a distal tip; the reservoir is configured to expand in the distal direction.

39. The pressure regulated vial adapter of claim 38.

41. A pressure regulated vial adapter as described in claim 38, wherein during inflation from the deflated state to the inflated state, a portion of the reservoir expands from the rigid enclosure such that a portion of the reservoir is in the interior space of the rigid enclosure and a portion of the reservoir is not in the interior space of the rigid enclosure.

42. A pressure-regulating vial adapter as described in claim 38, wherein the reservoir is annular.

43. A pressure-regulated vial adapter as described in claim 42, wherein the annular reservoir is substantially centered relative to the axial center of the pressure-regulated vial adapter.

44. A pressure-regulated vial adapter as described in claim 38, wherein when the housing is coupled to the vial in the deflated state, the bottom of the annular reservoir is above the top of the vial.

Images